Short-term Androgen Deprivation Research Articles

OC-0522: 3D-CRT/IMRT with/without short term androgen deprivation in localized T1b-cT2aN0M0 prostate cancer (EORTC 22991)

OC-0522: 3D-CRT/IMRT with/without short term androgen deprivation in localized T1b-cT2aN0M0 prostate cancer (EORTC 22991)

Unrecognized Kinetics of Serum Testosterone: Impact on Short-Term Androgen Deprivation Therapy for Prostate Cancer

PurposeTo evaluate the kinetics of serum testosterone (T) recovery following short-term androgen deprivation therapy (ADT), as the understanding thereof is essential for the proper management of prostate cancer (PCa), especially intermittent ADT.Materials and MethodsThis prospective analysis included male sex offenders who voluntarily received leuprolide acetate in order to alleviate sexual aberrance. Thirty-three and 25 patients who received 3 and 6 months of ADT were assigned to Group A and Group B, respectively. Serum T levels were obtained every week during the on-cycle period, then monthly during the off-cycle period for at least 12 months.ResultsThe kinetics of serum T during the on-cycle period were similar in both groups. After flare reaction at week 2, a nadir of 0.45±0.29 ng/mL was achieved. In Group A, an abrupt rebound-upsurge was observed during the first 2 month off-cycle period, which surpassed the baseline level and reached a plateau level of 8.74±2.11 ng/mL during the flare (p<0.001). This upsurge was followed by a gradual decline back to baseline over the following 10 months. In Group B, a gradual increase was observed, and a baseline level of 7.26±1.73 ng/mL was reached at 5 months. Thereafter, an ongoing upsurge that surpassed baseline levels was observed until 12 months (8.81±1.92 ng/mL; p=0.002).ConclusionThe kinetics of serum T recovery during the off-cycle period varied according to the duration of ADT. Serum T should be monitored beyond normalization, as an excessive rebound may improve quality-of-life, but hamper the treatment efficacy of PCa.

Secondary chemoprevention of localized prostate cancer by short-term androgen deprivation to select indolent tumors suitable for active surveillance: a prospective pilot phase II study

To investigate the impact of 3-month androgen deprivation therapy (st-ADT) a secondary chemoprevention of indolent-localized prostate cancer (PCa). A prospective phase II study enrolled men over 4 years with low-risk PCa and the following characteristics: PSA < 10 ng/mL, Gleason score of 6 (3 + 3) or less, three positive cores or less, and tumor stage T2a or less. Patients received a single sub-cutaneous injection of 22.5 mg of leuprolide acetate with Atrigel 3-month depot associated with a daily oral intake of bicalutamide 50 mg/day during 15 days around the injection. Follow-up included PSA and bioavailable testosterone blood tests every 3 months and yearly surveillance biopsies. Primary end point was the presence of PCa on biopsy at last follow-up. Secondary end points were detailed pathological features and adverse events. Overall, 98 men were included and 45 of them (45.9 %) had a negative biopsy after a median follow-up of 13 months [11-19.5]. Of the 53 patients with positive biopsy, 17 had pathologic progression because of upgraded Gleason score (11 patients), four or more positive cores (three patients) or both (three patients). The only significant predictive factor biopsy outcome was the number of positive cores at diagnosis. Secondary chemoprevention by st-ADT for localized PCa could be useful to pinpoint indolent tumors suitable for AS. Indeed, after st-ADT nearly one patient out of two had negative biopsies and 17 % had pathological progression. This is an innovative option to consider as an alternative to current AS protocols contingent upon confirmation in subsequent studies.

Short-term Androgen Deprivation Therapy Does Not Cause Long-term Testosterone Suppression or Increased Acute Side Effects in Patients Treated With Brachytherapy for Prostate Cancer

Short-term Androgen Deprivation Therapy Does Not Cause Long-term Testosterone Suppression or Increased Acute Side Effects in Patients Treated With Brachytherapy for Prostate Cancer

Ki-67 Is an Independent Predictor of Metastasis and Cause-Specific Mortality for Prostate Cancer Patients Treated on Radiation Therapy Oncology Group (RTOG) 94-08

The association of Ki-67 staining index (Ki67-SI) with overall survival (OS), disease-specific mortality (DSM), distant metastasis (DM), and biochemical failure (BF) was examined in men with favorable- to intermediate-risk prostate cancer receiving radiation therapy (RT) alone or with short-term androgen deprivation (ADT) in Radiation Therapy Oncology Group (RTOG) 94-08. 468 patients (23.6%) on RTOG 94-08 had sufficient tissue for Ki67-SI analysis. The median follow-up time was 7.9 years. Ki67-SI was determined by immunohistochemistry and quantified manually and by image analysis. Correlative analysis versus clinical outcome was performed using the third quartile (≥Q3) cutpoint. A proportional hazards multivariable analysis (MVA) dichotomized covariates in accordance with trial stratification and randomization criteria. In MVAs adjusted for all treatment covariates, high Ki67-SI (≥Q3) was correlated with increased DSM (hazard ratio [HR] 2.48, P=.03), DM (HR 3.5, P=.002), and BF (HR 3.55, P<.0001). MVA revealed similar Ki67-associated hazard ratios in each separate treatment arm for DSM, DM, and BF; these reached significance only for DM in the RT-alone arm and for BF in both arms. Ki67-SI was not a significant predictor of intraprostatic recurrence assessed by repeated biopsy 2 years after treatment. Patients with a high or low Ki67-SI seemed to experience a similar relative benefit from the addition of ADT to radiation. High Ki67-SI independently predicts for increased DSM, DM, and protocol BF in primarily intermediate-risk prostate cancer patients treated with RT with or without ADT on RTOG 94-08 but does not predict for local recurrence or for increased relative benefit from ADT. This and prior studies lend support for the use of Ki67-SI as a stratification factor in future trials.

Short-term Androgen Deprivation Decreases Distant Metastasis and Prostate Cancer-specific Mortality in Intermediate-risk Prostate Cancer Patients Undergoing Dose Escalated External Beam Radiation Therapy

Short-term Androgen Deprivation Decreases Distant Metastasis and Prostate Cancer-specific Mortality in Intermediate-risk Prostate Cancer Patients Undergoing Dose Escalated External Beam Radiation Therapy

Short-term Androgen-Deprivation Therapy Improves Prostate Cancer-Specific Mortality in Intermediate-Risk Prostate Cancer Patients Undergoing Dose-Escalated External Beam Radiation Therapy

We investigated the benefit of short-term androgen-deprivation therapy (ADT) in patients with intermediate-risk prostate cancer (PC) receiving dose-escalated external beam radiation therapy. The present retrospective study comprised 710 intermediate-risk PC patients receiving external beam radiation therapy with doses of ≥81 Gy at a single institution from 1992 to 2005, including 357 patients receiving neoadjuvant and concurrent ADT. Prostate-specific antigen recurrence-free survival (PSA-RFS) and distant metastasis (DM) were compared using the Kaplan-Meier method and Cox proportional hazards models. PC-specific mortality (PCSM) was assessed using competing-risks analysis. The median follow-up was 7.9 years. Despite being more likely to have higher PSA levels, Gleason score 4 + 3 = 7, multiple National Comprehensive Cancer Network intermediate-risk factors, and older age (P≤.001 for all comparisons), patients receiving ADT had improved PSA-RFS (hazard ratio [HR], 0.598; 95% confidence interval [CI], 0.435-0.841; P=.003), DM (HR, 0.424; 95% CI, 0.219-0.819; P=.011), and PCSM (HR, 0.380; 95% CI, 0.157-0.921; P=.032) on univariate analysis. Using multivariate analysis, ADT was an even stronger predictor of improved PSA-RFS (adjusted HR [AHR], 0.516; 95% CI, 0.360-0.739; P<.001), DM (AHR, 0.347; 95% CI, 0.176-0.685; P=.002), and PCSM (AHR, 0.297; 95% CI, 0.128-0.685; P=.004). Gleason score 4 + 3 = 7 and ≥50% positive biopsy cores were other independent predictors of PCSM. Short-term ADT improves PSA-RFS, DM, and PCSM in patients with intermediate-risk PC undergoing dose-escalated external beam radiation therapy.

Addition of short-term androgen deprivation therapy to dose-escalated radiation therapy improves failure-free survival for select men with intermediate-risk prostate cancer

Dose-escalated (DE) radiation therapy (RT) and androgen deprivation therapy (ADT) improve prostate cancer outcomes over standard-dose RT. The benefit of adding ADT to DE-RT for men with intermediate-risk prostate cancer (IR-PrCa) is uncertain. We identified 636 men treated for IR-PrCa with DE-RT (>75Gy). The adult comorbidity evaluation-27 index classifed comorbidity. Kaplan-Meier and log-rank tests compared failure-free survival (FFS) with and without ADT. Forty-five percent received DE-RT and 55% DE-RT with ADT (median 6 months). On Cox proportional hazard regression that adjusted for comorbidity and tumor characteristics, ADT improved FFS (adjusted hazard ratio 0.36; P = 0.004). Recursive partitioning analysis of men without ADT classified Gleason 4 + 3 = 7 or ≥50% positive cores as unfavorable disease. The addition of ADT to DE-RT improved 5-year FFS for men with unfavorable disease (81.6% versus 92.9%; P = 0.009) but did not improve FFS for men with favorable disease (96.3% versus 97.4%; P = 0.874). When stratified by comorbidity, ADT improved FFS for men with unfavorable disease and no or mild comorbidity (P = 0.006) but did not improve FFS for men with unfavorable disease and moderate or severe comorbidity (P = 0.380). The addition of ADT to DE-RT improves FFS for men with unfavorable IR-PrCa, especially those with no or minimal comorbidity.

Association hormonothérapie et radiothérapie dans le cancer de prostate localement avancé

Combination of radiotherapy and androgen deprivation is now considered as the standard of care for patients with a localized prostate cancer but poor prognostic factors. Two groups of randomized trials have led to this recommendation. Some have compared radiotherapy alone versus hormonal treatment and radiotherapy: these trials demonstrated, now with a long follow-up, an improvement in 10-year survival for the combined treatment. Three recent trials compared androgen deprivation alone or combined with radiotherapy; a benefit in survival was also demonstrated in favour of the combination. Some questions remained concerning the optimal duration of hormonal treatment, in view of its potential side effects. Patients in the intermediate prognostic groups could receive a short-term androgen deprivation, but those with a high Gleason score must be treated with a long-term hormonal treatment. Modalities of radiotherapy, regarding volumes and dose must also be precised in the next years.

Short-term androgen deprivation therapy for patients with intermediate-risk prostate cancer undergoing dose-escalated radiotherapy: the standard of care?

What is the best way to manage patients with intermediate-risk prostate cancer? One of the most controversial aspects of treatment is the role of short-term androgen deprivation therapy in combination with definitive radiotherapy. In two randomised trials of patients with mostly intermediate-risk prostate cancer, increased overall survival was reported when short-term androgen deprivation therapy was added to radiotherapy. However, radiation doses in these studies were far below the current standard of care. This limitation, in combination with the heterogeneous nature of the cancers classified as intermediate risk, has complicated the application of these trial results to modern clinical practice. In this Review, we discuss clinical evidence for and against use of short-term androgen deprivation therapy with dose-escalated radiotherapy for patients with intermediate-risk prostate cancer.

Cardiovascular mortality following short-term androgen deprivation in clinically localized prostate cancer: An analysis of RTOG 94-08.

18 Background: Androgen deprivation therapy (ADT) is associated with greater risk of diabetes and coronary heart disease in men with prostate cancer but there is significant controversy surrounding its potential impact on cardiovascular mortality especially among men with lower rates of cancer-specific death. We assessed the relationship between ADT and mortality in a large randomized trial of men treated with or without short-course ADT and radiation therapy (RT) for clinically-localized prostate cancer. Methods: Between 1994-2001, 1979 eligible men (median age 71) with clinically-localized (T1-2, PSA&lt;20) prostate cancer were enrolled on a phase III trial (RTOG 94-08) and randomized to RT and 4 months of neoadjuvant/concurrent ADT or RT alone. Fine-Gray proportional hazards model was used to evaluate the relationship between treatment arm and mortality (disease-specific and cardiovascular). Covariates included PSA, Gleason score, T-stage, age, race, weight, prevalent cardiovascular disease (CVD), diabetes (DM), and hypertension. Results: After a median follow-up of 8.2 years, use of ADT improved overall and disease-specific survival but there was no ADT-related increase in cardiovascular mortality or non-prostate cancer death. There were a total of 191 cardiovascular-related deaths. At 10-years, cardiovascular mortality for men treated with RT+ADT was 9.8% vs 10.7% for men treated with RT alone. In multivariate analyses, treatment arm was not significantly associated with an increased risk of cardiovascular mortality [adjusted hazard ratio (HR)=0.93, 95% confidence interval (CI) 0.69-1.26, p=0.64]. Traditional cardiac risk factors, including prevalent CVD and DM, were significantly associated with greater cardiovascular mortality. Results were similar when limiting analyses to patient subsets at high risk for cardiovascular mortality and at low risk for disease-specific mortality. Conclusions: Use of short-course ADT improves overall and disease-specific survival but does not appear to increase cardiovascular mortality in men with clinically-localized prostate cancer. Supported by RTOG grant U10 CA21661 and CCOP grant U10 CA37422 from NCI.

Effect of adding short-term androgen deprivation therapy to dose-escalated radiation therapy on failure-free survival for select men with intermediate-risk prostate cancer.

176 Background: Independently, dose-escalated external beam radiation therapy (DE-EBRT) and short-term androgen deprivation therapy (ADT) improve outcomes for men with intermediate-risk prostate cancer; however, the incremental benefit of adding short-term ADT to DE-EBRT is uncertain. The aim of this study was to determine the effect of adding ADT to DE-EBRT and to identify men most likely to benefit from ADT. Methods: We reviewed the medical records of 636 men treated for intermediate-risk prostate cancer with DE-EBRT (&gt;75 Gy) from 1995 to 2009. The adult comorbidity evaluation-27 index categorized severity of comorbidity. Recursive partitioning analysis defined unfavorable disease. Kaplan-Meier and log-rank tests compared failure-free survival (FFS) with and without ADT. Results: Median age was 70 years (interquartile range [IQR] 65–74). Overall, 45% received DE-EBRT alone and 55% DE-EBRT with ADT (median 6 months, IQR 6-8). Median follow up was 4.3 years. On Cox-proportional hazard regression analysis that adjusted for differences in comorbidities and tumor characteristics, administration of ADT improved FFS (adjusted hazard ratio 0.36, 95% confidence interval 0.18–0.72; p=0.004). Recursive partitioning analysis of men without ADT classified Gleason 4+3=7 or ≥ 50% positive cores as unfavorable disease (5-year FFS 96.3% favorable vs. 81.6% unfavorable; p&lt;0.001). The addition of ADT to DE-EBRT improved 5-year FFS for men with unfavorable disease (n=334; 81.6% vs. 92.9%; p=0.009) but did not improve FFS for men with favorable disease (n=302; 96.3% vs. 97.4%; p=0.874). When stratified by comorbidity, ADT improved FFS for men with unfavorable disease and no or mild comorbidity (p=0.006) but did not improve FFS for men with unfavorable disease and moderate to severe comorbidity (p=0.380). Conclusions: The addition of ADT to DE-EBRT improves FFS for men with unfavorable intermediate-risk prostate cancer (Gleason 4+3=7 or ≥ 50% positive cores) especially those with no or minimal comorbidity. Men with favorable intermediate-risk disease or with moderate to severe comorbidity may not benefit from the addition of ADT to DE-EBRT.

Re: Radiotherapy and Short-Term Androgen Deprivation for Localized Prostate Cancer

No AccessJournal of UrologyAdult Urology1 Mar 2012Re: Radiotherapy and Short-Term Androgen Deprivation for Localized Prostate Cancer Patrick C. WalshM.D. Patrick C. WalshPatrick C. Walsh More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.11.067AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "Re: Radiotherapy and Short-Term Androgen Deprivation for Localized Prostate Cancer." The Journal of Urology, 187(3), p. 910 Re: Radiotherapy and Short-Term Androgen Deprivation for Localized Prostate Cancer 1 : Risk-based management of prostate cancer. N Engl J Med2011; 365: 169. Google Scholar © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 3March 2012Page: 910 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Patrick C. Walsh More articles by this author Expand All Advertisement PDF downloadLoading ...

Radiotherapy and Short-Term Androgen Deprivation for Localized Prostate Cancer

Radiotherapy and Short-Term Androgen Deprivation for Localized Prostate Cancer

Phase I trial of tremelimumab in combination with short-term androgen deprivation in patients with PSA-recurrent prostate cancer

CTLA-4 blockade has demonstrated antitumor efficacy in human clinical trials. The antitumor mechanism is presumably mediated in part by the expansion of tumor-specific T cells. Androgen deprivation, the cornerstone of treatment for patients with metastatic prostate cancer, has been shown to elicit prostate tissue apoptosis and lymphocytic inflammation. We hypothesized that treatment with androgen deprivation, followed by an anti-CTLA-4 antibody, could augment a tumor-specific immune response elicited by androgen deprivation. We report here the results of a phase I trial evaluating a humanized monoclonal antibody targeting CTLA-4, CP-675,206 (tremelimumab), in combination with androgen deprivation using an antiandrogen. Eligible patients were those with PSA-recurrent prostate cancer after primary surgery and/or radiation therapy, not previously treated with androgen deprivation, and without radiographic evidence of metastatic disease. Subjects were treated in two cycles, 3 months apart, in which they received bicalutamide 150 mg daily days 1-28 and tremelimumab on day 29. The primary endpoint of the trial was safety. Secondary endpoints included measures of PSA kinetics and identification of a maximum tolerated dose. Eleven patients were enrolled and completed at least 1 year of follow-up. Dose-limiting toxicities included grade 3 diarrhea and skin rash. No favorable changes in PSA doubling time were observed in a period shortly after completing treatment; however, three patients experienced a prolongation in PSA doubling time detectable several months after completing treatment. The identification of delayed, prolonged favorable changes in serum PSA suggests that future studies could explore this combination in studies evaluating time to disease progression.

Short-Term Androgen Deprivation Therapy and Early-Stage Prostate Cancer Survival

Short-Term Androgen Deprivation Therapy and Early-Stage Prostate Cancer Survival

Adding short-term androgen-deprivation therapy to radiotherapy improved survival in localized prostate cancer

ACP Journal Club15 November 2011Adding short-term androgen-deprivation therapy to radiotherapy improved survival in localized prostate cancerSteven E. Canfield, MDSteven E. Canfield, MDUniversity of Texas Medical School at Houston, Houston, Texas, USA (S.E.C.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-155-10-201111150-02007 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationJones CU, Hunt D, McGowan DG, et al. Radiotherapy and short-term androgen deprivation for localized prostate cancer. N Engl J Med. 2011;365:107-18. https://pubmed.ncbi.nlm.nih.gov/21751904Clinical Impact RatingsGIM/FP/GP: References1 Bannuru RR, Dvorak T, Obadan N, et al. Comparative evaluation of radiation treatments for clinically localized prostate cancer: an updated systematic review. Ann Intern Med. 2011;155:171-8. [PMID: 21646550] Google Scholar2 Taylor LG, Canfield SE, Du XL. Review of major adverse effects of androgen-deprivation therapy in men with prostate cancer. Cancer. 2009;115:2388-99. [PMID: 19399748] Google Scholar Author, Article, and Disclosure InformationAffiliations: University of Texas Medical School at Houston, Houston, Texas, USA (S.E.C.)This article was published at Annals.org on 1 November 2011. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byGenomic analysis of DNA repair genes and androgen signaling in prostate cancer 15 November 2011Volume 155, Issue 10Page: JC5-7KeywordsAdenocarcinomaAndrogensCancer treatmentHormonal therapyLymph nodesProstate cancerSurvival analysis ePublished: 15 November 2011 Issue Published: 15 November 2011 Copyright & PermissionsCopyright © 2011 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...

Cardiovascular Mortality following Short-term Androgen Deprivation in Clinically Localized Prostate Cancer: An Analysis of RTOG 94-08

18 Background: Androgen deprivation therapy (ADT) is associated with greater risk of diabetes and coronary heart disease in men with prostate cancer but there is significant controversy surrounding...

Long-term vs. Short-term Androgen Deprivation Combined with High-dose Radiotherapy for Intermediate and High-risk Prostate Cancer: Preliminary Results of a GICOR Phase III Randomized Trial

Long-term vs. Short-term Androgen Deprivation Combined with High-dose Radiotherapy for Intermediate and High-risk Prostate Cancer: Preliminary Results of a GICOR Phase III Randomized Trial

Radiotherapy and Short-Term Androgen Deprivation for Localized Prostate Cancer

It is not known whether short-term androgen-deprivation therapy (ADT) before and during radiotherapy improves cancer control and overall survival among patients with early, localized prostate adenocarcinoma. From 1994 through 2001, we randomly assigned 1979 eligible patients with stage T1b, T1c, T2a, or T2b prostate adenocarcinoma and a prostate-specific antigen (PSA) level of 20 ng per milliliter or less to radiotherapy alone (992 patients) or radiotherapy with 4 months of total androgen suppression starting 2 months before radiotherapy (radiotherapy plus short-term ADT, 987 patients). The primary end point was overall survival. Secondary end points included disease-specific mortality, distant metastases, biochemical failure (an increasing level of PSA), and the rate of positive findings on repeat prostate biopsy at 2 years. The median follow-up period was 9.1 years. The 10-year rate of overall survival was 62% among patients receiving radiotherapy plus short-term ADT (the combined-therapy group), as compared with 57% among patients receiving radiotherapy alone (hazard ratio for death with radiotherapy alone, 1.17; P=0.03). The addition of short-term ADT was associated with a decrease in the 10-year disease-specific mortality from 8% to 4% (hazard ratio for radiotherapy alone, 1.87; P=0.001). Biochemical failure, distant metastases, and the rate of positive findings on repeat prostate biopsy at 2 years were significantly improved with radiotherapy plus short-term ADT. Acute and late radiation-induced toxic effects were similar in the two groups. The incidence of grade 3 or higher hormone-related toxic effects was less than 5%. Reanalysis according to risk showed reductions in overall and disease-specific mortality primarily among intermediate-risk patients, with no significant reductions among low-risk patients. Among patients with stage T1b, T1c, T2a, or T2b prostate adenocarcinoma and a PSA level of 20 ng per milliliter or less, the use of short-term ADT for 4 months before and during radiotherapy was associated with significantly decreased disease-specific mortality and increased overall survival. According to post hoc risk analysis, the benefit was mainly seen in intermediate-risk, but not low-risk, men. (Funded by the National Cancer Institute; RTOG 94-08 ClinicalTrials.gov number, NCT00002597.).