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BackgroundMen with grade group 2 or 3 prostate cancer are often considered ineligible for active surveillance; some patients with grade group 2 prostate cancer who are managed with active surveillance will have early disease progression requiring radical therapy. This study aimed to investigate whether MRI-guided focused ultrasound focal therapy can safely reduce treatment burden for patients with localised grade group 2 or 3 intermediate-risk prostate cancer.MethodsIn this single-arm, multicentre, phase 2b study conducted at eight health-care centres in the USA, we recruited men aged 50 years and older with unilateral, MRI-visible, primary, intermediate-risk, previously untreated prostate adenocarcinoma (prostate-specific antigen ≤20 ng/mL, grade group 2 or 3; tumour classification ≤T2) confirmed on combined biopsy (combining MRI-targeted and systematic biopsies). MRI-guided focused ultrasound energy, sequentially titrated to temperatures sufficient for tissue ablation (about 60-70°C), was delivered to the index lesion and a planned margin of 5 mm or more of normal tissue, using real-time magnetic resonance thermometry for intraoperative monitoring. Co-primary outcomes were oncological outcomes (absence of grade group 2 and higher cancer in the treated area at 6-month and 24-month combined biopsy; when 24-month biopsy data were not available and grade group 2 or higher cancer had occurred in the treated area at 6 months, the 6-month biopsy results were included in the final analysis) and safety (adverse events up to 24 months) in all patients enrolled in the study. This study is registered with ClinicalTrials.gov, NCT01657942, and is no longer recruiting.FindingsBetween May 4, 2017, and Dec 21, 2018, we assessed 194 patients for eligibility and treated 101 patients with MRI-guided focused ultrasound. Median age was 63 years (IQR 58-67) and median concentration of prostate-specific antigen was 5·7 ng/mL (IQR 4·2-7·5). Most cancers were grade group 2 (79 [78%] of 101). At 24 months, 78 (88% [95% CI 79-94]) of 89 men had no evidence of grade group 2 or higher prostate cancer in the treated area. No grade 4 or grade 5 treatment-related adverse events were reported, and only one grade 3 adverse event (urinary tract infection) was reported. There were no treatment-related deaths.Interpretation24-month biopsy outcomes show that MRI-guided focused ultrasound focal therapy is safe and effectively treats grade group 2 or 3 prostate cancer. These results support focal therapy for select patients and its use in comparative trials to determine if a tissue-preserving approach is effective in delaying or eliminating the need for radical whole-gland treatment in the long term.FundingInsightec and the National Cancer Institute.

Background:Preclinical and retrospective data suggest that cytoreductive radical prostatectomy may benefit a subset of men who present with metastatic prostate cancer (mPCa). Herein, we report the results of the first planned Phase 1 study on cytoreductive surgery. Methods:From four institutions, 36 patients consented to the study. However, four did not complete surgery because of rapid disease progression (n = 3) and another because of an intraoperatively discovered pericolonic abscess. Men with newly diagnosed clinical mPCa to lymph nodes or bones were eligible. The primary endpoint was the rate of major perioperative complications (Clavien-Dindo Grade 3 or higher) occurring within 90 days of surgery. Results:The mean age at surgery was 64.0 years. The 90-day overall complication rate was 31.2% (n = 10), of which two (6.25%) were considered major complications: one acute tubular necrosis requiring temporary dialysis and one death. In men with more than 6 months of follow-up, 67.9% had prostate specific antigen nadir ≤0.2 ng/mL, while one patient experienced a rapid rise in prostate specific antigen and another a widely disseminated disease that resulted in death 5 months after surgery. Altogether, these results demonstrate that cytoreductive radical prostatectomy is safe and surgically feasible in selected patients who present with mPCa . Yet, there may be a small subset of patients in whom surgery may cause a significant harm. Conclusion:Therefore, cytoreductive surgery in men with mPCa should be limited to clinical trials until robust data are available.

Emerging evidence has suggested that cytoreductive prostatectomy (CRP) allows superior oncologic control when compared to current standard of care androgen deprivation therapy alone. However, the safety and benefit of cytoreduction in metastatic prostate cancer (mPCa) has not been proven. Therefore, we evaluated the incidence of complications following CRP in men newly diagnosed with mPCa. A total of 68 patients who underwent CRP from 2006 to 2014 at four tertiary surgical centers were compared to 598 men who underwent radical prostatectomy for clinically localized prostate cancer (PCa). Urinary incontinence was defined as the use of any pad. CRP had longer operative times (200 min vs 140 min, P < 0.0001) and higher estimated blood loss (250 ml vs 125 ml, P < 0.0001) compared to the control group. However, both overall (8.82% vs 5.85%) and major complication rates (4.41% vs 2.17%) were comparable between the two groups. Importantly, urinary incontinence rate at 1-year after surgery was significantly higher in the CRP group (57.4% vs 90.8%, P < 0.0001). Univariate logistic analysis showed that the estimated blood loss was the only independent predictor of perioperative complications both in the unadjusted model (OR: 1.18; 95% CI: 1.02-1.37; P = 0.025) and surgery type-adjusted model (OR: 1.17; 95% CI: 1.01-1.36; P = 0.034). In conclusion, CRP is more challenging than radical prostatectomy and associated with a notably higher incidence of urinary incontinence. Nevertheless, CRP is a technically feasible and safe surgery for selecting PCa patients who present with node-positive or bony metastasis when performed by experienced surgeons. A prospective, multi-institutional clinical trial is currently underway to verify this concept.

BackgroundThe presence of lymph nodes (LN) within the prostatic anterior fat pad (PAFP) has been reported in several recent reports. These PAFP LNs rarely harbor metastatic disease, and the characteristics of patients with PAFP LN metastasis are not well-described in the literature. Our previous study suggested that metastatic disease to the PAFP LN was associated with less severe oncologic outcomes than those that involve the pelvic lymph node (PLN). Therefore, the objective of this study is to assess the oncologic outcome of prostate cancer (PCa) patients with PAFP LN metastasis in a larger patient population.MethodsData were analyzed on 8800 patients from eleven international centers in three countries. Eighty-eight patients were found to have metastatic disease to the PAFP LNs (PAFP+) and 206 men had isolated metastasis to the pelvic LNs (PLN+). Clinicopathologic features were compared using ANOVA and Chi square tests. The Kaplan-Meier method was used to calculate the time to biochemical recurrence (BCR).ResultsOf the eighty-eight patients with PAFP LN metastasis, sixty-three (71.6%) were up-staged based on the pathologic analysis of PAFP and eight (9.1%) had a low-risk disease. Patients with LNs present in the PAFP had a higher incidence of biopsy Gleason score (GS) 8-10, pathologic N1 disease, and positive surgical margin in prostatectomy specimens than those with no LNs detected in the PAFP. Men who were PAFP+ with or without PLN involvement had more aggressive pathologic features than those with PLN disease only. However, there was no significant difference in BCR-free survival regardless of adjuvant therapy. In 300 patients who underwent PAFP LN mapping, 65 LNs were detected. It was also found that 44 out of 65 (67.7%) nodes were located in the middle portion of the PAFP.ConclusionsThere was no significant difference in the rate of BCR between the PAFP LN+ and PLN+ groups. The PAFP likely represents a landing zone that is different from the PLNs for PCa metastasis. Therefore, the removal and pathologic analysis of PAFP should be adopted as a standard procedure in all patients undergoing radical prostatectomy.