Local prostate radiotherapy in metastatic prostate cancer and symptomatic local events.
Authors: Kwok Jaime Kirsten , Martell Kevin , Sia Michael , Bhindi Bimal , Abedin Tasnima , Lu Shuang , Quon Harvey Charles 
Published: March 2021

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Background: Local prostate radiotherapy (LPRT) is associated with improved overall survival in patients with low metastatic burden (MB) and is now standard of care. However, the role of LPRT in reducing symptomatic local events (SLE) in metastatic prostate cancer (MPC) remains unclear and requires long-term follow-up. The purpose of this study was two-fold: i) identify the risk factors associated with SLE, and ii) evaluate the association between LPRT and SLE in MPC. Methods: We conducted a retrospective, population-based cohort study of patients diagnosed with initial MPC between 2005 and 2016. Patients were identified through the Alberta Cancer Registry and patient, tumour, and treatment characteristics were collected by chart review. Data were linked to physician billing claims between 2004 and 2017 for diagnostic or therapeutic procedures potentially related to genitourinary (GU) and gastrointestinal (GI) SLE including percutaneous nephrostomy (PCN) and ureteric stent insertion (USI), cystoscopy, TURP, TURBT, colonoscopy and proctosigmoidoscopy. Both Andersen-Gill recurrent event and multivariable Cox regression time to first event analyses were conducted to evaluate the effect of LPRT on the occurrence of these procedures. Patients who underwent radical prostatectomy were excluded. LPRT was defined as 40 Gy or higher total dose to the prostate within one year of diagnosis. Patients with a SLE occurring after diagnosis but prior to LPRT were allocated to the control group. MB was defined as per STAMPEDE. Covariates for both models included MB, age at diagnosis, PSA at diagnosis, clinical T- and N-stage, and Gleason score (GS). Results: Of a total cohort of 1363 patients, 745 (54.7%) had high MB and 450 (33%) had low MB. Fifty-four (4%) received LPRT, of which 14.8% had high MB. Of those receiving LPRT, median PSA was 9.4, 79.6% had GS of 8-10, and 59.3% had T3-T4 disease. One or more SLE were observed in 43.5% and 37% of the control and LPRT groups, respectively. Among those with SLE, the median SLE frequency was 2 (interquartile range [IQR], 2-5) and 1 (IQR, 1-2.3) for the control and LPRT groups, respectively. On recurrent event analysis, LPRT was associated with lower risk of composite GU SLE (HR 0.34, 95% CI 0.17-0.67; p = 0.002), PCN and USI (HR 0.20, 95% CI 0.05-0.84; p = 0.027) and cystoscopy (HR 0.38, 95% CI 0.15-0.96; p = 0.041). Risk factors for GU SLE were T4 disease, GS of 8-10 and unknown GS. Risk factors for PCN and USI were T3, TX and N1 disease, GS of 8-10 and unknown GS. On time to first event analysis, there were no statistically significant differences for all outcomes between the control and LPRT groups. MB was not a risk factor for SLE in both analyses. Conclusions: LPRT was associated with lower risk for recurrent GU SLE, PCN and USI, and cystoscopy. The associated benefit in SLE reduction with LPRT warrants further study to determine if this effect is modified by MB and whether there may be a role for LPRT in patients with high MB.