Article
作者: Feng, Felix Y ; Mendez, Lucas C. ; Rosenthal, Seth A. ; Mendez, Lucas C ; Efstathiou, Jason A ; Hartford, Alan C ; Liu, Yang ; Feng, Felix Y. ; Patel, Krishnan R. ; Pra, Alan Dal ; Sandler, Howard M ; Davicioni, Elai ; Sandler, Howard M. ; Zeitzer, Kenneth L ; Proudfoot, James A ; Hall, William A ; Proudfoot, James A. ; Zeitzer, Kenneth L. ; Rosenthal, Seth A ; Patel, Krishnan R ; Spratt, Daniel E. ; Nguyen, Paul L. ; Hall, William A. ; Efstathiou, Jason A. ; Desai, Anand B. ; Simko, Jeffry P ; Pollack, Alan ; Spratt, Daniel E ; Simko, Jeffry P. ; Desai, Anand B ; Lawton, Colleen ; Nguyen, Paul L ; Tran, Phuoc T. ; Tran, Phuoc T ; Pugh, Stephanie L. ; Pugh, Stephanie L ; Hartford, Alan C.
BACKGROUND AND OBJECTIVE:Long-term (LT) androgen deprivation therapy (ADT) has been found to be beneficial to patients with high-risk prostate cancer (PCa). However, administration of LT-ADT to all patients with high-risk PCa may lead to overtreatment. Enhanced risk stratification using genomic classifiers (such as the recently developed prostate subtyping classifier [PSC]) might be useful. This study aims to characterize the prognostic and predictive ability of the PSC in patients with high-risk PCa undergoing radiotherapy long-term (LT; 24-28 mo) versus short-term (ST; 4 mo) ADT.
METHODS:Biopsy samples from three randomized, phase 3 trials-NRG/RTOG 9202, 9413, and 9902-were classified as either PSC basal or luminal. The prognostic and predictive values of PSC for each oncologic endpoint (biochemical failure [BF], distant metastasis [DM], metastasis-free survival [MFS], PCa-specific mortality [PCSM], overall survival [OS]) and other cause-mortality (OCM) were assessed with Cox proportional hazards (MFS, OCM, and OS), Fine-Gray (BF, DM, and PCSM), and restricted mean survival time (RMST) models.
KEY FINDINGS AND LIMITATIONS:On a multivariable analysis, the basal subtype was found to have a worse prognosis for MFS (hazard ratio [HR] 1.8 [1.3-2.5], p < 0.001), PCSM (subdistribution HR 2.4 [95% confidence interval {CI} 1.4-4.1], p = 0.001), and OS (HR 1.8 [1.3-2.6], p < 0.001). Ten-year PCSM was 15% better for the luminal subtype than for the basal subtype (11% [95% CI 6-15%] vs 26% [95% CI 17-35%]). A significant interaction between ADT duration (LT vs ST) and PSC subtype (basal vs luminal) was observed for PCSM (pinteraction = 0.008), leading to the observation that 10-yr PCSM was improved with LT-ADT only in patients with basal-type tumors (5% [95% CI 0-11%] vs 42% [29-56%], p < 0.001). Improvements in 10-yr RMST with LT-ADT were greater for basal tumors for oncologic endpoints with the exception of OCM.
CONCLUSIONS AND CLINICAL IMPLICATIONS:PSC is both a prognostic and a predictive biomarker for patients who benefit from LT-ADT. PSC subtypes may be used to personalize ADT recommendations for patients with high-risk PCa, pending further validation in a prospective study.
PATIENT SUMMARY:In this study, we tried to understand the usefulness of a new genomic test in patients with high-risk, nonmetastatic prostate cancer who underwent radiation therapy and hormonal therapy (HT). We found that this test can help determine a patient's prognosis (eg, a patient's chance of having the cancer return) and, more importantly, personalize treatment decisions by understanding which patients may benefit from long-term HT. This has the potential to save many patients who may not benefit from prolonged HT from "overtreatment" or the unnecessary side effects of such treatment.