San Francisco, CA USA (UroToday.com) Dr. Felix Feng from University of Michigan presented about the localized prostate cancer in radiation oncology literature.
Dr. Feng focused on two major themes:
1. Duration of androgen deprivation in the context of radiotherapy for intermediate or high-risk prostate cancer.
2. Long-term benefit of local therapy for high-risk disease.
Duration of ADT with RT for intermediate-risk prostate cancer was investigated in RTOG 9910 trial. The trial investigated the role of 4 months vs 9 months neoadjuvant +concurrent LHRH agonist and anti-androgen with RT. The primary end-point was disease-specific survival (DSS). The trial illustrated no difference in DSS and OS with 4 months or 9 months of ADT. Additionally, there were no significant differences in the incidence of biochemical failure, locoregional progression or distant metastasis between both arms. 9 months of ADT was associated with more short-term endocrine and sexual side effects.
Dr. Feng questions whether all intermediate-risk patients now receive 4 months of ADT rather than 9 months. He states that the duration should be individualized and risk-stratified. Not all intermediate-risk patients are same. Recent report by Zumsteg et al showed that intermediate-risk patients with greater proportion of Grade 4 component and %primary biopsy core >50% have an increased risk of prostate cancer specific mortality in men undergoing dose-escalated EBRT.
DART01/05GICOR investigated the role of ADT duration in intermediate to higher risk prostate cancer undergoing dose-escalated RT in a phase III clinical trial. The trial compared 6 month (short-term ADT) to 24 months (long-term ADT) with primary end-point being biochemical-DFS and secondary end-points of OS, CSS, and distant MFS. The trial showed an improvement in biochemical-DFS, OS, and MFS with long-term ADT. In subset analysis, high-risk patients benefited more from long-term ADT than intermediate-risk patients. Per this study, Dr. Feng again questions whether we should give long-term ADT to every high-risk patient. He answers that we should not and should rather risk-stratify those who benefit most with Long-term ADT. RTOG 92-02 in high-risk patients had shown that about 20% of patients are cured with short-term ADT, 15-20% benefited from long-term ADT, and remainder failed despite long-term ADT. Therefore, a biomarker is needed to identify those who benefit most from Long-term ADT.
Dr. Feng highlights a recent tissue-based biomarker model developed to identify those who benefit most from long-term ADT in RTOG 92-02 trial (Pollack et al). 4 biomarkers were identified that remained significant in this model—Ki67, Cox-2, p16, and MDM2. Depending on the biomarker levels, patients were then classified into quartiles—4th quartile = highest risk and 1st quartile = lowest risk. Largest benefit of long-term ADT was seen in those with highest-risk quartile. These patients had a 20% chance of dying of prostate cancer at 10 years with long-term ADT while 40% chance of dying with short-term ADT.
Dr. Feng then discussed a recent prospective randomized trial that showed a benefit of adding RT to ADT in those with high-risk prostate cancer (Mason MD et al, JCO 2015). The trial enrolled patients with T3-T4 N0M0 or T1-2 & PSA>40 or Gleason 8-10 & PSA 20-40. They were treated with life-long ADT. One arm received RT in addition to ADT while the other arm received only ADT. The primary end-point was OS and secondary end-points were DSS, time to progression, QOL, or toxicity. The trial showed that the addition of RT improved OS and DSS. There was no major long-term toxicity. The addition of RT to ADT had only a transient negative impact on QOL domains. Dr. Feng highlights that currently 25% of patients receive primary ADT nationally (JAMA 314: 1977; 2015) and efforts are needed where these patients are treated with combination of ADT and RT.
Dr. Feng concludes that ADT duration should be tailored in the context of radiation therapy for patients with intermediate to high-risk prostate cancer. Local therapy is the standard of care for patients with locally advanced high-risk disease and these patients should not be just treated with ADT.
Presented By:
Dr. Felix Feng
University of Michigan
Reported By:
Mohammed Haseebuddin, MD at the 2016 Genitourinary Cancers Symposium - January 7 - 9, 2016 – San Francisco, CA
Fox Chase Cancer Center, Philadelphia, PA