CHICAGO, IL USA (UroToday.com) - Dr. Howard Sandler of Cedars-Sinai presented the results of RTOG 0521. The study sought to improve outcomes associated with treatment of locally advanced or high-risk localized prostate cancers that traditionally have a high risk of recurrence despite the use of standard of care radiotherapy and 2-3 years of concurrent androgen deprivation therapy (ADT). The group hypothesized that using docetaxel chemotherapy immediately after treatment with radiation would improve overall survival in this population.
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Men included in the study had high-risk features at baseline and were planning to undergo radiation as primary therapy for their prostate cancer. High risk was defined as follows: any T stage with Gleason ≥ 9 and PSA < 150, any T stage with Gleason 7-8 and PSA ≥ 20 but < 150, and ≥ T2 with Gleason 8 and PSA < 20. Participants were randomized to treatment with standard of care ADT for 24 months with concurrent external beam radiation therapy for 8 weeks, with or without the addition of 6 cycles of docetaxel (75 mg/m2, plus daily prednisone) starting 4 weeks after completion of radiation.
The primary study endpoint was overall survival. Some important secondary objectives included freedom from PSA failure by Phoenix criteria or the initiation of non-protocol hormonal therapy, and disease-free survival (reached by PSA failure, local or distant failure, and death from any cause). The investigators also monitored for adverse events. A total of 612 men enrolled, and 563 were eligible for analysis due to 45 being ineligible and 4 men withdrawing consent. Included patients had predominantly Gleason ≥ 9 disease (53%), with a median age of 66, 27% with cT3-T4, and 33% having negative lymph nodes.
Over 45 months, the investigators reached target accrual. There was a median 6-year follow-up, with a 4-year overall survival of 89% among men receiving standard radiation plus ADT and 93% among men receiving standard therapy plus docetaxel chemotherapy (HR 0.70, 95% CI 0.51 – 0.98; p=0.04). There was no significant difference in biochemical failure rates between groups with a 6-year biochemical failure rate of 74% for the docetaxel arm and 66% for the standard radiation and ADT arm (HR 0.81, 95% CI 0.58 – 1.11; p= 0.19). There was a significant improvement in disease-free survival associated with the docetaxel arm, with 6-year disease-free survival of 65% with docetaxel vs 55% with standard therapy (HR 0.76, 95% CI 0.58 – 0.99; p=0.04). There was a reduction in distant metastasis at any time associated with docetaxel, with 26 events in the docetaxel arm and 41 events in the standard care arm, p=0.05. Two of 43 total deaths on study were associated with the protocol in the docetaxel arm, with no protocol-related deaths in the standard treatment arm. There were also more grade 3-4 adverse events associated with treatment with docetaxel, with 65% of adverse events being ≥ grade 3 in the docetaxel arm compared to 22% of events being grade ≥ 3 in the standard treatment arm.
The study concludes that there was an improvement in overall survival observed with the addition of 6 cycles of adjuvant docetaxel chemotherapy for men with high-risk localized or locally advanced prostate cancer as compared to standard treatment with radiation and 24 months of ADT. The authors note that this further supports the role for use of docetaxel in hormone-sensitive prostate cancer, and is consistent with studies such as CHAARTED and STAMPEDE. The authors caution that the analysis is an early one, and note that ongoing follow-up will provide further insights into the long-term outcomes. It remains to be seen whether this data will be incorporated as rapidly into treatment algorithms as the CHAARTED data was one year ago.
Presented by Howard Sandler, MD at the American Society of Clinical Oncology (ASCO) Annual Meeting - Illumination & Innovation: Transforming Data into Learning - May 29 - June 2, 2015 - Chicago, Illinois USA
Cedars-Sinai Medical Center, Los Angeles, CA USA