Prostate Cancer

Key clinical point: Higher baseline serum levels of choline, betaine, and phenylacetylglutamine are associated with increased risk for incident lethal prostate cancer.

Major finding: Compared with the patients in the first quartile, the risk for incident lethal prostate cancer was higher in those with higher baseline levels of choline (odds ratio [OR] for third and fourth quartile, 2.37 and 2.19, respectively; P for trend = .005), betaine (OR for third and fourth quartile, 2.13 and 1.86, respectively; P for trend = .11), and phenylacetylglutamine (OR for third and fourth quartile, 2.54 and 2.55, respectively; P for trend = .003).

Study details: A study of 173 patients with lethal prostate cancer and 519 healthy individuals from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening trial.

Disclosures: This study was supported by grants from National Cancer Institute and Prostate Cancer Foundation. The authors held patents and/or received consulting fees/research grants/royalties from various sources.

Source: Reichard CA et al. Cancer Epidemiol Biomarkers Prev. 2021 Oct 28. doi: 10.1158/1055-9965.

Key clinical point: Higher baseline serum levels of choline, betaine, and phenylacetylglutamine are associated with increased risk for incident lethal prostate cancer.

Major finding: Compared with the patients in the first quartile, the risk for incident lethal prostate cancer was higher in those with higher baseline levels of choline (odds ratio [OR] for third and fourth quartile, 2.37 and 2.19, respectively; P for trend = .005), betaine (OR for third and fourth quartile, 2.13 and 1.86, respectively; P for trend = .11), and phenylacetylglutamine (OR for third and fourth quartile, 2.54 and 2.55, respectively; P for trend = .003).

Study details: A study of 173 patients with lethal prostate cancer and 519 healthy individuals from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening trial.

Disclosures: This study was supported by grants from National Cancer Institute and Prostate Cancer Foundation. The authors held patents and/or received consulting fees/research grants/royalties from various sources.

Source: Reichard CA et al. Cancer Epidemiol Biomarkers Prev. 2021 Oct 28. doi: 10.1158/1055-9965.

Key clinical point: Higher baseline serum levels of choline, betaine, and phenylacetylglutamine are associated with increased risk for incident lethal prostate cancer.

Major finding: Compared with the patients in the first quartile, the risk for incident lethal prostate cancer was higher in those with higher baseline levels of choline (odds ratio [OR] for third and fourth quartile, 2.37 and 2.19, respectively; P for trend = .005), betaine (OR for third and fourth quartile, 2.13 and 1.86, respectively; P for trend = .11), and phenylacetylglutamine (OR for third and fourth quartile, 2.54 and 2.55, respectively; P for trend = .003).

Study details: A study of 173 patients with lethal prostate cancer and 519 healthy individuals from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening trial.

Disclosures: This study was supported by grants from National Cancer Institute and Prostate Cancer Foundation. The authors held patents and/or received consulting fees/research grants/royalties from various sources.

Source: Reichard CA et al. Cancer Epidemiol Biomarkers Prev. 2021 Oct 28. doi: 10.1158/1055-9965.

Key clinical point: Radical prostatectomy vs external beam radiotherapy (EBRT) is associated with lower cancer-specific mortality in African American patients with National Comprehensive Cancer Network (NCCN) high-risk and Johns Hopkins University (JH) very high-risk prostate cancer.

Major finding: Radical prostatectomy and EBRT were performed in 39% and 61% of patients, respectively. Radical prostatectomy vs EBRT was associated with lower risk for cancer-specific mortality at 5 years in NCCN high-risk (2.3% vs 3.9%; hazard ratio [HR], 0.52; P = .02) and JH very high-risk patients (3.3% vs 7.4%; HR, 0.42; P = .02).

Study details: A retrospective study of 4,165 NCCN high-risk African American patients with prostate cancer identified from the Surveillance, Epidemiology, and End Results database between 2010 and 2016. Patients were subcategorized into JH high-risk (n=1,944) and very high-risk (n=2,221) groups.

Disclosures: No funding source was identified for this work. The authors declared no conflict of interests.

Source: Hoeh B et al. Prostate. 2021 Oct 18. doi: 10.1002/pros.24253.

Key clinical point: Radical prostatectomy vs external beam radiotherapy (EBRT) is associated with lower cancer-specific mortality in African American patients with National Comprehensive Cancer Network (NCCN) high-risk and Johns Hopkins University (JH) very high-risk prostate cancer.

Major finding: Radical prostatectomy and EBRT were performed in 39% and 61% of patients, respectively. Radical prostatectomy vs EBRT was associated with lower risk for cancer-specific mortality at 5 years in NCCN high-risk (2.3% vs 3.9%; hazard ratio [HR], 0.52; P = .02) and JH very high-risk patients (3.3% vs 7.4%; HR, 0.42; P = .02).

Study details: A retrospective study of 4,165 NCCN high-risk African American patients with prostate cancer identified from the Surveillance, Epidemiology, and End Results database between 2010 and 2016. Patients were subcategorized into JH high-risk (n=1,944) and very high-risk (n=2,221) groups.

Disclosures: No funding source was identified for this work. The authors declared no conflict of interests.

Source: Hoeh B et al. Prostate. 2021 Oct 18. doi: 10.1002/pros.24253.

Key clinical point: Radical prostatectomy vs external beam radiotherapy (EBRT) is associated with lower cancer-specific mortality in African American patients with National Comprehensive Cancer Network (NCCN) high-risk and Johns Hopkins University (JH) very high-risk prostate cancer.

Major finding: Radical prostatectomy and EBRT were performed in 39% and 61% of patients, respectively. Radical prostatectomy vs EBRT was associated with lower risk for cancer-specific mortality at 5 years in NCCN high-risk (2.3% vs 3.9%; hazard ratio [HR], 0.52; P = .02) and JH very high-risk patients (3.3% vs 7.4%; HR, 0.42; P = .02).

Study details: A retrospective study of 4,165 NCCN high-risk African American patients with prostate cancer identified from the Surveillance, Epidemiology, and End Results database between 2010 and 2016. Patients were subcategorized into JH high-risk (n=1,944) and very high-risk (n=2,221) groups.

Disclosures: No funding source was identified for this work. The authors declared no conflict of interests.

Source: Hoeh B et al. Prostate. 2021 Oct 18. doi: 10.1002/pros.24253.

Key clinical point: Significant racial and ethnic disparities are reported in the use of prostate magnetic resonance imaging (MRI) following elevated prostate-specific antigen (PSA) test results.

Major finding: Black patients with PSA levels above 4 ng/mL and 10 ng/mL were 24.1% and 35.0% less likely to undergo subsequent prostate MRI, respectively, compared with White patients. Asian patients with PSA levels higher than 4 ng/mL were 24.1% less likely, and Hispanic patients with PSA levels above 10 ng/mL were 23.4% less likely to undergo subsequent prostate MRI than White patients.

Study details: A cohort study of 794,809 patients aged 40 years and above who received a single PSA result and no prior PSA screening or prostate MRI.

Disclosures: This work was supported by research funding from Harvey L. Neiman Health Policy Institute. Dr. Rosenkrantz reported employment with American Journal of Roentgenology. No other disclosures were reported.

Source: Abashidze N et al. JAMA Network Open. 2021 Nov 8. doi: 10.1001/jamanetworkopen.2021.32388.

Key clinical point: Significant racial and ethnic disparities are reported in the use of prostate magnetic resonance imaging (MRI) following elevated prostate-specific antigen (PSA) test results.

Major finding: Black patients with PSA levels above 4 ng/mL and 10 ng/mL were 24.1% and 35.0% less likely to undergo subsequent prostate MRI, respectively, compared with White patients. Asian patients with PSA levels higher than 4 ng/mL were 24.1% less likely, and Hispanic patients with PSA levels above 10 ng/mL were 23.4% less likely to undergo subsequent prostate MRI than White patients.

Study details: A cohort study of 794,809 patients aged 40 years and above who received a single PSA result and no prior PSA screening or prostate MRI.

Disclosures: This work was supported by research funding from Harvey L. Neiman Health Policy Institute. Dr. Rosenkrantz reported employment with American Journal of Roentgenology. No other disclosures were reported.

Source: Abashidze N et al. JAMA Network Open. 2021 Nov 8. doi: 10.1001/jamanetworkopen.2021.32388.

Key clinical point: Significant racial and ethnic disparities are reported in the use of prostate magnetic resonance imaging (MRI) following elevated prostate-specific antigen (PSA) test results.

Major finding: Black patients with PSA levels above 4 ng/mL and 10 ng/mL were 24.1% and 35.0% less likely to undergo subsequent prostate MRI, respectively, compared with White patients. Asian patients with PSA levels higher than 4 ng/mL were 24.1% less likely, and Hispanic patients with PSA levels above 10 ng/mL were 23.4% less likely to undergo subsequent prostate MRI than White patients.

Study details: A cohort study of 794,809 patients aged 40 years and above who received a single PSA result and no prior PSA screening or prostate MRI.

Disclosures: This work was supported by research funding from Harvey L. Neiman Health Policy Institute. Dr. Rosenkrantz reported employment with American Journal of Roentgenology. No other disclosures were reported.

Source: Abashidze N et al. JAMA Network Open. 2021 Nov 8. doi: 10.1001/jamanetworkopen.2021.32388.

Key clinical point: Prostrate-specific antigen (PSA) testing increased after the 2017 United States Preventive Services Task Force (USPSTF) draft statement for prostate cancer screening.

Major finding: A relative increase of 12.5% was seen in the PSA testing rate during 2016-2019. A relative increase of 10.1%, 12.1%, and 16.2% was seen in men aged 40-54 years, 55-69 years, and 70-89 years. A significantly increasing trend of PSA testing was seen after the release of USPSTF draft in April 2017 (0.30 tests per 100 person-years for each bimonthly period; P < .001).

Study details: This retrospective cohort study of 8,087,565 men aged 40 to 89 years who underwent prostate cancer screening between 2013 and 2019.

Disclosures: This work was funded by National Institutes of Health/National Cancer Institute. The authors received grants, honoraria, and consulting/personal/speaker fees from various sources.

Source: Leapman MS et al. JAMA Oncol. 2021 Nov 11. doi: 10.1001/jamaoncol.2021.5143.

Key clinical point: Prostrate-specific antigen (PSA) testing increased after the 2017 United States Preventive Services Task Force (USPSTF) draft statement for prostate cancer screening.

Major finding: A relative increase of 12.5% was seen in the PSA testing rate during 2016-2019. A relative increase of 10.1%, 12.1%, and 16.2% was seen in men aged 40-54 years, 55-69 years, and 70-89 years. A significantly increasing trend of PSA testing was seen after the release of USPSTF draft in April 2017 (0.30 tests per 100 person-years for each bimonthly period; P < .001).

Study details: This retrospective cohort study of 8,087,565 men aged 40 to 89 years who underwent prostate cancer screening between 2013 and 2019.

Disclosures: This work was funded by National Institutes of Health/National Cancer Institute. The authors received grants, honoraria, and consulting/personal/speaker fees from various sources.

Source: Leapman MS et al. JAMA Oncol. 2021 Nov 11. doi: 10.1001/jamaoncol.2021.5143.

Key clinical point: Prostrate-specific antigen (PSA) testing increased after the 2017 United States Preventive Services Task Force (USPSTF) draft statement for prostate cancer screening.

Major finding: A relative increase of 12.5% was seen in the PSA testing rate during 2016-2019. A relative increase of 10.1%, 12.1%, and 16.2% was seen in men aged 40-54 years, 55-69 years, and 70-89 years. A significantly increasing trend of PSA testing was seen after the release of USPSTF draft in April 2017 (0.30 tests per 100 person-years for each bimonthly period; P < .001).

Study details: This retrospective cohort study of 8,087,565 men aged 40 to 89 years who underwent prostate cancer screening between 2013 and 2019.

Disclosures: This work was funded by National Institutes of Health/National Cancer Institute. The authors received grants, honoraria, and consulting/personal/speaker fees from various sources.

Source: Leapman MS et al. JAMA Oncol. 2021 Nov 11. doi: 10.1001/jamaoncol.2021.5143.

Key clinical point: Enzalutamide improves outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC) in a prospective real-world study.

Major finding: The median time to treatment failure in chemotherapy and abiraterone-naïve patients was 12.9 months and those who were previously treated with chemotherapy and were abiraterone naïve was 8.4 months.

Study details: A prospective, observational PREMISE study of 1,732 patients with mCRPC who received enzalutamide.

Disclosures: This study was sponsored by Astellas Pharma Inc. The authors received honoraria, travel funds, grants, consulting/personal fees, and financial and nonfinancial support from various sources. Some authors reported being employed by an organization/foundation that receives funding from various private and public sector sources.

Source: Payne H et al. Int J Cancer. 2021 Oct 14. doi: 10.1002/ijc.33845.

Key clinical point: Enzalutamide improves outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC) in a prospective real-world study.

Major finding: The median time to treatment failure in chemotherapy and abiraterone-naïve patients was 12.9 months and those who were previously treated with chemotherapy and were abiraterone naïve was 8.4 months.

Study details: A prospective, observational PREMISE study of 1,732 patients with mCRPC who received enzalutamide.

Disclosures: This study was sponsored by Astellas Pharma Inc. The authors received honoraria, travel funds, grants, consulting/personal fees, and financial and nonfinancial support from various sources. Some authors reported being employed by an organization/foundation that receives funding from various private and public sector sources.

Source: Payne H et al. Int J Cancer. 2021 Oct 14. doi: 10.1002/ijc.33845.

Key clinical point: Enzalutamide improves outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC) in a prospective real-world study.

Major finding: The median time to treatment failure in chemotherapy and abiraterone-naïve patients was 12.9 months and those who were previously treated with chemotherapy and were abiraterone naïve was 8.4 months.

Study details: A prospective, observational PREMISE study of 1,732 patients with mCRPC who received enzalutamide.

Disclosures: This study was sponsored by Astellas Pharma Inc. The authors received honoraria, travel funds, grants, consulting/personal fees, and financial and nonfinancial support from various sources. Some authors reported being employed by an organization/foundation that receives funding from various private and public sector sources.

Source: Payne H et al. Int J Cancer. 2021 Oct 14. doi: 10.1002/ijc.33845.

Key clinical point: Salvage low-dose-rate (LDR) prostate brachytherapy shows good survival in patients with low-/intermediate-risk prostate cancer who had local failure after external beam radiotherapy (EBRT).

Major finding: The median follow-up was 6.7 years. At 10 years, the overall survival rate was 70%, disease-free survival rate was 33%, and disease-specific survival rate was 70%. Local-, distant-, and biochemical failure rates were 5%, 19%, and 46%, respectively.

Study details: A phase 2 study of 100 patients with low-/intermediate-risk prostate cancer who received salvage LDR prostate brachytherapy for local failure after EBRT.

Disclosures: This work was supported by National Cancer Institute.

Source: Crook J et al. Int J Radiat Oncol Biol Phys. 2021 Nov 2. doi: 10.1016/j.ijrobp.2021.10.138.

Key clinical point: Salvage low-dose-rate (LDR) prostate brachytherapy shows good survival in patients with low-/intermediate-risk prostate cancer who had local failure after external beam radiotherapy (EBRT).

Major finding: The median follow-up was 6.7 years. At 10 years, the overall survival rate was 70%, disease-free survival rate was 33%, and disease-specific survival rate was 70%. Local-, distant-, and biochemical failure rates were 5%, 19%, and 46%, respectively.

Study details: A phase 2 study of 100 patients with low-/intermediate-risk prostate cancer who received salvage LDR prostate brachytherapy for local failure after EBRT.

Disclosures: This work was supported by National Cancer Institute.

Source: Crook J et al. Int J Radiat Oncol Biol Phys. 2021 Nov 2. doi: 10.1016/j.ijrobp.2021.10.138.

Key clinical point: Salvage low-dose-rate (LDR) prostate brachytherapy shows good survival in patients with low-/intermediate-risk prostate cancer who had local failure after external beam radiotherapy (EBRT).

Major finding: The median follow-up was 6.7 years. At 10 years, the overall survival rate was 70%, disease-free survival rate was 33%, and disease-specific survival rate was 70%. Local-, distant-, and biochemical failure rates were 5%, 19%, and 46%, respectively.

Study details: A phase 2 study of 100 patients with low-/intermediate-risk prostate cancer who received salvage LDR prostate brachytherapy for local failure after EBRT.

Disclosures: This work was supported by National Cancer Institute.

Source: Crook J et al. Int J Radiat Oncol Biol Phys. 2021 Nov 2. doi: 10.1016/j.ijrobp.2021.10.138.

Key clinical point: After the first screening round, carriers of MSH2 and MSH6 pathogenic variants had a higher incidence of prostate cancer vs age-matched noncarrier controls.

Major finding: Men with MSH2 (P = .011) and MSH6 (P = .034) carriers showed a higher incidence of prostate cancer (prostate-specific antigen [PSA] threshold of 3 ng/mL or higher) vs noncarrier individuals. The overall positive predictive value of biopsy using a PSA threshold of 3 ng/mL was 51.4%.

Study details: An international, prospective IMPACT study of 644 men without a previous prostate cancer diagnosis and with a known germline pathogenic variant in the MLH1, MSH2, or MSH6 gene and 184 age-matched male controls without a familial pathogenic variant in these genes.

Disclosures: This study was supported by Cancer Research UK, the Ronald and Rita McAulay Foundation, and others. The authors received honoraria and/or speaker fees and reported owning patents licensed to and stocks in Arctic Partners.

Source: Bancroft EK et al. Lancet Oncol. 2021 Oct 19. doi: 10.1016/S1470-2045(21)00522-2.

Key clinical point: After the first screening round, carriers of MSH2 and MSH6 pathogenic variants had a higher incidence of prostate cancer vs age-matched noncarrier controls.

Major finding: Men with MSH2 (P = .011) and MSH6 (P = .034) carriers showed a higher incidence of prostate cancer (prostate-specific antigen [PSA] threshold of 3 ng/mL or higher) vs noncarrier individuals. The overall positive predictive value of biopsy using a PSA threshold of 3 ng/mL was 51.4%.

Study details: An international, prospective IMPACT study of 644 men without a previous prostate cancer diagnosis and with a known germline pathogenic variant in the MLH1, MSH2, or MSH6 gene and 184 age-matched male controls without a familial pathogenic variant in these genes.

Disclosures: This study was supported by Cancer Research UK, the Ronald and Rita McAulay Foundation, and others. The authors received honoraria and/or speaker fees and reported owning patents licensed to and stocks in Arctic Partners.

Source: Bancroft EK et al. Lancet Oncol. 2021 Oct 19. doi: 10.1016/S1470-2045(21)00522-2.

Key clinical point: After the first screening round, carriers of MSH2 and MSH6 pathogenic variants had a higher incidence of prostate cancer vs age-matched noncarrier controls.

Major finding: Men with MSH2 (P = .011) and MSH6 (P = .034) carriers showed a higher incidence of prostate cancer (prostate-specific antigen [PSA] threshold of 3 ng/mL or higher) vs noncarrier individuals. The overall positive predictive value of biopsy using a PSA threshold of 3 ng/mL was 51.4%.

Study details: An international, prospective IMPACT study of 644 men without a previous prostate cancer diagnosis and with a known germline pathogenic variant in the MLH1, MSH2, or MSH6 gene and 184 age-matched male controls without a familial pathogenic variant in these genes.

Disclosures: This study was supported by Cancer Research UK, the Ronald and Rita McAulay Foundation, and others. The authors received honoraria and/or speaker fees and reported owning patents licensed to and stocks in Arctic Partners.

Source: Bancroft EK et al. Lancet Oncol. 2021 Oct 19. doi: 10.1016/S1470-2045(21)00522-2.

A potential new urine biomarker for prostate cancer not only spots the presence of aggressive tumors, it also indicates the amount of these tumors, according to a recent report.

In a study of biopsy and prostatectomy samples, researchers found that the multigene Prostate Urine Risk-4 (PUR-4) signature was strongly associated with the presence and amount of Gleason pattern 4 tumors, but not tumors of less aggressive histology.

Given that increased Gleason pattern 4 tumor burden is associated with disease progression in men at intermediate risk, the results suggest that “PUR can show us which men at intermediate risk may require treatment and which may instead be managed conservatively with surveillance,” said senior author Jeremy Clark, PhD, of the University of East Anglia, Norwich, England. “PUR will also be useful for monitoring disease in men that do not currently require treatment and flag up the emergence and expansion of aggressive disease.”

The study by Dr. Clark and colleagues was published online on Nov. 3, 2021, in Life.

Tests using the traditional blood-based biomarker for prostate cancer – prostate-specific antigen (PSA) – have limited sensitivity and specificity, leading to unnecessary biopsies and overtreatment.

The PUR biomarker, one of several emerging alternatives to PSA, is a four-group classifier based on 36 genes, Dr. Clark and colleagues explained. Its categories correspond to the probabilities of the presence of normal tissue (PUR-1), and D’Amico low-risk (PUR-2), intermediate-risk (PUR-3), and high-risk (PUR-4) prostate cancer.

Dr. Clark’s team found in earlier research that the PUR-4 signature was able to predict disease progression in men on active surveillance for prostate cancer up to 5 years after a single urine sample. For their latest study, they sought to understand the relationship between PUR-4 and the amount and grade of tumor.

On the basis of biopsy samples from 215 men with prostate cancer, the researchers found that PUR-4 signature values correlated significantly with increasing Gleason grade.

There was no significant difference in PSA level by tumor volume for Gleason grade 1, 2, or 3. The same was true for PUR-4 and Gleason grade 1 tumors, which only contain less clinically significant Gleason pattern 3 cancer. However, PUR-4 values in men with Gleason grade 2 tumors larger than the median were significantly greater than for smaller tumors. PUR-4 values for large Gleason grade 3 tumors were also greater than for smaller ones, although the difference did not reach statistical significance.

“Since [Gleason grade] 2 and [Gleason grade] 3 contain both Gleason pattern 3 and 4 cancer these observations suggest that Gleason Pattern 4 cancer may be contributing to PUR-4 status,” the authors wrote.

The researchers also examined radical-prostatectomy specimens from nine men – three with Gleason grade 1, four with Gleason grade 2, and two with Gleason grade 3 tumors, as determined on the basis of presurgical biopsy.

There was no significant correlation between PUR-4 and PSA levels, nor were PUR-4 values linked to total tumor area or Gleason pattern 3 tumor area. But the amount of Gleason pattern 4 tumors showed a strong correlation with PUR-4 values, which did not change after adjusting for total prostate size.

“Our study shows that the PUR test can assess the amount of Gleason pattern 4 without the need for a biopsy,” Dr. Clark said in an interview. “It could therefore be a very useful tool indeed for assessing a man’s risk of dying from prostate cancer.”

Jack Schalken, PhD, a professor of experimental urology at Radboud University Medical Center in Nijmegen, the Netherlands, called PUR “another test” for prostate cancer the performance of which is in the same range as that of existing products.

“In fact, several tests are commercially available, but the clinical use is surprisingly low,” he told this news organization. Dr. Schalken, who was not involved in the new study, has reviewed several biomarkers for prostate cancer.

The PUR test is now undergoing validation in an international study that is expected to last another 2 years, Dr. Clark said. If successful, the test would stand out for several reasons.

First, it is based on many genes, so it is able to spot malignancies that other tests, which rely on just a few genes, may not pick up. In addition, although it is sensitive to the amount of Gleason pattern 4 tumor, it does not seem to detect the clinically less significant Gleason pattern 3 cancers.

“We have an at-home collection kit – the men do not have to come to a hospital to provide a urine sample,” Dr. Clark said.

The study did not receive commercial funding. Dr. Clark and two coauthors have filed a patent application related to their research.
 

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

A potential new urine biomarker for prostate cancer not only spots the presence of aggressive tumors, it also indicates the amount of these tumors, according to a recent report.

In a study of biopsy and prostatectomy samples, researchers found that the multigene Prostate Urine Risk-4 (PUR-4) signature was strongly associated with the presence and amount of Gleason pattern 4 tumors, but not tumors of less aggressive histology.

Given that increased Gleason pattern 4 tumor burden is associated with disease progression in men at intermediate risk, the results suggest that “PUR can show us which men at intermediate risk may require treatment and which may instead be managed conservatively with surveillance,” said senior author Jeremy Clark, PhD, of the University of East Anglia, Norwich, England. “PUR will also be useful for monitoring disease in men that do not currently require treatment and flag up the emergence and expansion of aggressive disease.”

The study by Dr. Clark and colleagues was published online on Nov. 3, 2021, in Life.

Tests using the traditional blood-based biomarker for prostate cancer – prostate-specific antigen (PSA) – have limited sensitivity and specificity, leading to unnecessary biopsies and overtreatment.

The PUR biomarker, one of several emerging alternatives to PSA, is a four-group classifier based on 36 genes, Dr. Clark and colleagues explained. Its categories correspond to the probabilities of the presence of normal tissue (PUR-1), and D’Amico low-risk (PUR-2), intermediate-risk (PUR-3), and high-risk (PUR-4) prostate cancer.

Dr. Clark’s team found in earlier research that the PUR-4 signature was able to predict disease progression in men on active surveillance for prostate cancer up to 5 years after a single urine sample. For their latest study, they sought to understand the relationship between PUR-4 and the amount and grade of tumor.

On the basis of biopsy samples from 215 men with prostate cancer, the researchers found that PUR-4 signature values correlated significantly with increasing Gleason grade.

There was no significant difference in PSA level by tumor volume for Gleason grade 1, 2, or 3. The same was true for PUR-4 and Gleason grade 1 tumors, which only contain less clinically significant Gleason pattern 3 cancer. However, PUR-4 values in men with Gleason grade 2 tumors larger than the median were significantly greater than for smaller tumors. PUR-4 values for large Gleason grade 3 tumors were also greater than for smaller ones, although the difference did not reach statistical significance.

“Since [Gleason grade] 2 and [Gleason grade] 3 contain both Gleason pattern 3 and 4 cancer these observations suggest that Gleason Pattern 4 cancer may be contributing to PUR-4 status,” the authors wrote.

The researchers also examined radical-prostatectomy specimens from nine men – three with Gleason grade 1, four with Gleason grade 2, and two with Gleason grade 3 tumors, as determined on the basis of presurgical biopsy.

There was no significant correlation between PUR-4 and PSA levels, nor were PUR-4 values linked to total tumor area or Gleason pattern 3 tumor area. But the amount of Gleason pattern 4 tumors showed a strong correlation with PUR-4 values, which did not change after adjusting for total prostate size.

“Our study shows that the PUR test can assess the amount of Gleason pattern 4 without the need for a biopsy,” Dr. Clark said in an interview. “It could therefore be a very useful tool indeed for assessing a man’s risk of dying from prostate cancer.”

Jack Schalken, PhD, a professor of experimental urology at Radboud University Medical Center in Nijmegen, the Netherlands, called PUR “another test” for prostate cancer the performance of which is in the same range as that of existing products.

“In fact, several tests are commercially available, but the clinical use is surprisingly low,” he told this news organization. Dr. Schalken, who was not involved in the new study, has reviewed several biomarkers for prostate cancer.

The PUR test is now undergoing validation in an international study that is expected to last another 2 years, Dr. Clark said. If successful, the test would stand out for several reasons.

First, it is based on many genes, so it is able to spot malignancies that other tests, which rely on just a few genes, may not pick up. In addition, although it is sensitive to the amount of Gleason pattern 4 tumor, it does not seem to detect the clinically less significant Gleason pattern 3 cancers.

“We have an at-home collection kit – the men do not have to come to a hospital to provide a urine sample,” Dr. Clark said.

The study did not receive commercial funding. Dr. Clark and two coauthors have filed a patent application related to their research.
 

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

A potential new urine biomarker for prostate cancer not only spots the presence of aggressive tumors, it also indicates the amount of these tumors, according to a recent report.

In a study of biopsy and prostatectomy samples, researchers found that the multigene Prostate Urine Risk-4 (PUR-4) signature was strongly associated with the presence and amount of Gleason pattern 4 tumors, but not tumors of less aggressive histology.

Given that increased Gleason pattern 4 tumor burden is associated with disease progression in men at intermediate risk, the results suggest that “PUR can show us which men at intermediate risk may require treatment and which may instead be managed conservatively with surveillance,” said senior author Jeremy Clark, PhD, of the University of East Anglia, Norwich, England. “PUR will also be useful for monitoring disease in men that do not currently require treatment and flag up the emergence and expansion of aggressive disease.”

The study by Dr. Clark and colleagues was published online on Nov. 3, 2021, in Life.

Tests using the traditional blood-based biomarker for prostate cancer – prostate-specific antigen (PSA) – have limited sensitivity and specificity, leading to unnecessary biopsies and overtreatment.

The PUR biomarker, one of several emerging alternatives to PSA, is a four-group classifier based on 36 genes, Dr. Clark and colleagues explained. Its categories correspond to the probabilities of the presence of normal tissue (PUR-1), and D’Amico low-risk (PUR-2), intermediate-risk (PUR-3), and high-risk (PUR-4) prostate cancer.

Dr. Clark’s team found in earlier research that the PUR-4 signature was able to predict disease progression in men on active surveillance for prostate cancer up to 5 years after a single urine sample. For their latest study, they sought to understand the relationship between PUR-4 and the amount and grade of tumor.

On the basis of biopsy samples from 215 men with prostate cancer, the researchers found that PUR-4 signature values correlated significantly with increasing Gleason grade.

There was no significant difference in PSA level by tumor volume for Gleason grade 1, 2, or 3. The same was true for PUR-4 and Gleason grade 1 tumors, which only contain less clinically significant Gleason pattern 3 cancer. However, PUR-4 values in men with Gleason grade 2 tumors larger than the median were significantly greater than for smaller tumors. PUR-4 values for large Gleason grade 3 tumors were also greater than for smaller ones, although the difference did not reach statistical significance.

“Since [Gleason grade] 2 and [Gleason grade] 3 contain both Gleason pattern 3 and 4 cancer these observations suggest that Gleason Pattern 4 cancer may be contributing to PUR-4 status,” the authors wrote.

The researchers also examined radical-prostatectomy specimens from nine men – three with Gleason grade 1, four with Gleason grade 2, and two with Gleason grade 3 tumors, as determined on the basis of presurgical biopsy.

There was no significant correlation between PUR-4 and PSA levels, nor were PUR-4 values linked to total tumor area or Gleason pattern 3 tumor area. But the amount of Gleason pattern 4 tumors showed a strong correlation with PUR-4 values, which did not change after adjusting for total prostate size.

“Our study shows that the PUR test can assess the amount of Gleason pattern 4 without the need for a biopsy,” Dr. Clark said in an interview. “It could therefore be a very useful tool indeed for assessing a man’s risk of dying from prostate cancer.”

Jack Schalken, PhD, a professor of experimental urology at Radboud University Medical Center in Nijmegen, the Netherlands, called PUR “another test” for prostate cancer the performance of which is in the same range as that of existing products.

“In fact, several tests are commercially available, but the clinical use is surprisingly low,” he told this news organization. Dr. Schalken, who was not involved in the new study, has reviewed several biomarkers for prostate cancer.

The PUR test is now undergoing validation in an international study that is expected to last another 2 years, Dr. Clark said. If successful, the test would stand out for several reasons.

First, it is based on many genes, so it is able to spot malignancies that other tests, which rely on just a few genes, may not pick up. In addition, although it is sensitive to the amount of Gleason pattern 4 tumor, it does not seem to detect the clinically less significant Gleason pattern 3 cancers.

“We have an at-home collection kit – the men do not have to come to a hospital to provide a urine sample,” Dr. Clark said.

The study did not receive commercial funding. Dr. Clark and two coauthors have filed a patent application related to their research.
 

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

In the study by Aggarwal et al., the investigators evaluated whether molecular subtypes as identified from biopsies of metastatic tumors in patients with metastatic castrate resistant prostate cancer (mCRPC) could result in improved prediction of response to therapies. In this retrospective study of 4 distinct cohorts, 45% of tumors were classified as luminal and 55% were classified as basal. Luminal tumors exhibited increased expression of androgen receptor pathway genes, and patients with luminal tumors had better survival after treatment with ASI compared with those with basal tumors. Genomic analyses of mCRPC metastases are challenging due to processing issues that can arise if bone decalcification needs to be done; therefore, this study provides an important next step to aid in the design appropriate clinical trials to investigate whether such genomic subtyping results in improved patient outcomes.

            In the study by Saad et al, the investigators evaluated whether the addition of the androgen receptor inhibitor apalutamide added to abiraterone would result in a higher radiographic progression free survival (rPFS) compared with abiraterone alone in patients with mCRPC. The combination resulted in an improvement in rPFS (24 versus 16.6 months); however, there was no improvement in overall survival. These results are similar to the Alliance A0321201 study, where enzalutamide was added to abiraterone, and no overall survival was observed. Further study is needed to determine if this combination strategy can work.

            Supportive care aside from ASIs or chemotherapy directed against prostate cancer is also of critical importance to patients with metastatic prostate cancer. Previous studies have demonstrated that BMAs, such as denosumab or zoledronic acid, result in the prevention of skeletal-related events (SREs) in patients with mCRPC. However, this same benefit has not been demonstrated in metastatic castrate sensitive prostate cancer (mCSPC); therefore, BMAs are not recommended in this population unless they are at high risk for osteoporotic fracture. Mitchell et al. evaluated a retrospective cohort identified from Surveillance, Epidemiology, and End Results (SEER)-Medicare data to determine the number of patients with likely mCSPC treated with a BMA (defined as prescribed a BMA within 180 or 90 days after initial diagnosis of metastatic disease). A significant number of patients with likely mCSPC were prescribed BMAs within 180 days of diagnosis (23.6% of the cohort) and within 90 days (18.4% of the cohort). It is likely that most of these patients inappropriately received BMAs and were potentially subject to unnecessary costs and toxicity. Further study of strategies to reduce inappropriate BMA use could lead to less toxicity and lower costs.

In the study by Aggarwal et al., the investigators evaluated whether molecular subtypes as identified from biopsies of metastatic tumors in patients with metastatic castrate resistant prostate cancer (mCRPC) could result in improved prediction of response to therapies. In this retrospective study of 4 distinct cohorts, 45% of tumors were classified as luminal and 55% were classified as basal. Luminal tumors exhibited increased expression of androgen receptor pathway genes, and patients with luminal tumors had better survival after treatment with ASI compared with those with basal tumors. Genomic analyses of mCRPC metastases are challenging due to processing issues that can arise if bone decalcification needs to be done; therefore, this study provides an important next step to aid in the design appropriate clinical trials to investigate whether such genomic subtyping results in improved patient outcomes.

            In the study by Saad et al, the investigators evaluated whether the addition of the androgen receptor inhibitor apalutamide added to abiraterone would result in a higher radiographic progression free survival (rPFS) compared with abiraterone alone in patients with mCRPC. The combination resulted in an improvement in rPFS (24 versus 16.6 months); however, there was no improvement in overall survival. These results are similar to the Alliance A0321201 study, where enzalutamide was added to abiraterone, and no overall survival was observed. Further study is needed to determine if this combination strategy can work.

            Supportive care aside from ASIs or chemotherapy directed against prostate cancer is also of critical importance to patients with metastatic prostate cancer. Previous studies have demonstrated that BMAs, such as denosumab or zoledronic acid, result in the prevention of skeletal-related events (SREs) in patients with mCRPC. However, this same benefit has not been demonstrated in metastatic castrate sensitive prostate cancer (mCSPC); therefore, BMAs are not recommended in this population unless they are at high risk for osteoporotic fracture. Mitchell et al. evaluated a retrospective cohort identified from Surveillance, Epidemiology, and End Results (SEER)-Medicare data to determine the number of patients with likely mCSPC treated with a BMA (defined as prescribed a BMA within 180 or 90 days after initial diagnosis of metastatic disease). A significant number of patients with likely mCSPC were prescribed BMAs within 180 days of diagnosis (23.6% of the cohort) and within 90 days (18.4% of the cohort). It is likely that most of these patients inappropriately received BMAs and were potentially subject to unnecessary costs and toxicity. Further study of strategies to reduce inappropriate BMA use could lead to less toxicity and lower costs.

In the study by Aggarwal et al., the investigators evaluated whether molecular subtypes as identified from biopsies of metastatic tumors in patients with metastatic castrate resistant prostate cancer (mCRPC) could result in improved prediction of response to therapies. In this retrospective study of 4 distinct cohorts, 45% of tumors were classified as luminal and 55% were classified as basal. Luminal tumors exhibited increased expression of androgen receptor pathway genes, and patients with luminal tumors had better survival after treatment with ASI compared with those with basal tumors. Genomic analyses of mCRPC metastases are challenging due to processing issues that can arise if bone decalcification needs to be done; therefore, this study provides an important next step to aid in the design appropriate clinical trials to investigate whether such genomic subtyping results in improved patient outcomes.

            In the study by Saad et al, the investigators evaluated whether the addition of the androgen receptor inhibitor apalutamide added to abiraterone would result in a higher radiographic progression free survival (rPFS) compared with abiraterone alone in patients with mCRPC. The combination resulted in an improvement in rPFS (24 versus 16.6 months); however, there was no improvement in overall survival. These results are similar to the Alliance A0321201 study, where enzalutamide was added to abiraterone, and no overall survival was observed. Further study is needed to determine if this combination strategy can work.

            Supportive care aside from ASIs or chemotherapy directed against prostate cancer is also of critical importance to patients with metastatic prostate cancer. Previous studies have demonstrated that BMAs, such as denosumab or zoledronic acid, result in the prevention of skeletal-related events (SREs) in patients with mCRPC. However, this same benefit has not been demonstrated in metastatic castrate sensitive prostate cancer (mCSPC); therefore, BMAs are not recommended in this population unless they are at high risk for osteoporotic fracture. Mitchell et al. evaluated a retrospective cohort identified from Surveillance, Epidemiology, and End Results (SEER)-Medicare data to determine the number of patients with likely mCSPC treated with a BMA (defined as prescribed a BMA within 180 or 90 days after initial diagnosis of metastatic disease). A significant number of patients with likely mCSPC were prescribed BMAs within 180 days of diagnosis (23.6% of the cohort) and within 90 days (18.4% of the cohort). It is likely that most of these patients inappropriately received BMAs and were potentially subject to unnecessary costs and toxicity. Further study of strategies to reduce inappropriate BMA use could lead to less toxicity and lower costs.

Key clinical point: Stereotactic body radiation therapy (SBRT) is safe and shows low incidence of high-grade bleeding in older patients with localized prostate cancer who received anticoagulant or antiplatelet treatment.

Major finding: Overall, 18.2% of patients reported hematuria with a median time of 10.5 months and 38.6% experienced hematochezia with a median time of 6 months. Rates of grade 2 or more hematuria and hematochezia were 4.6% and 2.5%, respectively. No grade 4 or 5 toxicities were reported.

Study details: A retrospective study of 44 patients with localized prostate cancer (median age, 72 years) who were treated with SBRT between 2007 and 2017 and received anticoagulant or antiplatelet at baseline. Patients with rectal spacer were not included.

Disclosures: The study was funded by Accuray, National Institute on Minority Health and Health Disparities and The James and Theodore Pedas Family Foundation. The authors did not declare any conflict of interests.

Source: Pepin A et al. Front Oncol. 2021 Sep 17. doi: 10.3389/fonc.2021.722852.

Key clinical point: Stereotactic body radiation therapy (SBRT) is safe and shows low incidence of high-grade bleeding in older patients with localized prostate cancer who received anticoagulant or antiplatelet treatment.

Major finding: Overall, 18.2% of patients reported hematuria with a median time of 10.5 months and 38.6% experienced hematochezia with a median time of 6 months. Rates of grade 2 or more hematuria and hematochezia were 4.6% and 2.5%, respectively. No grade 4 or 5 toxicities were reported.

Study details: A retrospective study of 44 patients with localized prostate cancer (median age, 72 years) who were treated with SBRT between 2007 and 2017 and received anticoagulant or antiplatelet at baseline. Patients with rectal spacer were not included.

Disclosures: The study was funded by Accuray, National Institute on Minority Health and Health Disparities and The James and Theodore Pedas Family Foundation. The authors did not declare any conflict of interests.

Source: Pepin A et al. Front Oncol. 2021 Sep 17. doi: 10.3389/fonc.2021.722852.

Key clinical point: Stereotactic body radiation therapy (SBRT) is safe and shows low incidence of high-grade bleeding in older patients with localized prostate cancer who received anticoagulant or antiplatelet treatment.

Major finding: Overall, 18.2% of patients reported hematuria with a median time of 10.5 months and 38.6% experienced hematochezia with a median time of 6 months. Rates of grade 2 or more hematuria and hematochezia were 4.6% and 2.5%, respectively. No grade 4 or 5 toxicities were reported.

Study details: A retrospective study of 44 patients with localized prostate cancer (median age, 72 years) who were treated with SBRT between 2007 and 2017 and received anticoagulant or antiplatelet at baseline. Patients with rectal spacer were not included.

Disclosures: The study was funded by Accuray, National Institute on Minority Health and Health Disparities and The James and Theodore Pedas Family Foundation. The authors did not declare any conflict of interests.

Source: Pepin A et al. Front Oncol. 2021 Sep 17. doi: 10.3389/fonc.2021.722852.