scholarly journals Potential Risk of Other-Cause Mortality Due to Long-Term Androgen Deprivation Therapy in Elderly Patients with Clinically Localized Prostate Cancer Treated with Radiotherapy—A Confirmation Study

2020 ◽  
Vol 9 (7) ◽  
pp. 2296
Author(s):  
Hideya Yamazaki ◽  
Koji Masui ◽  
Gen Suzuki ◽  
Norihiro Aibe ◽  
Daisuke Shimizu ◽  
...  

Androgen deprivation therapy (ADT) is used to improve overall survival (OS) in prostate cancer treatment; however, we encountered that long-term ADT in elderly patients may be related to high other-cause mortality (OCM). This study aimed to confirm the potential risk associated with long-term ADT in elderly patients using a different large cohort. A comparison analysis was conducted between the ≥2- and <2-year ADT groups using open, large data from 1840 patients with clinically localized prostate cancer treated with radiotherapy (1172 treated with high-dose-rate brachytherapy (HDR) + external beam radiotherapy (EBRT) and 668 treated with external beam radiotherapy). The OCM-free survival (OCMFS), overall survival, and prostate cancer-specific survival rates were measured. The 10-year OCMFS rates in patients aged ≥75 years were 94.6% and 86% in the <2- and ≥2-year ADT groups, respectively, but were 96.3% and 93.5% (p = 0.0006) in their younger counterparts. If dividing into HDR and EBRT groups. This inclination was found in brachytherapy group but not in EBRT group. The overall survival rate was also lower in the elderly patients in the ≥2-year ADT group than in the <2-year ADT group; however, the 10-year prostate cancer-specific survival rate was the same in both groups. Long-term ADT in elderly patients resulted in not only higher OCM rates but also poorer OS rates; therefore, longer-term ADT in elderly patients should be performed with meticulous care.

2008 ◽  
Vol 26 (4) ◽  
pp. 585-591 ◽  
Author(s):  
Mack Roach ◽  
Kyounghwa Bae ◽  
Joycelyn Speight ◽  
Harvey B. Wolkov ◽  
Phillip Rubin ◽  
...  

Purpose Radiation Therapy Oncology Group (RTOG) 8610 was the first phase III randomized trial to evaluate neoadjuvant androgen deprivation therapy (ADT) in combination with external-beam radiotherapy (EBRT) in men with locally advanced prostate cancer. This report summarizes long-term follow-up results. Materials and Methods Between 1987 and 1991, 456 assessable patients (median age, 70 years) were enrolled. Eligible patients had bulky (5 × 5 cm) tumors (T2-4) with or without pelvic lymph node involvement according to the 1988 American Joint Committee on Cancer TNM staging system. Patients received combined ADT that consisted of goserelin 3.6 mg every 4 weeks and flutamide 250 mg tid for 2 months before and concurrent with EBRT, or they received EBRT alone. Study end points included overall survival (OS), disease-specific mortality (DSM), distant metastasis (DM), disease-free survival (DFS), and biochemical failure (BF). Results Ten-year OS estimates (43% v 34%) and median survival times (8.7 v 7.3 years) favored ADT and EBRT, respectively; however, these differences did not reach statistical significance (P = .12). There was a statistically significant improvement in 10-year DSM (23% v 36%; P = .01), DM (35% v 47%; P = .006), DFS (11% v 3%; P < .0001), and BF (65% v 80%; P < .0001) with the addition of ADT, but no differences were observed in the risk of fatal cardiac events. Conclusion The addition of 4 months of ADT to EBRT appears to have a dramatic impact on clinically meaningful end points in men with locally advanced disease with no statistically significant impact on the risk of fatal cardiac events.


2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 23-23
Author(s):  
David Dewei Yang ◽  
Brandon Arvin Virgil Mahal ◽  
Vinayak Muralidhar ◽  
Neil E. Martin ◽  
Peter F. Orio ◽  
...  

23 Background: While the addition of androgen deprivation therapy (ADT) to external beam radiotherapy is known to improve overall survival in Gleason 8-10 prostate cancer, it has been hypothesized that Gleason 9-10 disease, which is less differentiated than Gleason 8 disease, may be less sensitive to ADT. To investigate this idea, we examined the association between ADT and overall survival for Gleason 8 versus Gleason 9-10 prostate cancer. Methods: We identified 20,139 men in the National Cancer Database diagnosed with localized or locally advanced, Gleason 8-10 prostate cancer from 2004 through 2011 who received external beam radiotherapy. Patients with clinical evidence of nodal or metastatic disease were excluded. Cox proportional hazards regression was used to examine the association between ADT and overall survival. Results: Median follow-up was 4.0 years. 78.2% (9,509) of the 12,160 men with Gleason 8 disease and 86.6% (6,908) of the 7,979 men with Gleason 9-10 disease received ADT. On multivariable analysis, ADT was associated with a significant improvement in overall survival for Gleason 8 patients (adjusted hazard ratio 0.79, 95% confidence interval 0.71-0.88, P< 0.001) but not Gleason 9-10 patients (adjusted hazard ratio 0.96, 95% confidence interval 0.83-1.10, P= 0.532), with a significant interaction ( Pinteraction= 0.020). When considering Gleason 9-10 patients separately as Gleason 9 and Gleason 10, a higher Gleason score correlated with an increased adjusted hazard ratio for the association between ADT and overall survival ( Pinteraction= 0.012). Conclusions: In contrast to the significant survival advantage of ADT for Gleason 8 disease, our results strongly suggest that Gleason 9-10 disease may be less sensitive to ADT and that a higher Gleason score predicts lesser sensitivity. Consideration should be given to treatment intensification for Gleason 9-10 patients through enrollment in clinical trials or potentially adding novel antiandrogens or docetaxel, which have shown efficacy in both castration-resistant and castration-sensitive settings.


2020 ◽  
Vol 38 (26) ◽  
pp. 3024-3031 ◽  
Author(s):  
William C. Jackson ◽  
Holly E. Hartman ◽  
Robert T. Dess ◽  
Sam R. Birer ◽  
Payal D. Soni ◽  
...  

PURPOSE In men with localized prostate cancer, the addition of androgen-deprivation therapy (ADT) or a brachytherapy boost (BT) to external beam radiotherapy (EBRT) have been shown to improve various oncologic end points. Practice patterns indicate that those who receive BT are significantly less likely to receive ADT, and thus we sought to perform a network meta-analysis to compare the predicted outcomes of a randomized trial of EBRT plus ADT versus EBRT plus BT. MATERIALS AND METHODS A systematic review identified published randomized trials comparing EBRT with or without ADT, or EBRT (with or without ADT) with or without BT, that reported on overall survival (OS). Standard fixed-effects meta-analyses were performed for each comparison, and a meta-regression was conducted to adjust for use and duration of ADT. Network meta-analyses were performed to compare EBRT plus ADT versus EBRT plus BT. Bayesian analyses were also performed, and a rank was assigned to each treatment after Markov Chain Monte Carlo analyses to create a surface under the cumulative ranking curve. RESULTS Six trials compared EBRT with or without ADT (n = 4,663), and 3 compared EBRT with or without BT (n = 718). The addition of ADT to EBRT improved OS (hazard ratio [HR], 0.71 [95% CI, 0.62 to 0.81]), whereas the addition of BT did not significantly improve OS (HR, 1.03 [95% CI, 0.78 to 1.36]). In a network meta-analysis, EBRT plus ADT had improved OS compared with EBRT plus BT (HR, 0.68 [95% CI, 0.52 to 0.89]). Bayesian modeling demonstrated an 88% probability that EBRT plus ADT resulted in superior OS compared with EBRT plus BT. CONCLUSION Our findings suggest that current practice patterns of omitting ADT with EBRT plus BT may result in inferior OS compared with EBRT plus ADT in men with intermediate- and high-risk prostate cancer. ADT for these men should remain a critical component of treatment regardless of radiotherapy delivery method until randomized evidence demonstrates otherwise.


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