3271 - Metastasis-Free Survival after Adjuvant or Salvage Radiation Therapy Following Radical Prostatectomy in a National Healthcare Delivery System

S. N. Regan¹, D. J. Herr¹, D. A. Elliott², C. H. Chapman³, M. E. Caram⁴, J. Burns⁵, B. Hollenbeck⁶, J. B. Sparks⁷, C. Shin⁸, A. Zaslavsky⁹, A. Tsodikov⁸, and T. Skolarus¹⁰; ¹Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, ²Department of Radiation Oncology, Veterans Affairs Ann Arbor Health System, Ann Arbor, MI, ³Department of Radiation Oncology, Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, ⁴Division of Medical Oncology, Department of Medicine, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, MI, ⁵Veterans Administration Ann Arbor Healthcare System, Ann Arbor, MI, ⁶Massachusetts General Hospital, Boston, MA, ⁷HSR&D Center for Clinical Management Research, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, MI, ⁸University of Michigan, Ann Arbor, MI, ⁹University of Michigan, Department of Urology, Ann Arbor, MI, ¹⁰University of Chicago, Department of Surgery, Section of Urology, Chicago, IL

Purpose/Objective(s): Some men benefit from post-operative radiation after radical prostatectomy (RP) for localized prostate cancer. A recent meta-analysis indicated early salvage (SRT) was comparable to adjuvant radiation therapy (ART) primarily based on biochemical endpoints (i.e., PSA), known to be poor surrogates of survival. In addition, the optimal PSA threshold to initiate SRT remains unclear. While awaiting long-term prospective data to confirm survival endpoints for these treatments, we evaluated metastasis-free (MFS) and prostate cancer-specific survival (PCSS) after post-operative radiation in a large contemporary national cohort of men previously treated with RP. Materials/

Methods: We used Veterans Health Administration Corporate Data Warehouse and Central Cancer Registry to identify men with localized prostate cancer treated with RP from 2005 to 2016, with follow up through 2019. We identified incident metastatic disease using a validated natural language processing algorithm and cause of death with National Death Index data. We defined ART as start of radiation =1 year after RP; SRT was >1 year after RP and early SRT was considered pre-SRT PSA =0.2 ng/mL. We used Cox models to identify factors associated with MFS/PCSS, adjusting for age, year of RP, comorbidity, pT/N stage, margin status, grade group, initial post-op PSA, and ADT use. We conducted sensitivity analyses for SRT patients across pre-SRT PSA groups.

Results: Of 27,823 patients treated with RP, 2,990 received ART, 948 received early SRT, and 981 received late SRT. The ART cohort, compared to SRT, was more likely to have adverse features, including pT3b (28% vs 12%), pN1 (8% vs 3%), grade group 5 (20% vs 11%), and initial post-op PSA >0.1 ng/mL (48% vs 26%) (all p<0.05). Median PSA for early vs. late SRT was 0.07 ng/mL (IQR 0.01-0.14) vs. 0.47 ng/mL (IQR 0.30-1.00). Compared to early SRT, ART may be associated with worse MFS (adjusted HR=1.24, 95% CI 1.00-1.54, p=0.05) but not PCSS (aHR=1.23, 95% CI 0.76-1.99, p=0.40). Compared to early SRT, late SRT was associated with both worse MFS (aHR=1.73, 95% CI 1.29-1.97, p<0.001) and PCSS (aHR=2.44, 95% CI 1.48- 4.00, p<0.001). Increasing pre-SRT PSA was significantly associated with worse MFS, but only the PSA >0.6 ng/mL subgroup was associated with worse PCSS (Table).

Conclusion: For men receiving radiation therapy after RP within a national healthcare system, late SRT was associated with worse survival endpoints, possibly driven by the subset with a pre-SRT PSA >0.6 ng/mL. Early SRT and ART had similar outcomes after adjusting for adverse pathology. These findings support the use of early SRT with further work needed to define optimal PSA thresholds and kinetics to initiate treatment.

Abstract 3271 – Table 1

Pre-SRT PSA, ng/mL	MFS aHR (95% CI)	MFS p-value	PCSS aHR (95% CI)	PCSS p-value
<0.1	Ref	-	Ref	-
0.1 – 0.2	1.88 (1.27 – 2.77)	0.002	2.33 (0.96 – 5.63)	0.06
>0.2 – 0.35	1.68 (1.12 – 2.51)	0.01	2.00 (0.82 – 4.87)	0.13
>0.35 – 0.6	1.71 (1.11 – 2.64)	0.01	2.31 (0.95 – 5.65)	0.07
>0.6	4.66 (3.26 – 6.68)	<0.001	7.02 (3.35 – 14.69)	<0.001