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Prostate-Specific Antigen After Neoadjuvant Androgen Suppression in Prostate Cancer Patients Receiving Short-Term Androgen Suppression and External Beam Radiation Therapy: Pooled Analysis of Four NRG Oncology Radiation Therapy Oncology Group Randomized Clinical Trials.

ABSTRACT: PURPOSE:To validate whether prostate-specific antigen (PSA) level after neoadjuvant androgen suppression (neoAS) is associated with long-term outcome after neoAS and external beam radiation therapy (RT) with concurrent short-term androgen suppression (AS) in patients with prostate cancer. METHODS AND MATERIALS:This study included 2404 patients. The patients were treated with neoAS before RT and concurrent AS (without post-RT AS) and were pooled from NRG Oncology/RTOG trials 9202, 9408, 9413, and 9910. Multivariable models were used to test associations between the prespecified dichotomized post-neoAS, pre-RT PSA level (?0.1 vs >0.1 ng/mL) groupings, and clinical outcomes. RESULTS:The median follow-up for surviving patients was 9.4 years. The median post-neoAS, pre-RT PSA level was 0.3 ng/mL, with 32% of patients having levels ?0.1 ng/mL. Race, Gleason score, tumor stage, node stage, pretreatment PSA level, and duration of neoAS were associated with the groups of patients with PSA levels ?0.1 and >0.1 ng/mL. In univariate analyses, post-neoAS, pre-RT PSA level >0.1 ng/mL was associated with increased risks of biochemical failure (hazard ratio [HR], 2.04; P < .0001); local failure (HR, 2.51; P < .0001); distant metastases (HR, 1.73; P = .0006); cause-specific mortality (HR, 2.36; P < .0001); and all-cause mortality (HR, 1.24; P = .005). In multivariable models that also included baseline and treatment variables, post-neoAS, pre-RT PSA level >0.1 ng/mL was independently associated with increased risk of biochemical failure (HR, 2.00; P < .0001); local failure (HR, 2.33; P < .0001); and cause-specific mortality (HR, 1.75; P = .03). CONCLUSIONS:Patients with a PSA level >0.1 ng/mL after neoAS and before the start of RT had less favorable clinical outcomes than patients whose PSA level was ?0.1 ng/mL. The role of post-neoAS, pre-RT PSA level relative to PSA levels obtained along the continuum of medical care is not presently defined but could be tested in future clinical trials.

SUBMITTER: Hallemeier CL

PROVIDER: S-EPMC6646073 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Prostate-Specific Antigen After Neoadjuvant Androgen Suppression in Prostate Cancer Patients Receiving Short-Term Androgen Suppression and External Beam Radiation Therapy: Pooled Analysis of Four NRG Oncology Radiation Therapy Oncology Group Randomized Clinical Trials.

Hallemeier Christopher L CL Zhang Peixin P Pisansky Thomas M TM Hanks Gerald E GE McGowan David G DG Roach Mack M Zeitzer Kenneth L KL Firat Selim Y SY Husain Siraj M SM D'Souza David P DP Souhami Luis L Parliament Matthew B MB Rosenthal Seth A SA Lukka Himanshu R HR Rotman Marvin M Horwitz Eric M EM Miles Edward F EF Paulus Rebecca R Sandler Howard M HM

International journal of radiation oncology, biology, physics 20190406 5

<h4>Purpose</h4>To validate whether prostate-specific antigen (PSA) level after neoadjuvant androgen suppression (neoAS) is associated with long-term outcome after neoAS and external beam radiation therapy (RT) with concurrent short-term androgen suppression (AS) in patients with prostate cancer.<h4>Methods and materials</h4>This study included 2404 patients. The patients were treated with neoAS before RT and concurrent AS (without post-RT AS) and were pooled from NRG Oncology/RTOG trials 9202, ...[more]

PMID: 30959123

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Project description:PURPOSE:Only retrospective data are available for low-dose-rate (LDR) salvage prostate brachytherapy for local recurrence after external beam radiation therapy (EBRT). The primary objective of this prospective phase 2 trial (NCT00450411) was to evaluate late gastrointestinal and genitourinary adverse events (AEs) after salvage LDR brachytherapy. METHODS AND MATERIALS:Eligible patients had low- or intermediate-risk prostate cancer before EBRT and biopsy-proven recurrence >30 months after EBRT, with prostate-specific antigen levels <10 ng/mL and no regional/distant disease. The primary endpoint was grade 3 or higher late treatment-related gastrointestinal or genitourinary AEs occurring 9 to 24 months after brachytherapy. These AEs were projected to be ?10%, with ?20% considered unacceptable. All events were graded with National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. Multivariate analyses investigated associations of pretreatment or treatment variables with AEs. RESULTS:One hundred patients from 20 centers were registered from May 2007 to January 2014. The 92 analyzable patients had a median follow-up of 54 months (range, 4-97) and a median age of 70 years (interquartile range [IQR], 65-74). The initial Gleason score was 7 in 48% of patients. The median dose of EBRT was 74 Gy (IQR, 70-76) at a median interval of 85 months previously (IQR, 60-119). Only 16% had androgen deprivation at study entry. Twelve patients (14%) had late grade 3 gastrointestinal/genitourinary AEs, with no treatment-related grade 4 or 5 AEs. No pretreatment variable predicted late AEs, including prior EBRT dose and elapsed interval. Higher V100 (percentage of prostate enclosed by prescription isodose) predicted both occurrence of late AEs (odds ratio, 1.24; 95% confidence interval, 1.02-1.52; P = .03) and earlier time to first occurrence (hazard ratio, 1.18; 95% CI, 1.03-1.34; P = .02). CONCLUSIONS:This prospective multicenter trial reports outcomes of salvage LDR brachytherapy for post-EBRT recurrence. The rate of late grade 3 AEs did not exceed the unacceptable threshold. The only factor predictive of late AEs was implant dosimetry reflected by V100. Efficacy outcomes will be reported at a minimum of 5-year follow-up.

Project description:Long-term (LT) androgen suppression (AS) with radiation therapy (RT) is a standard treatment of high-risk, localized prostate cancer (PCa). Radiation Therapy Oncology Group 9902 was a randomized trial testing the hypothesis that adjuvant combination chemotherapy (CT) with paclitaxel, estramustine, and oral etoposide plus LT AS plus RT would improve overall survival (OS).Patients with high-risk PCa (prostate-specific antigen 20-100 ng/mL and Gleason score [GS] ? 7 or clinical stage ? T2 and GS ? 8) were randomized to RT and AS (AS + RT) alone or with adjuvant CT (AS + RT + CT). CT was given as four 21-day cycles, delivered beginning 28 days after 70.2 Gy of RT. AS was given as luteinizing hormone-releasing hormone for 24 months, beginning 2 months before RT plus an oral antiandrogen for 4 months before and during RT. The study was designed based on a 6% improvement in OS from 79% to 85% at 5 years, with 90% power and a 2-sided alpha of 0.05.A total of 397 patients (380 eligible) were randomized. The patients had high-risk PCa, 68% with GS 8 to 10 and 34% T3 to T4 tumors, and median prostate-specific antigen of 22.6 ng/mL. The median follow-up period was 9.2 years. The trial closed early because of excess thromboembolic toxicity in the CT arm. The 10-year results for all randomized patients revealed no significant difference between the AS + RT and AS + RT + CT arms in OS (65% vs 63%; P=.81), biochemical failure (58% vs 54%; P=.82), local progression (11% vs 7%; P=.09), distant metastases (16% vs 14%; P=.42), or disease-free survival (22% vs 26%; P=.61).NRG Oncology RTOG 9902 showed no significant differences in OS, biochemical failure, local progression, distant metastases, or disease-free survival with the addition of adjuvant CT to LT AS + RT. The trial results provide valuable data regarding the natural history of high-risk PCa treated with LT AS + RT and have implications for the feasibility of clinical trial accrual and tolerability using CT for PCa.

Project description:PurposeTo determine whether prolonged androgen suppression (AS) duration before radiotherapy improves survival and disease control in prostate cancer.Patients and methodsOne thousand five hundred seventy-nine men with intermediate-risk prostate cancer were randomly assigned to 8 weeks of AS followed by radiotherapy with an additional 8 weeks of concurrent AS (16 weeks total) or to 28 weeks of AS followed by radiotherapy with an additional 8 weeks of AS (36 weeks total). The trial sought primarily to detect a 33% reduction in the hazard of prostate cancer death in the 28-week assignment. Time-to-event end points are reported for up to 10 years of follow-up.ResultsThere were no between-group differences in baseline characteristics of 1,489 eligible patients with follow-up. For the 8- and 28-week assignments, 10-year disease-specific survival rates were 95% (95% CI, 93.3% to 97.0%) and 96% (95% CI, 94.6% to 98.0%; hazard ratio [HR], 0.81; P = .45), respectively, and 10-year overall survival rates were 66% (95% CI, 62.0% to 69.9%) and 67% (95% CI, 63.0% to 70.8%; HR, 0.95; P = .62), respectively. For the 8- and 28-week assignments, 10-year cumulative incidences of locoregional progression were 6% (95% CI, 4.3% to 8.0%) and 4% (95% CI, 2.5% to 5.7%; HR, 0.65; P = .07), respectively; 10-year distant metastasis cumulative incidences were 6% (95% CI, 4.0% to 7.7%) and 6% (95% CI, 4.0% to 7.6%; HR, 1.07; P = .80), respectively; and 10-year prostate-specific antigen-based recurrence cumulative incidences were 27% (95% CI, 23.1% to 29.8%) and 27% (95% CI, 23.4% to 30.3%; HR, 0.97; P = .77), respectively.ConclusionExtending AS duration from 8 weeks to 28 weeks before radiotherapy did not improve outcomes. A lower than expected prostate cancer death rate reduced ability to detect a between-group difference in disease-specific survival. The schedule of 8 weeks of AS before radiotherapy plus 8 weeks of AS during radiotherapy remains a standard of care in intermediate-risk prostate cancer.

Dataset Information

Prostate-Specific Antigen After Neoadjuvant Androgen Suppression in Prostate Cancer Patients Receiving Short-Term Androgen Suppression and External Beam Radiation Therapy: Pooled Analysis of Four NRG Oncology Radiation Therapy Oncology Group Randomized Clinical Trials.

Publications

Prostate-Specific Antigen After Neoadjuvant Androgen Suppression in Prostate Cancer Patients Receiving Short-Term Androgen Suppression and External Beam Radiation Therapy: Pooled Analysis of Four NRG Oncology Radiation Therapy Oncology Group Randomized Clinical Trials.

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