Early Versus Delayed Androgen Deprivation for Prostate Cancer: New Fuel for an Old Debate

2005 ◽  
Vol 23 (32) ◽  
pp. 8225-8231 ◽  
Author(s):  
Charles J. Ryan ◽  
Eric J. Small
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
High Risk ◽  
Retrospective Analysis ◽  
Survival Benefit ◽  
Clinical Course ◽  
Local Therapy ◽  
Androgen Deprivation ◽  
Androgen Ablation ◽  
Overall Survival Benefit

The purpose of this review is to discuss the recent increase in data supporting the use of androgen ablation early in the clinical course for patients with nonmetastatic prostate cancer. We systematically reviewed recent publications that report on the use of androgen deprivation (AD) in nonmetastatic prostate cancer patients from the 2003 and 2004 procedings of the American Society of Clinical Oncology, the 2003 and 2004 procedings of the American Urological Association as well as published literature from 2003 to 2005. Five recently published mature randomized trials of AD plus local therapy were evaluated plus two large data sets on the use of AD for patients with serologic relapse after local therapy. Four mature randomized studies demonstrate an overall survival benefit to the use of AD in conjunction with definitive local therapy (three with radiation and one with surgery). One retrospective analysis suggests that AD administered early after serologic progression improves overall survival, and one retrospective analysis shows a reduction in metastasis-free survival but has not yet shown an overall survival benefit. For patients with nonmetastatic prostate cancer with high-risk features, as well as those for serologic relapse, the use of AD before the development of metastatic disease is supported by long-term outcomes from a series of clinical trials. Consideration of AD is therefore warranted early in the clinical course of high-risk patients.

Age-dependent overall survival benefit of androgen deprivation therapy for metastatic prostate cancer

2019 ◽  
Vol 25 (8) ◽  
pp. 1927-1932 ◽  
Author(s):  
Matthew J Keating ◽  
Lisa Giscombe ◽  
Toufic Tannous ◽  
Nishitha Reddy ◽  
Shiva Kumar R Mukkamalla ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Androgen Deprivation Therapy ◽  
Survival Benefit ◽  
Metastatic Prostate Cancer ◽  
Androgen Deprivation ◽  
National Cancer Database ◽  
Younger Patients ◽  
Significant Difference ◽  
Overall Survival Benefit

Background Androgen deprivation therapy (ADT) remains a standard of care in metastatic prostate cancer. Recent prospective trials have explored addition of chemotherapy to ADT. We retrospectively examined overall survival in metastatic prostate cancer patients treated with ADT, chemotherapy plus ADT (C + ADT), or observation from 2004 to 2010 using National Cancer Database data. Methods Using the National Cancer Database, 21,977 patients with metastatic prostate cancer diagnosed from 2004 to 2010 were identified. Multivariate logistic regression, Kaplan-Meier survival analysis and Cox proportional hazards regression modeling were implemented, with overall survival as the primary endpoint. Results Five-year overall survival was 13.6% in patients aged ≥ 75 years vs. 30.1% (age 65–74) and 34.5% (age 18–64). Subgroup analysis of age-based cohorts (<65 and ≥65 years) showed poor overall survival for C + ADT vs. ADT alone, both in younger (HR 1.35, 95% CI 1.21–1.50; p < 0.0001) as well as older (HR 1.21, 95% CI 1.08–1.34; p = 0.0006) populations. Younger patients had no significant difference in overall survival for observation vs. ADT (HR 0.99, 95% CI 0.92–1.08; p = 0.9121). Besides age, other factors impacting overall survival included race, rural/urban settings, comorbidity score, income, PSA and radiation. Discussion Younger patients had no significant difference in overall survival between observation or ADT. This implies a group of younger patients in whom ADT does not confer any overall survival benefit. Future clinical trials with genetic and biologic markers are needed to delineate which subgroups would not benefit from C + ADT or ADT alone. This is of utmost clinical importance given the negative impact of ADT on quality of life and comorbidities.

Immediate or Deferred Androgen Deprivation for Patients With Prostate Cancer Not Suitable for Local Treatment With Curative Intent: European Organisation for Research and Treatment of Cancer (EORTC) Trial 30891

2006 ◽  
Vol 24 (12) ◽  
pp. 1868-1876 ◽  
Author(s):  
Urs E. Studer ◽  
Peter Whelan ◽  
Walter Albrecht ◽  
Jacques Casselman ◽  
Theo de Reijke ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Local Treatment ◽  
Androgen Deprivation ◽  
Cancer Specific Survival ◽  
Deferred Treatment ◽  
Symptomatic Disease ◽  
Androgen Ablation ◽  
Number Of Patients ◽  
Significant Difference

Purpose This study (EORTC 30891) attempted to demonstrate equivalent overall survival in patients with localized prostate cancer not suitable for local curative treatment treated with immediate or deferred androgen ablation. Patients and Methods We randomly assigned 985 patients with newly diagnosed prostate cancer T0-4 N0-2 M0 to receive androgen deprivation either immediately (n = 493) or on symptomatic disease progression or occurrence of serious complications (n = 492). Results Baseline characteristics were well balanced in the two groups. Median age was 73 years (range, 52 to 81). At a median follow-up of 7.8 years, 541 of 985 patients had died, mostly of prostate cancer (n = 193) or cardiovascular disease (n = 185). The overall survival hazard ratio was 1.25 (95% CI, 1.05 to 1.48; noninferiority P > .1) favoring immediate treatment, seemingly due to fewer deaths of nonprostatic cancer causes (P = .06). The time from randomization to progression of hormone refractory disease did not differ significantly, nor did prostate-cancer specific survival. The median time to the start of deferred treatment after study entry was 7 years. In this group 126 patients (25.6%) died without ever needing treatment (44% of the deaths in this arm). Conclusion Immediate androgen deprivation resulted in a modest but statistically significant increase in overall survival but no significant difference in prostate cancer mortality or symptom-free survival. This must be weighed on an individual basis against the adverse effects of life-long androgen deprivation, which may be avoided in a substantial number of patients with a deferred treatment policy.

Survival impact of initial local therapy selection for men under 60 with high risk prostate cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 5082-5082
Author(s):  
Adeel Kaiser ◽  
Soren Bentzen ◽  
Minhaj Siddiqui ◽  
Michael J Naslund ◽  
Young Kwok ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
High Risk ◽  
Hormonal Therapy ◽  
Local Therapy ◽  
External Beam Radiation ◽  
Comorbidity Score ◽  
High Risk Prostate Cancer ◽  
Risk Prostate Cancer ◽  
The Impact

5082 Background: The impact of initial local therapy selection on survival for high risk prostate cancer (PCa) patients remains uncertain. We sought to assess this effect, while limiting competing causes of death, through the examination of a younger PCa patient cohort within the National Cancer Database. Methods: We evaluated the overall survival (OS) of men under 60 with high risk PCa receiving either radiation therapy (RT) or radical prostatectomy (RP). All men in this age group were treated between 2004 and 2013, harbored cN0M0 disease, and presented with Gleason Scores (GS) of 8 to 10. The RT group included patients who received external beam radiation (EBRT) alone or EBRT in combination with brachytherapy (BT). Overall survival and covariates were evaluated using multivariable Cox regression analysis. Results: A total of 16,944 patients met inclusion criteria of which 12,155 underwent RP and 4,789 received RT as initial therapy. 82.5% of RT patients received hormonal therapy, and the median dose was 77.4 Gy. In the RP group, 17.2% of patients received postoperative radiation, and 87% of these cases received a dose exceeding 64.80 Gy. The RP group had a higher proportion of cases with Charlson-Deyo comorbidity score > 0 (15.2% v. 11.2%, p < 0.000001). At a median follow-up of 50 months (0 - 131 months), RP was associated with improved OS in comparison to RT (hazard ratio = 0.52; 95% CI (0.47, 0.58); p < 0.000001). The estimated 8-year OS (±1 standard error of the estimate) was 85.1±0.7% and 74.9±0.7%, after RP and RT, respectively. This benefit remained present when adjusting for age, year of treatment, race, comorbidity score, Gleason score, T stage, hormonal therapy, chemotherapy, form of radiation, PSA, or insurance status. Conclusions: Compared to RT, initial treatment of men under 60 with high risk PCa with RP results in a large, statistically significant improvement in overall survival that remains consistent over time and remains significant in a multivariable model adjusting for known prognostic variables. These results are limited by the retrospective nature of the database analysis, and the lack of cancer specific survival information.

scholarly journals Seven-Month Prostate-Specific Antigen Is Prognostic in Metastatic Hormone-Sensitive Prostate Cancer Treated With Androgen Deprivation With or Without Docetaxel

2018 ◽  
Vol 36 (4) ◽  
pp. 376-382 ◽  
Author(s):  
Lauren C. Harshman ◽  
Yu-Hui Chen ◽  
Glenn Liu ◽  
Michael A. Carducci ◽  
David Jarrard ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Prostate Specific Antigen ◽  
Multivariable Analysis ◽  
Specific Antigen ◽  
Androgen Deprivation ◽  
Androgen Ablation ◽  
Hormone Sensitive ◽  
Low Volume

Purpose We evaluated the relationship between prostate-specific antigen (PSA) and overall survival in the context of a prospectively randomized clinical trial comparing androgen-deprivation therapy (ADT) plus docetaxel with ADT alone for initial metastatic hormone-sensitive prostate cancer. Methods We performed a landmark survival analysis at 7 months using the E3805 Chemohormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer (CHAARTED) database ( ClinicalTrials.gov identifier: NCT00309985). Inclusion required at least 7 months of follow-up and PSA levels at 7 months from ADT initiation. We used the prognostic classifiers identified in a previously reported trial (Southwest Oncology Group 9346) of PSA ≤ 0.2, > 0.2 to 4, and > 4 ng/mL. Results Seven hundred nineteen of 790 patients were eligible for this subanalysis; 358 were treated with ADT plus docetaxel, and 361 were treated with ADT alone. Median follow-up time was 23.1 months. On multivariable analysis, achieving a 7-month PSA ≤ 0.2 ng/mL was more likely with docetaxel, low-volume disease, prior local therapy, and lower baseline PSAs (all P ≤ .01). Across all patients, median overall survival was significantly longer if 7-month PSA reached ≤ 0.2 ng/mL compared with > 4 ng/mL (median survival, 60.4 v 22.2 months, respectively; P < .001). On multivariable analysis, 7-month PSA ≤ 0.2 and low volume disease were prognostic of longer overall survival (all P < 0.01). The addition of docetaxel increased the likelihood of achieving a PSA ≤ 0.2 ng/mL at 7 months (45.3% v 28.8% of patients on ADT alone). Patients on ADT alone who achieved a 7-month PSA ≤ 0.2 ng/mL had the best survival and were more likely to have low-volume disease (56.7%). Conclusion PSA ≤ 0.2 ng/mL at 7 months is prognostic for longer overall survival with ADT for metastatic hormone-sensitive prostate cancer irrespective of docetaxel administration. Adding docetaxel increased the likelihood of a lower PSA and improved survival.

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