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Prostate cancer: Exercise during active surveillance improves cardiorespiratory fitness
Key clinical point: High-intensity interval training (HIIT) improves cardiorespiratory fitness levels and lowers prostate-specific antigen (PSA) levels, PSA velocity, and prostate cancer cell growth in patients with localized prostate cancer undergoing active surveillance.
Major finding: The peak oxygen consumption increased by 0.9 mL/kg/minute in the HIIT group and decreased by 0.5 mL/kg/minute in the usual-care group (P = .01). Compared with the usual care, HIIT was associated with a significant decrease in PSA levels (P = .04), PSA velocity (P = .04), and growth of prostate cancer cell line (P = .02).
Study details: Phase 2 ERASE study of 52 men with prostate cancer undergoing active surveillance who were randomly assigned to HIIT or to usual care.
Disclosures: This study was supported by Canadian Institutes of Health Research and Prostate Cancer Canada. The authors reported no conflict of interests.
Source: Kang DW et al. JAMA Oncol. 2021 Aug 19. doi: 10.1001/jamaoncol.2021.3067.
Key clinical point: High-intensity interval training (HIIT) improves cardiorespiratory fitness levels and lowers prostate-specific antigen (PSA) levels, PSA velocity, and prostate cancer cell growth in patients with localized prostate cancer undergoing active surveillance.
Major finding: The peak oxygen consumption increased by 0.9 mL/kg/minute in the HIIT group and decreased by 0.5 mL/kg/minute in the usual-care group (P = .01). Compared with the usual care, HIIT was associated with a significant decrease in PSA levels (P = .04), PSA velocity (P = .04), and growth of prostate cancer cell line (P = .02).
Study details: Phase 2 ERASE study of 52 men with prostate cancer undergoing active surveillance who were randomly assigned to HIIT or to usual care.
Disclosures: This study was supported by Canadian Institutes of Health Research and Prostate Cancer Canada. The authors reported no conflict of interests.
Source: Kang DW et al. JAMA Oncol. 2021 Aug 19. doi: 10.1001/jamaoncol.2021.3067.
Key clinical point: High-intensity interval training (HIIT) improves cardiorespiratory fitness levels and lowers prostate-specific antigen (PSA) levels, PSA velocity, and prostate cancer cell growth in patients with localized prostate cancer undergoing active surveillance.
Major finding: The peak oxygen consumption increased by 0.9 mL/kg/minute in the HIIT group and decreased by 0.5 mL/kg/minute in the usual-care group (P = .01). Compared with the usual care, HIIT was associated with a significant decrease in PSA levels (P = .04), PSA velocity (P = .04), and growth of prostate cancer cell line (P = .02).
Study details: Phase 2 ERASE study of 52 men with prostate cancer undergoing active surveillance who were randomly assigned to HIIT or to usual care.
Disclosures: This study was supported by Canadian Institutes of Health Research and Prostate Cancer Canada. The authors reported no conflict of interests.
Source: Kang DW et al. JAMA Oncol. 2021 Aug 19. doi: 10.1001/jamaoncol.2021.3067.
Radium-223 plus enzalutamide safe in mCRPC
Key clinical point: Radium-223 in combination with enzalutamide is safe in the long term and improves second-line prostate-specific antigen (PSA)-progression-free survival (PFS) in patients with metastatic castration-resistant prostate cancer (mCRPC) vs. enzalutamide alone.
Major finding: Median follow-up was 22 months. Radium-223 plus enzalutamide vs. enzalutamide alone did not improve median overall survival (P = .73), PSA-PFS (P = .97), and radiographic PFS (P= .96). Radium-223 plus enzalutamide vs enzalutamide alone significantly improved second-line PSA-PFS (18.7 months vs 8.41 months; P = .033).
Study details: A phase 2 randomized trial of 47 patients with mCRPC randomly assigned to receive either radium-223 dichloride with enzalutamide or enzalutamide alone.
Disclosures: The study was supported by the University of Utah. The authors did not disclose any conflict of interests.
Source: Maughan BL et al. Oncologist. 2021 Aug 22. doi: 10.1002/onco.13949.
Key clinical point: Radium-223 in combination with enzalutamide is safe in the long term and improves second-line prostate-specific antigen (PSA)-progression-free survival (PFS) in patients with metastatic castration-resistant prostate cancer (mCRPC) vs. enzalutamide alone.
Major finding: Median follow-up was 22 months. Radium-223 plus enzalutamide vs. enzalutamide alone did not improve median overall survival (P = .73), PSA-PFS (P = .97), and radiographic PFS (P= .96). Radium-223 plus enzalutamide vs enzalutamide alone significantly improved second-line PSA-PFS (18.7 months vs 8.41 months; P = .033).
Study details: A phase 2 randomized trial of 47 patients with mCRPC randomly assigned to receive either radium-223 dichloride with enzalutamide or enzalutamide alone.
Disclosures: The study was supported by the University of Utah. The authors did not disclose any conflict of interests.
Source: Maughan BL et al. Oncologist. 2021 Aug 22. doi: 10.1002/onco.13949.
Key clinical point: Radium-223 in combination with enzalutamide is safe in the long term and improves second-line prostate-specific antigen (PSA)-progression-free survival (PFS) in patients with metastatic castration-resistant prostate cancer (mCRPC) vs. enzalutamide alone.
Major finding: Median follow-up was 22 months. Radium-223 plus enzalutamide vs. enzalutamide alone did not improve median overall survival (P = .73), PSA-PFS (P = .97), and radiographic PFS (P= .96). Radium-223 plus enzalutamide vs enzalutamide alone significantly improved second-line PSA-PFS (18.7 months vs 8.41 months; P = .033).
Study details: A phase 2 randomized trial of 47 patients with mCRPC randomly assigned to receive either radium-223 dichloride with enzalutamide or enzalutamide alone.
Disclosures: The study was supported by the University of Utah. The authors did not disclose any conflict of interests.
Source: Maughan BL et al. Oncologist. 2021 Aug 22. doi: 10.1002/onco.13949.
MRI with PSMA-PET lowers false negatives for clinically significant prostate cancer
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.
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.
Avelumab with SBRT shows good response in castration-resistant prostate cancer
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.
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.
Prostate cancer: Cardiovascular safety of hormone therapies remains unresolved
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.
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.
Localized prostate cancer: No OS benefit beyond 15 years with added short-term ADT
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.
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.
Prostate cancer: Patient-reported outcomes support hypofractionated radiotherapy
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.
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.
CRPC: Add-on apalutamide maintains quality of life
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.
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.
Concordance of DNA Repair Gene Mutations in Paired Primary Prostate Cancer Samples and Metastatic Tissue or Cell-free DNA
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.
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.
Methods of Identifying Real World mCRPC Patients from the Veterans Health Administration System
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.
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.