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 ◽  
...  

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.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 324-324
Author(s):  
Matthew Keating ◽  
Lisa Giscombe ◽  
Andre Desouza ◽  
Shiva Kumar Reddy Mukkamalla ◽  
Ritesh Rathore

324 Background: Androgen deprivation therapy (ADT) remains a standard of care in the treatment of locally advanced prostate cancer. But thanks to a few key trials (STAMPEDE, CHAARTED, and LATITUDE) reported within the past three years, docetaxel and abiraterone now have roles in extending overall survival in a patient population traditionally treated with ADT alone. These treatments when combined with ADT have been shown to extend overall survival in metastatic hormone-sensitive prostate cancer patients. The role of ADT in relation to other therapies continues to evolve rapidly. We intend to revisit ADT’s longstanding role in prostate cancer treatment using a national cancer database. Our aim is to look beyond traditional standards of care to identify patients more likely to have overall survival benefit from ADT. Are there any subgroups of patients with intermediate or high risk disease that have improved survival outcomes with androgen deprivation therapy, besides patients with localized disease that underwent radiation? Could there be other variables besides PSA and localization of the prostate cancer that should be considered when identifying ADT treatment candidates, or identifying survival trends in these groups? Methods: We are currently analyzing variables present in the National Cancer Database to retrospectively identify predictive factors for overall survival and progression to metastatic castrate resistant prostate cancer in locally advanced prostate cancers treated with ADT. We will evaluate time-to-death from the initiation of ADT and from the diagnosis of metastatic castrate resistant prostate cancer. The following variables in localized, locally advanced, and metastatic prostate cancer will be analyzed with Statistical Analysis Software: age, locally advanced, site-specific metastasis (M1a, M1b, M1c), Gleason score, local treatment (radical prostatectomy or radiation), stage (T, N, and M), prostate lobe (one vs. both; T2a/b vs. T2c), chemotherapy (date, time from M1 stage), comorbidity score, ethnicity, facility type, insurance, and risk groups (low/intermediate/high as per NCCN guidelines).


2018 ◽  
Author(s):  
Derya Tilki ◽  
Marc A Dall’era ◽  
Christopher P Evans

Oncologic outcome of patients with newly diagnosed metastatic prostate cancer (mPCa) is poor. The treatment paradigm for newly diagnosed mPCa has changed. The standard of care for men with metastatic hormone-naive prostate cancer has been systemic androgen deprivation therapy (ADT). Previous randomized studies demonstrated an overall survival benefit by the addition of early chemotherapy with six cycles of docetaxel. More recently, results from randomized trials also demonstrated a survival benefit by the addition of abiraterone acetate to the ADT in men with metastatic disease. The aim of this review is to summarize the results from most recent studies, including men with newly diagnosed metastatic hormone-naive prostate cancer, focusing on chemotherapy and ADT. This review contains 1 figure, 2 tables, and 47 references.  Key Words: abiraterone acetate, androgen deprivation therapy, androgen deprivation, castrate sensitive, chemotherapy, continuous androgen deprivation, docetaxel, hormone-naive, intermittent androgen deprivation, metastatic prostate cancer


Cancers ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 189
Author(s):  
Szu-Yuan Wu ◽  
Su-Chen Fang ◽  
Olivia Rachel Hwang ◽  
Hung-Jen Shih ◽  
Yu-Hsuan Joni Shao

Few studies have assessed the benefits of androgen deprivation therapy (ADT) in men with metastatic prostate cancer (PC; mPC) at an old age or with major cardiovascular conditions. A retrospective cohort consisted of 3835 men with newly diagnosed mPC from the Taiwan Cancer Registry of 2008–2014. Among them, 2692 patients received only ADT in the first year after the cancer diagnosis, and 1143 patients were on watchful waiting. The inverse probability of treatment-weighted Cox model was used to estimate the effects of ADT on all-cause mortality and PC-specific mortality according to age, and the status of congestive heart failure (CHF), coronary arterial diseases (CADs), and stroke at the baseline. After a median follow-up of 2.65 years, 1650 men had died. ADT was associated with a 17–22% risk reduction in all-cause and PC-specific mortality in men without stroke, CAD, or CHF in the 65–79-year group. The survival benefit diminished in men with any of these preexisting conditions. In contrast, ADT was not found to be associated with any survival benefit in the ≥80-year group, even though they did not present with any major cardiovascular disease at the baseline. Patients who had CHF, CAD, or stroke at the baseline did not show a survival benefit following ADT in any of the age groups. Men who have preexisting major cardiovascular diseases or are ≥80 years do not demonstrate a survival benefit from ADT for mPC. The risk–benefit ratio should be considered when using ADT for mPC in older men especially those with major cardiovascular comorbidities.


2018 ◽  
Vol 36 (15_suppl) ◽  
pp. e17046-e17046
Author(s):  
Matthew Keating ◽  
Shiva Kumar Reddy Mukkamalla ◽  
Lisa Giscombe ◽  
Nishitha Reddy ◽  
Andre Desouza ◽  
...  

2005 ◽  
Vol 23 (32) ◽  
pp. 8225-8231 ◽  
Author(s):  
Charles J. Ryan ◽  
Eric J. Small

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.


2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 205-205
Author(s):  
Kin Chung Lai ◽  
Toiya Turknett ◽  
Parminder Singh

205 Background: Metastatic prostate cancer (mPC) is treated with androgen deprivation therapy( ADT). Duration of response to ADT predicts patient’s survival. It has been shown in observational studies that concurrent statin use may prolong response to ADT. Studies in mice have shown negative interactions. We wanted to examine the effect of this interaction in patients being followed at Mayo Clinic Arizona (MCA). Methods: We examined 441 patients with mPC, who received ADT and were treated at MCA from year 2011 to 2017. . Our study evaluated the time to progression (TTP) and overall survival(OS) for patients with mPC on ADT with or without concurrent statin use. Among the patients who were evaluated, there was a subset of 156 patients taking abiraterone (ABI). Characteristics were compared between statin users and nonusers using Chi squared test and Wilcoxon rank-sum tests. The primary outcome was TTP defined as the duration from ADT initiation to disease progression. The association between statin use and TTP was analyzed by multivariable Cox regression to estimate hazard ratios (HRs) and 95% Conference Interval (CI), and adjusted for Gleason score, primary therapy type, prior ADT, metastatic status, and PSA at ADT initiation. Results: There was no significant difference in TTP when comparing patients with statin to those without a statin. The HR for statin use vs no statin use is 1.049 with CI (0.838, 1.314) and p-value is 0.677. There was no significant difference in overall survival when comparing statin vs no statin use. The HR for statin use vs no statin use was 0.928(CI 0.642, 1.342) with p-value at 0.693. In the ABI population, there was no significant difference in TTP for patients with statin vs no statin. HR was 1.00 CI (0.725, 1.377) with p-value at 0.998. For overall survival, there was no significant difference with HR at 0.852 (CI 0.502, 1.446) with p-value at 0.553. Conclusions: Despite retrospective studies showing benefit of use of statin in men with prostate cancer, our study observed no difference in long term outcomes. Possible explanations could be smaller sample size, inability to verify data as medication intake was not verified directly. Also, patient’s compliance with medications could be a confounding variable.


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