The Precision Prostatectomy: an IDEAL Stage 0, 1 and 2a Study

Abstract

Objective This study aimed to develop a preclinical model of prostate cancer (CaP) for studying focal/hemiablation of the prostate (IDEAL stage 0), and to use the information from the stage 0 investigation to design a novel focal surgical treatment approach—the precision prostatectomy (IDEAL stage 1/2a).Methods The IDEAL stage 0 study included simulation of focal/hemiablation in whole-mount prostate specimens obtained from 100 men who had undergone radical prostatectomies, but met the criteria for focal/hemiablation. The IDEAL stage 1/2a was a prospective, single-arm, Institutional Review Board-approved study of precision prostatectomy undertaken in eight men, who met the predetermined criteria. Criteria for both stages included (1) prostate-specific antigen (PSA) ≤15 ng/mL, (2) stage ≤cT2, (3) dominant unilateral lesion with Gleason ≤4+3 with any number of cores or % cores involved ipsilaterally on transrectal biopsy, (4) no primary Gleason ≥4 contralaterally on transrectal biopsy, and (5) preoperative erectile function score (International Index of Erectile Function (IIEF)-5) of ≥17 (out of 25) without PDE-5i (applicable only to the stage 1/2a study participants). Feasibility and safety of the precision prostatectomy technique, and short-term urinary, sexual and oncological outcomes were studied.Results Analysis of whole-mount specimens in the 100 men showed an index lesion (>1 cm in diameter) in all. Ninety-eight men had satellite lesions smaller than 0.5 cm∧3 in volume—46 on the side of the dominant lesions and 52 in the contralateral lobe. If the men in this modeling cohort had undergone focal ablation with a 5–10 mm untreated margin, all except one would have had at least Gleason 6 residual cancer. If they had undergone hemiablation with no untreated tissue on the ablated side, 56 men would have had residual cancer on the contralateral side, of whom 21 would have had clinically significant cancer (Gleason 7 or higher). If these men had undergone precision prostatectomy, with preservation of 5–10 mm of tissue on the non-dominant side, 10% and 4% would have had Gleason 3+4 and Gleason 4+3 disease left behind, respectively. For the stage 1/2a study, the median (IQR) age, PSA and IIEF-5 scores at the time of surgery were 54 (52–57) years, 4.4 (3.8–6.1) ng/mL and 24 (23-25), respectively. All eight patients were continent and sexually active at 12 months with a median IIEF-5 score of 21 (out of 25). At 24–30 months from surgery, the median PSA was 0.2 (range 0.1–0.7) ng/mL. Six men had undergone follow-up protocol biopsies, two, with undetectable PSA, had refused. Two men had residual Gleason 3+3 cancer, with PSA of 0.7 and 0.4 ng/mL, and remain on active surveillance. No man has undergone secondary whole-gland therapy.Conclusions Examination of whole-mount radical prostatectomy specimens in men who fit the conventional criteria of focal/hemiablation showed that approximately 21%–68% of men would have clinically significant CaP in the untreated tissue. In a small development cohort, precision prostatectomy was technically feasible, with excellent postoperative functional recovery. At 30 months of follow-up, no patient had clinically significant residual cancer or required secondary treatment. Pending long-term follow-up, a risk-stratified surgical approach may avoid whole-gland therapy and preserve erectile function in the majority of men with intermediate-risk CaP.