Renal Cell Carcinoma

Although the two major subtypes of papillary renal cell carcinoma (PRCC) differ on a variety of measures of aggressiveness, subtype is not independently prognostic, according to a retrospective cohort study conducted by the German Network of Kidney Cancer.

Investigators led by Iris Polifka, an intern at the Institute of Pathology at the University Hospital Erlangen (Germany), characterized 376 renal tumors initially diagnosed as PRCC. They reviewed histologic features and performed immunohistochemical staining for a range of markers.

Main study results, which were reported in Human Pathology, showed that 65.4% of the tumors were PRCC subtype 1 and 34.6% were PRCC subtype 2. The former more commonly had foamy macrophages and expressed cytokeratin 7, whereas the latter more commonly had abundant cytoplasm, expressed E-cadherin and p53, and had high MIB1 expression (staining of more than 15% of cells), which indicated a high proliferation rate (P less than .05 for each). The latter also had higher stage and higher grade.

Univariate analysis in the entire study cohort showed that racemase expression and cytokeratin 7 expression were favorable prognostic factors for overall survival, whereas presence of abundant cytoplasm and psammoma bodies, high MIB1 expression, and PRCC subtype 2 were unfavorable prognostic factors.

However, in multivariate analysis, only four factors were independent predictors of death: high tumor MIB1 expression (hazard ratio, 2.465; P = .033), higher T stage (P = .036), metastases (HR, 4.334; P = .011), and age older than the median of 63 years at surgery (HR, 2.384; P = .005). Notably, tumor subtype did not independently predict this outcome.

“[T]he better [overall survival] in PRCC1 is mainly a reflection of its encapsulated nature associated with lower TNM stage … while enhanced proliferation might add to the aggressive nature of high grade and high stage tumors independently from PRCC subtype,” the investigators propose.

“PRCC subtype on its own is not suitable for estimating survival. More data focusing on PRCC tumor biology is needed to define prognostic subgroups, especially in PRCC2,” they conclude.

The investigators disclosed that they had no relevant conflicts of interest. The study did not receive any specific funding.

SOURCE: Polifka I et al. Hum Pathol. 2018 Aug 16. doi: 10.1016/j.humpath.2018.08.006.

Although the two major subtypes of papillary renal cell carcinoma (PRCC) differ on a variety of measures of aggressiveness, subtype is not independently prognostic, according to a retrospective cohort study conducted by the German Network of Kidney Cancer.

Investigators led by Iris Polifka, an intern at the Institute of Pathology at the University Hospital Erlangen (Germany), characterized 376 renal tumors initially diagnosed as PRCC. They reviewed histologic features and performed immunohistochemical staining for a range of markers.

Main study results, which were reported in Human Pathology, showed that 65.4% of the tumors were PRCC subtype 1 and 34.6% were PRCC subtype 2. The former more commonly had foamy macrophages and expressed cytokeratin 7, whereas the latter more commonly had abundant cytoplasm, expressed E-cadherin and p53, and had high MIB1 expression (staining of more than 15% of cells), which indicated a high proliferation rate (P less than .05 for each). The latter also had higher stage and higher grade.

Univariate analysis in the entire study cohort showed that racemase expression and cytokeratin 7 expression were favorable prognostic factors for overall survival, whereas presence of abundant cytoplasm and psammoma bodies, high MIB1 expression, and PRCC subtype 2 were unfavorable prognostic factors.

However, in multivariate analysis, only four factors were independent predictors of death: high tumor MIB1 expression (hazard ratio, 2.465; P = .033), higher T stage (P = .036), metastases (HR, 4.334; P = .011), and age older than the median of 63 years at surgery (HR, 2.384; P = .005). Notably, tumor subtype did not independently predict this outcome.

“[T]he better [overall survival] in PRCC1 is mainly a reflection of its encapsulated nature associated with lower TNM stage … while enhanced proliferation might add to the aggressive nature of high grade and high stage tumors independently from PRCC subtype,” the investigators propose.

“PRCC subtype on its own is not suitable for estimating survival. More data focusing on PRCC tumor biology is needed to define prognostic subgroups, especially in PRCC2,” they conclude.

The investigators disclosed that they had no relevant conflicts of interest. The study did not receive any specific funding.

SOURCE: Polifka I et al. Hum Pathol. 2018 Aug 16. doi: 10.1016/j.humpath.2018.08.006.

Although the two major subtypes of papillary renal cell carcinoma (PRCC) differ on a variety of measures of aggressiveness, subtype is not independently prognostic, according to a retrospective cohort study conducted by the German Network of Kidney Cancer.

Investigators led by Iris Polifka, an intern at the Institute of Pathology at the University Hospital Erlangen (Germany), characterized 376 renal tumors initially diagnosed as PRCC. They reviewed histologic features and performed immunohistochemical staining for a range of markers.

Main study results, which were reported in Human Pathology, showed that 65.4% of the tumors were PRCC subtype 1 and 34.6% were PRCC subtype 2. The former more commonly had foamy macrophages and expressed cytokeratin 7, whereas the latter more commonly had abundant cytoplasm, expressed E-cadherin and p53, and had high MIB1 expression (staining of more than 15% of cells), which indicated a high proliferation rate (P less than .05 for each). The latter also had higher stage and higher grade.

Univariate analysis in the entire study cohort showed that racemase expression and cytokeratin 7 expression were favorable prognostic factors for overall survival, whereas presence of abundant cytoplasm and psammoma bodies, high MIB1 expression, and PRCC subtype 2 were unfavorable prognostic factors.

However, in multivariate analysis, only four factors were independent predictors of death: high tumor MIB1 expression (hazard ratio, 2.465; P = .033), higher T stage (P = .036), metastases (HR, 4.334; P = .011), and age older than the median of 63 years at surgery (HR, 2.384; P = .005). Notably, tumor subtype did not independently predict this outcome.

“[T]he better [overall survival] in PRCC1 is mainly a reflection of its encapsulated nature associated with lower TNM stage … while enhanced proliferation might add to the aggressive nature of high grade and high stage tumors independently from PRCC subtype,” the investigators propose.

“PRCC subtype on its own is not suitable for estimating survival. More data focusing on PRCC tumor biology is needed to define prognostic subgroups, especially in PRCC2,” they conclude.

The investigators disclosed that they had no relevant conflicts of interest. The study did not receive any specific funding.

SOURCE: Polifka I et al. Hum Pathol. 2018 Aug 16. doi: 10.1016/j.humpath.2018.08.006.

Hypofractionated radiation therapy (RT) may be a more viable treatment option for oligometastatic renal cell carcinoma (RCC) than is generally recognized, a recent literature review has suggested.

Advances in stereotactic RT offer “new opportunities in RCC management” with limited toxicity, reported Francesca De Felice, PhD, of Sapienza University in Rome and her coauthor. The authors suggested that future studies investigate RT in combination with immunotherapy.

“Due to the assumption that RCC is a radioresistant tumor,” the authors wrote in Critical Reviews in Oncology/Hematology, “RT has long been considered a futile approach to manage primary disease” and is predominantly used for treatment of distant metastases with palliative intent. “This review provides highlights in current RCC strategies to potentially suggest a more tailored treatment approach in clinical daily practice.”

The investigators concluded that hypofractionated RT (greater than 3 Gy/fraction) deserves more serious consideration. “It has enormous advantages,” the authors wrote, “assuring ablative doses to the target meanwhile preserving surrounding normal tissues. Using stereotactic technique, surprising high local control rates have been achieved in several tumors (such as lung, liver, and bone), in both primary and oligometastatic setting[s].”

In five studies, single-dose RT (ranging from 8 to 24 Gy) was used to treat patients with RCC and extracranial metastases. Of the patients in these studies, 89% of them achieved local control, median overall survival (OS) ranged from 11.7 months to 21 months, and severe RT-related toxicity occurred 0%-4% of the time.

“Although [there is a] high level of data heterogeneity,” the authors wrote, “this systematic review suggested that stereotactic RT is associated with excellent local control rates and low toxicity incidence. Thus, if feasible, stereotactic RT represents an effective and safe approach to treat RCC metastasis.”

The authors cautioned that “the optimal high dose required for local tumor control has not yet been defined.”

The authors suggested that, in the future, immunotherapy in combination with RT may “produce synergistic effects, resulting in better response rate and duration, given the known immune-modulated abscopal effect of RT.” First, questions about treatment sequencing, dosing, and patient selection would need to be answered. “Further research should be aimed at these clinical needs in order to achieve the maximum benefit to RCC patient[s].”

This study did not receive specific funding.

SOURCE: Felice F et al. Crit Rev Oncol Hematol. 2018 Aug 1. doi: 10.1016/j.critrevonc.2018.06.002

Hypofractionated radiation therapy (RT) may be a more viable treatment option for oligometastatic renal cell carcinoma (RCC) than is generally recognized, a recent literature review has suggested.

Advances in stereotactic RT offer “new opportunities in RCC management” with limited toxicity, reported Francesca De Felice, PhD, of Sapienza University in Rome and her coauthor. The authors suggested that future studies investigate RT in combination with immunotherapy.

“Due to the assumption that RCC is a radioresistant tumor,” the authors wrote in Critical Reviews in Oncology/Hematology, “RT has long been considered a futile approach to manage primary disease” and is predominantly used for treatment of distant metastases with palliative intent. “This review provides highlights in current RCC strategies to potentially suggest a more tailored treatment approach in clinical daily practice.”

The investigators concluded that hypofractionated RT (greater than 3 Gy/fraction) deserves more serious consideration. “It has enormous advantages,” the authors wrote, “assuring ablative doses to the target meanwhile preserving surrounding normal tissues. Using stereotactic technique, surprising high local control rates have been achieved in several tumors (such as lung, liver, and bone), in both primary and oligometastatic setting[s].”

In five studies, single-dose RT (ranging from 8 to 24 Gy) was used to treat patients with RCC and extracranial metastases. Of the patients in these studies, 89% of them achieved local control, median overall survival (OS) ranged from 11.7 months to 21 months, and severe RT-related toxicity occurred 0%-4% of the time.

“Although [there is a] high level of data heterogeneity,” the authors wrote, “this systematic review suggested that stereotactic RT is associated with excellent local control rates and low toxicity incidence. Thus, if feasible, stereotactic RT represents an effective and safe approach to treat RCC metastasis.”

The authors cautioned that “the optimal high dose required for local tumor control has not yet been defined.”

The authors suggested that, in the future, immunotherapy in combination with RT may “produce synergistic effects, resulting in better response rate and duration, given the known immune-modulated abscopal effect of RT.” First, questions about treatment sequencing, dosing, and patient selection would need to be answered. “Further research should be aimed at these clinical needs in order to achieve the maximum benefit to RCC patient[s].”

This study did not receive specific funding.

SOURCE: Felice F et al. Crit Rev Oncol Hematol. 2018 Aug 1. doi: 10.1016/j.critrevonc.2018.06.002

Hypofractionated radiation therapy (RT) may be a more viable treatment option for oligometastatic renal cell carcinoma (RCC) than is generally recognized, a recent literature review has suggested.

Advances in stereotactic RT offer “new opportunities in RCC management” with limited toxicity, reported Francesca De Felice, PhD, of Sapienza University in Rome and her coauthor. The authors suggested that future studies investigate RT in combination with immunotherapy.

“Due to the assumption that RCC is a radioresistant tumor,” the authors wrote in Critical Reviews in Oncology/Hematology, “RT has long been considered a futile approach to manage primary disease” and is predominantly used for treatment of distant metastases with palliative intent. “This review provides highlights in current RCC strategies to potentially suggest a more tailored treatment approach in clinical daily practice.”

The investigators concluded that hypofractionated RT (greater than 3 Gy/fraction) deserves more serious consideration. “It has enormous advantages,” the authors wrote, “assuring ablative doses to the target meanwhile preserving surrounding normal tissues. Using stereotactic technique, surprising high local control rates have been achieved in several tumors (such as lung, liver, and bone), in both primary and oligometastatic setting[s].”

In five studies, single-dose RT (ranging from 8 to 24 Gy) was used to treat patients with RCC and extracranial metastases. Of the patients in these studies, 89% of them achieved local control, median overall survival (OS) ranged from 11.7 months to 21 months, and severe RT-related toxicity occurred 0%-4% of the time.

“Although [there is a] high level of data heterogeneity,” the authors wrote, “this systematic review suggested that stereotactic RT is associated with excellent local control rates and low toxicity incidence. Thus, if feasible, stereotactic RT represents an effective and safe approach to treat RCC metastasis.”

The authors cautioned that “the optimal high dose required for local tumor control has not yet been defined.”

The authors suggested that, in the future, immunotherapy in combination with RT may “produce synergistic effects, resulting in better response rate and duration, given the known immune-modulated abscopal effect of RT.” First, questions about treatment sequencing, dosing, and patient selection would need to be answered. “Further research should be aimed at these clinical needs in order to achieve the maximum benefit to RCC patient[s].”

This study did not receive specific funding.

SOURCE: Felice F et al. Crit Rev Oncol Hematol. 2018 Aug 1. doi: 10.1016/j.critrevonc.2018.06.002

The incidence of metastatic renal cell carcinoma (RCC) continues to rise, according to a recent study. In turn, skeletal-related events are also becoming more common.

Many patients with metastatic disease have skeletal involvement, so knowledge of skeletal-related events (SREs) is more important than ever, reported Masood Umer, MD, of Aga Khan University Hospital in Karachi, Pakistan, and his coauthors. SREs include nerve compression, hypercalcemia, impending fractures, and pathological fractures, any one of which may require medical or surgical intervention.

Beyond SREs, “bone metastases in RCC [have a] negative impact on progression-free survival and overall survival of patients treated with systemic therapies,” the authors wrote in Annals of Medicine and Surgery.

The authors conducted a literature review of skeletal metastasis in RCC, which included 947 patients, assessing incidence and discussing appropriate medical and surgical interventions.

A total of 26.7% of patients with RCC also had skeletal metastasis. The most common sites of metastasis were the proximal femur, pelvis, and spine. It was estimated that 85% of patients with metastatic RCC may experience SREs and related complications, with an average of more than two events per individual.

A multimodal approach is required, potentially involving surgical and medical interventions. For isolated bony metastases and fractures, surgery is often beneficial. Denosumab is the leading medical treatment; compared with zoledronic acid, denosumab prolongs time to first SRE by a median of approximately 8 months and reduces risk of first SRE by almost 20%. Risks of osteonecrosis are similar between agents.

The authors noted that research concerning the impact of targeted therapies on rates of bone metastasis and SREs is limited by patient exclusions in clinical trials. Granted, these agents have likely made for better outcomes.

“Advancement in targeted therapy in recent decades [has] made some improvement in treatment of SREs and has helped in improving patent’s quality of life, but still we are in need of further improvement in treatment modalities,” they concluded

This study did not receive specific funding.

SOURCE: Umer M et al. Ann Med Surg. 2018 Jan 21. doi: 10.1016/j.amsu.2018.01.002.

The incidence of metastatic renal cell carcinoma (RCC) continues to rise, according to a recent study. In turn, skeletal-related events are also becoming more common.

Many patients with metastatic disease have skeletal involvement, so knowledge of skeletal-related events (SREs) is more important than ever, reported Masood Umer, MD, of Aga Khan University Hospital in Karachi, Pakistan, and his coauthors. SREs include nerve compression, hypercalcemia, impending fractures, and pathological fractures, any one of which may require medical or surgical intervention.

Beyond SREs, “bone metastases in RCC [have a] negative impact on progression-free survival and overall survival of patients treated with systemic therapies,” the authors wrote in Annals of Medicine and Surgery.

The authors conducted a literature review of skeletal metastasis in RCC, which included 947 patients, assessing incidence and discussing appropriate medical and surgical interventions.

A total of 26.7% of patients with RCC also had skeletal metastasis. The most common sites of metastasis were the proximal femur, pelvis, and spine. It was estimated that 85% of patients with metastatic RCC may experience SREs and related complications, with an average of more than two events per individual.

A multimodal approach is required, potentially involving surgical and medical interventions. For isolated bony metastases and fractures, surgery is often beneficial. Denosumab is the leading medical treatment; compared with zoledronic acid, denosumab prolongs time to first SRE by a median of approximately 8 months and reduces risk of first SRE by almost 20%. Risks of osteonecrosis are similar between agents.

The authors noted that research concerning the impact of targeted therapies on rates of bone metastasis and SREs is limited by patient exclusions in clinical trials. Granted, these agents have likely made for better outcomes.

“Advancement in targeted therapy in recent decades [has] made some improvement in treatment of SREs and has helped in improving patent’s quality of life, but still we are in need of further improvement in treatment modalities,” they concluded

This study did not receive specific funding.

SOURCE: Umer M et al. Ann Med Surg. 2018 Jan 21. doi: 10.1016/j.amsu.2018.01.002.

The incidence of metastatic renal cell carcinoma (RCC) continues to rise, according to a recent study. In turn, skeletal-related events are also becoming more common.

Many patients with metastatic disease have skeletal involvement, so knowledge of skeletal-related events (SREs) is more important than ever, reported Masood Umer, MD, of Aga Khan University Hospital in Karachi, Pakistan, and his coauthors. SREs include nerve compression, hypercalcemia, impending fractures, and pathological fractures, any one of which may require medical or surgical intervention.

Beyond SREs, “bone metastases in RCC [have a] negative impact on progression-free survival and overall survival of patients treated with systemic therapies,” the authors wrote in Annals of Medicine and Surgery.

The authors conducted a literature review of skeletal metastasis in RCC, which included 947 patients, assessing incidence and discussing appropriate medical and surgical interventions.

A total of 26.7% of patients with RCC also had skeletal metastasis. The most common sites of metastasis were the proximal femur, pelvis, and spine. It was estimated that 85% of patients with metastatic RCC may experience SREs and related complications, with an average of more than two events per individual.

A multimodal approach is required, potentially involving surgical and medical interventions. For isolated bony metastases and fractures, surgery is often beneficial. Denosumab is the leading medical treatment; compared with zoledronic acid, denosumab prolongs time to first SRE by a median of approximately 8 months and reduces risk of first SRE by almost 20%. Risks of osteonecrosis are similar between agents.

The authors noted that research concerning the impact of targeted therapies on rates of bone metastasis and SREs is limited by patient exclusions in clinical trials. Granted, these agents have likely made for better outcomes.

“Advancement in targeted therapy in recent decades [has] made some improvement in treatment of SREs and has helped in improving patent’s quality of life, but still we are in need of further improvement in treatment modalities,” they concluded

This study did not receive specific funding.

SOURCE: Umer M et al. Ann Med Surg. 2018 Jan 21. doi: 10.1016/j.amsu.2018.01.002.

Expression of leptin could help differentiate benign renal oncocytomas from chromophobe renal cell carcinoma (RCC), results of a recent pathology study suggest.

Renal oncocytomas had significantly increased nuclear expression of leptin, compared with the eosinophilic subtype of chromophobe RCC, according to the study.

If translated into clinical urology and pathology practice, quantification of leptin expression could help in the difficult task of differentiating between these renal lesions, according to the investigators, led by Glenda Gobe, PhD, of the Kidney Disease Research Group at the University of Queensland in Brisbane, Australia.

“This may have a major clinical impact in reducing unnecessary intervention and treatment-related harm,” Dr. Gobe and her colleagues reported in Pathology.

They obtained archived paraffin blocks from human renal tumor tissue obtained between 2009 and 2014. Paraffin sections were immunostained for leptin and leptin receptors.

The investigators evaluated 30 chromophobe RCC specimens – 15 eosinophilic and 15 noneosinophilic variants – and 15 renal oncocytomas. They also included 30 clear cell RCCs, the most common histological subtype of RCC, to verify immunohistochemistry (IHC) staining patterns.

Results showed that both leptin and leptin receptor IHC was significantly increased in tumor versus in matched, noncancerous kidney tissue.

Expression of both leptin and leptin receptor was highest for renal oncocytomas versus both the chromophobe and clear cell RCCs. On closer scrutiny, the investigators said, nuclear expression of leptin in renal oncocytomas had a significantly higher intensity versus chromophobe RCC.

“This important finding could prove to be helpful in the distinction between chromophobe RCC and renal oncocytoma,” Dr. Gobe and her coauthors wrote in their report.

In a subgroup analysis, they found a significantly increased nuclear leptin intensity for the renal oncocytomas as compared to the eosinophilic variants of chromophobe RCC (P = .016 by Dunn’s multiple comparisons test).

By contrast, testing did not reveal a significant difference for renal oncocytomas versus noneosinophilic chromophobe RCC (P = .0939) or versus clear cell RCC (P greater than .999).

Leptin, secreted by adipose cells that help regulate energy balance through inhibition of hunger, may play a role in carcinogenesis, according to investigators. Studies to date have shown that the hormone may impact carcinogenesis through cell proliferation, inhibition of apoptosis, and other potential mechanisms.

Applying this biomarker in clinical practice could more reliably characterize renal lesions with no or limited malignant potential, according to the investigators.

“The distinction of renal oncocytoma from chromophobe RCC will dictate different management pathways, as renal oncocytoma is benign while chromophobe RCC is a malignant subtype which will require further surveillance,” Dr. Gobe and her coinvestigators wrote.

The University of Malaya, Kuala Lumpur, Malaysia, funded the study. Dr. Gobe and her coauthors stated that they had no conflicts of interest.

SOURCE: Gobe G et al. Pathology. 2018 Aug;50(5):504-10.

Expression of leptin could help differentiate benign renal oncocytomas from chromophobe renal cell carcinoma (RCC), results of a recent pathology study suggest.

Renal oncocytomas had significantly increased nuclear expression of leptin, compared with the eosinophilic subtype of chromophobe RCC, according to the study.

If translated into clinical urology and pathology practice, quantification of leptin expression could help in the difficult task of differentiating between these renal lesions, according to the investigators, led by Glenda Gobe, PhD, of the Kidney Disease Research Group at the University of Queensland in Brisbane, Australia.

“This may have a major clinical impact in reducing unnecessary intervention and treatment-related harm,” Dr. Gobe and her colleagues reported in Pathology.

They obtained archived paraffin blocks from human renal tumor tissue obtained between 2009 and 2014. Paraffin sections were immunostained for leptin and leptin receptors.

The investigators evaluated 30 chromophobe RCC specimens – 15 eosinophilic and 15 noneosinophilic variants – and 15 renal oncocytomas. They also included 30 clear cell RCCs, the most common histological subtype of RCC, to verify immunohistochemistry (IHC) staining patterns.

Results showed that both leptin and leptin receptor IHC was significantly increased in tumor versus in matched, noncancerous kidney tissue.

Expression of both leptin and leptin receptor was highest for renal oncocytomas versus both the chromophobe and clear cell RCCs. On closer scrutiny, the investigators said, nuclear expression of leptin in renal oncocytomas had a significantly higher intensity versus chromophobe RCC.

“This important finding could prove to be helpful in the distinction between chromophobe RCC and renal oncocytoma,” Dr. Gobe and her coauthors wrote in their report.

In a subgroup analysis, they found a significantly increased nuclear leptin intensity for the renal oncocytomas as compared to the eosinophilic variants of chromophobe RCC (P = .016 by Dunn’s multiple comparisons test).

By contrast, testing did not reveal a significant difference for renal oncocytomas versus noneosinophilic chromophobe RCC (P = .0939) or versus clear cell RCC (P greater than .999).

Leptin, secreted by adipose cells that help regulate energy balance through inhibition of hunger, may play a role in carcinogenesis, according to investigators. Studies to date have shown that the hormone may impact carcinogenesis through cell proliferation, inhibition of apoptosis, and other potential mechanisms.

Applying this biomarker in clinical practice could more reliably characterize renal lesions with no or limited malignant potential, according to the investigators.

“The distinction of renal oncocytoma from chromophobe RCC will dictate different management pathways, as renal oncocytoma is benign while chromophobe RCC is a malignant subtype which will require further surveillance,” Dr. Gobe and her coinvestigators wrote.

The University of Malaya, Kuala Lumpur, Malaysia, funded the study. Dr. Gobe and her coauthors stated that they had no conflicts of interest.

SOURCE: Gobe G et al. Pathology. 2018 Aug;50(5):504-10.

Expression of leptin could help differentiate benign renal oncocytomas from chromophobe renal cell carcinoma (RCC), results of a recent pathology study suggest.

Renal oncocytomas had significantly increased nuclear expression of leptin, compared with the eosinophilic subtype of chromophobe RCC, according to the study.

If translated into clinical urology and pathology practice, quantification of leptin expression could help in the difficult task of differentiating between these renal lesions, according to the investigators, led by Glenda Gobe, PhD, of the Kidney Disease Research Group at the University of Queensland in Brisbane, Australia.

“This may have a major clinical impact in reducing unnecessary intervention and treatment-related harm,” Dr. Gobe and her colleagues reported in Pathology.

They obtained archived paraffin blocks from human renal tumor tissue obtained between 2009 and 2014. Paraffin sections were immunostained for leptin and leptin receptors.

The investigators evaluated 30 chromophobe RCC specimens – 15 eosinophilic and 15 noneosinophilic variants – and 15 renal oncocytomas. They also included 30 clear cell RCCs, the most common histological subtype of RCC, to verify immunohistochemistry (IHC) staining patterns.

Results showed that both leptin and leptin receptor IHC was significantly increased in tumor versus in matched, noncancerous kidney tissue.

Expression of both leptin and leptin receptor was highest for renal oncocytomas versus both the chromophobe and clear cell RCCs. On closer scrutiny, the investigators said, nuclear expression of leptin in renal oncocytomas had a significantly higher intensity versus chromophobe RCC.

“This important finding could prove to be helpful in the distinction between chromophobe RCC and renal oncocytoma,” Dr. Gobe and her coauthors wrote in their report.

In a subgroup analysis, they found a significantly increased nuclear leptin intensity for the renal oncocytomas as compared to the eosinophilic variants of chromophobe RCC (P = .016 by Dunn’s multiple comparisons test).

By contrast, testing did not reveal a significant difference for renal oncocytomas versus noneosinophilic chromophobe RCC (P = .0939) or versus clear cell RCC (P greater than .999).

Leptin, secreted by adipose cells that help regulate energy balance through inhibition of hunger, may play a role in carcinogenesis, according to investigators. Studies to date have shown that the hormone may impact carcinogenesis through cell proliferation, inhibition of apoptosis, and other potential mechanisms.

Applying this biomarker in clinical practice could more reliably characterize renal lesions with no or limited malignant potential, according to the investigators.

“The distinction of renal oncocytoma from chromophobe RCC will dictate different management pathways, as renal oncocytoma is benign while chromophobe RCC is a malignant subtype which will require further surveillance,” Dr. Gobe and her coinvestigators wrote.

The University of Malaya, Kuala Lumpur, Malaysia, funded the study. Dr. Gobe and her coauthors stated that they had no conflicts of interest.

SOURCE: Gobe G et al. Pathology. 2018 Aug;50(5):504-10.

What appears at first glance to be a renal vascular tumor may in fact be a rare type of renal cell carcinoma (RCC), authors of a case study cautioned.

A tumor recovered from a 62-year old woman who underwent a partial nephrectomy for an incidentally discovered asymptomatic left renal mass contained arborizing vessels that mimicked hemangioma. Immunohistochemical staining of the tumor highlighted the vascular component but masked epithelial cells, a situation that, in the absence of other clues, might cause a misdiagnosis, reported Kanika Taneja, MD, from the Henry Ford Cancer Institute in Detroit, and her colleagues.

The authors were tipped off to an unusual presentation, however, by mixed signals from immunohistochemical staining, leading them to an admittedly fuzzy diagnosis of “unclassified hemangioma-like RCC.”

“This case highlights that renal cell carcinoma must be strongly considered in the differential diagnosis of renal vascular tumors, and broadens the spectrum of histologies that may mimic hemangioma,” they wrote in Human Pathology.

Although there are a few recent reports in the medical literature of clear cell RCC tumors that mimic hemangiomas, the authors noted that, “to our knowledge, non–clear cell hemangioma-like renal cell carcinoma has not been previously reported.”

The tumor in question was removed from the patient with clear surgical margins during a partial nephrectomy.

Gross examination showed a 2.6 by 2.5 by 2.5 cm, well-circumscribed, tan-brown hemorrhagic mass. On microscopic examination the tumor had hemangioma-like features and lacked typical clear cell morphology, and immunohistochemical staining did little to clarify the picture.

Specifically, although staining highlighted the epithelial component of the tumor, the investigators saw what they described as “an abnormal combination of positive markers” that are normally used to distinguish clear cell from papillary histologies, effectively throwing a monkey wrench into the diagnostic works.

The marker profile in this case included cytokeratin 7, high molecular weight cytokeratin, and carbonic anhydrase IX, but only minimal labeling for alpha-methylacyl-CoA racemase and absence of GATA3.

To add to the confusion, fluorescent in situ hybridization “revealed negative studies for chromosome 3p, trisomy 7 or 17, and MITF family translocations, failing to further place this unique neoplasm into a definitive category,” Dr. Taneja and her colleagues wrote, adding that further study of the tumor may help to clarify whether it represents a distinct tumor type or is simply an unusual pattern caused by degeneration and involution of a known tumor type.

The authors did not disclose a study funding source, but reported having no conflicts of interest.

SOURCE: Taneja K et al. Hum Pathol. 2017 Nov 2. doi: 10.1016/j.humpath.2017.09.015.

What appears at first glance to be a renal vascular tumor may in fact be a rare type of renal cell carcinoma (RCC), authors of a case study cautioned.

A tumor recovered from a 62-year old woman who underwent a partial nephrectomy for an incidentally discovered asymptomatic left renal mass contained arborizing vessels that mimicked hemangioma. Immunohistochemical staining of the tumor highlighted the vascular component but masked epithelial cells, a situation that, in the absence of other clues, might cause a misdiagnosis, reported Kanika Taneja, MD, from the Henry Ford Cancer Institute in Detroit, and her colleagues.

The authors were tipped off to an unusual presentation, however, by mixed signals from immunohistochemical staining, leading them to an admittedly fuzzy diagnosis of “unclassified hemangioma-like RCC.”

“This case highlights that renal cell carcinoma must be strongly considered in the differential diagnosis of renal vascular tumors, and broadens the spectrum of histologies that may mimic hemangioma,” they wrote in Human Pathology.

Although there are a few recent reports in the medical literature of clear cell RCC tumors that mimic hemangiomas, the authors noted that, “to our knowledge, non–clear cell hemangioma-like renal cell carcinoma has not been previously reported.”

The tumor in question was removed from the patient with clear surgical margins during a partial nephrectomy.

Gross examination showed a 2.6 by 2.5 by 2.5 cm, well-circumscribed, tan-brown hemorrhagic mass. On microscopic examination the tumor had hemangioma-like features and lacked typical clear cell morphology, and immunohistochemical staining did little to clarify the picture.

Specifically, although staining highlighted the epithelial component of the tumor, the investigators saw what they described as “an abnormal combination of positive markers” that are normally used to distinguish clear cell from papillary histologies, effectively throwing a monkey wrench into the diagnostic works.

The marker profile in this case included cytokeratin 7, high molecular weight cytokeratin, and carbonic anhydrase IX, but only minimal labeling for alpha-methylacyl-CoA racemase and absence of GATA3.

To add to the confusion, fluorescent in situ hybridization “revealed negative studies for chromosome 3p, trisomy 7 or 17, and MITF family translocations, failing to further place this unique neoplasm into a definitive category,” Dr. Taneja and her colleagues wrote, adding that further study of the tumor may help to clarify whether it represents a distinct tumor type or is simply an unusual pattern caused by degeneration and involution of a known tumor type.

The authors did not disclose a study funding source, but reported having no conflicts of interest.

SOURCE: Taneja K et al. Hum Pathol. 2017 Nov 2. doi: 10.1016/j.humpath.2017.09.015.

What appears at first glance to be a renal vascular tumor may in fact be a rare type of renal cell carcinoma (RCC), authors of a case study cautioned.

A tumor recovered from a 62-year old woman who underwent a partial nephrectomy for an incidentally discovered asymptomatic left renal mass contained arborizing vessels that mimicked hemangioma. Immunohistochemical staining of the tumor highlighted the vascular component but masked epithelial cells, a situation that, in the absence of other clues, might cause a misdiagnosis, reported Kanika Taneja, MD, from the Henry Ford Cancer Institute in Detroit, and her colleagues.

The authors were tipped off to an unusual presentation, however, by mixed signals from immunohistochemical staining, leading them to an admittedly fuzzy diagnosis of “unclassified hemangioma-like RCC.”

“This case highlights that renal cell carcinoma must be strongly considered in the differential diagnosis of renal vascular tumors, and broadens the spectrum of histologies that may mimic hemangioma,” they wrote in Human Pathology.

Although there are a few recent reports in the medical literature of clear cell RCC tumors that mimic hemangiomas, the authors noted that, “to our knowledge, non–clear cell hemangioma-like renal cell carcinoma has not been previously reported.”

The tumor in question was removed from the patient with clear surgical margins during a partial nephrectomy.

Gross examination showed a 2.6 by 2.5 by 2.5 cm, well-circumscribed, tan-brown hemorrhagic mass. On microscopic examination the tumor had hemangioma-like features and lacked typical clear cell morphology, and immunohistochemical staining did little to clarify the picture.

Specifically, although staining highlighted the epithelial component of the tumor, the investigators saw what they described as “an abnormal combination of positive markers” that are normally used to distinguish clear cell from papillary histologies, effectively throwing a monkey wrench into the diagnostic works.

The marker profile in this case included cytokeratin 7, high molecular weight cytokeratin, and carbonic anhydrase IX, but only minimal labeling for alpha-methylacyl-CoA racemase and absence of GATA3.

To add to the confusion, fluorescent in situ hybridization “revealed negative studies for chromosome 3p, trisomy 7 or 17, and MITF family translocations, failing to further place this unique neoplasm into a definitive category,” Dr. Taneja and her colleagues wrote, adding that further study of the tumor may help to clarify whether it represents a distinct tumor type or is simply an unusual pattern caused by degeneration and involution of a known tumor type.

The authors did not disclose a study funding source, but reported having no conflicts of interest.

SOURCE: Taneja K et al. Hum Pathol. 2017 Nov 2. doi: 10.1016/j.humpath.2017.09.015.

Plasma glycosaminoglycan (GAG) measurements can accurately distinguish metastatic clear-cell renal cell carcinoma (ccRCC) from healthy samples, and can provide accurate diagnostic and prognostic information that may be of value in managing the disease, according to new findings.

A new GAG score had 93.5% sensitivity and 94.7% specificity (discovery set) for differentiating RCC from healthy samples, and the sensitivity estimate was independently validated. The score remained independent and uncorrelated to tumor stage, grade, size, and histology, or confounders such as age or gender, according to investigators. The report is in European Oncology Urology.

The authors note that in both retrospective and prospective studies of metastatic ccRCC cases, the composition and levels of plasma and urine GAGs are significantly different when compared with healthy specimens, and GAG scores have correlated with patient outcomes including progression free and overall survival in some cohorts. But it remains unclear if the alterations in plasma and urine GAGs are limited to just metastatic cases of ccRCC or if they correlate with other histopathologic characteristics in RCC. It is also unclear if the correlation between GAG scores and prognosis is limited to patients who receive systemic therapy or if it is applicable to those who are surgically treated RCC as well.

“These results expand our knowledge on the diagnostic and prognostic potential of plasma GAGs in RCC, which was so far limited to metastatic ccRCC in our previous studies,” wrote Francesco Gatto, MD, of Chalmers University of Technology, Göteborg, Sweden, and his colleagues. “Plasma GAG alterations appear to originate as a response to the tumor and occur early if not concomitantly with tumor formation, and probably independent of its progression.”

To investigate the sensitivity and specificity of plasma GAGs for detection of early-stage RCC as well as its utility in predicting recurrence and death after RCC surgery, Dr. Gatto and his team conducted a retrospective case-control study that included 175 RCC patients who underwent surgery between May 2011 and February 2014 and 19 healthy controls.

Plasma GAGs were measured in both preoperative and postoperative RCC cases and the control group, and a discovery set was analyzed to update the historical GAG score. The sensitivity of the new GAG score that was developed for detecting RCC versus controls was then validated using the remaining samples.

In the first discovery set, which included 67 participants, the new GAG score distinguished RCC from controls with an area under the receiver operating characteristic curve (AUC) of 0.999. In their validation cohort (n = 108), the new GAG score achieved an AUC of 0.991 (95% CI 0.977-1) and at the prespecified cutoff, the validated sensitivity was 93.5%. Specificity could not be validated because the same control group was used in both sets.

Factors including tumor size, grade, and stage, radical nephrectomy, and positive surgical margins were significantly associated with overall survival as were three of five GAG properties in the new scoring system, although the new GAG score did not reach significance by itself (hazard ratio, 1.25; P = 0.08). When looking at whether the new GAG score changed after surgery, the authors found that it was quite variable across patients, and an increased score was observed for 53% of cases and a decrease for 47% after surgery. This change did not appear correlated with outcomes as shown by the recurrence rate within 2 years of surgery.

SOURCE: Gatto F et al. Eur Urol Oncol. 2018 Jun 13. doi: 10.1016/j.euo.2018.04.015.

Plasma glycosaminoglycan (GAG) measurements can accurately distinguish metastatic clear-cell renal cell carcinoma (ccRCC) from healthy samples, and can provide accurate diagnostic and prognostic information that may be of value in managing the disease, according to new findings.

A new GAG score had 93.5% sensitivity and 94.7% specificity (discovery set) for differentiating RCC from healthy samples, and the sensitivity estimate was independently validated. The score remained independent and uncorrelated to tumor stage, grade, size, and histology, or confounders such as age or gender, according to investigators. The report is in European Oncology Urology.

The authors note that in both retrospective and prospective studies of metastatic ccRCC cases, the composition and levels of plasma and urine GAGs are significantly different when compared with healthy specimens, and GAG scores have correlated with patient outcomes including progression free and overall survival in some cohorts. But it remains unclear if the alterations in plasma and urine GAGs are limited to just metastatic cases of ccRCC or if they correlate with other histopathologic characteristics in RCC. It is also unclear if the correlation between GAG scores and prognosis is limited to patients who receive systemic therapy or if it is applicable to those who are surgically treated RCC as well.

“These results expand our knowledge on the diagnostic and prognostic potential of plasma GAGs in RCC, which was so far limited to metastatic ccRCC in our previous studies,” wrote Francesco Gatto, MD, of Chalmers University of Technology, Göteborg, Sweden, and his colleagues. “Plasma GAG alterations appear to originate as a response to the tumor and occur early if not concomitantly with tumor formation, and probably independent of its progression.”

To investigate the sensitivity and specificity of plasma GAGs for detection of early-stage RCC as well as its utility in predicting recurrence and death after RCC surgery, Dr. Gatto and his team conducted a retrospective case-control study that included 175 RCC patients who underwent surgery between May 2011 and February 2014 and 19 healthy controls.

Plasma GAGs were measured in both preoperative and postoperative RCC cases and the control group, and a discovery set was analyzed to update the historical GAG score. The sensitivity of the new GAG score that was developed for detecting RCC versus controls was then validated using the remaining samples.

In the first discovery set, which included 67 participants, the new GAG score distinguished RCC from controls with an area under the receiver operating characteristic curve (AUC) of 0.999. In their validation cohort (n = 108), the new GAG score achieved an AUC of 0.991 (95% CI 0.977-1) and at the prespecified cutoff, the validated sensitivity was 93.5%. Specificity could not be validated because the same control group was used in both sets.

Factors including tumor size, grade, and stage, radical nephrectomy, and positive surgical margins were significantly associated with overall survival as were three of five GAG properties in the new scoring system, although the new GAG score did not reach significance by itself (hazard ratio, 1.25; P = 0.08). When looking at whether the new GAG score changed after surgery, the authors found that it was quite variable across patients, and an increased score was observed for 53% of cases and a decrease for 47% after surgery. This change did not appear correlated with outcomes as shown by the recurrence rate within 2 years of surgery.

SOURCE: Gatto F et al. Eur Urol Oncol. 2018 Jun 13. doi: 10.1016/j.euo.2018.04.015.

Plasma glycosaminoglycan (GAG) measurements can accurately distinguish metastatic clear-cell renal cell carcinoma (ccRCC) from healthy samples, and can provide accurate diagnostic and prognostic information that may be of value in managing the disease, according to new findings.

A new GAG score had 93.5% sensitivity and 94.7% specificity (discovery set) for differentiating RCC from healthy samples, and the sensitivity estimate was independently validated. The score remained independent and uncorrelated to tumor stage, grade, size, and histology, or confounders such as age or gender, according to investigators. The report is in European Oncology Urology.

The authors note that in both retrospective and prospective studies of metastatic ccRCC cases, the composition and levels of plasma and urine GAGs are significantly different when compared with healthy specimens, and GAG scores have correlated with patient outcomes including progression free and overall survival in some cohorts. But it remains unclear if the alterations in plasma and urine GAGs are limited to just metastatic cases of ccRCC or if they correlate with other histopathologic characteristics in RCC. It is also unclear if the correlation between GAG scores and prognosis is limited to patients who receive systemic therapy or if it is applicable to those who are surgically treated RCC as well.

“These results expand our knowledge on the diagnostic and prognostic potential of plasma GAGs in RCC, which was so far limited to metastatic ccRCC in our previous studies,” wrote Francesco Gatto, MD, of Chalmers University of Technology, Göteborg, Sweden, and his colleagues. “Plasma GAG alterations appear to originate as a response to the tumor and occur early if not concomitantly with tumor formation, and probably independent of its progression.”

To investigate the sensitivity and specificity of plasma GAGs for detection of early-stage RCC as well as its utility in predicting recurrence and death after RCC surgery, Dr. Gatto and his team conducted a retrospective case-control study that included 175 RCC patients who underwent surgery between May 2011 and February 2014 and 19 healthy controls.

Plasma GAGs were measured in both preoperative and postoperative RCC cases and the control group, and a discovery set was analyzed to update the historical GAG score. The sensitivity of the new GAG score that was developed for detecting RCC versus controls was then validated using the remaining samples.

In the first discovery set, which included 67 participants, the new GAG score distinguished RCC from controls with an area under the receiver operating characteristic curve (AUC) of 0.999. In their validation cohort (n = 108), the new GAG score achieved an AUC of 0.991 (95% CI 0.977-1) and at the prespecified cutoff, the validated sensitivity was 93.5%. Specificity could not be validated because the same control group was used in both sets.

Factors including tumor size, grade, and stage, radical nephrectomy, and positive surgical margins were significantly associated with overall survival as were three of five GAG properties in the new scoring system, although the new GAG score did not reach significance by itself (hazard ratio, 1.25; P = 0.08). When looking at whether the new GAG score changed after surgery, the authors found that it was quite variable across patients, and an increased score was observed for 53% of cases and a decrease for 47% after surgery. This change did not appear correlated with outcomes as shown by the recurrence rate within 2 years of surgery.

SOURCE: Gatto F et al. Eur Urol Oncol. 2018 Jun 13. doi: 10.1016/j.euo.2018.04.015.

In patients with clear cell renal cell carcinoma (ccRCC), radiogenomic analysis can reveal associations between specific features on CT imaging and messenger RNA-based tumor subtyping, authors of a preliminary analysis contend.

Among 177 patients with ccRCC for whom CT data and molecular subtyping information were available, well-defined vs. poorly-defined tumor margins were significantly associated with messenger RNA (mRNA) subtype m1 tumors, and a combination of margin definition and other qualitative tumor features was significantly associated with m3 subtype, reported Lan Bowen, MD, and Li Xiaojing, MD, from Huizhou (China) Central People’s Hospital.

“We demonstrated m1-subtype is positively associated with well-defined margin while m3-subtype is positively associated with ill-defined margin, renal vein invasion, and collecting-system invasion. These findings should be further investigated and validated in other cohorts,” they wrote. The report was published in Academic Radiology.

Radiogenomic analysis is a method for identifying associations between imaging features and gene expression profiles to provide information that can be used for clinical decision making.

The investigators used the technique to retrospectively explore associations between ccRCC mRNA-based subtyping and CT features.

They identified data on a total of 177 patients with ccRCC from The Cancer Genome Atlas for whom complete CT imaging, including contrast-enhanced images, and mRNA-based subtyping were available.

CT features studied included calcifications, margin definition, renal vein invasion, collecting-system invasion, multicystic tumors, nodular tumor enhancement, and intratumoral vasculature.

In univariate logistic regression analysis, well-defined tumor margins (vs. poorly-defined margins) were significant associated with m1 subtype (odd ratio [OR] 2.104, P = .041).

Similarly, a combination of well-defined tumor margins (OR 2.104, P = .013), no collecting system invasion (OR 0.421, P = .028), and renal vein invasion (OR 2.164, P = .026) were significantly associated with the m3 subtype.

They were no significant associations between CT imaging features and either the m2 or m4 subtypes, the authors found.

The authors did not report study funding sources or potential conflicts of interest.

SOURCE: Bowen L, Xiaojing L. Acad Radiol. doi: 10.1016/j.acra.2018.05.002.

In patients with clear cell renal cell carcinoma (ccRCC), radiogenomic analysis can reveal associations between specific features on CT imaging and messenger RNA-based tumor subtyping, authors of a preliminary analysis contend.

Among 177 patients with ccRCC for whom CT data and molecular subtyping information were available, well-defined vs. poorly-defined tumor margins were significantly associated with messenger RNA (mRNA) subtype m1 tumors, and a combination of margin definition and other qualitative tumor features was significantly associated with m3 subtype, reported Lan Bowen, MD, and Li Xiaojing, MD, from Huizhou (China) Central People’s Hospital.

“We demonstrated m1-subtype is positively associated with well-defined margin while m3-subtype is positively associated with ill-defined margin, renal vein invasion, and collecting-system invasion. These findings should be further investigated and validated in other cohorts,” they wrote. The report was published in Academic Radiology.

Radiogenomic analysis is a method for identifying associations between imaging features and gene expression profiles to provide information that can be used for clinical decision making.

The investigators used the technique to retrospectively explore associations between ccRCC mRNA-based subtyping and CT features.

They identified data on a total of 177 patients with ccRCC from The Cancer Genome Atlas for whom complete CT imaging, including contrast-enhanced images, and mRNA-based subtyping were available.

CT features studied included calcifications, margin definition, renal vein invasion, collecting-system invasion, multicystic tumors, nodular tumor enhancement, and intratumoral vasculature.

In univariate logistic regression analysis, well-defined tumor margins (vs. poorly-defined margins) were significant associated with m1 subtype (odd ratio [OR] 2.104, P = .041).

Similarly, a combination of well-defined tumor margins (OR 2.104, P = .013), no collecting system invasion (OR 0.421, P = .028), and renal vein invasion (OR 2.164, P = .026) were significantly associated with the m3 subtype.

They were no significant associations between CT imaging features and either the m2 or m4 subtypes, the authors found.

The authors did not report study funding sources or potential conflicts of interest.

SOURCE: Bowen L, Xiaojing L. Acad Radiol. doi: 10.1016/j.acra.2018.05.002.

In patients with clear cell renal cell carcinoma (ccRCC), radiogenomic analysis can reveal associations between specific features on CT imaging and messenger RNA-based tumor subtyping, authors of a preliminary analysis contend.

Among 177 patients with ccRCC for whom CT data and molecular subtyping information were available, well-defined vs. poorly-defined tumor margins were significantly associated with messenger RNA (mRNA) subtype m1 tumors, and a combination of margin definition and other qualitative tumor features was significantly associated with m3 subtype, reported Lan Bowen, MD, and Li Xiaojing, MD, from Huizhou (China) Central People’s Hospital.

“We demonstrated m1-subtype is positively associated with well-defined margin while m3-subtype is positively associated with ill-defined margin, renal vein invasion, and collecting-system invasion. These findings should be further investigated and validated in other cohorts,” they wrote. The report was published in Academic Radiology.

Radiogenomic analysis is a method for identifying associations between imaging features and gene expression profiles to provide information that can be used for clinical decision making.

The investigators used the technique to retrospectively explore associations between ccRCC mRNA-based subtyping and CT features.

They identified data on a total of 177 patients with ccRCC from The Cancer Genome Atlas for whom complete CT imaging, including contrast-enhanced images, and mRNA-based subtyping were available.

CT features studied included calcifications, margin definition, renal vein invasion, collecting-system invasion, multicystic tumors, nodular tumor enhancement, and intratumoral vasculature.

In univariate logistic regression analysis, well-defined tumor margins (vs. poorly-defined margins) were significant associated with m1 subtype (odd ratio [OR] 2.104, P = .041).

Similarly, a combination of well-defined tumor margins (OR 2.104, P = .013), no collecting system invasion (OR 0.421, P = .028), and renal vein invasion (OR 2.164, P = .026) were significantly associated with the m3 subtype.

They were no significant associations between CT imaging features and either the m2 or m4 subtypes, the authors found.

The authors did not report study funding sources or potential conflicts of interest.

SOURCE: Bowen L, Xiaojing L. Acad Radiol. doi: 10.1016/j.acra.2018.05.002.

Clear cell papillary renal cell carcinoma (CCPRCC), a recently identified, rare type of renal tumor, appears to have an indolent course with low risk of either local invasion or distant metastasis, results of a small retrospective study suggest.

Among 25 patients with CCPRCC followed for as long as 119 months, there were no cases of local recurrence or distant metastasis, reported Wei-Jen Chen, MD, of Tapei (Taiwan) Veterans General Hospital, and colleagues.

“Based on our findings, CCPRCC has an indolent behavior even if the patients are immunosuppressed or if they receive less invasive therapy. Microscopically, CCPRCC is considered to be a tumor of low malignant potential, as all tumors in our series were of low nuclear grade,” they wrote in a study published online in the Journal of the Chinese Medical Association.

“Whenever the diagnosis is made in a high grade renal tumor, it should be carefully re-confirmed by either cytogenetic or molecular genetic methods,” the authors reported.

CCPRCC was newly recognized as a distinct renal malignancy in the 2016 World Health Organization Classification of Tumors of the Urinary System and Male Genital Organs. The classification describes CCPRCC as “a renal epithelial neoplasm composed of low-grade clear epithelial cells arranged in tubules and papillae with a predominantly linear nuclear alignment away from the basement membrane.”

Although rare, these tumors account for up to 5% of all resected renal tumors, and arise sporadically in patients with end-stage renal disease (ESRD) and von Hippel-Lindau syndrome, the classification states, adding that “according to current knowledge, these tumors have indolent behavior.”

To see if they could verify that last statement, Dr. Chen and associates collected data on all patients diagnosed at their institution with CCPRCC from January 2008 through September 2016.

They identified a total of 25 patients (11 men and 14 women) with a mean age at diagnosis of 62.8 years. Of this group, three patients with poor general condition underwent cryotherapy after a biopsy-confirmed diagnosis of CCPRCC.

All of the remaining 22 patients underwent surgical resection. Of this group, four had ESRD; three of these patients had received a kidney transplant prior to diagnosis of CCPRCC in the native kidneys, and one had three tumors over both kidneys.

“Three patients had other types of synchronous RCC; one with acquired cystic kidney disease-associated RCC, and the others with ccRCC. All CCPRCCs were localized and low grade (pT1a- pT1b, Fuhrman grade 2), and all of the patients are currently alive with no evidence of disease,” the investigators wrote.

Mean follow-up was 49.7 months (range 12 to 119 months).

One additional patient who was not included in the series was initially diagnosed with CCPRCC with lung metastasis. This patient, who died 3 years and 8 months after cytoreductive nephrectomy, had a clinical course distinct from that of all the other patients, leading the investigators to reexamine his kidney specimen with whole-exome sequencing. The sequencing led to a revision of the diagnosis to clear cell RCC.

The investigators noted that clear cell RCC, papillary RCC, and translocation RCC are three RCC subtypes that should be considered in the differential diagnosis of CCPRCC.

SOURCE: Chen W-J et al. J Chinese Med Assoc. 2018 July 20. doi: 10.1016/j.jcma.2018.04.005.

Clear cell papillary renal cell carcinoma (CCPRCC), a recently identified, rare type of renal tumor, appears to have an indolent course with low risk of either local invasion or distant metastasis, results of a small retrospective study suggest.

Among 25 patients with CCPRCC followed for as long as 119 months, there were no cases of local recurrence or distant metastasis, reported Wei-Jen Chen, MD, of Tapei (Taiwan) Veterans General Hospital, and colleagues.

“Based on our findings, CCPRCC has an indolent behavior even if the patients are immunosuppressed or if they receive less invasive therapy. Microscopically, CCPRCC is considered to be a tumor of low malignant potential, as all tumors in our series were of low nuclear grade,” they wrote in a study published online in the Journal of the Chinese Medical Association.

“Whenever the diagnosis is made in a high grade renal tumor, it should be carefully re-confirmed by either cytogenetic or molecular genetic methods,” the authors reported.

CCPRCC was newly recognized as a distinct renal malignancy in the 2016 World Health Organization Classification of Tumors of the Urinary System and Male Genital Organs. The classification describes CCPRCC as “a renal epithelial neoplasm composed of low-grade clear epithelial cells arranged in tubules and papillae with a predominantly linear nuclear alignment away from the basement membrane.”

Although rare, these tumors account for up to 5% of all resected renal tumors, and arise sporadically in patients with end-stage renal disease (ESRD) and von Hippel-Lindau syndrome, the classification states, adding that “according to current knowledge, these tumors have indolent behavior.”

To see if they could verify that last statement, Dr. Chen and associates collected data on all patients diagnosed at their institution with CCPRCC from January 2008 through September 2016.

They identified a total of 25 patients (11 men and 14 women) with a mean age at diagnosis of 62.8 years. Of this group, three patients with poor general condition underwent cryotherapy after a biopsy-confirmed diagnosis of CCPRCC.

All of the remaining 22 patients underwent surgical resection. Of this group, four had ESRD; three of these patients had received a kidney transplant prior to diagnosis of CCPRCC in the native kidneys, and one had three tumors over both kidneys.

“Three patients had other types of synchronous RCC; one with acquired cystic kidney disease-associated RCC, and the others with ccRCC. All CCPRCCs were localized and low grade (pT1a- pT1b, Fuhrman grade 2), and all of the patients are currently alive with no evidence of disease,” the investigators wrote.

Mean follow-up was 49.7 months (range 12 to 119 months).

One additional patient who was not included in the series was initially diagnosed with CCPRCC with lung metastasis. This patient, who died 3 years and 8 months after cytoreductive nephrectomy, had a clinical course distinct from that of all the other patients, leading the investigators to reexamine his kidney specimen with whole-exome sequencing. The sequencing led to a revision of the diagnosis to clear cell RCC.

The investigators noted that clear cell RCC, papillary RCC, and translocation RCC are three RCC subtypes that should be considered in the differential diagnosis of CCPRCC.

SOURCE: Chen W-J et al. J Chinese Med Assoc. 2018 July 20. doi: 10.1016/j.jcma.2018.04.005.

Clear cell papillary renal cell carcinoma (CCPRCC), a recently identified, rare type of renal tumor, appears to have an indolent course with low risk of either local invasion or distant metastasis, results of a small retrospective study suggest.

Among 25 patients with CCPRCC followed for as long as 119 months, there were no cases of local recurrence or distant metastasis, reported Wei-Jen Chen, MD, of Tapei (Taiwan) Veterans General Hospital, and colleagues.

“Based on our findings, CCPRCC has an indolent behavior even if the patients are immunosuppressed or if they receive less invasive therapy. Microscopically, CCPRCC is considered to be a tumor of low malignant potential, as all tumors in our series were of low nuclear grade,” they wrote in a study published online in the Journal of the Chinese Medical Association.

“Whenever the diagnosis is made in a high grade renal tumor, it should be carefully re-confirmed by either cytogenetic or molecular genetic methods,” the authors reported.

CCPRCC was newly recognized as a distinct renal malignancy in the 2016 World Health Organization Classification of Tumors of the Urinary System and Male Genital Organs. The classification describes CCPRCC as “a renal epithelial neoplasm composed of low-grade clear epithelial cells arranged in tubules and papillae with a predominantly linear nuclear alignment away from the basement membrane.”

Although rare, these tumors account for up to 5% of all resected renal tumors, and arise sporadically in patients with end-stage renal disease (ESRD) and von Hippel-Lindau syndrome, the classification states, adding that “according to current knowledge, these tumors have indolent behavior.”

To see if they could verify that last statement, Dr. Chen and associates collected data on all patients diagnosed at their institution with CCPRCC from January 2008 through September 2016.

They identified a total of 25 patients (11 men and 14 women) with a mean age at diagnosis of 62.8 years. Of this group, three patients with poor general condition underwent cryotherapy after a biopsy-confirmed diagnosis of CCPRCC.

All of the remaining 22 patients underwent surgical resection. Of this group, four had ESRD; three of these patients had received a kidney transplant prior to diagnosis of CCPRCC in the native kidneys, and one had three tumors over both kidneys.

“Three patients had other types of synchronous RCC; one with acquired cystic kidney disease-associated RCC, and the others with ccRCC. All CCPRCCs were localized and low grade (pT1a- pT1b, Fuhrman grade 2), and all of the patients are currently alive with no evidence of disease,” the investigators wrote.

Mean follow-up was 49.7 months (range 12 to 119 months).

One additional patient who was not included in the series was initially diagnosed with CCPRCC with lung metastasis. This patient, who died 3 years and 8 months after cytoreductive nephrectomy, had a clinical course distinct from that of all the other patients, leading the investigators to reexamine his kidney specimen with whole-exome sequencing. The sequencing led to a revision of the diagnosis to clear cell RCC.

The investigators noted that clear cell RCC, papillary RCC, and translocation RCC are three RCC subtypes that should be considered in the differential diagnosis of CCPRCC.

SOURCE: Chen W-J et al. J Chinese Med Assoc. 2018 July 20. doi: 10.1016/j.jcma.2018.04.005.

An analysis of conditional survival outcomes for patients with metastatic renal cell carcinoma (mRCC) has suggested that first-line therapy with a tyrosine kinase inhibitor (TKI) can result in improved survival odds over time.

Patients with mRCC treated with a TKI upfront had gradual increases over time in conditional overall survival estimates when compared with baseline survival predictions, a retrospective review has indicated.

Patients who survived at least 36 months after the start of therapy had an estimated 36-month conditional overall survival (OS) rate that was 7.3% higher than the predicted survival at the initiation of therapy, reported Seong Il Seo, MD, PhD, from Samsung Medical Center in Seoul, North Korea, and his colleagues.

The investigators also found that, while predictors of survival changed over time, previous metastasectomy was a key prognosticator of conditional overall survival throughout 36 months of follow-up, they reported in The Journal of Urology.

“To our knowledge, our data are the first to reveal the beneficial role of metastasectomy on conditional OS probabilities with time since an initial survival estimation, particularly in patients at intermediate and poor risk. [Conditional survival] estimates can be beneficial to counsel patients with mRCC about more practical prognoses and helpful to continuously adjust surveillance planning in these patients,” they wrote.

Conditional survival is an analytical method for providing more accurate estimates of how prognoses change over time when patients with aggressive metastatic disease, such as mRCC, are exposed to therapies such as nephrectomy or TKIs.

The investigators retrospectively reviewed records for 1,131 patients with mRCC in the Korean Renal Cancer Study Group database. They calculated conditional OS using a nomogram that indicated the likelihood that a patient would survive an additional number of years given that he or she had already survived a certain number of years. They also created a multivariate regression model to identify predictors of conditional survival over time.

They found that, at all survival times after the start of TKI therapy (6, 12, 18, 24, and 36 months), conditional overall survival gradually increased when compared with baseline survival estimates.

“While the actual overall survival rate decreased with time, the 36-month conditional overall survival rate was calculated as 7.3% higher in patients who had already survived 36 months compared to baseline estimations at the time of initial tyrosine kinase inhibitor treatment,” they wrote.

In the multivariate model, prognostic factors such as gender, pathologic T stage, and Heng risk classification became nonsignificant over time, but previous metastasectomy remained a significant independent predictor of survival after TKI therapy at all time points except for 18 months.

“This study largely corroborates previous data from the IMDC (International Metastatic Renal Cell Carcinoma Database Consortium), and it provides useful information on prognostication,” commented Adam B. Weiner, MD, of Northwestern University in Chicago, in a brief accompanying editorial.

The study was supported by a National Research Foundation of Korea research grant funded by the Ministry of Science and Information and Communications Technology and by a Korea Health Technology R&D Project grant through the Korea Health Industry Development Institute funded by the Ministry of Health and Welfare in South Korea. No conflicts of interest were reported.

SOURCE: Kang M et al. J Urol. 2018 June 22. doi: 10.1016/j.juro.2018.06.030.

 

An analysis of conditional survival outcomes for patients with metastatic renal cell carcinoma (mRCC) has suggested that first-line therapy with a tyrosine kinase inhibitor (TKI) can result in improved survival odds over time.

Patients with mRCC treated with a TKI upfront had gradual increases over time in conditional overall survival estimates when compared with baseline survival predictions, a retrospective review has indicated.

Patients who survived at least 36 months after the start of therapy had an estimated 36-month conditional overall survival (OS) rate that was 7.3% higher than the predicted survival at the initiation of therapy, reported Seong Il Seo, MD, PhD, from Samsung Medical Center in Seoul, North Korea, and his colleagues.

The investigators also found that, while predictors of survival changed over time, previous metastasectomy was a key prognosticator of conditional overall survival throughout 36 months of follow-up, they reported in The Journal of Urology.

“To our knowledge, our data are the first to reveal the beneficial role of metastasectomy on conditional OS probabilities with time since an initial survival estimation, particularly in patients at intermediate and poor risk. [Conditional survival] estimates can be beneficial to counsel patients with mRCC about more practical prognoses and helpful to continuously adjust surveillance planning in these patients,” they wrote.

Conditional survival is an analytical method for providing more accurate estimates of how prognoses change over time when patients with aggressive metastatic disease, such as mRCC, are exposed to therapies such as nephrectomy or TKIs.

The investigators retrospectively reviewed records for 1,131 patients with mRCC in the Korean Renal Cancer Study Group database. They calculated conditional OS using a nomogram that indicated the likelihood that a patient would survive an additional number of years given that he or she had already survived a certain number of years. They also created a multivariate regression model to identify predictors of conditional survival over time.

They found that, at all survival times after the start of TKI therapy (6, 12, 18, 24, and 36 months), conditional overall survival gradually increased when compared with baseline survival estimates.

“While the actual overall survival rate decreased with time, the 36-month conditional overall survival rate was calculated as 7.3% higher in patients who had already survived 36 months compared to baseline estimations at the time of initial tyrosine kinase inhibitor treatment,” they wrote.

In the multivariate model, prognostic factors such as gender, pathologic T stage, and Heng risk classification became nonsignificant over time, but previous metastasectomy remained a significant independent predictor of survival after TKI therapy at all time points except for 18 months.

“This study largely corroborates previous data from the IMDC (International Metastatic Renal Cell Carcinoma Database Consortium), and it provides useful information on prognostication,” commented Adam B. Weiner, MD, of Northwestern University in Chicago, in a brief accompanying editorial.

The study was supported by a National Research Foundation of Korea research grant funded by the Ministry of Science and Information and Communications Technology and by a Korea Health Technology R&D Project grant through the Korea Health Industry Development Institute funded by the Ministry of Health and Welfare in South Korea. No conflicts of interest were reported.

SOURCE: Kang M et al. J Urol. 2018 June 22. doi: 10.1016/j.juro.2018.06.030.

 

An analysis of conditional survival outcomes for patients with metastatic renal cell carcinoma (mRCC) has suggested that first-line therapy with a tyrosine kinase inhibitor (TKI) can result in improved survival odds over time.

Patients with mRCC treated with a TKI upfront had gradual increases over time in conditional overall survival estimates when compared with baseline survival predictions, a retrospective review has indicated.

Patients who survived at least 36 months after the start of therapy had an estimated 36-month conditional overall survival (OS) rate that was 7.3% higher than the predicted survival at the initiation of therapy, reported Seong Il Seo, MD, PhD, from Samsung Medical Center in Seoul, North Korea, and his colleagues.

The investigators also found that, while predictors of survival changed over time, previous metastasectomy was a key prognosticator of conditional overall survival throughout 36 months of follow-up, they reported in The Journal of Urology.

“To our knowledge, our data are the first to reveal the beneficial role of metastasectomy on conditional OS probabilities with time since an initial survival estimation, particularly in patients at intermediate and poor risk. [Conditional survival] estimates can be beneficial to counsel patients with mRCC about more practical prognoses and helpful to continuously adjust surveillance planning in these patients,” they wrote.

Conditional survival is an analytical method for providing more accurate estimates of how prognoses change over time when patients with aggressive metastatic disease, such as mRCC, are exposed to therapies such as nephrectomy or TKIs.

The investigators retrospectively reviewed records for 1,131 patients with mRCC in the Korean Renal Cancer Study Group database. They calculated conditional OS using a nomogram that indicated the likelihood that a patient would survive an additional number of years given that he or she had already survived a certain number of years. They also created a multivariate regression model to identify predictors of conditional survival over time.

They found that, at all survival times after the start of TKI therapy (6, 12, 18, 24, and 36 months), conditional overall survival gradually increased when compared with baseline survival estimates.

“While the actual overall survival rate decreased with time, the 36-month conditional overall survival rate was calculated as 7.3% higher in patients who had already survived 36 months compared to baseline estimations at the time of initial tyrosine kinase inhibitor treatment,” they wrote.

In the multivariate model, prognostic factors such as gender, pathologic T stage, and Heng risk classification became nonsignificant over time, but previous metastasectomy remained a significant independent predictor of survival after TKI therapy at all time points except for 18 months.

“This study largely corroborates previous data from the IMDC (International Metastatic Renal Cell Carcinoma Database Consortium), and it provides useful information on prognostication,” commented Adam B. Weiner, MD, of Northwestern University in Chicago, in a brief accompanying editorial.

The study was supported by a National Research Foundation of Korea research grant funded by the Ministry of Science and Information and Communications Technology and by a Korea Health Technology R&D Project grant through the Korea Health Industry Development Institute funded by the Ministry of Health and Welfare in South Korea. No conflicts of interest were reported.

SOURCE: Kang M et al. J Urol. 2018 June 22. doi: 10.1016/j.juro.2018.06.030.

 

Gene expression profiling and/or immunohistochemistry can identify occult renal cell carcinoma (RCC) in a subset of patients diagnosed with carcinoma of unknown primary (CUP), suggesting that these patients could benefit from RCC-specific targeted therapy or immunotherapy, investigators contend.

Of 539 patients presenting at a single center with CUP, a 92-gene reverse transcription polymerase chain reaction molecular cancer classifier assay (MCCA) performed on biopsy specimens identified 24 as having RCC. All of the patients had clinical characteristics typical of advanced RCC, but none had suspicious renal lesions on CT scans, reported F. Anthony Greco, MD and John D. Hainsworth, MD, of the Sarah Cannon Cancer Center and Research Institute in Nashville, Tenn.

“Although further experience is necessary, these patients responded to RCC-specific therapy in a manner consistent with advanced RCC. These patients are unlikely to benefit from treatment with empiric chemotherapy. The reliable identification of RCC patients within the heterogeneous CUP population is possible using MCCA, and has potentially important therapeutic implications,” they wrote. The report was published in Clinical Genitourinary Cancer.

They noted that previously the only therapeutic option for patients with CUP suspected of being renal in origin was ineffective systemic chemotherapy, making a specific diagnosis of more academic interest than clinical importance.

“This situation has now changed because of the introduction of several targeted agents and immune checkpoint blockers that improve survival in patients with advanced RCC. It is likely that these new RCC treatments are also more effective than empiric chemotherapy for patients with CUP who have an occult renal primary site. Therefore, recognition of the RCC subset of patients within the CUP population has practical therapeutic importance,” they wrote.

Dr. Greco and Dr. Hainsworth conducted a retrospective review of patients at their center with CUP from 2008 through 2013 who had RCC predicted by MCCA.

A total of 539 patients presented with CUP during the study period, and of this group, 24 (4.4%) had RCC identified by MCCA.

The patients, 18 men and 6 women, with a median age of 61 years, all had abdominal CT scans that failed to show renal lesions suggestive of a primary RCC. Nine of the 24 patients had baseline MCCA performed as part of a prospective phase 2 clinical trial; the other 15 were patients treated at the center who had MCCA performed later in the clinical course, usually during or after first-line empiric chemotherapy.

Sixteen patients had metastases in the retroperitoneum, 10 in the mediastinum, 6 in bone, 5 in the liver, and 5 in lungs and/or pleura.

Pathologic studies using light microscopy showed poorly differentiated carcinomas in eight patients, poorly differentiated adenocarcinomas in nine, and well or moderately differentiated adenocarcinomas in seven patients.

A pathologist identified RCC as the possible primary in only 4 of the 24 patients. Immunohistochemistry tests in these patients were consistent with a diagnosis of RCC. Only 5 of the 24 had focal features suggestive of RCC, including one clear-cell and four papillary histologies.

Sixteen of the 24 patients received first-line treatment for advanced RCC, including sunitinib, temsirolimus, bevacizumab, and/or interleukin 1. Four other patients received RCC-specific therapy following empiric chemotherapy (three patients who received RCC-specific therapies in the first line also received it in the second line).

Among the 16 patients who received first-line RCC-specific therapies there were 3 partial responses (PR), 10 cases of stable disease (SD), 2 of progressive disease (PD), and 1 patient was not evaluable. The median duration of both PR and SD was 8 months.

Of the eight patients who received first-line empiric chemotherapy, one had a PR, two had SD, and five had PD.

For the seven patients who received second-line RCC-specific therapy after either first-line chemotherapy or site-specific therapy, responses included one PR, two SD, two PD, and two not evaluable.

Median survival for all 24 patients was 12 months (range 2 to more than 43 months). Median survival of the 16 patients who received first-line RCC-specific treatment was 14 months (range 2-25 months).

Median survival for all 20 patients who received RCC-specific treatment at some time during their course was 16 months (range, 2 to more than 43 months).

The authors called for further prospective studies of this subset of patients with CUP.

SOURCE: Greco FA, Hainsworth JD. Clin Genitourin Cancer. 2018 Aug;16(4):e893-8.

Gene expression profiling and/or immunohistochemistry can identify occult renal cell carcinoma (RCC) in a subset of patients diagnosed with carcinoma of unknown primary (CUP), suggesting that these patients could benefit from RCC-specific targeted therapy or immunotherapy, investigators contend.

Of 539 patients presenting at a single center with CUP, a 92-gene reverse transcription polymerase chain reaction molecular cancer classifier assay (MCCA) performed on biopsy specimens identified 24 as having RCC. All of the patients had clinical characteristics typical of advanced RCC, but none had suspicious renal lesions on CT scans, reported F. Anthony Greco, MD and John D. Hainsworth, MD, of the Sarah Cannon Cancer Center and Research Institute in Nashville, Tenn.

“Although further experience is necessary, these patients responded to RCC-specific therapy in a manner consistent with advanced RCC. These patients are unlikely to benefit from treatment with empiric chemotherapy. The reliable identification of RCC patients within the heterogeneous CUP population is possible using MCCA, and has potentially important therapeutic implications,” they wrote. The report was published in Clinical Genitourinary Cancer.

They noted that previously the only therapeutic option for patients with CUP suspected of being renal in origin was ineffective systemic chemotherapy, making a specific diagnosis of more academic interest than clinical importance.

“This situation has now changed because of the introduction of several targeted agents and immune checkpoint blockers that improve survival in patients with advanced RCC. It is likely that these new RCC treatments are also more effective than empiric chemotherapy for patients with CUP who have an occult renal primary site. Therefore, recognition of the RCC subset of patients within the CUP population has practical therapeutic importance,” they wrote.

Dr. Greco and Dr. Hainsworth conducted a retrospective review of patients at their center with CUP from 2008 through 2013 who had RCC predicted by MCCA.

A total of 539 patients presented with CUP during the study period, and of this group, 24 (4.4%) had RCC identified by MCCA.

The patients, 18 men and 6 women, with a median age of 61 years, all had abdominal CT scans that failed to show renal lesions suggestive of a primary RCC. Nine of the 24 patients had baseline MCCA performed as part of a prospective phase 2 clinical trial; the other 15 were patients treated at the center who had MCCA performed later in the clinical course, usually during or after first-line empiric chemotherapy.

Sixteen patients had metastases in the retroperitoneum, 10 in the mediastinum, 6 in bone, 5 in the liver, and 5 in lungs and/or pleura.

Pathologic studies using light microscopy showed poorly differentiated carcinomas in eight patients, poorly differentiated adenocarcinomas in nine, and well or moderately differentiated adenocarcinomas in seven patients.

A pathologist identified RCC as the possible primary in only 4 of the 24 patients. Immunohistochemistry tests in these patients were consistent with a diagnosis of RCC. Only 5 of the 24 had focal features suggestive of RCC, including one clear-cell and four papillary histologies.

Sixteen of the 24 patients received first-line treatment for advanced RCC, including sunitinib, temsirolimus, bevacizumab, and/or interleukin 1. Four other patients received RCC-specific therapy following empiric chemotherapy (three patients who received RCC-specific therapies in the first line also received it in the second line).

Among the 16 patients who received first-line RCC-specific therapies there were 3 partial responses (PR), 10 cases of stable disease (SD), 2 of progressive disease (PD), and 1 patient was not evaluable. The median duration of both PR and SD was 8 months.

Of the eight patients who received first-line empiric chemotherapy, one had a PR, two had SD, and five had PD.

For the seven patients who received second-line RCC-specific therapy after either first-line chemotherapy or site-specific therapy, responses included one PR, two SD, two PD, and two not evaluable.

Median survival for all 24 patients was 12 months (range 2 to more than 43 months). Median survival of the 16 patients who received first-line RCC-specific treatment was 14 months (range 2-25 months).

Median survival for all 20 patients who received RCC-specific treatment at some time during their course was 16 months (range, 2 to more than 43 months).

The authors called for further prospective studies of this subset of patients with CUP.

SOURCE: Greco FA, Hainsworth JD. Clin Genitourin Cancer. 2018 Aug;16(4):e893-8.

Gene expression profiling and/or immunohistochemistry can identify occult renal cell carcinoma (RCC) in a subset of patients diagnosed with carcinoma of unknown primary (CUP), suggesting that these patients could benefit from RCC-specific targeted therapy or immunotherapy, investigators contend.

Of 539 patients presenting at a single center with CUP, a 92-gene reverse transcription polymerase chain reaction molecular cancer classifier assay (MCCA) performed on biopsy specimens identified 24 as having RCC. All of the patients had clinical characteristics typical of advanced RCC, but none had suspicious renal lesions on CT scans, reported F. Anthony Greco, MD and John D. Hainsworth, MD, of the Sarah Cannon Cancer Center and Research Institute in Nashville, Tenn.

“Although further experience is necessary, these patients responded to RCC-specific therapy in a manner consistent with advanced RCC. These patients are unlikely to benefit from treatment with empiric chemotherapy. The reliable identification of RCC patients within the heterogeneous CUP population is possible using MCCA, and has potentially important therapeutic implications,” they wrote. The report was published in Clinical Genitourinary Cancer.

They noted that previously the only therapeutic option for patients with CUP suspected of being renal in origin was ineffective systemic chemotherapy, making a specific diagnosis of more academic interest than clinical importance.

“This situation has now changed because of the introduction of several targeted agents and immune checkpoint blockers that improve survival in patients with advanced RCC. It is likely that these new RCC treatments are also more effective than empiric chemotherapy for patients with CUP who have an occult renal primary site. Therefore, recognition of the RCC subset of patients within the CUP population has practical therapeutic importance,” they wrote.

Dr. Greco and Dr. Hainsworth conducted a retrospective review of patients at their center with CUP from 2008 through 2013 who had RCC predicted by MCCA.

A total of 539 patients presented with CUP during the study period, and of this group, 24 (4.4%) had RCC identified by MCCA.

The patients, 18 men and 6 women, with a median age of 61 years, all had abdominal CT scans that failed to show renal lesions suggestive of a primary RCC. Nine of the 24 patients had baseline MCCA performed as part of a prospective phase 2 clinical trial; the other 15 were patients treated at the center who had MCCA performed later in the clinical course, usually during or after first-line empiric chemotherapy.

Sixteen patients had metastases in the retroperitoneum, 10 in the mediastinum, 6 in bone, 5 in the liver, and 5 in lungs and/or pleura.

Pathologic studies using light microscopy showed poorly differentiated carcinomas in eight patients, poorly differentiated adenocarcinomas in nine, and well or moderately differentiated adenocarcinomas in seven patients.

A pathologist identified RCC as the possible primary in only 4 of the 24 patients. Immunohistochemistry tests in these patients were consistent with a diagnosis of RCC. Only 5 of the 24 had focal features suggestive of RCC, including one clear-cell and four papillary histologies.

Sixteen of the 24 patients received first-line treatment for advanced RCC, including sunitinib, temsirolimus, bevacizumab, and/or interleukin 1. Four other patients received RCC-specific therapy following empiric chemotherapy (three patients who received RCC-specific therapies in the first line also received it in the second line).

Among the 16 patients who received first-line RCC-specific therapies there were 3 partial responses (PR), 10 cases of stable disease (SD), 2 of progressive disease (PD), and 1 patient was not evaluable. The median duration of both PR and SD was 8 months.

Of the eight patients who received first-line empiric chemotherapy, one had a PR, two had SD, and five had PD.

For the seven patients who received second-line RCC-specific therapy after either first-line chemotherapy or site-specific therapy, responses included one PR, two SD, two PD, and two not evaluable.

Median survival for all 24 patients was 12 months (range 2 to more than 43 months). Median survival of the 16 patients who received first-line RCC-specific treatment was 14 months (range 2-25 months).

Median survival for all 20 patients who received RCC-specific treatment at some time during their course was 16 months (range, 2 to more than 43 months).

The authors called for further prospective studies of this subset of patients with CUP.

SOURCE: Greco FA, Hainsworth JD. Clin Genitourin Cancer. 2018 Aug;16(4):e893-8.