A phase III trial of short-term androgen deprivation therapy in intermediate-risk prostate cancer treated with radiotherapy.

5 Background: The place of short term androgen deprivation therapy (STADT) in combination with radiation therapy (RT) for patients with intermediate risk prostate cancer (IRPC) remains controversial. The purpose of this prospective, randomized trial was to compare outcomes between patients with IRPC treated with different doses of RT with or without STADT, (PCS III trial, Clinical Trials.gov, NCT00223145). Methods: From December 2000 to September 2010, 600 patients with IRPC were randomized to 6 months of STADT and two levels of prostate RT doses of 70 (arm 1) or 76 Gy (arm 2) versus prostate dose-escalated RT alone at 76 Gy (arm 3). STADT consisted of bicalutamide and gosereline for six months. RT (2 Gy per fraction) started four months after the beginning of STADT. Biochemical failure and disease-free survival (DFS) were primary end-points, with overall survival (OS) as secondary endpoint. DFS and OS rates were estimated with Kaplan-Meier and compared with log rank test and Cox regression. Results: Patient’s characteristics were well balanced among the 3 arms (median age 71 years, median PSA 10 ng/ml, median Gleason score 7). At a median follow-up of 75.4 months, biochemical failure occurred in 84 (14%) patients (arms 1 to 3: 12.5%, 8.0%, 21.5%) with statistical difference between arm 1 and 3 (p = 0.023) and arm 2 and 3 (p < 0.001). There was no significant difference between arm 1 and 2. A total of 113 (19%) patients had died with only 6 deaths (1%) attributed to prostate cancer. The 5-/10-year DFS rates were 93%, 97.5% and 86%, and 77%, 90% and 64.5%, respectively. Significant differences in DFS between the treatment arms were observed at 5 years but at 10 years it was observed only between arm 1 and 3 (p=0.01) and arm 2 and 3 (p<0.001). The 5-/10-year OS rates were 91%, 95% and 93%, and 64%, 70% and 78%, respectively. There was no statistical difference in OS between arms at 5 and 10 years. Conclusions: In patients with IRPC, the use of STADT in association with RT, even at lower doses, leads to a superior biochemical control and DFS as compared to dose-escalated RT alone. These outcomes did not translate into an improved OS. Source of Funding: AstraZeneca Pharmaceuticals Grant. Clinical trial information: NCT00223145.

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Is there a relationship between testosterone levels at the end of short-term androgen deprivation therapy and outcomes in intermediate risk prostate cancer? Prospective data from a phase III trial.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.6_suppl.78 ◽

2017 ◽

Vol 35 (6_suppl) ◽

pp. 78-78 ◽

Cited By ~ 1

Author(s):

Abdenour Nabid ◽

Marie-Pierre Garant ◽

Eric Vigneault ◽

Luis Souhami ◽

Celine Lemaire ◽

...

Keyword(s):

Prostate Cancer ◽

Androgen Deprivation Therapy ◽

Testosterone Level ◽

Cox Regression ◽

Androgen Deprivation ◽

Phase Iii ◽

Intermediate Risk ◽

Short Term ◽

Testosterone Levels ◽

Risk Prostate Cancer

78 Background: The purpose of this analysis was to assess whether the testosterone level measured at the end of short term androgen deprivation therapy (STADT) and prostate radiotherapy (RT) has an impact on treatment outcomes in patients with intermediate risk prostate cancer (IRPC) treated on a randomized trial (PCS III ClinicalTrials.gov #NCT00223145). Methods: From December 2000 to September 2010, 400 patients with IRPC received 6 months of STADT (bicalutamide 50mg die and goserelin 10.8mg x 2) and RT. Castrate level of testosterone was defined as <1.7 nmol/L: lower level <0.7 and upper level 0.7-1.7. In 347/400 patients, testosterone levels were available at the end of STADT and were divided into 3 groups based on measured testosterone levels: <0.7, 0.7 to 1.7 and >1.7 nmol/L. Patient’s characteristics were compared with ANOVA and Fisher’s exact test. Biochemical failure, prostate cancer recurrence and death were compared with Cox regression. Results: Patient’s characteristics were well balanced between the 3 groups with no statistical difference for age, performance status, PSA at start, Gleason score and stage. At the end of STADT 55.3% (192/347) presented testosterone levels <0.7 and 38.9% (135/347) levels between 0.7 and 1.7 for a total of 94.2% (327/ 347) reaching castrate levels ≤1.7 nmol/L. In 5.8% of patients (20/347) a castrate testosterone level was not achieved. With a median follow-up of 8.1 years, outcomes are shown in the table. Conclusions: In IRPC patients treated with STADT and RT, the majority of patients (94.2%) achieve a castrate level of testosterone (<1.7 nmol/L). Although we could not show a difference in outcomes between castrate and non-castrate patients, these data have to be viewed with caution given the small number of non-castrate patients studied. Source of Funding: AstraZeneca Pharmaceuticals Grant. Clinical trial information: NCT00223145. [Table: see text]

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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.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.5_suppl.176 ◽

2012 ◽

Vol 30 (5_suppl) ◽

pp. 176-176

Author(s):

Shelly Bian ◽

Deborah A. Kuban ◽

Lawrence B. Levy ◽

Jeong Hoon Oh ◽

Katherine Castle ◽

...

Keyword(s):

Prostate Cancer ◽

Radiation Therapy ◽

Androgen Deprivation Therapy ◽

Recursive Partitioning ◽

Androgen Deprivation ◽

Intermediate Risk ◽

Short Term ◽

Free Survival ◽

Risk Prostate Cancer ◽

Severe Comorbidity

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 (>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<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.

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