Nonsurgical treatments for prostate cancer include traditional radiation (external beam radiotherapy and brachytherapy) and new minimally invasive therapies such as high intensity focused ultrasound, cryotherapy and electroporation. Salvage radical prostatectomy (SRP) in men with local recurrence after nonsurgical treatment has been traditionally associated with poor outcomes. Early studies with small sample sizes have reported a high degree of technical difficulty and complication rates due to post-radiation changes.^1,2 However, recent studies with modern radiation therapies (RT) and improved surgical experience have shown reasonable outcomes in select patients.³

Figure. Kaplan-Meier curves of progression-free survival by biochemical recurrence after focal therapy (FT) and radiotherapy (RT) salvage prostatectomies (n=164). Log-rank test: p=0.67.

Outcomes of salvage surgery following local recurrence after focal therapy are limited given its relative modernity. As focal therapies (FT) are designed to cause less tissue damage,⁴ the toxicity of SRP after FT could be hypothesized to be significantly less than after RT. Our goal was to compare the toxicity profile and oncological outcome of salvage radical prostatectomy following focal therapy versus salvage radical prostatectomy after radiation therapies. Data concerning all men undergoing salvage radical prostatectomy for recurrent prostate cancer after either focal therapy, external beam radiation therapy or brachytherapy were retrospectively collected from 4 high volume surgical centers: Guy’s Hospital (London, UK), Institut Mutualiste Montsouris (Paris, France), Imperial College Healthcare Trust (London, UK) and The Peter MacCallum Cancer Centre (Melbourne, Australia).

The primary outcome measure of the study was toxicity of salvage radical prostatectomy characterized by 30-day postoperative Clavien-Dindo complication rate, 12-month continence rate and 12-month potency rate. The secondary outcome was oncological outcome after salvage radical prostatectomy including positive margin rate and 12-month biochemical recurrence rate. Between April 2007 and September 2018, 185 patients underwent salvage radical prostatectomy of whom 95 had salvage radical prostatectomy after focal therapy and 90 had salvage radical prostatectomy after radiation therapy (external beam radiation therapy or brachytherapy). Median follow-up was 29.5 months.

Our results demonstrated that men undergoing SRP after FT experience lower postoperative complication rates and better urinary continence outcomes compared to men undergoing SRP after RT. SRP after RT was associated with a significantly higher 30-day Clavien-Dindo complication rate (34% vs 5%, p <0.001, see table). In the RT group, 4% of men experienced an anastomotic leak and 10% experienced an anastomotic stricture. Comparative figures in the FT group were 1% and 0% respectively. There was 1 rectal injury in the RT group and 0 in the FT group.

At 12 months following surgery, patients undergoing SRP after FT had significantly better continence (83% pad-free vs 49%) while potency outcomes were similar (14% vs 11%). Presalvage potency rates were similar between the two groups (FT: 67% vs RT: 65%). 74% of men in the FT group had some form of nerve sparing compared to 10% in the RT group. The similarly low potency rates in both groups are likely due to short follow up times and longer follow up may reveal further differences between the two groups.

Men undergoing SRP after RT had a significantly higher stage and grade of disease together with a higher positive surgical margin rate (37% vs 13%, p<0.001). The 3-year biochemical recurrence rates after FT were 35% compared to 32% after RT (p=0.76). Kaplan-Meier curves were also not significantly different (figure, log-rank test: p=0.67) In multivariable analysis, men undergoing SRP after FT experienced a higher risk of biochemical recurrence (HR 0.36, 95% CI 0.16-0.82, p=0.02) despite lower stage, grade, and positive margin rates compared to the RT group. The reasoning for this is unclear however it suggests that all men considering SRP after FT should undergo cross-sectional imaging, such as prostate specific membrane antigen positron emission tomography, to exclude micrometastatic disease.

To our knowledge only 1 other study has compared the toxicity and outcomes of SRP after RT versus FT. Onol and colleagues in their single institution study report similar functional and oncological outcomes to our study.⁵

Traditionally SRP has been associated with significant functional toxicity. However, in our multicenter study, we demonstrate that the functional outcome of SRP is not universally poor and is dependent on primary prostate cancer treatment. Patients receiving focal therapy prior to SRP have lower rates of perioperative complications and better long-term urinary continence outcomes.

Therefore, we would encourage urologists reviewing men with recurrent prostate cancer after FT to consider salvage surgery as an alternative to salvage radiotherapy or whole gland ablation. Furthermore, by performing SRP on men with recurrent prostate cancer after FT, these men still have radiation to the prostate bed in reserve if the SRP is not curative.