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MRI with PSMA-PET lowers false negatives for clinically significant prostate cancer

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Key clinical point: Magnetic resonance imaging (MRI) in combination with prostate-specific membrane antigen (PSMA)-positron emission tomography (PET) decreases false negatives for clinically significant prostate cancer vs. MRI alone in men with suspected prostate cancer.

Major finding: PSMA-PET+MRI vs. MRI alone improved negative predictive value (91% vs 72%; test ratio, 1.27; P < .001) and sensitivity (97% vs 83%; P < .001). PSMA-PET+MRI missed 5 cases of clinically significant cancer.

Study details: A prospective, phase 2, multicenter PRIMARY trial of 291 men with suspected prostate cancer who underwent MRI, PSMA-PET, and biopsy.

Disclosures: The study was supported by grants from St Vincent’s Curran Foundation, St Vincent’s Clinic Foundation, Cancer Institute of New South Wales, and Sydney Partnership for Health, Education, Research, and Enterprise. The authors declared no conflict of interests.

Source: Emmett L et al. Eur Urol. 2021 Aug 28. doi: 10.1016/j.eururo.2021.08.002.

 

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Key clinical point: Magnetic resonance imaging (MRI) in combination with prostate-specific membrane antigen (PSMA)-positron emission tomography (PET) decreases false negatives for clinically significant prostate cancer vs. MRI alone in men with suspected prostate cancer.

Major finding: PSMA-PET+MRI vs. MRI alone improved negative predictive value (91% vs 72%; test ratio, 1.27; P < .001) and sensitivity (97% vs 83%; P < .001). PSMA-PET+MRI missed 5 cases of clinically significant cancer.

Study details: A prospective, phase 2, multicenter PRIMARY trial of 291 men with suspected prostate cancer who underwent MRI, PSMA-PET, and biopsy.

Disclosures: The study was supported by grants from St Vincent’s Curran Foundation, St Vincent’s Clinic Foundation, Cancer Institute of New South Wales, and Sydney Partnership for Health, Education, Research, and Enterprise. The authors declared no conflict of interests.

Source: Emmett L et al. Eur Urol. 2021 Aug 28. doi: 10.1016/j.eururo.2021.08.002.

 

Key clinical point: Magnetic resonance imaging (MRI) in combination with prostate-specific membrane antigen (PSMA)-positron emission tomography (PET) decreases false negatives for clinically significant prostate cancer vs. MRI alone in men with suspected prostate cancer.

Major finding: PSMA-PET+MRI vs. MRI alone improved negative predictive value (91% vs 72%; test ratio, 1.27; P < .001) and sensitivity (97% vs 83%; P < .001). PSMA-PET+MRI missed 5 cases of clinically significant cancer.

Study details: A prospective, phase 2, multicenter PRIMARY trial of 291 men with suspected prostate cancer who underwent MRI, PSMA-PET, and biopsy.

Disclosures: The study was supported by grants from St Vincent’s Curran Foundation, St Vincent’s Clinic Foundation, Cancer Institute of New South Wales, and Sydney Partnership for Health, Education, Research, and Enterprise. The authors declared no conflict of interests.

Source: Emmett L et al. Eur Urol. 2021 Aug 28. doi: 10.1016/j.eururo.2021.08.002.

 

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Avelumab with SBRT shows good response in castration-resistant prostate cancer

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Key clinical point: In patients with advanced and heavily pretreated metastatic castration-resistant prostate cancer (CRPC), stereotactic body radiotherapy (SBRT) in combination with avelumab shows good response and is well tolerated.

Major finding: Avelumab in combination with SBRT shows a disease control rate of 48% and an objective response rate of 31%. The confirmed prostate-specific antigen response rate was 23%. Grade 3-4 treatment-related adverse event rate was 16%.

Study details: A phase 2 ICE-PAC study of 31 patients with progressive metastatic CRPC who previously received at least 1 androgen receptor-directed therapy were treated with avelumab with SBRT.

Disclosures: The study was supported by Merck Healthcare Pty. Ltd., Australia. The authors received consulting/advisory/speaker fees, travel/accommodation expenses, honoraria, and research funding from various sources. Some authors declared being employed and/or owning stocks in Predicine Inc.

Source: Kwan EM et al. Eur Urol. 2021 Sep 4. doi: 10.1016/j.eururo.2021.08.011.

 

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Key clinical point: In patients with advanced and heavily pretreated metastatic castration-resistant prostate cancer (CRPC), stereotactic body radiotherapy (SBRT) in combination with avelumab shows good response and is well tolerated.

Major finding: Avelumab in combination with SBRT shows a disease control rate of 48% and an objective response rate of 31%. The confirmed prostate-specific antigen response rate was 23%. Grade 3-4 treatment-related adverse event rate was 16%.

Study details: A phase 2 ICE-PAC study of 31 patients with progressive metastatic CRPC who previously received at least 1 androgen receptor-directed therapy were treated with avelumab with SBRT.

Disclosures: The study was supported by Merck Healthcare Pty. Ltd., Australia. The authors received consulting/advisory/speaker fees, travel/accommodation expenses, honoraria, and research funding from various sources. Some authors declared being employed and/or owning stocks in Predicine Inc.

Source: Kwan EM et al. Eur Urol. 2021 Sep 4. doi: 10.1016/j.eururo.2021.08.011.

 

Key clinical point: In patients with advanced and heavily pretreated metastatic castration-resistant prostate cancer (CRPC), stereotactic body radiotherapy (SBRT) in combination with avelumab shows good response and is well tolerated.

Major finding: Avelumab in combination with SBRT shows a disease control rate of 48% and an objective response rate of 31%. The confirmed prostate-specific antigen response rate was 23%. Grade 3-4 treatment-related adverse event rate was 16%.

Study details: A phase 2 ICE-PAC study of 31 patients with progressive metastatic CRPC who previously received at least 1 androgen receptor-directed therapy were treated with avelumab with SBRT.

Disclosures: The study was supported by Merck Healthcare Pty. Ltd., Australia. The authors received consulting/advisory/speaker fees, travel/accommodation expenses, honoraria, and research funding from various sources. Some authors declared being employed and/or owning stocks in Predicine Inc.

Source: Kwan EM et al. Eur Urol. 2021 Sep 4. doi: 10.1016/j.eururo.2021.08.011.

 

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Prostate cancer: Cardiovascular safety of hormone therapies remains unresolved

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Key clinical point: Degarelix and leuprolide showed no difference in major adverse cardiovascular events (MACEs) at 1 year in patients with prostate cancer.

Major finding: There was no significant difference in the incidence of MACEs between degarelix and leuprolide groups (5.5% vs 4.1%; hazard ratio [HR], 1.28; P = .53). The rate of disease progression was similar between the groups (HR, 0.89; 95% confidence interval, 0.51-1.54). A lower rate of injection site reactions was seen with degarelix vs leuprolide (60.4% vs 26.8%).

Study details: A randomized, open-label, multinational phase 3 PRONOUNCE trial of 545 patients with prostate cancer and established atherosclerotic cardiovascular disease who were randomly assigned to receive degarelix or leuprolide.

Disclosures: This work was supported by Ferring Pharmaceuticals. The authors received grants, consulting/personal fees, membership fees, honoraria, and/or nonfinancial support from various sources. Some of the authors reported being employed at pharmaceutical companies.

Source: Lopes RD et al. Circulation. 2021 Aug 30. doi: 10.1161/CIRCULATIONAHA.121.056810.

 

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Key clinical point: Degarelix and leuprolide showed no difference in major adverse cardiovascular events (MACEs) at 1 year in patients with prostate cancer.

Major finding: There was no significant difference in the incidence of MACEs between degarelix and leuprolide groups (5.5% vs 4.1%; hazard ratio [HR], 1.28; P = .53). The rate of disease progression was similar between the groups (HR, 0.89; 95% confidence interval, 0.51-1.54). A lower rate of injection site reactions was seen with degarelix vs leuprolide (60.4% vs 26.8%).

Study details: A randomized, open-label, multinational phase 3 PRONOUNCE trial of 545 patients with prostate cancer and established atherosclerotic cardiovascular disease who were randomly assigned to receive degarelix or leuprolide.

Disclosures: This work was supported by Ferring Pharmaceuticals. The authors received grants, consulting/personal fees, membership fees, honoraria, and/or nonfinancial support from various sources. Some of the authors reported being employed at pharmaceutical companies.

Source: Lopes RD et al. Circulation. 2021 Aug 30. doi: 10.1161/CIRCULATIONAHA.121.056810.

 

Key clinical point: Degarelix and leuprolide showed no difference in major adverse cardiovascular events (MACEs) at 1 year in patients with prostate cancer.

Major finding: There was no significant difference in the incidence of MACEs between degarelix and leuprolide groups (5.5% vs 4.1%; hazard ratio [HR], 1.28; P = .53). The rate of disease progression was similar between the groups (HR, 0.89; 95% confidence interval, 0.51-1.54). A lower rate of injection site reactions was seen with degarelix vs leuprolide (60.4% vs 26.8%).

Study details: A randomized, open-label, multinational phase 3 PRONOUNCE trial of 545 patients with prostate cancer and established atherosclerotic cardiovascular disease who were randomly assigned to receive degarelix or leuprolide.

Disclosures: This work was supported by Ferring Pharmaceuticals. The authors received grants, consulting/personal fees, membership fees, honoraria, and/or nonfinancial support from various sources. Some of the authors reported being employed at pharmaceutical companies.

Source: Lopes RD et al. Circulation. 2021 Aug 30. doi: 10.1161/CIRCULATIONAHA.121.056810.

 

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Localized prostate cancer: No OS benefit beyond 15 years with added short-term ADT

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Key clinical point: In a long-term follow-up, adding short-term androgen deprivation therapy (ADT) to radiotherapy in patients with localized prostate cancer does not show overall survival (OS) benefit after 15 years.

Major finding: The OS curves of the 2 groups converge at 15 years. In the radiotherapy-alone vs combination treatment group, the OS rate at 18 years was 23% vs 23% (hazard ratio, 0.94; P =.94).

Study details: A randomized, phase 3 NRG/RTOG 9408 study of 2,028 patients with localized prostate cancer and prostate-specific antigen of ≤20 ng/mL who were randomly assigned to radiotherapy alone or radiotherapy plus short-term ADT.

Disclosures: This work was supported by National Cancer Institute. The authors performed advisory/consulting roles, received personal fees/grants and/or salary/stipend, chaired committees, and/or were employed by/owned stocks in pharmaceutical companies.

Source: Jones CU et al. Int J Radiat Oncol Biol Phys. 2021 Aug 31. doi: 10.1016/j.ijrobp.2021.08.031.

 

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Key clinical point: In a long-term follow-up, adding short-term androgen deprivation therapy (ADT) to radiotherapy in patients with localized prostate cancer does not show overall survival (OS) benefit after 15 years.

Major finding: The OS curves of the 2 groups converge at 15 years. In the radiotherapy-alone vs combination treatment group, the OS rate at 18 years was 23% vs 23% (hazard ratio, 0.94; P =.94).

Study details: A randomized, phase 3 NRG/RTOG 9408 study of 2,028 patients with localized prostate cancer and prostate-specific antigen of ≤20 ng/mL who were randomly assigned to radiotherapy alone or radiotherapy plus short-term ADT.

Disclosures: This work was supported by National Cancer Institute. The authors performed advisory/consulting roles, received personal fees/grants and/or salary/stipend, chaired committees, and/or were employed by/owned stocks in pharmaceutical companies.

Source: Jones CU et al. Int J Radiat Oncol Biol Phys. 2021 Aug 31. doi: 10.1016/j.ijrobp.2021.08.031.

 

Key clinical point: In a long-term follow-up, adding short-term androgen deprivation therapy (ADT) to radiotherapy in patients with localized prostate cancer does not show overall survival (OS) benefit after 15 years.

Major finding: The OS curves of the 2 groups converge at 15 years. In the radiotherapy-alone vs combination treatment group, the OS rate at 18 years was 23% vs 23% (hazard ratio, 0.94; P =.94).

Study details: A randomized, phase 3 NRG/RTOG 9408 study of 2,028 patients with localized prostate cancer and prostate-specific antigen of ≤20 ng/mL who were randomly assigned to radiotherapy alone or radiotherapy plus short-term ADT.

Disclosures: This work was supported by National Cancer Institute. The authors performed advisory/consulting roles, received personal fees/grants and/or salary/stipend, chaired committees, and/or were employed by/owned stocks in pharmaceutical companies.

Source: Jones CU et al. Int J Radiat Oncol Biol Phys. 2021 Aug 31. doi: 10.1016/j.ijrobp.2021.08.031.

 

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Prostate cancer: Patient-reported outcomes support hypofractionated radiotherapy

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Key clinical point: Patient-reported outcomes were similar with hypofractionated vs. conventional radiotherapy at 5 years in patients with prostate cancer.

Major finding: There were no differences in the Expanded Prostate Cancer Index Composite or University of California Los Angeles Prostate Cancer Index in the overall bowel, urinary, and sexual symptoms between the 3 groups at 5 years.

Study details: Quality of life substudy of phase 3 randomized CHHiP trial of 2,100 patients with intermediate-risk prostate cancer who received conventional (74 Gy in 37 fractions over 7.4 weeks) or hypofractionated (60 Gy in 20 fractions over 4 weeks or 57 Gy in 19 fractions over 3.8 weeks) radiotherapy.

Disclosures: This study was supported by Cancer Research UK, Institute for Health Research Cancer Research Network, and National Health Service.

Source: Staffurth JN et al. Eur Urol Oncol. 2021 Sep 3. doi: 10.1016/j.euo.2021.07.005.

 

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Key clinical point: Patient-reported outcomes were similar with hypofractionated vs. conventional radiotherapy at 5 years in patients with prostate cancer.

Major finding: There were no differences in the Expanded Prostate Cancer Index Composite or University of California Los Angeles Prostate Cancer Index in the overall bowel, urinary, and sexual symptoms between the 3 groups at 5 years.

Study details: Quality of life substudy of phase 3 randomized CHHiP trial of 2,100 patients with intermediate-risk prostate cancer who received conventional (74 Gy in 37 fractions over 7.4 weeks) or hypofractionated (60 Gy in 20 fractions over 4 weeks or 57 Gy in 19 fractions over 3.8 weeks) radiotherapy.

Disclosures: This study was supported by Cancer Research UK, Institute for Health Research Cancer Research Network, and National Health Service.

Source: Staffurth JN et al. Eur Urol Oncol. 2021 Sep 3. doi: 10.1016/j.euo.2021.07.005.

 

Key clinical point: Patient-reported outcomes were similar with hypofractionated vs. conventional radiotherapy at 5 years in patients with prostate cancer.

Major finding: There were no differences in the Expanded Prostate Cancer Index Composite or University of California Los Angeles Prostate Cancer Index in the overall bowel, urinary, and sexual symptoms between the 3 groups at 5 years.

Study details: Quality of life substudy of phase 3 randomized CHHiP trial of 2,100 patients with intermediate-risk prostate cancer who received conventional (74 Gy in 37 fractions over 7.4 weeks) or hypofractionated (60 Gy in 20 fractions over 4 weeks or 57 Gy in 19 fractions over 3.8 weeks) radiotherapy.

Disclosures: This study was supported by Cancer Research UK, Institute for Health Research Cancer Research Network, and National Health Service.

Source: Staffurth JN et al. Eur Urol Oncol. 2021 Sep 3. doi: 10.1016/j.euo.2021.07.005.

 

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CRPC: Add-on apalutamide maintains quality of life

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Key clinical point: Overall health-related quality of life (HRQoL) was maintained with the addition of apalutamide to androgen deprivation therapy (ADT) in patients with nonmetastatic castration-resistant prostate cancer (CRPC).

Major finding: The change in Functional Assessment of Cancer Therapy-Prostate (FACT-P) total score significantly favored apalutamide vs placebo at treatment cycles 21 (P = .0138) and 25 (P = .0009). No difference was seen in the median time to deterioration in scores for FACT-P and subscales.

Study details: HRQoL analysis of phase 3, randomized SPARTAN trial of patients with nmCRPC who were randomly assigned to receive apalutamide or placebo. All patients continued ADT.

Disclosures: This study was funded by Janssen Research & Development. The authors received consulting/personal/advisory/speaker fees, honoraria, royalties, research funding, lectureship fees, and/or travel expenses from various sources. Some authors reported being an investigator in clinical trials and stock ownership in pharmaceutical companies.

Source: Oudard S et al. Eur Urol Focus. 2021 Aug 31. doi: 10.1016/j.euf.2021.08.005.

 

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Key clinical point: Overall health-related quality of life (HRQoL) was maintained with the addition of apalutamide to androgen deprivation therapy (ADT) in patients with nonmetastatic castration-resistant prostate cancer (CRPC).

Major finding: The change in Functional Assessment of Cancer Therapy-Prostate (FACT-P) total score significantly favored apalutamide vs placebo at treatment cycles 21 (P = .0138) and 25 (P = .0009). No difference was seen in the median time to deterioration in scores for FACT-P and subscales.

Study details: HRQoL analysis of phase 3, randomized SPARTAN trial of patients with nmCRPC who were randomly assigned to receive apalutamide or placebo. All patients continued ADT.

Disclosures: This study was funded by Janssen Research & Development. The authors received consulting/personal/advisory/speaker fees, honoraria, royalties, research funding, lectureship fees, and/or travel expenses from various sources. Some authors reported being an investigator in clinical trials and stock ownership in pharmaceutical companies.

Source: Oudard S et al. Eur Urol Focus. 2021 Aug 31. doi: 10.1016/j.euf.2021.08.005.

 

Key clinical point: Overall health-related quality of life (HRQoL) was maintained with the addition of apalutamide to androgen deprivation therapy (ADT) in patients with nonmetastatic castration-resistant prostate cancer (CRPC).

Major finding: The change in Functional Assessment of Cancer Therapy-Prostate (FACT-P) total score significantly favored apalutamide vs placebo at treatment cycles 21 (P = .0138) and 25 (P = .0009). No difference was seen in the median time to deterioration in scores for FACT-P and subscales.

Study details: HRQoL analysis of phase 3, randomized SPARTAN trial of patients with nmCRPC who were randomly assigned to receive apalutamide or placebo. All patients continued ADT.

Disclosures: This study was funded by Janssen Research & Development. The authors received consulting/personal/advisory/speaker fees, honoraria, royalties, research funding, lectureship fees, and/or travel expenses from various sources. Some authors reported being an investigator in clinical trials and stock ownership in pharmaceutical companies.

Source: Oudard S et al. Eur Urol Focus. 2021 Aug 31. doi: 10.1016/j.euf.2021.08.005.

 

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Concordance of DNA Repair Gene Mutations in Paired Primary Prostate Cancer Samples and Metastatic Tissue or Cell-free DNA

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Importance

DNA damage response repair (DDR) gene mutations represent actionable alterations that can guide precision medicine strategies in men with advanced prostate cancer (PC). However, acquisition of contemporary tissue samples for molecular testing can be a barrier to deploying precision medicine approaches. We hypothesized that DDR alterations represent truncal events in PC and that primary tissue would reflect mutations found in cell-free circulating tumor (ctDNA) and/or metastatic tissue. OBJECTIVE: To assess concordance in DDR gene alterations between primary PC and metastases or ctDNA specimens.

Methods

Patients were included if a DDR pathway mutation was detected in metastatic tissue or ctDNA and primary tissue sequencing was available for comparison. Sequencing data from three cohorts were analyzed: (1) FoundationOne; (2) University of Washington (UW-OncoPlex or SU2C/PCF International Dream Team sequencing pipelines); and (3) University of Washington rapid autopsy series. Only pathogenic somatic mutations were included and we required 30 days between primary tumor tissue and ctDNA/ metastatic tissue acquisition. Clonal hematopoiesis of indeterminant potential (CHIP) and germline events were adjudicated by an expert molecular pathologist and excluded. DDR gene mutations detected in primary prostate tissue matched with metastatic tissue and/or ctDNA findings.

Results

Paired primary and ctDNA/metastatic samples were sequenced from 72 individuals with known DDR alterations. After excluding ctDNA studies where only CHIP and/or germline events (N=21) were observed, 51 subjects remained and were included in the final analysis. The median time from acquisition of primary tissue to acquisition of ctDNA or tumor tissue was 55 months (range: 5-193 months). Concordance in DDR gene mutation status across samples was 84% (95% CI: 71-92%). Rates of concordance between metastatic-primary and ctDNAprimary pairs were similar when CHIP cases were excluded. BRCA2 reversion mutations associated with resistance to PARP inhibitors and platinum chemotherapy were detected in ctDNA from two subjects.

 

Discussion

Primary prostate tissue accurately reflected the mutational status of actionable DDR genes in metastatic tissue, consistent with DDR alterations being truncal in most cases. After excluding likely CHIP events, ctDNA profiling accurately captured these DDR mutations, while also detecting reversion alterations that may suggest resistance mechanisms.

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Importance

DNA damage response repair (DDR) gene mutations represent actionable alterations that can guide precision medicine strategies in men with advanced prostate cancer (PC). However, acquisition of contemporary tissue samples for molecular testing can be a barrier to deploying precision medicine approaches. We hypothesized that DDR alterations represent truncal events in PC and that primary tissue would reflect mutations found in cell-free circulating tumor (ctDNA) and/or metastatic tissue. OBJECTIVE: To assess concordance in DDR gene alterations between primary PC and metastases or ctDNA specimens.

Methods

Patients were included if a DDR pathway mutation was detected in metastatic tissue or ctDNA and primary tissue sequencing was available for comparison. Sequencing data from three cohorts were analyzed: (1) FoundationOne; (2) University of Washington (UW-OncoPlex or SU2C/PCF International Dream Team sequencing pipelines); and (3) University of Washington rapid autopsy series. Only pathogenic somatic mutations were included and we required 30 days between primary tumor tissue and ctDNA/ metastatic tissue acquisition. Clonal hematopoiesis of indeterminant potential (CHIP) and germline events were adjudicated by an expert molecular pathologist and excluded. DDR gene mutations detected in primary prostate tissue matched with metastatic tissue and/or ctDNA findings.

Results

Paired primary and ctDNA/metastatic samples were sequenced from 72 individuals with known DDR alterations. After excluding ctDNA studies where only CHIP and/or germline events (N=21) were observed, 51 subjects remained and were included in the final analysis. The median time from acquisition of primary tissue to acquisition of ctDNA or tumor tissue was 55 months (range: 5-193 months). Concordance in DDR gene mutation status across samples was 84% (95% CI: 71-92%). Rates of concordance between metastatic-primary and ctDNAprimary pairs were similar when CHIP cases were excluded. BRCA2 reversion mutations associated with resistance to PARP inhibitors and platinum chemotherapy were detected in ctDNA from two subjects.

 

Discussion

Primary prostate tissue accurately reflected the mutational status of actionable DDR genes in metastatic tissue, consistent with DDR alterations being truncal in most cases. After excluding likely CHIP events, ctDNA profiling accurately captured these DDR mutations, while also detecting reversion alterations that may suggest resistance mechanisms.

Importance

DNA damage response repair (DDR) gene mutations represent actionable alterations that can guide precision medicine strategies in men with advanced prostate cancer (PC). However, acquisition of contemporary tissue samples for molecular testing can be a barrier to deploying precision medicine approaches. We hypothesized that DDR alterations represent truncal events in PC and that primary tissue would reflect mutations found in cell-free circulating tumor (ctDNA) and/or metastatic tissue. OBJECTIVE: To assess concordance in DDR gene alterations between primary PC and metastases or ctDNA specimens.

Methods

Patients were included if a DDR pathway mutation was detected in metastatic tissue or ctDNA and primary tissue sequencing was available for comparison. Sequencing data from three cohorts were analyzed: (1) FoundationOne; (2) University of Washington (UW-OncoPlex or SU2C/PCF International Dream Team sequencing pipelines); and (3) University of Washington rapid autopsy series. Only pathogenic somatic mutations were included and we required 30 days between primary tumor tissue and ctDNA/ metastatic tissue acquisition. Clonal hematopoiesis of indeterminant potential (CHIP) and germline events were adjudicated by an expert molecular pathologist and excluded. DDR gene mutations detected in primary prostate tissue matched with metastatic tissue and/or ctDNA findings.

Results

Paired primary and ctDNA/metastatic samples were sequenced from 72 individuals with known DDR alterations. After excluding ctDNA studies where only CHIP and/or germline events (N=21) were observed, 51 subjects remained and were included in the final analysis. The median time from acquisition of primary tissue to acquisition of ctDNA or tumor tissue was 55 months (range: 5-193 months). Concordance in DDR gene mutation status across samples was 84% (95% CI: 71-92%). Rates of concordance between metastatic-primary and ctDNAprimary pairs were similar when CHIP cases were excluded. BRCA2 reversion mutations associated with resistance to PARP inhibitors and platinum chemotherapy were detected in ctDNA from two subjects.

 

Discussion

Primary prostate tissue accurately reflected the mutational status of actionable DDR genes in metastatic tissue, consistent with DDR alterations being truncal in most cases. After excluding likely CHIP events, ctDNA profiling accurately captured these DDR mutations, while also detecting reversion alterations that may suggest resistance mechanisms.

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Methods of Identifying Real World mCRPC Patients from the Veterans Health Administration System

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Purpose

Prostate cancer is the fifth leading cause of death in the United States. Genomic testing is essential to guide treatment decisions in patients with metastatic castration resistant prostate cancer (mCRPC), the most advanced stage of prostate cancer. However, identifying mCRPC patients from administrative data is challenging and hinders researchers’ ability to assess testing among these patients. This study aims to develop algorithms using structured data and unstructured data with Natural language processing (NLP) methods to identify veterans by disease stage and hormone sensitivity, and to assess patient characteristics as well as receipt of tumor NGS testing.

Methods

We used biopsy, pathology, and diagnosis codes, to identify veterans with newly diagnosed PC within the Veterans Health Administration (VA) from January 1, 2017 to December 31, 2020. We developed and deployed: 1. A structured algorithm that used medication and Prostate-Specific Antigen (PSA) data to assess hormone sensitivity. 2. NLP tools to extract disease stage and hormone sensitivity from clinical notes. We report descriptive statistics on patient demographics, clinical characteristics, disease status, androgen deprivation therapy (ADT), and receipt of tumor NGS testing.

Results

There were 42,485 veterans with newly diagnosed prostate cancer between 2017-2020. This represented ~0.18% of veterans served in the VA and consisted of Whites (57%), Blacks (33%), and others (10%). During the study period, 3,113 (7.3%) patients had documentation of assessment for intraductal carcinoma, 5,160 (12.1%) had ADT treatment, 1,481 (3.5%) had CRPC, and 3,246 (7.6%) had metastatic disease. Among the 42,485 veterans, 422 received tumor NGS testing within VA, and 300 of them had metastatic disease. NLP tool and structured data algorithm collectively showed that 38% of the 422 tumor NGS testing recipients had mCRPC. Among all newly diagnosed PC patients, White patients had highest rates of tumor-based testing (2.3%), then Native Hawaiians (1.7%), Asians and Blacks (1.2% each), compared to Native Americans (0.4%).

 

Implications

NLP tools alongside structured data algorithms successfully identified variables required to measure access to tumor NGS testing. Efforts to validate and apply this method is ongoing to assess receipt of precision prostate cancer care in VA.

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VA Salt Lake City Healthcare System, Durham VA Medical Center, Astra Zeneca, Philadelphia VA Medical Center

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VA Salt Lake City Healthcare System, Durham VA Medical Center, Astra Zeneca, Philadelphia VA Medical Center

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VA Salt Lake City Healthcare System, Durham VA Medical Center, Astra Zeneca, Philadelphia VA Medical Center

Purpose

Prostate cancer is the fifth leading cause of death in the United States. Genomic testing is essential to guide treatment decisions in patients with metastatic castration resistant prostate cancer (mCRPC), the most advanced stage of prostate cancer. However, identifying mCRPC patients from administrative data is challenging and hinders researchers’ ability to assess testing among these patients. This study aims to develop algorithms using structured data and unstructured data with Natural language processing (NLP) methods to identify veterans by disease stage and hormone sensitivity, and to assess patient characteristics as well as receipt of tumor NGS testing.

Methods

We used biopsy, pathology, and diagnosis codes, to identify veterans with newly diagnosed PC within the Veterans Health Administration (VA) from January 1, 2017 to December 31, 2020. We developed and deployed: 1. A structured algorithm that used medication and Prostate-Specific Antigen (PSA) data to assess hormone sensitivity. 2. NLP tools to extract disease stage and hormone sensitivity from clinical notes. We report descriptive statistics on patient demographics, clinical characteristics, disease status, androgen deprivation therapy (ADT), and receipt of tumor NGS testing.

Results

There were 42,485 veterans with newly diagnosed prostate cancer between 2017-2020. This represented ~0.18% of veterans served in the VA and consisted of Whites (57%), Blacks (33%), and others (10%). During the study period, 3,113 (7.3%) patients had documentation of assessment for intraductal carcinoma, 5,160 (12.1%) had ADT treatment, 1,481 (3.5%) had CRPC, and 3,246 (7.6%) had metastatic disease. Among the 42,485 veterans, 422 received tumor NGS testing within VA, and 300 of them had metastatic disease. NLP tool and structured data algorithm collectively showed that 38% of the 422 tumor NGS testing recipients had mCRPC. Among all newly diagnosed PC patients, White patients had highest rates of tumor-based testing (2.3%), then Native Hawaiians (1.7%), Asians and Blacks (1.2% each), compared to Native Americans (0.4%).

 

Implications

NLP tools alongside structured data algorithms successfully identified variables required to measure access to tumor NGS testing. Efforts to validate and apply this method is ongoing to assess receipt of precision prostate cancer care in VA.

Purpose

Prostate cancer is the fifth leading cause of death in the United States. Genomic testing is essential to guide treatment decisions in patients with metastatic castration resistant prostate cancer (mCRPC), the most advanced stage of prostate cancer. However, identifying mCRPC patients from administrative data is challenging and hinders researchers’ ability to assess testing among these patients. This study aims to develop algorithms using structured data and unstructured data with Natural language processing (NLP) methods to identify veterans by disease stage and hormone sensitivity, and to assess patient characteristics as well as receipt of tumor NGS testing.

Methods

We used biopsy, pathology, and diagnosis codes, to identify veterans with newly diagnosed PC within the Veterans Health Administration (VA) from January 1, 2017 to December 31, 2020. We developed and deployed: 1. A structured algorithm that used medication and Prostate-Specific Antigen (PSA) data to assess hormone sensitivity. 2. NLP tools to extract disease stage and hormone sensitivity from clinical notes. We report descriptive statistics on patient demographics, clinical characteristics, disease status, androgen deprivation therapy (ADT), and receipt of tumor NGS testing.

Results

There were 42,485 veterans with newly diagnosed prostate cancer between 2017-2020. This represented ~0.18% of veterans served in the VA and consisted of Whites (57%), Blacks (33%), and others (10%). During the study period, 3,113 (7.3%) patients had documentation of assessment for intraductal carcinoma, 5,160 (12.1%) had ADT treatment, 1,481 (3.5%) had CRPC, and 3,246 (7.6%) had metastatic disease. Among the 42,485 veterans, 422 received tumor NGS testing within VA, and 300 of them had metastatic disease. NLP tool and structured data algorithm collectively showed that 38% of the 422 tumor NGS testing recipients had mCRPC. Among all newly diagnosed PC patients, White patients had highest rates of tumor-based testing (2.3%), then Native Hawaiians (1.7%), Asians and Blacks (1.2% each), compared to Native Americans (0.4%).

 

Implications

NLP tools alongside structured data algorithms successfully identified variables required to measure access to tumor NGS testing. Efforts to validate and apply this method is ongoing to assess receipt of precision prostate cancer care in VA.

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Diagnosis of Prostate Cancer and Prostate-specific Antigen Level on Initial Prostate Biopsy: Does Race Matter?

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Objective

To determine whether Black Veterans are at higher risk for prostate cancer diagnosis on their first prostate biopsy compared to non-Hispanic White (White) Veterans.

Background

Prostate-specific antigen (PSA) testing is widely used to screen for prostate cancer. Although men of African ancestry display an increased incidence of prostate cancer and more aggressive disease, specific PSA thresholds for biopsy referral have yet to be proposed for this population.

Methods

We used the VHA’s electronic medical record data to collect Veterans’ demographic and clinical characteristics including self-identified race/ethnicity, age, date of first prostate biopsy, PSA results, and prostate cancer diagnosis. Veterans’ ZIP code of residence was used to determine urban/rural status, income, and education. We estimated multivariable logistic regression models to predict the likelihood of prostate cancer diagnosis on the first biopsy using race, baseline PSA, age at first PSA test, age at initial biopsy, smoking status, use of statins, and socioeconomic factors as predictors. We calculated adjusted predicted probabilities of cancer detection on the first prostate biopsy from the logistic models at different PSA levels.

Results

We identified 246,056 White and 71,653 Black Veterans who underwent their first prostate biopsy through February 28, 2020 and who had no previous prostate cancer diagnosis or treatment prior to that biopsy. Black Veterans appeared to receive their first PSA test four years earlier and undergo their first prostate biopsy two years earlier than their White counterparts (median age of 57 vs. 61 and 63 vs. 65, respectively). After controlling for selected covariates, we found that Black Veterans were 52% more likely to be diagnosed with prostate cancer on their first prostate biopsy compared to White Veterans (OR 1.52, 95% CI 1.49-1.55). Our model indicated that a Black Veteran with a PSA of 4.0 ng/ml has an equivalent risk of prostate cancer detection as a White Veteran with a PSA of 9.7 ng/ml.

 

Implications

Our findings suggested that developing a risk-based PSA threshold for referral to prostate biopsy may lead to earlier diagnosis of clinically significant prostate cancer in a population of Veterans known to have an increased incidence and risk of aggressive disease.

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Brent S. Rose VA Informatics and Computing Infrastructure, VA Salt Lake City Health Care System, VA Greater Los Angeles Healthcare System, David Geffen School of Medicine at UCLA, VA San Diego Healthcare System, University of California, San Diego

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Brent S. Rose VA Informatics and Computing Infrastructure, VA Salt Lake City Health Care System, VA Greater Los Angeles Healthcare System, David Geffen School of Medicine at UCLA, VA San Diego Healthcare System, University of California, San Diego

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Brent S. Rose VA Informatics and Computing Infrastructure, VA Salt Lake City Health Care System, VA Greater Los Angeles Healthcare System, David Geffen School of Medicine at UCLA, VA San Diego Healthcare System, University of California, San Diego

Objective

To determine whether Black Veterans are at higher risk for prostate cancer diagnosis on their first prostate biopsy compared to non-Hispanic White (White) Veterans.

Background

Prostate-specific antigen (PSA) testing is widely used to screen for prostate cancer. Although men of African ancestry display an increased incidence of prostate cancer and more aggressive disease, specific PSA thresholds for biopsy referral have yet to be proposed for this population.

Methods

We used the VHA’s electronic medical record data to collect Veterans’ demographic and clinical characteristics including self-identified race/ethnicity, age, date of first prostate biopsy, PSA results, and prostate cancer diagnosis. Veterans’ ZIP code of residence was used to determine urban/rural status, income, and education. We estimated multivariable logistic regression models to predict the likelihood of prostate cancer diagnosis on the first biopsy using race, baseline PSA, age at first PSA test, age at initial biopsy, smoking status, use of statins, and socioeconomic factors as predictors. We calculated adjusted predicted probabilities of cancer detection on the first prostate biopsy from the logistic models at different PSA levels.

Results

We identified 246,056 White and 71,653 Black Veterans who underwent their first prostate biopsy through February 28, 2020 and who had no previous prostate cancer diagnosis or treatment prior to that biopsy. Black Veterans appeared to receive their first PSA test four years earlier and undergo their first prostate biopsy two years earlier than their White counterparts (median age of 57 vs. 61 and 63 vs. 65, respectively). After controlling for selected covariates, we found that Black Veterans were 52% more likely to be diagnosed with prostate cancer on their first prostate biopsy compared to White Veterans (OR 1.52, 95% CI 1.49-1.55). Our model indicated that a Black Veteran with a PSA of 4.0 ng/ml has an equivalent risk of prostate cancer detection as a White Veteran with a PSA of 9.7 ng/ml.

 

Implications

Our findings suggested that developing a risk-based PSA threshold for referral to prostate biopsy may lead to earlier diagnosis of clinically significant prostate cancer in a population of Veterans known to have an increased incidence and risk of aggressive disease.

Objective

To determine whether Black Veterans are at higher risk for prostate cancer diagnosis on their first prostate biopsy compared to non-Hispanic White (White) Veterans.

Background

Prostate-specific antigen (PSA) testing is widely used to screen for prostate cancer. Although men of African ancestry display an increased incidence of prostate cancer and more aggressive disease, specific PSA thresholds for biopsy referral have yet to be proposed for this population.

Methods

We used the VHA’s electronic medical record data to collect Veterans’ demographic and clinical characteristics including self-identified race/ethnicity, age, date of first prostate biopsy, PSA results, and prostate cancer diagnosis. Veterans’ ZIP code of residence was used to determine urban/rural status, income, and education. We estimated multivariable logistic regression models to predict the likelihood of prostate cancer diagnosis on the first biopsy using race, baseline PSA, age at first PSA test, age at initial biopsy, smoking status, use of statins, and socioeconomic factors as predictors. We calculated adjusted predicted probabilities of cancer detection on the first prostate biopsy from the logistic models at different PSA levels.

Results

We identified 246,056 White and 71,653 Black Veterans who underwent their first prostate biopsy through February 28, 2020 and who had no previous prostate cancer diagnosis or treatment prior to that biopsy. Black Veterans appeared to receive their first PSA test four years earlier and undergo their first prostate biopsy two years earlier than their White counterparts (median age of 57 vs. 61 and 63 vs. 65, respectively). After controlling for selected covariates, we found that Black Veterans were 52% more likely to be diagnosed with prostate cancer on their first prostate biopsy compared to White Veterans (OR 1.52, 95% CI 1.49-1.55). Our model indicated that a Black Veteran with a PSA of 4.0 ng/ml has an equivalent risk of prostate cancer detection as a White Veteran with a PSA of 9.7 ng/ml.

 

Implications

Our findings suggested that developing a risk-based PSA threshold for referral to prostate biopsy may lead to earlier diagnosis of clinically significant prostate cancer in a population of Veterans known to have an increased incidence and risk of aggressive disease.

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Old saying about prostate cancer not true when it’s metastatic

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Nearly 80% of men with metastatic prostate cancer died from their malignancy, according to a retrospective cohort study involving 26,000-plus American men diagnosed with advanced disease in roughly the last 20 years.

The findings fill an information gap because, remarkably, “data are lacking” on causes of death among men whose prostate cancer has spread to other sites, say lead author Ahmed Elmehrath, MD, of Cairo University, Egypt, and colleagues.

“It was an important realization by our team that prostate cancer was the cause of death in 78% of patients,” said senior author Omar Alhalabi, MD, of University of Texas MD Anderson Cancer Center, Houston, in an email.

“Most patients with metastatic prostate cancer die from it, rather than other possible causes of death,” confirm Samuel Merriel, MSc, Tanimola Martins, PhD, and Sarah Bailey, PhD, University of Exeter, United Kingdom, in an accompanying editorial. The study was published last month in JAMA Network Open.

The findings represent the near opposite of a commonly held – and comforting – belief about early-stage disease: “You die with prostate cancer, not from it.”

That old saying is articulated in various ways, such as this from the Prostate Cancer Foundation: “We can confirm that there are those prostate cancers a man may die with and not of, while others are very aggressive.” The American Cancer Society says this: “Prostate cancer can be a serious disease, but most men diagnosed with prostate cancer do not die from it.”

However, these commonplace comments do not cover metastatic disease, which is what the authors of the new study decided to focus on.  

The team used data from the Surveillance, Epidemiology, and End Results Program (SEER) database to gather a sample of 26,168 U.S. men who received a diagnosis of metastatic prostate cancer from January 2000 to December 2016. They then analyzed the data in 2020 and found that 16,732 men (64%) had died during the follow-up period.

The majority of these deaths (77.8%) were from prostate cancer, 5.5% were from other cancers, and 16.7% were from noncancer causes, including cardiovascular diseases, chronic obstructive pulmonary disease, and cerebrovascular diseases.

Senior author Dr. Alhalabi acknowledged a limitation in these findings – that the SEER database relies on causes of death extracted from death certificates. “Death certificates have limited granularity in terms of the details they can contain about the cause of death and also have reporting bias,” he said.

Most of the prostate cancer deaths (59%) occurred within 2 years. The 5-year overall survival rate in the study group was 26%.

The deadliness of metastatic disease “reinforces the need for innovations to promote early-stage diagnosis,” comment the editorialists. Striking a hopeful note, they also say that “new tests for prostate cancer detection may reduce the proportion of patients who receive a diagnosis at a late stage.”
 

Death from other causes

The mean age at metastatic prostate cancer diagnosis in the study was roughly 71 years. Most of the cohort was White (74.5%) and had a diagnosis of stage M1b metastatic prostate cancer (72.7%), which means the cancer had spread to the bones.

Among men in the cohort, the rates of death from septicemia, suicide, accidents, COPD, and cerebrovascular diseases were significantly increased compared with the general U.S. male population, the team observes.

Thus, the study authors were concerned with not only with death from metastatic prostate cancer but death from other causes.

That concern is rooted in the established fact that there is now improved survival among patients with prostate cancer in the U.S., including among men with advanced disease. “Patients tend to live long enough after a prostate cancer diagnosis for non–cancer-related comorbidities to be associated with their overall survival,” they write.

The editorialists agree: Prostate cancer “has a high long-term survival rate compared with almost all other cancer types and signals the need for greater holistic care for patients.”

As noted above, cardiovascular diseases were the most common cause of nonprostate cancer–related deaths in the new study.

As in the management of other cancers, there is concern among clinicians and researchers about the cardiotoxic effects of prostate cancer treatments.

The study authors point to a 2017 analysis that showed that men with prostate cancer and no prior cardiac disease had greater risk of heart failure after taking androgen deprivation therapy (ADT), a common treatment used when the disease recurs after definitive treatment. Another study suggested an association between cardiotoxic effects of ADT and myocardial infarction regardless of medical history in general.

The authors of the current study say that such findings highlight “the importance of multidisciplinary care for such patients and the role of primary care physicians in optimizing cardiovascular risk prevention and providing early referrals to cardiologists.”

Further, the team says that tailoring “ADT to each patient’s needs may be associated with improved survival, especially for patients with factors associated with cardiovascular disease.”

Who should lead the way in multidisciplinary care? “The answer probably is case-by-case,” said Dr. Alhalabi, adding that it might depend on the presence of underlying morbidities such as cardiovascular disease and COPD.

“It is also important for the oncologist (‘the gatekeeper’) to try to mitigate the potential metabolic effects of hormonal deprivation therapy such as weight gain, decreased muscle mass, hyperlipidemia, etc.,” he added.

The study had no specific funding. The study authors and editorialists have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

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Nearly 80% of men with metastatic prostate cancer died from their malignancy, according to a retrospective cohort study involving 26,000-plus American men diagnosed with advanced disease in roughly the last 20 years.

The findings fill an information gap because, remarkably, “data are lacking” on causes of death among men whose prostate cancer has spread to other sites, say lead author Ahmed Elmehrath, MD, of Cairo University, Egypt, and colleagues.

“It was an important realization by our team that prostate cancer was the cause of death in 78% of patients,” said senior author Omar Alhalabi, MD, of University of Texas MD Anderson Cancer Center, Houston, in an email.

“Most patients with metastatic prostate cancer die from it, rather than other possible causes of death,” confirm Samuel Merriel, MSc, Tanimola Martins, PhD, and Sarah Bailey, PhD, University of Exeter, United Kingdom, in an accompanying editorial. The study was published last month in JAMA Network Open.

The findings represent the near opposite of a commonly held – and comforting – belief about early-stage disease: “You die with prostate cancer, not from it.”

That old saying is articulated in various ways, such as this from the Prostate Cancer Foundation: “We can confirm that there are those prostate cancers a man may die with and not of, while others are very aggressive.” The American Cancer Society says this: “Prostate cancer can be a serious disease, but most men diagnosed with prostate cancer do not die from it.”

However, these commonplace comments do not cover metastatic disease, which is what the authors of the new study decided to focus on.  

The team used data from the Surveillance, Epidemiology, and End Results Program (SEER) database to gather a sample of 26,168 U.S. men who received a diagnosis of metastatic prostate cancer from January 2000 to December 2016. They then analyzed the data in 2020 and found that 16,732 men (64%) had died during the follow-up period.

The majority of these deaths (77.8%) were from prostate cancer, 5.5% were from other cancers, and 16.7% were from noncancer causes, including cardiovascular diseases, chronic obstructive pulmonary disease, and cerebrovascular diseases.

Senior author Dr. Alhalabi acknowledged a limitation in these findings – that the SEER database relies on causes of death extracted from death certificates. “Death certificates have limited granularity in terms of the details they can contain about the cause of death and also have reporting bias,” he said.

Most of the prostate cancer deaths (59%) occurred within 2 years. The 5-year overall survival rate in the study group was 26%.

The deadliness of metastatic disease “reinforces the need for innovations to promote early-stage diagnosis,” comment the editorialists. Striking a hopeful note, they also say that “new tests for prostate cancer detection may reduce the proportion of patients who receive a diagnosis at a late stage.”
 

Death from other causes

The mean age at metastatic prostate cancer diagnosis in the study was roughly 71 years. Most of the cohort was White (74.5%) and had a diagnosis of stage M1b metastatic prostate cancer (72.7%), which means the cancer had spread to the bones.

Among men in the cohort, the rates of death from septicemia, suicide, accidents, COPD, and cerebrovascular diseases were significantly increased compared with the general U.S. male population, the team observes.

Thus, the study authors were concerned with not only with death from metastatic prostate cancer but death from other causes.

That concern is rooted in the established fact that there is now improved survival among patients with prostate cancer in the U.S., including among men with advanced disease. “Patients tend to live long enough after a prostate cancer diagnosis for non–cancer-related comorbidities to be associated with their overall survival,” they write.

The editorialists agree: Prostate cancer “has a high long-term survival rate compared with almost all other cancer types and signals the need for greater holistic care for patients.”

As noted above, cardiovascular diseases were the most common cause of nonprostate cancer–related deaths in the new study.

As in the management of other cancers, there is concern among clinicians and researchers about the cardiotoxic effects of prostate cancer treatments.

The study authors point to a 2017 analysis that showed that men with prostate cancer and no prior cardiac disease had greater risk of heart failure after taking androgen deprivation therapy (ADT), a common treatment used when the disease recurs after definitive treatment. Another study suggested an association between cardiotoxic effects of ADT and myocardial infarction regardless of medical history in general.

The authors of the current study say that such findings highlight “the importance of multidisciplinary care for such patients and the role of primary care physicians in optimizing cardiovascular risk prevention and providing early referrals to cardiologists.”

Further, the team says that tailoring “ADT to each patient’s needs may be associated with improved survival, especially for patients with factors associated with cardiovascular disease.”

Who should lead the way in multidisciplinary care? “The answer probably is case-by-case,” said Dr. Alhalabi, adding that it might depend on the presence of underlying morbidities such as cardiovascular disease and COPD.

“It is also important for the oncologist (‘the gatekeeper’) to try to mitigate the potential metabolic effects of hormonal deprivation therapy such as weight gain, decreased muscle mass, hyperlipidemia, etc.,” he added.

The study had no specific funding. The study authors and editorialists have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Nearly 80% of men with metastatic prostate cancer died from their malignancy, according to a retrospective cohort study involving 26,000-plus American men diagnosed with advanced disease in roughly the last 20 years.

The findings fill an information gap because, remarkably, “data are lacking” on causes of death among men whose prostate cancer has spread to other sites, say lead author Ahmed Elmehrath, MD, of Cairo University, Egypt, and colleagues.

“It was an important realization by our team that prostate cancer was the cause of death in 78% of patients,” said senior author Omar Alhalabi, MD, of University of Texas MD Anderson Cancer Center, Houston, in an email.

“Most patients with metastatic prostate cancer die from it, rather than other possible causes of death,” confirm Samuel Merriel, MSc, Tanimola Martins, PhD, and Sarah Bailey, PhD, University of Exeter, United Kingdom, in an accompanying editorial. The study was published last month in JAMA Network Open.

The findings represent the near opposite of a commonly held – and comforting – belief about early-stage disease: “You die with prostate cancer, not from it.”

That old saying is articulated in various ways, such as this from the Prostate Cancer Foundation: “We can confirm that there are those prostate cancers a man may die with and not of, while others are very aggressive.” The American Cancer Society says this: “Prostate cancer can be a serious disease, but most men diagnosed with prostate cancer do not die from it.”

However, these commonplace comments do not cover metastatic disease, which is what the authors of the new study decided to focus on.  

The team used data from the Surveillance, Epidemiology, and End Results Program (SEER) database to gather a sample of 26,168 U.S. men who received a diagnosis of metastatic prostate cancer from January 2000 to December 2016. They then analyzed the data in 2020 and found that 16,732 men (64%) had died during the follow-up period.

The majority of these deaths (77.8%) were from prostate cancer, 5.5% were from other cancers, and 16.7% were from noncancer causes, including cardiovascular diseases, chronic obstructive pulmonary disease, and cerebrovascular diseases.

Senior author Dr. Alhalabi acknowledged a limitation in these findings – that the SEER database relies on causes of death extracted from death certificates. “Death certificates have limited granularity in terms of the details they can contain about the cause of death and also have reporting bias,” he said.

Most of the prostate cancer deaths (59%) occurred within 2 years. The 5-year overall survival rate in the study group was 26%.

The deadliness of metastatic disease “reinforces the need for innovations to promote early-stage diagnosis,” comment the editorialists. Striking a hopeful note, they also say that “new tests for prostate cancer detection may reduce the proportion of patients who receive a diagnosis at a late stage.”
 

Death from other causes

The mean age at metastatic prostate cancer diagnosis in the study was roughly 71 years. Most of the cohort was White (74.5%) and had a diagnosis of stage M1b metastatic prostate cancer (72.7%), which means the cancer had spread to the bones.

Among men in the cohort, the rates of death from septicemia, suicide, accidents, COPD, and cerebrovascular diseases were significantly increased compared with the general U.S. male population, the team observes.

Thus, the study authors were concerned with not only with death from metastatic prostate cancer but death from other causes.

That concern is rooted in the established fact that there is now improved survival among patients with prostate cancer in the U.S., including among men with advanced disease. “Patients tend to live long enough after a prostate cancer diagnosis for non–cancer-related comorbidities to be associated with their overall survival,” they write.

The editorialists agree: Prostate cancer “has a high long-term survival rate compared with almost all other cancer types and signals the need for greater holistic care for patients.”

As noted above, cardiovascular diseases were the most common cause of nonprostate cancer–related deaths in the new study.

As in the management of other cancers, there is concern among clinicians and researchers about the cardiotoxic effects of prostate cancer treatments.

The study authors point to a 2017 analysis that showed that men with prostate cancer and no prior cardiac disease had greater risk of heart failure after taking androgen deprivation therapy (ADT), a common treatment used when the disease recurs after definitive treatment. Another study suggested an association between cardiotoxic effects of ADT and myocardial infarction regardless of medical history in general.

The authors of the current study say that such findings highlight “the importance of multidisciplinary care for such patients and the role of primary care physicians in optimizing cardiovascular risk prevention and providing early referrals to cardiologists.”

Further, the team says that tailoring “ADT to each patient’s needs may be associated with improved survival, especially for patients with factors associated with cardiovascular disease.”

Who should lead the way in multidisciplinary care? “The answer probably is case-by-case,” said Dr. Alhalabi, adding that it might depend on the presence of underlying morbidities such as cardiovascular disease and COPD.

“It is also important for the oncologist (‘the gatekeeper’) to try to mitigate the potential metabolic effects of hormonal deprivation therapy such as weight gain, decreased muscle mass, hyperlipidemia, etc.,” he added.

The study had no specific funding. The study authors and editorialists have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

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