(UroToday.com) The 2025 American Society of Clinical Oncology (ASCO) Genitourinary (GU) Annual Symposium held in San Francisco, CA between February 13–15, 2025 was host to a prostate cancer poster session. Dr. Alan Pollack presented a study of the Decipher® score as a predictor of response to treatment intensification in the NRG Oncology-RTOG 0534 (SPPORT) phase III randomized post-prostatectomy salvage radiotherapy trial.
The three-arm randomized SPPORT trial evaluated treatment intensification in men (n=1,792) undergoing salvage radiotherapy (RT) for biochemical recurrence following a radical prostatectomy. The trial compared prostate bed RT (PBRT) alone (Arm 1) to PBRT with short-term androgen deprivation therapy (STADT) (Arm 2) and PBRT + STADT + pelvic lymph node RT (PLNRT) (Arm 3).
While treatment intensification in Arms 2 and 3 led to significant improvements in freedom from progression (FFP), metastasis-free survival (MFS) was not significantly improved at a median follow-up of ~8 years despite fewer metastatic events. Decipher score (DS) is strongly prognostic for metastasis and was hypothesized to be independently significant of clinical-pathologic covariates in predicting the need for treatment intensification. The main objective was to determine if gene expression estimates of metastatic risk using Decipher score result in significant interactions with treatment, especially for PLNRT.
Prospectively collected prostatectomy tissue from 916 patients was used for RNA extraction and DS generation (Veracyte, San Diego, CA). A total of 709 patients (median follow-up: 7.9 years) had available DS (median 0.61; IQR: 0.45-0.79), with 215 in Arm 1, 247 in Arm 2, and 247 in Arm 3. The primary FFP endpoint included biochemical failure (nadir+2 ng/mL), clinical failure, or death from any cause. MFS included distant metastasis or death from any cause. Multivariable Cox models were adjusted for key clinicopathologic variables, including Gleason score, margin status, pT-stage, pre-RT PSA, age, and race.
A total of 226 FFP and 136 MFS events were observed. DS (per 0.1-unit increase) was prognostic for FFP (HR 1.10, 95% CI 1.03-1.17, p=0.007) and borderline significant for MFS (HR 1.08, 95% CI 0.99-1.18, p=0.08).
No significant DS-related benefit was observed from adding STADT to PBRT. However, patients with high DS (>0.60) derived greater benefit from PLNRT + STADT compared to those with lower DS (≤0.60). Specifically, the addition of PLNRT + STADT to PBRT led to a hazard ratio (HR) of 0.36 (95% CI 0.25-0.54, p<0.001) in high-DS patients versus HR 0.76 (95% CI 0.46-1.26, p=0.29) in lower-DS patients, with an absolute benefit of 27% vs. 11%, respectively.
A significant treatment interaction was observed on multivariable analysis (p-int = 0.04).
For MFS, the relative benefit of adding PLNRT + STADT to PBRT ± STADT was greater in patients with high DS (HR 0.60, 95% CI 0.37-0.97, p=0.04) versus lower DS (HR 1.14, 95% CI 0.66-1.98, p=0.63), with a 10-year absolute benefit of 6% vs. 0%. A borderline significant treatment interaction was noted for MFS (p-int = 0.06).
Dr. Pollack concluded that the SPPORT trial’s intensification study design facilitated the discovery that high metastatic risk, as assessed by DS, may be mitigated by PLNRT, suggesting that lymph node micrometastases contribute significantly to metastasis in some patients. DS emerged as a key predictor of benefit from PLNRT, reinforcing its potential role in guiding treatment intensification strategies in salvage radiotherapy.
Presented by: Alan Pollack, MD, PhD, Professor and Chair Emeritus of the Department of Radiation Oncology, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL
Written by: Rashid K. Sayyid, MD, MSc – Robotic Urologic Oncology Fellow at The University of Southern California, @rksayyid on Twitter during the 2025 Genitourinary (GU) American Society of Clinical Oncology (ASCO) Annual Meeting, San Francisco, CA, Thurs, Feb 13 – Sat, Feb 15, 2025.
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