Focal and tissue-preserving treatment of prostate cancer

Focal therapy is an attempt to escape the choice in `prostate-treatment-choice-localised` by treating less. High-intensity focused ultrasound, cryotherapy, focal laser ablation, irreversible electroporation, focal brachytherapy and vascular-targeted photodynamic therapy have all been used.

The only randomised phase 3 trial of a focal therapy against active surveillance is PCM301, which tested padeliporfin vascular-targeted photodynamic therapy. It randomised 413 men with low-risk, Gleason pattern 3 prostate cancer at 47 European centres, 206 to treatment and 207 to active surveillance. At 24 months, disease progression from low to moderate or high risk, or death, had occurred in 58 of 206 (28 percent) after treatment and 120 of 207 (58 percent) under surveillance, adjusted hazard ratio 0.34 (95 percent confidence interval 0.24 to 0.46, p<0.0001). A negative prostate biopsy at 24 months was found in 101 men (49 percent) against 28 (14 percent), adjusted risk ratio 3.67 (2.53 to 5.33, p<0.0001). The commonest grade 3 to 4 events after treatment were prostatitis, acute urinary retention and erectile dysfunction, each in 1 to 2 percent, and 15 men had serious urinary retention that resolved within 2 months in all cases.

NICE TA546 does not recommend padeliporfin for untreated, unilateral, low-risk prostate cancer. The committee's reasoning is worth reading because it applies to the whole field: long-term studies show that men with low-risk disease live as long under active surveillance, radical therapies carry long-term severe side effects, and better diagnostics mean low-risk disease is now identified more accurately. The comparison that matters for a low-risk cancer is not against radical treatment; it is against doing nothing, and against doing nothing the harms of a focal treatment are additional rather than avoided.

The non-randomised evidence is summarised in a 2023 systematic review of prospective studies with protocol-mandated post-treatment biopsy, covering 29 studies and 1,079 men treated with targeted focal therapy. At baseline 65.0 percent harboured grade group 2 or higher cancer. One year after treatment, in-field failure with grade group 1 or higher occurred in 25.7 percent (range 11.1 to 66.7) and with grade group 2 or higher in 8.8 percent (0 to 27.8). Where whole-gland biopsy was performed at 1 year, residual grade group 1 or higher cancer was found anywhere in the prostate in 43.7 percent (19.4 to 71.7) and grade group 2 or higher in 13.0 percent (0 to 35.9). Erectile function was better preserved than after radical treatment: 78.7 percent were potent at 1 year across seven studies and 197 men, with a mean 8.8 percent decrease in erectile function scores across 21 studies and 760 men.

So the honest summary is that focal therapy leaves cancer behind in a substantial minority, preserves function in most, and has never been compared with surgery or radiotherapy in a randomised trial with a cancer endpoint. The UK trials designed to change that, PART and CHRONOS, are the ones to watch.