Early versus delayed initiation of salvage androgen deprivation therapy and the risk of prostate cancer-specific mortality.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 189-189
Author(s):  
Brandon Arvin Virgil Mahal ◽  
Ming-Hui Chen ◽  
Andrew A. Renshaw ◽  
Philip W. Kantoff ◽  
Anthony Victor D'Amico
Keyword(s):  
Prostate Cancer ◽  
Androgen Deprivation Therapy ◽  
Specific Antigen ◽  
Androgen Deprivation ◽  
Early Initiation ◽  
Study Cohort ◽  
Increased Risk ◽  
Specific Mortality ◽  
Salvage Androgen Deprivation Therapy

189 Background: We sought to ascertain whether there is an association between prostate cancer (PC)-specific mortality (PCSM) and salvage androgen deprivation therapy (ADT) timing amongst men with short versus long prostate-specific antigen doubling times (PSA-DT)s. Methods: The study cohort was selected from 206 men with localized unfavorable-risk PC who were randomized to radiation therapy (RT) or RT plus 6 months of ADT between 1995 and 2001. Fifty-four men who received salvage ADT for PSA failure after a median follow up of 18.72 years following randomization defined the study cohort. Fine-Gray competing risks regression analyzed whether the timing of salvage ADT was associated with an increased risk of PCSM after adjusting for age, comorbidity, known PC prognostic factors, and previously identified interactions. Results: After a median follow-up of 5.68 years (IQR 3.05 - 9.56) following salvage ADT 49 of the 54 men (91%) died, 27 from PC (54% of deaths). Increasing PSA-DT as a continuous covariate was associated with a decreasing risk of PCSM (adjusted hazard ratio [AHR] 0.33, 95% CI 0.13, 0.82; P=0.02). Amongst men with a long PSA-DT (≥6 months), initiating salvage ADT later (PSA>12ng/mL, upper quartile) versus earlier was associated with an increased risk of PCSM (AHR 8.84, 95% CI 1.99-39.27; P=0.004); whereas for men with a short (<6 months) PSA-DT (AHR 1.16, 95% CI 0.38-3.54; P=0.79) this was not true. Conclusions: Early initiation of salvage ADT for post-RT PSA recurrence in men with a PSA-DT of 6 months or more may reduce the risk of PCSM, arguing against the unproven assumption that patients with a short PSA-DT are those most likely to benefit from early initiation of salvage ADT. Clinical trial information: NCT00116220.

Proportion of biochemically-recurrent prostate cancer patients with durable undetectable PSA after short-course androgen deprivation therapy.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 207-207
Author(s):  
Daniel M. Lim ◽  
Roman Gulati ◽  
Serge Aleshin-Guendel ◽  
Heather H. Cheng ◽  
Agnes M. Gawne ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Deprivation Therapy ◽  
Specific Antigen ◽  
Initial Therapy ◽  
Androgen Deprivation ◽  
Clinical Value ◽  
Short Course ◽  
Increased Risk ◽  
The University ◽  
Trial Endpoint

207 Background: Optimal utilization of novel therapies for advanced prostate cancer is challenging without a validated surrogate efficacy endpoint. Ongoing trials are using durable undetectable prostate specific antigen (PSA) levels as a marker of efficacy. The proportion of patients and clinical relevance of those with a prolonged undetectable PSA after a short course of androgen deprivation therapy (ADT) is uncertain. Methods: The University of Washington Caisis database was queried for radical prostatectomy patients who received 6–12 months of ADT after biochemical recurrence (BCR), defined as PSA ≥ 0.2 ng/mL and no radiographically detectable metastasis. Proportions of patients with undetectable PSA 12 and 24 months after ending ADT were compared to a hypothesized 5% rate using exact binomial tests. Associations with patient and tumor characteristics were examined using logistic regression, and associations with risk of subsequent metastasis and death from any cause were evaluated by log-rank tests. Results: After ineligibility exclusions, data were abstracted from 93 patients. Proportions of patients with undetectable PSA 12 and 24 months after ending ADT were n=23/93 (24.7%; 95% CI 16.4–34.8%; P<0.001) and n=14/93 (15.1%; 95% CI 8.5–24.0%; P<0.001), respectively. Proportions of patients with undetectable PSA 12 and 24 months after testosterone recovery ≥ 50 ng/dL were n=16/65 (24.6%; 95% CI 14.8-36.9%) and n=10/65 (15.4%; 95% CI 7.6-26.5%), respectively. Being 1 year older at diagnosis was associated with an 11.5% (95% CI 3.1–21.9%; P=0.01) increase in the odds of having a detectable PSA after controlling for PSA at diagnosis, Gleason sum and time from initial therapy to BCR. Detectable PSA was associated with increased risk of metastasis (P=0.006) with marginal evidence of association with death from any cause (P=0.07). Conclusions: This single-institution retrospective analysis shows that it is not uncommon to have undetectable PSA 12 or 24 months after a short course of ADT. Additional analysis is needed to demonstrate the clinical value of this measure as a surrogate for prostate cancer outcomes and for consideration as a trial endpoint.

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 risk of death from prostate cancer in men with Gleason Score 3+4 prostate cancer treated using brachytherapy with or without a short course of androgen deprivation therapy.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 330-330
Author(s):  
David Dewei Yang ◽  
Ming-Hui Chen ◽  
Michelle H. Braccioforte ◽  
Brian Joseph Moran ◽  
Anthony Victor D'Amico
Keyword(s):  
Prostate Cancer ◽  
Androgen Deprivation Therapy ◽  
Gleason Score ◽  
Specific Antigen ◽  
Androgen Deprivation ◽  
Risk Of Death ◽  
Short Course ◽  
Increased Risk ◽  
Adenocarcinoma Of The Prostate ◽  
Biopsy Gleason Score

330 Background: We evaluated whether the intermediate-risk factors of percentage of positive biopsies (PPB), clinical tumor category, and prostate-specific antigen (PSA) level, in addition to age, were associated with the risk of prostate cancer-specific mortality (PCSM) among men with Gleason 3+4 prostate cancer treated with brachytherapy (BT) alone or BT and a short course of androgen deprivation therapy (ADT). Methods: We conducted a prospective cohort study of 1920 consecutively treated men with Gleason 3+4 adenocarcinoma of the prostate who received BT or BT and a median of 4 months of ADT between 10/14/1997 and 5/28/2013. Separate multivariable Fine and Gray competing risks regression models among men treated with BT or BT and ADT were used to assess whether PPB, cT2b-T2c, and PSA of 10.1-20.0 ng/ml, in addition to age greater than the median of 70 years, were associated with the risk of PCSM after adjustment for comorbidity. Results: After a median follow-up of 7.8 years (interquartile range 5.2-10.4 years), 284 men (14.8%) had died, including 31 (10.9% of deaths) from PC of which 18 (58.1%) and 13 (41.9%) occurred in men treated with BT or BT and ADT, respectively. For men treated with BT alone, increasing PPB, PSA of 10.1-20.0 vs 4.0-10.0 ng/mL, and age >70 vs ≤70 years were significantly associated with an increased risk of PCSM (adjusted hazard ratio [AHR] 1.015 95% confidence interval [CI] 1.000-1.031, P=0.048; AHR 5.55, 95% CI 2.01-15.29, P<0.001; and AHR 3.66, 95% CI 1.16-11.56, P=0.03, respectively). The respective results for men treated with BT and ADT were AHR 1.009, 95% CI 0.987-1.031, P=0.44; AHR 4.17, 95% CI 1.29-13.50, P=0.02; and AHR 3.74, 95% CI 0.87-16.05, P=0.08. The clinical tumor category was not significantly associated with the risk of PCSM. Conclusions: Among men with biopsy Gleason score 3+4 PC, both age >70 years and PSA of 10.1-20.0 ng/ml were significantly associated with an increased risk of PCSM following BT, and adding 4 months of ADT may not be sufficient to mitigate this risk. Advanced imaging and targeted biopsy of suspicious areas should be considered to personalize treatment in order to minimize the risk of PCSM in these men.

scholarly journals Obesity and the Odds of Weight Gain following Androgen Deprivation Therapy for Prostate Cancer

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Lior Z. Braunstein ◽  
Ming-Hui Chen ◽  
Marian Loffredo ◽  
Philip W. Kantoff ◽  
Anthony V. D'Amico
Keyword(s):  
Prostate Cancer ◽  
Weight Gain ◽  
Androgen Deprivation Therapy ◽  
Cancer Control ◽  
Androgen Deprivation ◽  
Study Cohort ◽  
Survival Difference ◽  
Risk Of Mortality ◽  
Increased Risk ◽  
Baseline Bmi

Background. Increasing body mass index (BMI) is associated with increased risk of mortality; however, quantifying weight gain in men undergoing androgen deprivation therapy (ADT) for prostate cancer (PC) remains unexplored.Methods. Between 1995 and 2001, 206 men were enrolled in a randomized trial evaluating the survival difference of adding 6 months of ADT to radiation therapy (RT). BMI measurements were available in 171 men comprising the study cohort. The primary endpoint was weight gain of ≥10 lbs by 6-month followup. Logistic regression analysis was performed to assess whether baseline BMI or treatment received was associated with this endpoint adjusting for known prognostic factors.Results. By the 6-month followup, 12 men gained ≥10 lbs, of which 10 (83%) received RT + ADT and, of these, 7 (70%) were obese at randomization. Men treated with RT as compared to RT + ADT were less likely to gain ≥10 lbs (adjusted odds ratio (AOR): 0.18 [95% CI: 0.04–0.89];P=0.04), whereas this risk increased with increasing BMI (AOR: 1.15 [95% CI: 1.01–1.31];P=0.04).Conclusions. Consideration should be given to avoid ADT in obese men with low- or favorable-intermediate risk PC where improved cancer control has not been observed, but shortened life expectancy from weight gain is expected.

scholarly journals Early Detection of Neuroendocrine Prostate Cancer as Lineage Plasticity in Recurrent Prostate Cancer After Radiation and Androgen Deprivation Therapy: A Case Report

2020 ◽  
Author(s):  
Takahiro Komori ◽  
Takeo Kosaka ◽  
Keitaro Watanabe ◽  
Yota Yasumizu ◽  
Shuji Mikami ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Deprivation Therapy ◽  
Cancer Detection ◽  
External Beam Radiotherapy ◽  
Specific Antigen ◽  
Androgen Deprivation ◽  
Resonance Imaging ◽  
Prostate Cancer Detection ◽  
Neuroendocrine Prostate Cancer ◽  
Salvage Androgen Deprivation Therapy

Abstract Background: Neuroendocrine prostate cancer is one of the most aggressive prostate cancers, with severely poor prognosis. However, its detection is difficult because no useful marker has been found so far. In addition, serum prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA), and PSMA positron emission tomography/computed tomography don’t help in neuroendocrine prostate cancer. However, its early detection is necessary because its prognosis is poor.Case presentation: We described three cases of early neuroendocrine prostate cancer detection after initial external beam radiotherapy followed by salvage androgen deprivation therapy (ADT). We used Magnetic Resonance Imaging for three ADT-resistant patients, and it detected neuroendocrine prostate cancer in all three, although the PSA level was <2 ng/mL.Conclusions: Magnetic resonance imaging might be a better modality for neuroendocrine prostate cancer detection despite low serum prostate-specific-antigen levels.. Our findings in these three cases will help establish better criteria or better follow-up for patients administered salvage androgen deprivation therapy for biochemical recurrence of prostate cancer after external beam radiotherapy.

scholarly journals PSA Nadir and Time to PSA Nadir Following Androgen Deprivation Therapy are the Predictors for Castration-Resistant Prostate Cancer in Patients with Metastatic Prostate Cancer

2021 ◽  
Vol 1 (1) ◽  
Author(s):  
Patranuch Noppakulsatit
Keyword(s):  
Prostate Cancer ◽  
Disease Progression ◽  
Androgen Deprivation Therapy ◽  
Specific Antigen ◽  
Androgen Deprivation ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Hormone Sensitive ◽  
Psa Nadir

Purpose: To evaluate the influence of nadir prostate-specific antigen (PSA) level and time to PSA nadir following androgen deprivation therapy (ADT)on disease progression of castration-resistant prostate cancer (CRPC) in patients with metastatic, hormone-sensitive prostate cancer (mHSPC). Patients and methods: A total of 90 patients with metastatic, hormone-sensitive prostate cancer treated with androgen deprivation therapy in our hospital were included in our retrospective study. Patients’ characteristics, PSA at PADT initiation (initial PSA), PSA nadir, TTN, follow up time, CRPC event were analyzed using Kaplan-Meier analysis and Cox regression model. Results: At a median follow-up of 12 months, 57 patients (63.3%) showed disease progression of CRPC Both PSA nadir and time to PSA nadir (TTN) was independent and significant predictors of CRPC event. Patients with higher PSA nadir (≥0.2ng/dL) and shorter time to PSA nadir (TTN <6 months) had significant shorter time to CRPC. Meanwhile, the Gleason score, age and initial PSA werenot significant predictors of disease progression. In the combined analyses showed patients with higher of PSA nadir and shorter TTN had significantly higher risk for CRPC event compared to lower PSA nadir and longer TTN (HR 69.243, p-value< 0.001) Conclusion: We concluded that both higher PSA nadir and shorter time to PSA nadir are significant predictors of CRPC in patients with metastatic, hormone-sensitive prostate cancer receiving ADT.

Impact of Hypertension on Early Renal Dysfunction in Japanese Prostate Cancer Patients Treated With Androgen Deprivation Therapy

2021 ◽  
Vol 1 (3) ◽  
pp. 179-183
Author(s):  
HIROSHI MASUDA ◽  
MASAHIRO SUGIURA ◽  
KYOKUSIN HOU ◽  
KAZUHIRO ARAKI ◽  
SATOKO KOJIMA ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Renal Function ◽  
Renal Dysfunction ◽  
Cancer Patients ◽  
Androgen Deprivation Therapy ◽  
Salt Intake ◽  
Specific Antigen ◽  
Androgen Deprivation ◽  
Rate Of Change ◽  
Increased Risk

Background/Aim: Recently, it was reported that the use of androgen deprivation therapy (ADT) is significantly associated with an increased risk of acute kidney injury (AKI) in patients with newly diagnosed non-metastatic prostate cancer. This study aimed to investigate the incidence of early renal dysfunction in Japanese prostate cancer patients receiving ADT and the factors associated with it. Patients and Methods: A total of 135 patients who had been pathologically diagnosed with prostate cancer and had received ADT for at least 6 months were eligible for study inclusion. The estimated glomerular filtration rate (eGFR) before treatment, and at 1, 3, and 6 months of ADT were evaluated retrospectively. We assessed renal function using eGFR and investigated the rate of change in the eGFR (ΔeGFR) during ADT. Univariate and multivariate logistic analyses were carried out to identify clinical factors that were significantly associated with renal dysfunction after 6 months ADT. Results: A total of 110 cases were evaluated in this study. The incidence of renal dysfunction after 6 months ADT was 63% (69/110). The mean ΔeGFR after 1, 3, and 6 months of ADT were –0.6%, –3.1% and –1.7%, respectively (p<0.001). Multivariate analysis showed that renal dysfunction after 3 months of ADT and hypertension were independent risk factors for renal dysfunction after 6 months ADT. Conclusion: Renal dysfunction occurs from 1 month of ADT and hypertensive prostate cancer patients receiving ADT are at high risk of developing renal dysfunction, and that such patients should be treated very carefully. Therefore, patients that are started on ADT should undergo periodic prostate-specific antigen, renal function, and urinary salt intake examinations.

scholarly journals Final Report of the Intergroup Randomized Study of Combined Androgen-Deprivation Therapy Plus Radiotherapy Versus Androgen-Deprivation Therapy Alone in Locally Advanced Prostate Cancer

2015 ◽  
Vol 33 (19) ◽  
pp. 2143-2150 ◽  
Author(s):  
Malcolm D. Mason ◽  
Wendy R. Parulekar ◽  
Matthew R. Sydes ◽  
Michael Brundage ◽  
Peter Kirkbride ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Androgen Deprivation Therapy ◽  
Advanced Prostate Cancer ◽  
Locally Advanced ◽  
Specific Antigen ◽  
Androgen Deprivation ◽  
Final Report ◽  
Locally Advanced Prostate Cancer

Purpose We have previously reported that radiotherapy (RT) added to androgen-deprivation therapy (ADT) improves survival in men with locally advanced prostate cancer. Here, we report the prespecified final analysis of this randomized trial. Patients and Methods NCIC Clinical Trials Group PR.3/Medical Research Council PR07/Intergroup T94-0110 was a randomized controlled trial of patients with locally advanced prostate cancer. Patients with T3-4, N0/Nx, M0 prostate cancer or T1-2 disease with either prostate-specific antigen (PSA) of more than 40 μg/L or PSA of 20 to 40 μg/L plus Gleason score of 8 to 10 were randomly assigned to lifelong ADT alone or to ADT+RT. The RT dose was 64 to 69 Gy in 35 to 39 fractions to the prostate and pelvis or prostate alone. Overall survival was compared using a log-rank test stratified for prespecified variables. Results One thousand two hundred five patients were randomly assigned between 1995 and 2005, 602 to ADT alone and 603 to ADT+RT. At a median follow-up time of 8 years, 465 patients had died, including 199 patients from prostate cancer. Overall survival was significantly improved in the patients allocated to ADT+RT (hazard ratio [HR], 0.70; 95% CI, 0.57 to 0.85; P < .001). Deaths from prostate cancer were significantly reduced by the addition of RT to ADT (HR, 0.46; 95% CI, 0.34 to 0.61; P < .001). Patients on ADT+RT reported a higher frequency of adverse events related to bowel toxicity, but only two of 589 patients had grade 3 or greater diarrhea at 24 months after RT. Conclusion This analysis demonstrates that the previously reported benefit in survival is maintained at a median follow-up of 8 years and firmly establishes the role of RT in the treatment of men with locally advanced prostate cancer.

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