Case Western Reserve University School of Medicine, Cleveland, OH
Shree Agrawal , Jason A. Efstathiou , Jeff M. Michalski , Thomas Michael Pisansky , Bridget F. Koontz , Stanley L. Liauw , Matthew Abramowitz , Alan Pollack , Mitchell Steven Anscher , Drew Moghanaki , Robert B. Den , Anthony L. Zietman , W. Robert Lee , Kevin L. Stephans , Jason W.D. Hearn , Daniel Eidelberg Spratt , Tianming Gao , Michael W. Kattan , Andrew J. Stephenson , Rahul D. Tendulkar
Background: Early salvage radiation therapy (SRT) following radical prostatectomy (RP) has been shown to reduce biochemical recurrence and distant metastases. We aim to identify factors predictive of prostate cancer-specific mortality (PCSM) and all-cause mortality (ACM) from a consortium database from 10 academic institutions. Methods: 2,454 node-negative patients (pts) with detectable post-prostatectomy PSA ( ≥ 0.01 ng/mL) treated with SRT ± neoadjuvant/concurrent androgen deprivation therapy (N/C ADT) were included. Cumulative incidence and Kaplan-Meier methods were used to estimate rates of PCSM and ACM, respectively. Univariate and multivariable analyses (MVA) were performed by competing risks regression and Cox proportional hazards methods for PCSM and ACM. Results: Median follow-up was 5 years from SRT completion and 8 years from date of RP; 24% had pathologic Gleason score (GS) of ≤ 6, 56% GS 7, and 19% GS ≥ 8; 56% extraprostatic extension (EPE), 18% seminal vesicle invasion (SVI), 58% positive surgical margins, and 16% received N/C ADT. Median age at RP and SRT were 62 years (IQR 56-66) and 64 years (59-69), respectively. Median SRT dose was 66 Gy (IQR 65-68) and median pre-SRT PSA was 0.5 ng/mL (IQR 0.3-1.1). MVA performed from SRT completion date demonstrated higher pre-SRT PSA (HR = 2.1), higher GS (GS 7 vs. ≤ 6: HR 2.0; GS ≥ 8 vs. 6: HR 3.3) , SVI (HR 2.5), year of SRT (2000-2004, 1995-1999, 1985-1994 vs. 2005-2012; HR 2.9, HR 2.5, HR 3.6, respectively) were significantly associated with higher PCSM. These same variables were all significantly associated with higher PCSM and ACM rates calculated from both SRT completion date and date of RP. Conclusions: Initiation of early SRT at lower post-operative PSA levels following RP is associated with reduced risk of PCSM and ACM, even when calculated from RP date to account for lead time bias. Other factors significantly associated with PCSM include higher GS, SVI, and earlier year of SRT.
Pre-SRT PSA, ng/ml | From SRT Completion | From Date of RP | ||
---|---|---|---|---|
10 year PCSM | 10 year ACM | 10 year PCSM | 10 year ACM | |
≤ 0.2 | 5% | 14% | 3% | 9% |
0.21 – 0.50 | 6% | 16% | 3% | 8% |
0.51 – 1.00 | 8% | 23% | 5% | 11% |
1.01 – 2.00 | 18% | 30% | 10% | 17% |
> 2.00 | 22% | 38% | 12% | 18% |
P-value | < 0.0001 | < 0.0001 | < 0.0001 | < 0.0001 |
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