麻豆传媒

SAN FRANCISCO -- Men with low-risk prostate cancer had more than a 50% decrease in conversion to definitive therapy if they underwent vascular targeted phototherapy (VTP) prior to beginning active surveillance, a randomized trial showed.

During the first 2 years of follow-up, 6% of the VTP group converted to surgery or radiation therapy as compared with 32% of men who entered active surveillance without VTP. Three times as many men in the VTP group had negative biopsies at 2 years.

At 4 years the conversion rates were 24% with VTP and 53% with active surveillance alone. Erectile function and urinary continence were similar in the two groups, reported Inderbir Gill, MD, of the University of Southern California in Los Angeles, at the American Urological Association (AUA) annual meeting.

"This is the only prospective, multi-institutional randomized trial comparing partial gland ablation versus active surveillance for low-risk prostate cancer," said Gill. "At 4 years of follow-up, VTP decreased the risk of overall progression and progression in grade. VTP decreased conversion to radical therapy, a clinically meaningful outcome that lowers treatment-related morbidity and improves cancer control compared to active surveillance."

Published results appeared previously in the.

Two other AUA studies provided evidence for other interventions that might allow more men to delay or avoid conversion from active surveillance to radical treatment for prostate cancer. A 3-month course of androgen deprivation therapy (ADT) at the beginning of active surveillance significant increase in negative biopsies at 12 months. A year after MRI-guided transurethral ultrasound ablation (TULSA), 95% of 115 men with low- and intermediate-risk prostate cancer met a prespecified PSA endpoint.

Though definitive radiation therapy and radical prostatectomy offer effective treatment for early-stage prostate cancer, both are associated with significant adverse effects, particularly incontinence and erectile dysfunction. In the U.S., as many as half of men with newly diagnosed localized prostate cancer choose active surveillance as the initial approach to management. Half of them convert to radical therapy in 5 years or less.

"There is an unmet need for a less morbid way to manage these low-risk cancers; focal therapy offers that method," said Gill.

VTP involves injection of the photosensitizer padeliporfin and exposure to low-level laser light via optical fibers inserted into the predefined treatment area of the prostate. Light activation of padeliporfin causes "instantaneous complete vascular occlusion within the tumor microvasculature."

Gill reported findings from a randomized trial involving 413 men with newly diagnosed, low-risk prostate cancer (by D'Amico criteria). Investigators at 47 centers in Europe randomized the patients to VTP followed by active surveillance or active surveillance alone. The men had a mean age of 63-64, 86-87% had stage T1c disease, and mean prostate volume was 42.5 grams.

After 2 years of follow-up, 14% of the VTP had converted to radical treatment as compared with 49% of the active surveillance group. Progression to clinically significant cancer had occurred in 16% of the VTP group and 41% of the control arm, which represented a 58% reduction in the hazard ratio (95% CI 0.29-0.59). At 4 years, the 29% absolute difference in conversion to radical therapy represented a 69% reduction in the hazard in favor of the VTP group (95% CI 0.21-0.45).

was evaluated in a randomized phase III trial involving 115 men with low-risk prostate cancer (T1c-T2a, PSA ≤10 ng/mL, Gleason score ≤6, 12-core biopsy with no more than three positive cores). They all entered active surveillance and were randomized to 3 months of combined ADT (leuprolide/bicalutamide) or no additional treatment. The primary endpoint was the proportion of patients with negative biopsies at 12 months.

At the 12-month follow-up, 53% of the control group had positive biopsies as compared with 31.5% of the ADT arm, reported Olivier Cussenot, MD, PhD, of the University of Paris. The difference represented a 2.7-fold increase in the odds ratio for positive prostate biopsy in the control arm (95% CI 1.10-5.54).

The patients randomized to ADT had significantly fewer prostate symptoms at 3, 6, and 9 months (P<0.000) and lower PSA values at 3 and 6 months (P<0.0001, P=0.0039).

The study of evaluated whole-gland ablation in men with clinically significant prostate cancer (≤cT2b, PSA ≤15 ng/mL, Gleason score ≤3+4) said Laurence Klotz, MD, of the University of Toronto. Investigators at 13 centers in the U.S., Canada, and Europe treated 115 patients with a transurethral device that emits directional ultrasound to ablate a tissue volume shaped to patient-specific anatomy using active MRI thermometry feedback control.

The trial had a primary endpoint of achieving a PSA nadir ≤25% of the pretreatment baseline value. The mean pretreatment PSA for the cohort was 6-7 ng/mL. At the 12-month follow-up, 95% of the patients met the endpoint. Klotz reported a median PSA reduction of 95% and a median PSA nadir of 0.36 ng/mL.

The results were achieved with a high degree of safety and a low rate of adverse events, he added. Additional studies of the TULSA device have begun in different settings, included targeted (as opposed to whole-gland) therapy, salvage treatment, and benign prostatic hyperplasia.