Androgen Deprivation Therapy In Patients Research Articles

Experience with androgen deprivation therapy for prostate cancer in Japan and future perspectives.

Novel anti-androgens and androgen biosynthesis inhibitors have been developed to treat castration-resistant prostate cancer. However, knowledge of androgen deprivation therapy (ADT) has not been developed in the criticism, including information regarding the adverse effects of hormonal therapy. We hypothesize that there are ethnic differences in the efficacy and adverse effects of ADT; therefore, this review summarizes the experience of ADT, mainly in Japan. A risk stratification instrument, the Japan Cancer of the Prostate Risk Assessment (J-CAPRA) score, was developed based on the Japan Study Group of Prostate Cancer registry, which is a large, multicenter, population-based database. It revealed that clinical outcomes were substantially better for males treated with ADT in Japan compared with those in the United States. Moreover, there were small survival differences in patients with localized and locally advanced cancer who received local therapy and primary ADT in another Japanese cohort study. In terms of adverse effects, including bone loss and cardiovascular risk, ADT appears to be better tolerated in Japanese populations than in Western cohorts. An ongoing randomized controlled trial of a trimodality treatment comprising brachytherapy, external beam radiation therapy, and neoadjuvant with or without adjuvant ADT in patients with localized high-risk prostate cancer will provide novel insights regarding adjuvant ADT. As a future perspective, the optimal selection of the type of primary ADT, including combining androgen blockade and novel hormonal compounds, adjusted according to each patient's clinicopathological background, may provide better clinical outcomes in patients with advanced prostate cancer.

PCN23 - Heterogeneity of Treatment Effect of Androgen Deprivation Therapy In Patients With Incident Metastatic Prostate Cancer

PCN23 - Heterogeneity of Treatment Effect of Androgen Deprivation Therapy In Patients With Incident Metastatic Prostate Cancer

MP73-04 THE ASSOCIATION BETWEEN STATIN USE AND OUTCOMES IN PATIENTS INITIATING ANDROGEN DEPRIVATION THERAPY

Abstract Background Studies have conflicting results regarding the association between statin use and biochemical recurrence for prostate cancer (PCa). A limited number of studies examining statins in advanced stages report positive results, with a few specifically examining statins and androgen deprivation therapy (ADT). Objective To perform a post hoc secondary analysis of a randomised controlled trial (RCT) of men initiating ADT to examine the association between statin use and outcomes. Design, setting, and participants Patients with prostate-specific antigen (PSA) >3 ng/ml >1 yr following primary/salvage radiotherapy were enrolled in an RCT of intermittent androgen deprivation (IAD) versus continuous ADT (NCT00003653). Baseline and on-study statin use was modelled as a time-dependent covariate. Outcome measurements and statistical analysis The primary endpoint was overall survival. Models were adjusted for age, time from radiotherapy to ADT, baseline PSA, and prior ADT. Results and limitations Of 1364 patients, statin users (585; 43%) were younger (72.7 vs 73.8 yr, p = 0.001) and less likely to have PSA >15 ng/ml (20% vs 25%, p = 0.04). After a median follow-up of 6.9 yr, statin use was associated with reduced overall (hazard ratio [HR]: 0.64; 95% confidence interval [CI] 0.53–0.78, p Conclusions In men treated with ADT following primary or salvage radiotherapy, statin use was associated with improved overall and PCa-specific survival. In patients treated with IAD, statin use was associated with a trend towards longer time off treatment. A prospective trial of statins in men commencing ADT is warranted. Patient summary We found a favourable association between statin use and survival outcomes in patients initiating androgen deprivation therapy.

PD30-09 THE EFFECT OF ANDROGEN DEPRIVATION THERAPY FOR LOCALIZED PROSTATE CANCER ON CARDIOVASCULAR MORBIDITY ACCORDING TO LIFE EXPECTANCY

You have accessJournal of UrologyProstate Cancer: Localized II1 Apr 2015PD30-09 THE EFFECT OF ANDROGEN DEPRIVATION THERAPY FOR LOCALIZED PROSTATE CANCER ON CARDIOVASCULAR MORBIDITY ACCORDING TO LIFE EXPECTANCY Marianne Schmid, Jesse Sammon, Gally Reznor, Victor Kapoor, Jaqueline Speed, Firas Abdollah, Akshay Sood, Felix Chun, Adam Kibel, Mani Menon, Margit Fisch, Maxine Sun, and Quoc-Dien Trinh Marianne SchmidMarianne Schmid More articles by this author , Jesse SammonJesse Sammon More articles by this author , Gally ReznorGally Reznor More articles by this author , Victor KapoorVictor Kapoor More articles by this author , Jaqueline SpeedJaqueline Speed More articles by this author , Firas AbdollahFiras Abdollah More articles by this author , Akshay SoodAkshay Sood More articles by this author , Felix ChunFelix Chun More articles by this author , Adam KibelAdam Kibel More articles by this author , Mani MenonMani Menon More articles by this author , Margit FischMargit Fisch More articles by this author , Maxine SunMaxine Sun More articles by this author , and Quoc-Dien TrinhQuoc-Dien Trinh More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.1830AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Prior studies indicate increased risk of cardiac disease in patients with non-metastatic prostate cancer (PCa) undergoing androgen deprivation therapy (ADT). We investigate the dose-dependent effect of ADT on cardiac morbidity in PCa patients stratified according to life expectancy (LE). METHODS 62,215 men diagnosed with localized PCa between 1991 and 2007 were identified within SEER registry areas and stratified according to LE (<5, 5-10, >10 years). We compared those who did not receive ADT to those who underwent ADT within 2 years of PCa diagnosis, calculated as monthly equivalent doses (1-7, 7-11, >11 doses), or orchiectomy. Adjusted Cox hazard models assessed the risk of coronary heart disease (CHD), acute myocardial infarction (AMI), sudden cardiac death (SCD), and related interventions. RESULTS Patients undergoing ADT more frequently experienced any cardiovascular event compared to men who did not receive ADT (40.9 vs. 37.7%, p<0.001; Table 1). The hazard ratio (HR) for experiencing a cardiovascular event increased with the patients' LE and/or the doses of ADT. Specifically, men with a LE >10 years receiving >11 doses of ADT were at greatest hazard for CHD (HR: 1.32, 95% CI: 1.25-1.39, p<0.001), AMI (HR: 1.24, 95% CI: 1.12-1.37, p<0.001), SCD (HR: 1.42, 95% CI: 1.23-1.63, p<0.001) and intervention HR: 1.13, 95% CI: 1.05-1.23, p<0.001). CONCLUSIONS For PCa patients with localized disease and a decent LE, cumulative exposure to ADT with GnRH agonists is associated with increased risk of cardiac morbidity or mortality. Clinicians should carefully weigh the risks and benefits of ADT in patients with a prolonged LE. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e657 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Marianne Schmid More articles by this author Jesse Sammon More articles by this author Gally Reznor More articles by this author Victor Kapoor More articles by this author Jaqueline Speed More articles by this author Firas Abdollah More articles by this author Akshay Sood More articles by this author Felix Chun More articles by this author Adam Kibel More articles by this author Mani Menon More articles by this author Margit Fisch More articles by this author Maxine Sun More articles by this author Quoc-Dien Trinh More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Quantifying the evidence for the risk of metabolic syndrome and its components following androgen deprivation therapy for prostate cancer: a meta-analysis.

BackgroundNo meta-analysis is yet available for the risk of metabolic syndrome (MetS) following androgen deprivation therapy (ADT) for men with prostate cancer. To summarize the evidence for the link between ADT and MetS or its components quantitatively with a meta-analysis including all studies published to date.MethodsPubMed and Embase were searched using predefined inclusion criteria to perform meta-analyses on the association between metabolic syndrome, hyperglycemia, diabetes, hypertension, dyslipidemia or obesity and androgen deprivation therapy in patients with prostate cancer. Random effects methods were used to estimate pooled relative risks (RRs) and 95% confidence intervals (CI).ResultsA total of nine studies was included. There was a positive association between ADT and risk of MetS (RR: 1.75 (95% CI: 1.27–2.41)). Diabetes was the only MetS component present in more than 3 studies, and also showed an increased risk following ADT (RR: 1.36 (95% CI: 1.17–1.58)).ConclusionThis is the first quantitative summary addressing the potential risk of MetS following ADT in men with PCa. The positive RRs indicate that there is a need to further elucidate how type and duration of ADT affect these increased risks of MetS and diabetes as the number of men with PCa treated with ADT is increasing.

Cessation of Primary Androgen Deprivation Therapy for Men With Localized Prostate Cancer

IntroductionSubstantial numbers of men with localized prostate cancer undergo long-term primary androgen deprivation therapy (ADT). Whether long-term ADT is required for patients with localized prostate cancer, especially elderly men, remains unknown. In the present study, we explored the possibility of ADT cessation after a favorable response to primary ADT in patients with localized prostate cancer. Patients and MethodsWe retrospectively reviewed men with localized prostate cancer who had achieved a good initial response to primary ADT and stopped it thereafter. Prostate-specific antigen (PSA) recurrence was defined as 2 consecutive increases > 4 ng/mL. A total of 34 patients (age, 62-89 years) were followed up for > 24 months after ADT cessation. ResultsThe ADT duration and follow-up period after ADT cessation was 10 to 162 months (median, 33.5 months) and 24 to 95 months (median, 37 months), respectively. PSA recurrence was observed in 10 of 34 patients (29.4%), and the 5-year PSA progression-free rate was 66.2%. PSA recurrence was observed in 100% (6 of 6) and 14.3% (4 of 28) of men who had received ADT for < 16 months and > 16 months, respectively. ADT was reinstated in 5 patients after PSA recurrence; and their PSA levels declined rapidly, and no clinical progression was observed. The 5-year overall and disease-specific survival rate was 65.1% and 100%, respectively. ConclusionADT can be stopped for men with localized prostate cancer, especially elderly men, after a favorable response to primary ADT.

The association between statin use and outcomes in patients initiating androgen deprivation therapy.

145 Background: Studies are conflicting regarding the association between statin use and biochemical recurrence after surgery or radiotherapy for localized prostate cancer. A handful of studies have observed favorable associations between statins and prostate cancer-specific (PCSM) and overall mortality (OS), however, this has not been studied in an advanced disease cohort nor has the combination of statins and androgen deprivation therapy (ADT) been specifically studied. Methods: Patients with PSA &gt;3 ng/mL after &gt;1 year following primary or salvage radiotherapy (RT) were enrolled in a randomized trial of intermittent (IAD) vs. continuous (CAD) ADT (NCT00003653). Statin use at baseline and during the study was captured and modeled as a time-dependent covariate. The primary end-point was OS. Models were adjusted for age, time from RT to ADT and PSA at baseline. As results were nearly identical between the IAD and CAD arms they are reported as aggregates unless otherwise indicated. Results: Of 1,364 patients enrolled, 585 (43%) reported statin use during the study. Statin users were younger (72.7 vs. 73.8, p=0.001) and less likely to have PSA &gt;15 (20 vs. 25%, p=0.04). Median follow-up was 6.9 years and 524 deaths occurred. Statin use was associated with a reduced risk of overall death (HR: 0.64; 95% C.I. 0.53 – 0.78, p&lt;0.001) and PCSM (HR: 0.64, 95% C.I. 0.48 – 0.86, p=0.003). Statin users had 14% longer time to castration resistance but this did not reach statistical significance (p=0.15). In the IAD arm, statin users had more off-treatment intervals (p=0.04) and longer time off-treatment (median: 0.85 vs. 0.64 years, p=0.06). Across 6 functional domains, statin users reported better quality of life scores. Conclusions: In men treated with ADT following primary or salvage RT, statin use was associated with improved overall and prostate cancer-specific survival and improved quality of life. In patients treated with IAD, statin use was associated with more off-treatment intervals and longer time off-treatment. A prospective trial of statins in men commencing ADT is warranted to confirm this observation.

Cardiovascular events associated with androgen deprivation therapy in patients with prostate cancer: a systematic review and meta-analysis.

A recently published meta-analysis of randomized clinical trials (RCT) showed that androgen deprivation therapy (ADT) did not significantly increase cardiovascular mortality in prostate cancer patients. However, cardiovascular morbidity, which can impact quality of life, was not evaluated. To evaluate the risk of cardiovascular morbidity associated with ADT in patients with prostate cancer. We conducted a literature search from January 1960 to June 2012. RCT and large cohort studies that evaluated first-line endocrine therapy and ADT longer than 6 months were screened for inclusion. In total, 126,898 patients were included in four cohort studies, and 10,760 patients were included in nine RCTs. Analysis of the RCTs showed no differences in the development of acute myocardial infarction (AMI) (OR 1.23; 95 % CI 0.92-1.64; I (2): 0 %) among the patients receiving ADT or not. The analysis of randomized studies that reported other nonfatal cardiovascular events demonstrated a significant increase in such events in the group receiving ADT (OR 1.55; 95 % CI 1.09-2.20; I (2): 0 %). When the large cohort studies were included in the analysis, an increased risk of AMI among men with ADT was found (OR 2.01, 95 % CI 1.90-2.13; I (2): 91,3 %). The use of ADT in prostate cancer patients corresponded with a significant increase in cardiovascular morbidity associated with AMI and with nonfatal events. Therefore, ADT is linked to a significant negative impact on quality of life. Periodic cardiovascular evaluation is required for these patients.

5α-Reductase Inhibition Coupled with Short Off Cycles Increases Survival in the LNCaP Xenograft Prostate Tumor Model on Intermittent Androgen Deprivation Therapy

Intermittent androgen deprivation therapy in patients with prostate specific antigen progression after localized prostate cancer treatment is an alternative to standard continuous androgen deprivation therapy. Intermittent androgen deprivation therapy allows for testosterone recovery during off cycles. This stimulates regrowth and differentiation of the regressed prostate tumor, lessens the side effects of continuous androgen deprivation therapy and potentially prolongs survival. Previously intermittent androgen deprivation therapy coupled with finasteride was shown to prolong survival in animals bearing androgen sensitive prostate tumors when the off cycle duration was not prolonged but rather fixed at 10 to 14 days. Regressed prostate tumor xenografts with testosterone replacement were initially responsive to 5α-reductase inhibition but growth resumed after several days. In shorter off cycles of testosterone recovery 5α-reductase inhibition might maximize tumor growth inhibition during intermittent androgen deprivation therapy and perhaps increase survival. We used the LNCaP xenograft tumor model to evaluate the effectiveness of short off cycles of 4 days coupled with 5α-reductase inhibition on survival and tumor regrowth while on intermittent androgen deprivation therapy. Dutasteride inhibited initial testosterone induced tumor regrowth off cycles 1 and 2, and significantly increased survival. These results further support the potential for intermittent androgen deprivation therapy combined with 5α-reductase inhibition to improve survival in patients with prostate cancer when off cycle duration is short or very short.

Androgen Deprivation Therapy for Patients With Localized Prostate Cancer Treated With High-Dose-Rate Brachytherapy Boost

Purpose/Objective(s): To evaluate the effectiveness and tolerability of neo-adjuvant/concomitant/adjuvant androgen deprivation therapy (ADT) for patients treated with external beam radiation therapy (EBRT) combined with high-dose-rate (HDR) brachytherapy boost for localized prostate cancer. Our hypothesis was that ADT does not add to the efficacy of the combined treatments. Materials/Methods: This is a retrospective cohort study conducted in a Canadian academic oncology center. All patients treated at our institution with EBRT followed by 192Ir HDR brachytherapy boost for localized prostate cancer between 1998 and 2010 were included in the study. Data on patients’ age, disease severity at diagnosis, androgen deprivation and radiation treatments received and follow up were collected from the patients’ medical records. The primary outcome was biochemical recurrence-free survival (bRFS). The secondary outcomes were genitourinary and gastrointestinal toxicities. Biochemical recurrence was determined according to the Phoenix consensus definition. Survival curves were calculated with the Kaplan-Meier method and compared between the two groups (ADT versus no ADT) with a logrank test. Multivariate Cox regressions were also performed to take into account potentially confounding variables such as age, PSA at diagnosis, TNM stage, Gleason score, biologically effective dose and type and duration of ADT. Genitourinary toxicities were assessed with the IPSS tool and compared between groups with student t-tests. Gastrointestinal toxicities (diarrhea, tenesmus, rectal bleeding) were evaluated with a three points scale (0: never, 1: occasionally, 2: frequently) and compared between groups with chi-squared tests. Results: Six hundred thirty-eight patients were treated with EBRT and HDR brachytherapy boost. Of those, 186 received ADT and 452 received no ADT. Doses ranged from 40 to 45 Gy in 20 to 25 fractions for EBRT and from 15 to 20 Gy in 1 to 3 fractions for the boost. According to NCCN risk classification, 7.8% of patients were low risk, 81.8% were intermediate risk and 10.3% were high risk. Median follow-up was 53 months. There was no significant difference in bRFS between groups in univariate (HR: 0.83; 95% CI: 0.51-1.38; p Z 0.48) and in multivariate analyses (HR: 0.72; 95% CI: 0.42-1.26; p Z 0.20). bRFS at 7 years was 86% in the ADT group and 92% in the no-ADT group (p Z 0.48). We observed no significant difference between groups in mean global IPSS scores at 3 months (ADT: 11.17 vs. no-ADT: 10.4; pZ 0.49) and at 12 months (ADT: 9.64 vs. no-ADT: 10.75; p Z 0.28) post-radiation therapy as well as in gastrointestinal toxicities at 3 and 12 months. Conclusions: For patients with a localized prostate cancer treated with EBRT combined with HDR brachytherapy boost, the addition of ADT does not seem to yield to a significant increased in bRFS neither to be associated with increased genitourinary and gastrointestinal toxicities. Author Disclosure: S. Magnan: None. P. Despres: None. W. Foster: None. A. Martin: None. E. Vigneault: None.

Biochemical and Survival Outcomes in Patients With T3 Prostate Adenocarcinoma Treated With Brachytherapy

Purpose/Objective(s): To evaluate the freedom from biochemical failure (FFBF), prostate cancer-specific survival (PCSS), and overall survival (OS) in patients with cT3a-b prostate adenocarcinoma treated at a single institution. Materials/Methods: One hundred seven patients with cT3a-b, N0, M0 prostate adenocarcinoma underwent I-125 (72%) or Pd-103 (28%) low dose rate brachytherapy from 1998-2007. Seventy-five patients (70%) received supplemental external beam radiation therapy as part of combined modality therapy (CMT). Thirty-two patients (30%) underwent implant alone (MT). Ninety-two patients (86%) received androgen deprivation therapy (ADT). Median (range) age, pre-treatment PSA (iPSA), duration of ADT and follow-up were 69 years (47-93), 12.7 ng/ml (1.4-160), 4 months (2-36) and 73 months (9-160), respectively. Fifty-five men (51%) had Gleason sum (GS) 8-10. Eighty-nine patients (86%) had 50% of cores involved. Univariate analysis (UVA) was performed using the logrank test and Cox proportional hazards for continuous variables with the following covariates: age, T-stage (T3a vs. T3b), GS, iPSA, percent positive cores (PPC), ADT use, and implant setting (CMT vs. MT). Multivariable analysis (MVA) was performed using Cox proportional hazards modeling and included T-stage, GS, iPSA and all covariates with p-value <0.1 on UVA. Results: Kaplan-Meier estimates for FFBF, PCSS and OS are described in Table 1. On UVA, only CMT was associated with improved FFBF. CMT, younger age (p Z 0.09), and lower PSA (p<0.01) were associated with improved PCSS. CMT, younger age (p<0.01), higher GS (p Z 0.09), and lower iPSA (p Z 0.04) were associated with improved OS. ADT was not associated with FFBF, PCSS, or OS for the overall cohort or on subgroup analysis. MVA revealed CMTwas associated with improved FFBF (Hazard ratio [HR]: 0.28, 95% Confidence Interval [CI]: 0.14-0.59; p<0.01). Lower iPSA was associated with improved PCSS (HR: 0.98, 95% CI: .96-1.00; p Z 0.01), but CMTwas not (HR: 0.41, 95% CI: 0.1-1.73; pZ 0.23). Lower iPSA was associated with improved OS (HR: 0.98, 95% CI: 0.97-1.00; p<0.01). CMT had a trend towards improved OS (0.44, 95% CI: 0.171.12; p Z 0.09) and higher GS had a trend towards worse OS (HR: 1.35, 95% CI: 0.944-1.93; p<0.1). Conclusions: In patients with cT3a-b prostate adenocarcinoma, CMT is associated with improved biochemical control but may not be associated with PCSS or OS when controlling for other factors. The benefit of ADT in patients treated with brachytherapy is unclear.

Similar Benefit of Immediate or Deferred ADT in PSA-Only Relapsed Prostate Cancer

Mortality rates were similar among patients with prostate antigen (PSA)—only relapsed prostate cancer who received immediate or deferred androgen deprivation therapy (ADT). This article presents data from a study of the immediate versus deferred initiation of ADT in patients with PSA-only relapsed prostate cancer [Garcia-Albeniz X et al. J Clin Oncol 2014].

Cardiovascular events associated with androgen deprivation therapy in patients with prostate cancer: A systematic review and meta-analysis.

40 Background: A recently published meta-analysis of randomized clinical trials (RCT) showed that androgen deprivation therapy (ADT) did not significantly increase cardiovascular mortality in prostate cancer patients. However, cardiovascular morbidity, which can impact quality of life, was not evaluated. Objectives: To evaluate the risk of cardiovascular morbidity and mortality associated with long-term ADT in patients with prostate cancer. Methods: We conducted a literaturesearch from 1960 and June 2012. We selected RCT and large cohort studies that evaluated first-line endocrine therapy, ADT greater than 6 months, and follow up greater than 1 year. Results: Thirteen studies (137,658 patients) were included. Of four cohort studies, 126,898 patients were included and 10,760 patients were part of nine RCTs. Analysis of the RCTs showed no differences in development of acute myocardial infarction (AMI) (OR 1.23; 95% CI: 0.92 – 1.64; I2: 0%) or stroke (OR 1.02; 95% CI: 0.71 – 1.46; I2: 0%) among patients receiving ADT or not. The analysis of three randomized studies that reported other nonfatal cardiovascular events demonstrated a significant increase in such events in the group receiving ADT (OR 1.55; 95% CI: 1.09 – 2.20; I2: 0%). When large cohort studies were included in the analysis, an increased risk of AMI among men who had ADT was found ( OR 2.01, 95% CI:1.90 – 2.13; I2: 91.3%). Conclusions: ADT in prostate cancer patients for at least 6 months is not associated with cardiovascular mortality, acute myocardial infarct and stroke. However, patients receiving ADT had a significant increase in nonfatal cardiovascular events.

Improving intermittent androgen deprivation therapy: lessons learned from basic and translational research.

Intermittent androgen deprivation therapy (IADT) is an alternative to continuous androgen deprivation therapy (ADT) in prostate cancer patients with nonmetastatic disease. ADT is associated with numerous side effects such as hot flashes, sexual dysfunction, anemia, fatigue, loss of muscle mass, osteoporosis, metabolic syndrome and premature cardiovascular disease. IADT was developed with the intention of improving the quality of life and to delay progression of prostate cancer to castration resistance. The benefits of slightly improved quality of life by IADT compared to ADT were demonstrated in multiple clinical trials. IADT was noted to be noninferior to ADT in patients with biochemical recurrence of prostate cancer but in studies performed in patients with metastatic prostate cancer, the results were inconclusive. Our recent studies suggested that the administration of 5 alpha-reductase inhibitors during the off-cycle of IADT can significantly prolong the survival of mice bearing androgen-sensitive prostate tumors when off-cycle duration was short. This review discusses the survival benefit of 5 alpha-reductase inhibition in IADT in animal models and the potential translation of this finding into clinic.

Intermittent LHRH Therapy in the Management of Castrate-resistant Prostate Cancer (CRPCa)

Patients who develop castration-resistant prostate cancer (CRPCa) typically continue on androgen deprivation therapy (ADT). Whether these patients need to remain on ADT has not been well studied. We conducted a multicenter randomized trial to compare an intermittent versus continuous approach to ADT in CRPCa patients. Overall survival, health-related quality of life (QOL), and cost were the main endpoints. CRPCa patients were randomized 2:1 to intermittent or continuous luteinizing hormone-releasing hormone agonists (LHRHa). Patients were followed with clinical assessments, laboratory investigations, and QOL questionnaires (EORTC QLQ-C30 or PROSQOLI) every 2 months. If the serum testosterone rose above castrate levels (1.75 nmol/L), LHRHa were reinitiated. The study was designed to close if >50% of patients needed to restart ADT in the intermittent arm. Thirty-one patients were followed with a median follow-up of 26.8 months-18 in the intermittent arm and 13 in the continuous. Twelve of 18 patients on the intermittent arm were reinitiated on LHRHa at a median time of 17.9 months. There was no difference in overall or cancer-specific survival between the 2 arms. There was no statistically significant difference in QOL between the 2 arms at 0 and 12 months. The total mean costs at 24 months were significantly lower in the intermittent arm ($3135 vs. $8253 Canadian dollars, P=0.0167) compared with the continuous. The main limitation of this study is the small sample size. We have observed that intermittent ADT in patients with CRPCa, using a testosterone of >1.75 ngmol/L as a trigger to reinitiate LHRHa, results in a substantial cost savings with no negative impact on oncologic and QOL outcomes.

Clinical outcomes after salvage radiotherapy without androgen deprivation therapy in patients with persistently detectable PSA after radical prostatectomy: results from a national multicentre study

To assess oncologic outcomes after salvage radiotherapy (SRT) without androgen deprivation therapy (ADT) in patients with persistently detectable PSA after radical prostatectomy (RT). Two hundred and one patients who failed to achieve an undetectable PSA received SRT without ADT. The primary endpoint was failure to SRT that was defined by clinical progression or use of second-line ADT. Clinicopathological parameters, 6-week PSA level, PSAV and pre-SRT PSA levels were assessed using time-dependent analyses. Median postoperative 6-week PSA and pre-SRT PSA levels were 0.25 and 0.48 ng/mL, respectively. Median time between surgery and SRT was 7 months. Failure to SRT was reported in 42.8 % of cases with the need for second-line ADT in 26.9 % of cases. Pre-SRT PSA was strongly correlated with postoperative 6-week PSA (p < 0.001) but not with PSAV. The risk of SRT failure was increased by threefold in case of Gleason score 8-10 (p = 0.036) or pT3b cancer (p = 0.006). Risk group classification based on these prognostic factors improved SRT failure prediction. Survival curves confirmed that 5-year ADT-free survival rates were significantly influenced by PSAV (p = 0.002) and pre-SRT PSA (p = 0.030). In patients with persistently detectable PSA after RP and selected for local salvage treatment, SRT offers good oncologic clinical outcomes. The most powerful pathologic predictive factors of SRT failure include a pT3b stage, a Gleason score 8 or more cancer and high PSAV and pre-SRT PSA levels. Patients having a high PSAV >0.04 ng/mL/mo would be potentially better candidates for a systemic therapy due to a high SRT failure rate.

Multi-institutional Outcomes Following External Beam Radiation Therapy and Androgen Deprivation Therapy in Patients With Extreme-Risk Prostate Cancer

Multi-institutional Outcomes Following External Beam Radiation Therapy and Androgen Deprivation Therapy in Patients With Extreme-Risk Prostate Cancer

Postacute and Long-Term Care Teams Increasingly Participate in Cancer Care

Postacute and Long-Term Care Teams Increasingly Participate in Cancer Care

Reply

The editorial comment for our published article titled “Efficacy of Intermittent Androgen Deprivation Therapy vs Conventional Continuous Androgen Deprivation Therapy for Advanced Prostate Cancer: A Meta-analysis” discussed several important methodological features of meta-analyses. We would like to respond to comments regarding (1) quality assessment of primary studies, (2) publication bias detection using funnel plots or Egger's test, (3) heterogeneity reduction using meta-regression analysis, and (4) interpretations of study findings. Editorial CommentUrologyVol. 82Issue 2PreviewThe authors performed a systematic review and meta-analysis, comparing the efficacy of intermittent androgen deprivation therapy (IADT) vs continuous androgen deprivation therapy for patients with advanced prostate cancer. They pooled data from 8 trials (including over 4600 men), in which participants were randomized to IADT or continuous androgen deprivation therapy. Results of their meta-analysis suggest that the use of IADT does not significantly increase the risk of cancer-specific or overall mortality, but it significantly reduces a man's risk of hot flashes. Full-Text PDF

Quality of Life After Sipuleucel-T Therapy: Results From a Randomized, Double-blind Study in Patients With Androgen-dependent Prostate Cancer

To collect and analyze quality-of-life (QOL) data from PROvenge Treatment and Early Cancer Treatment trial (PROTECT, NCT00779402), a phase III, randomized controlled trial of sipuleucel-T in patients with asymptomatic androgen-dependent prostate cancer. Patients experiencing prostate-specific antigen relapse after radical prostatectomy entered a 3- to 4-month run-in phase of androgen-deprivation therapy (ADT), followed by 2:1 randomization to sipuleucel-T or control. QOL was assessed throughout the run-in and 26-week post-randomization phases using the Brief Fatigue Inventory (BFI), Linear Analog Self-Assessment (LASA) scale, Global Rating of Change (GRoC) scale, and an elicited symptoms list. One hundred seventy-six patients were randomized into 2 groups, the sipuleucel-T group (n = 117) or the control group (n = 59). The sample provided 80% power to detect a difference in fatigue interference score between treatment arms of 0.9 points. QOL declined predictably during ADT. At week 26, 26.2% of sipuleucel-T-treated patients and 21.6% of control-treated patients (P = .68) reported fatigue in the previous week, and the mean score for fatigue interference in the past 24 hours was 0.9 for both arms (P = .88). Results were comparable for usual fatigue (P = .91) and worst fatigue (P >.99). Mean LASA scores decreased in both groups (P = .26). The proportion of patients reporting better overall QOL on GRoC was similar (P = .62). There is no clinically significant negative impact on QOL after sipuleucel-T treatment compared with control after a period of ADT in patients with asymptomatic androgen-dependent prostate cancer.