The impact of comorbidity and PSA doubling time on the risk of death in men experiencing PSA failure following radiation therapy with or with androgen deprivation therapy for unfavorable-risk prostate cancer

2017 ◽  
Vol 20 (2) ◽  
pp. 234-240 ◽  
Author(s):  
S A Patel ◽  
M-H Chen ◽  
M Loffredo ◽  
A Renshaw ◽  
P W Kantoff ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radiation Therapy ◽  
Androgen Deprivation Therapy ◽  
Doubling Time ◽  
Androgen Deprivation ◽  
Risk Of Death ◽  
Psa Doubling Time ◽  
Psa Failure ◽  
Risk Prostate Cancer ◽  
The Impact

Impact of comorbidity and PSA doubling time on the risk of death in men experiencing PSA failure following radiation therapy with or without androgen deprivation therapy for unfavorable-risk prostate cancer.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 68-68
Author(s):  
Sagar Anil Patel ◽  
Ming-Hui Chen ◽  
Marian Loffredo ◽  
Andrew A. Renshaw ◽  
Philip W. Kantoff ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radiation Therapy ◽  
Androgen Deprivation Therapy ◽  
Doubling Time ◽  
Androgen Deprivation ◽  
Psa Doubling Time ◽  
Psa Failure ◽  
Severe Comorbidity ◽  
The Impact

68 Background: The optimal management of men with PSA failure following initial prostate cancer therapy based on comorbidity is unknown. We investigated the impact that PSA doubling time (DT) and comorbidity had on the risk of all cause (AC), prostate cancer-specific (PCS) and other cause mortality (OCM) following PSA failure. Methods: Between 1995 and 2001, 206 men with unfavorable-risk PC were randomized to receive radiation therapy alone or in combination with 6 months of androgen deprivation therapy (ADT). After a median follow up of 16.2 years, 108 men experienced PSA failure (85, no or minimal; 23, moderate to severe comorbidity) and formed the study cohort. Cox and Fine-Gray regression analysis was used to determine whether PSA DT was associated with the risk of ACM and PCSM/OCM respectively, stratified by ACE-27 comorbidity score. Results: After a median follow up of 13.71 years following PSA failure, 81 of the 108 men (75%) died. Longer PSA DT was associated with a decreased risk of PCSM in men with no/minimal (AHR 0.33, 95% CI 0.17-0.65, p= 0.001) and moderate/severe comorbidity (AHR 0.014, 95% CI 0.002-0.129, p= 0.0002) with a trend toward an increased risk of OCM in men with no/minimal (AHR 1.42, 95% CI 0.94-2.16, p= 0.10) and moderate/severe comorbidity (AHR 1.68, 95% CI 0.85-3.35, p= 0.14). However, increasing PSA DT was only associated with a decreased risk of ACM in men with no/minimal (AHR 0.69, 95% CI 0.50-0.96, p = 0.03) but not moderate/severe comorbidity (AHR 0.95, 95% CI 0.51-1.78, p= 0.87). Conclusions: The extent and natural history of comorbidity as well as PSA DT should be taken into consideration when deciding on appropriate management and/or clinical trial eligibility at the time of PSA failure. Specifically, randomized studies are needed to determine whether survival is prolonged in men with life-shortening comorbidity with salvage ADT at the time of PSA failure versus surveillance and reserving ADT use for symptomatic progression. For all other men, trials comparing ADT with or without novel agents shown to prolong survival in men with metastatic castrate resistant PC is warranted.

scholarly journals Stereotactic body radiotherapy versus conventional/moderate fractionated radiation therapy with androgen deprivation therapy for unfavorable risk prostate cancer

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Sagar A. Patel ◽  
Jeffrey M. Switchenko ◽  
Ben Fischer-Valuck ◽  
Chao Zhang ◽  
Brent S. Rose ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Deprivation Therapy ◽  
Stereotactic Body Radiotherapy ◽  
Multivariable Analysis ◽  
Androgen Deprivation ◽  
Sensitivity Analyses ◽  
External Beam Radiation ◽  
Beam Radiation ◽  
Risk Of Death ◽  
Risk Prostate Cancer

Abstract Background Ultrahypofractionation using stereotactic body radiotherapy (SBRT) is an increasingly utilized technique for men with prostate cancer (PC). The comparative efficacy of SBRT plus androgen deprivation therapy (ADT) compared to fractionated radiotherapy (EBRT) plus ADT in higher-risk prostate cancer is unknown. Methods Men > 40 years old with localized PC treated with external beam radiation and concomitant ADT for curative intent between 2004 and 2016 were analyzed from the National Cancer Database. Patients who lacked ADT or risk stratification data were excluded. 558 men treated with SBRT versus 40,797 men treated with conventional or moderately hypofractionated EBRT were included. Patients were stratified by unfavorable intermediate (UIR) and high (HR) risk using NCCN criteria. Kaplan Meier and Cox proportional hazards were used to compare overall survival (OS) between RT modality, adjusting for age, race, and comorbidity index. Results With a median follow up of 74 months, there was no difference in estimated 6-year OS between men treated with SBRT versus EBRT regardless of risk group. On multivariable analysis, there was no difference in risk of death for men treated with SBRT compared to EBRT (UIR: adjusted HR 1.09, 95% CI 0.68–1.74, p = .72; HR: adjusted HR 0.93, 95% CI 0.76–1.14, p = .51). On sensitivity analyses, when confining the cohort to men treated with NCCN-preferred dose fractionations, with no comorbidities, or < 65 years old, there remained no survival difference between treatment groups for both UIR and HR. Conclusion Within study limitations, we found no difference in survival between SBRT+ADT and standard of care EBRT+ADT for UIR or HR PC. These results support recent NCCN guideline updates, which include SBRT as a non-preferred option for higher risk men. Prospective validation would further strengthen the evidence basis behind these recommendations.

Effect of adding short-term androgen deprivation therapy to dose-escalated radiation therapy on failure-free survival for select men with intermediate-risk prostate cancer.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 176-176
Author(s):  
Shelly Bian ◽  
Deborah A. Kuban ◽  
Lawrence B. Levy ◽  
Jeong Hoon Oh ◽  
Katherine Castle ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radiation Therapy ◽  
Androgen Deprivation Therapy ◽  
Recursive Partitioning ◽  
Androgen Deprivation ◽  
Intermediate Risk ◽  
Short Term ◽  
Free Survival ◽  
Risk Prostate Cancer ◽  
Severe Comorbidity

176 Background: Independently, dose-escalated external beam radiation therapy (DE-EBRT) and short-term androgen deprivation therapy (ADT) improve outcomes for men with intermediate-risk prostate cancer; however, the incremental benefit of adding short-term ADT to DE-EBRT is uncertain. The aim of this study was to determine the effect of adding ADT to DE-EBRT and to identify men most likely to benefit from ADT. Methods: We reviewed the medical records of 636 men treated for intermediate-risk prostate cancer with DE-EBRT (>75 Gy) from 1995 to 2009. The adult comorbidity evaluation-27 index categorized severity of comorbidity. Recursive partitioning analysis defined unfavorable disease. Kaplan-Meier and log-rank tests compared failure-free survival (FFS) with and without ADT. Results: Median age was 70 years (interquartile range [IQR] 65–74). Overall, 45% received DE-EBRT alone and 55% DE-EBRT with ADT (median 6 months, IQR 6-8). Median follow up was 4.3 years. On Cox-proportional hazard regression analysis that adjusted for differences in comorbidities and tumor characteristics, administration of ADT improved FFS (adjusted hazard ratio 0.36, 95% confidence interval 0.18–0.72; p=0.004). Recursive partitioning analysis of men without ADT classified Gleason 4+3=7 or ≥ 50% positive cores as unfavorable disease (5-year FFS 96.3% favorable vs. 81.6% unfavorable; p<0.001). The addition of ADT to DE-EBRT improved 5-year FFS for men with unfavorable disease (n=334; 81.6% vs. 92.9%; p=0.009) but did not improve FFS for men with favorable disease (n=302; 96.3% vs. 97.4%; p=0.874). When stratified by comorbidity, ADT improved FFS for men with unfavorable disease and no or mild comorbidity (p=0.006) but did not improve FFS for men with unfavorable disease and moderate to severe comorbidity (p=0.380). Conclusions: The addition of ADT to DE-EBRT improves FFS for men with unfavorable intermediate-risk prostate cancer (Gleason 4+3=7 or ≥ 50% positive cores) especially those with no or minimal comorbidity. Men with favorable intermediate-risk disease or with moderate to severe comorbidity may not benefit from the addition of ADT to DE-EBRT.

scholarly journals Radiation and Androgen Deprivation Therapy With or Without Docetaxel in the Management of Nonmetastatic Unfavorable-Risk Prostate Cancer: A Prospective Randomized Trial

2021 ◽  
pp. JCO.21.00596
Author(s):  
Anthony V. D'Amico ◽  
Wanling Xie ◽  
Elizabeth McMahon ◽  
Marian Loffredo ◽  
Shana Medeiros ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Deprivation Therapy ◽  
Treatment Effect ◽  
Specific Antigen ◽  
Androgen Deprivation ◽  
Hazard Ratio ◽  
Adjusted Hazard Ratio ◽  
Specific Mortality ◽  
Risk Prostate Cancer ◽  
The Impact

PURPOSE Although docetaxel is not recommended when managing men with unfavorable-risk prostate cancer (PC) given negative or inconclusive results from previous randomized trials, unstudied benefits may exist. METHODS Between September 21, 2005, and January 13, 2015, we randomly assigned 350 men 1:1 with T1c-4N0M0 unfavorable-risk PC to receive radiation therapy (RT) and androgen deprivation therapy (ADT) plus docetaxel (60 mg/m2 once every 3 weeks for three cycles before RT and 20 mg/m2 once weekly during RT) versus ADT + RT. We evaluated the treatment effect of adding docetaxel to ADT + RT on the primary end point of overall survival (OS) and the incidence of RT-induced cancers and explored whether the impact of the treatment effect on OS differed within prostate-specific antigen (PSA) subgroups (< 4, > 20 v 4-20 ng/mL) using the interaction test for heterogeneity adjusted for age and PC prognostic factors. RESULTS After a median follow-up of 10.2 years, 89 men died (25.43%); of these, 42 from PC (47.19%). Although OS was not significantly increased in the docetaxel arm (the restricted mean survival time over 10 years was 9.11 v 8.82 years; P = .22), significantly fewer RT-induced cancers were observed (10-year estimates: 0.61% v 4.90%; age-adjusted hazard ratio of 0.13; 95% CI, 0.02 to 0.97; P = .046). The treatment effect of adding docetaxel to ADT + RT on OS significantly differed in men with a PSA < 4 ng/mL versus 4-20 ng/mL (adjusted hazard ratio: 0.27 and 1.51, respectively) because of less PC-specific mortality on the docetaxel arm (0.00% v 28.57%) among men with PSA < 4 ng/mL. CONCLUSION Adding docetaxel to ADT + RT did not prolong OS in men with unfavorable-risk PC, but decreased RT-induced cancer incidence, and may prolong OS in the subgroup of men with a PSA < 4 ng/mL by reducing PC-specific mortality.

The impact of multifocal perineural invasion on biochemical recurrence and timing of adjuvant androgen-deprivation therapy in high-risk prostate cancer following radical prostatectomy.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. e595-e595
Author(s):  
Pengfei Shen ◽  
Guangxi Sun ◽  
Hao Zeng ◽  
Xingming Zhang
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Radical Prostatectomy ◽  
Androgen Deprivation Therapy ◽  
Biochemical Recurrence ◽  
Perineural Invasion ◽  
Androgen Deprivation ◽  
High Risk Prostate Cancer ◽  
Risk Prostate Cancer ◽  
The Impact

e595 Background: Perineural invasion (PNI) is a distinct pathologic entity and a recognized source of tumor spread. However, the role of PNI in high-risk prostate cancer (PCa) has not been explored. We investigated the impact of the severity of PNI on biochemical recurrence (BCR) and optimal timing of adjuvant androgen deprivation therapy (ADT) post radical prostatectomy (RP). Methods: Of 265 prostatectomies, median follow-up 45 months, were assessed for the presence of PNI and its intensity (unifocal PNI and multifocal PNI) in RP specimen. Kaplan-Merier curves were used to estimate BCR probabilities. Cox proportional hazard models were used to address predictors of BCR. Harrell’s C-index was conducted to further validate prognostic value of multi-PNI. Results: A total of 123 patients (46.4%) were PNI positive, among which, 91 (74%) and 32 (26%) had unifocal PNI (uni-PNI) and multifocal PNI (multi-PNI), respectively. Other than uni-PNI, the presence of multi-PNI was strongly associated with increasing incidence of BCR (HR = 3.87, 95% CI: 1.66-9.01, p = 0.002). Patients with uni-PNI seemed to have a similar BCR rate to those without PNI after adjuvant ADT. For men with multi-PNI, immediate ADT obviously appeared to be superior to delayed ADT in decreasing biochemical failure. Conclusions: Multi-PNI detected in high-risk RP specimens could be a prognosticator for early biochemical relapse post-surgery. Our findings suggest that patients with multi-PNI appear appropriate to choose adjuvant therapy as soon as possible after surgery.

Optimizing the use of androgen deprivation therapy in men with localized intermediate-risk prostate cancer in the era of modern dose-escalated radiation therapy.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 109-109
Author(s):  
Sagar Anil Patel ◽  
Kevin H. Nguyen ◽  
Alan K. Lee ◽  
David Jeffrey Demanes ◽  
Albert Chang
Keyword(s):  
Prostate Cancer ◽  
Androgen Deprivation Therapy ◽  
Dose Escalation ◽  
Clinical Stage ◽  
Androgen Deprivation ◽  
High Dose ◽  
Intermediate Risk ◽  
Risk Prostate Cancer ◽  
The Impact ◽  
Group D

109 Background: While level one evidence has shown an overall survival (OS) advantage with the addition of androgen deprivation therapy (ADT) to radiotherapy (RT) for intermediate risk prostate cancer (PCa), the benefit in the era of modern dose escalation is controversial, especially given the heterogeneity within this risk group. We assessed the impact of adding ADT to high dose RT on OS for intermediate risk PCa stratified by number of intermediate risk factors (IRF). Methods: We identified 114,339 men with intermediate risk PCa (Gleason 7, clinical stage T1-2, PSA < 20 ng/mL) using the National Cancer Database. Men were stratified into the following subgroups based on the number of IRFs (Gleason 7, cT2b-c, PSA > 10-20 ng/mL): A) Gleason 3+4 and no other IRF, B) Gleason 4+3 and no other IRF, C) two IRFs, and D) three IRFs. The addition of ADT to dose-escalated external beam RT (DE-EBRT, ≥ 75.6 Gy), brachytherapy (BT), or combination EBRT+BT on OS was assessed within each subgroup using Kaplan-Meier and log-rank tests in propensity score-matched cohorts in all men and subsequently only in those with Charlson-Deyo comorbidity index (CDI) of zero. Results: There was no OS benefit with the addition of ADT to DE-EBRT, BT, or EBRT+BT in groups A, B, and C, even after limiting the cohort to men with CDI = 0. However, in group D, the addition of ADT to DE-EBRT was associated with a trend for OS improvement in patients with CDI = 0 only (8-year OS with and without ADT 68.3% and 62.4%, respectively, log-rank P= .07). Conversely, there was a trend for OS decrement with the addition of ADT to DE-EBRT in men with CDI ≥ 1 (8-year OS with and without ADT 61.8% and 67.5%, respectively, log-rank P= .06). There was no OS benefit of ADT in group D treated with BT or EBRT+BT, regardless of comorbidity status. Conclusions: The OS benefit of ADT in men with intermediate risk PCa may be limited to those with 3 IRFs and minimal comorbidities treated with DE-EBRT. If prospectively validated, extreme dose escalation achieved with BT (alone or in combination with EBRT) may obviate the addition of ADT in all men with intermediate risk disease, especially in an era of advanced molecular imaging.

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