Karnes, Robert Jeffrey

Importance Patients with recurrent prostate cancer after previous radiotherapy typically have poor survival. Those with recurrences prostate confined might be suitable for salvage focal therapy (sFT) or salvage radical prostatectomy (sRP). sFT may offer good cancer control with comparatively less toxic effects, but outcomes beyond 5 years have not been reported, and no study has compared sFT to sRP. Objective To compare cancer control and perioperative complications among patients after sFT vs sRP. Design, Setting, and Participants In this international, multicenter cohort study of matched comparison data, patients undergoing sFT were derived from the prospective UK HIFU (high-intensity focused ultrasound) Evaluation and Treatment and International Cryotherapy Evaluation registries (9 centers; 2006-2024) and the prospective UK Focal Recurrent Assessment and Salvage Treatment cohort study (6 centers; 2014-2018). Patients undergoing sRP were derived from an international retrospective registry (12 centers in 8 countries; 2000-2021). Patients with biopsy-confirmed, localized recurrent prostate cancer postradiotherapy, either external beam radiotherapy, brachytherapy, or both, were included. Data were analyzed from March to July 2025. Exposures sFT using HIFU or cryotherapy vs sRP. Main Outcomes and Measures The primary outcome was cancer-specific survival up to 10 years. Secondary outcomes were overall survival, any perioperative complications (Clavien-Dindo grades 1-5), and major perioperative complications (Clavien-Dindo grades 3-5). Comparisons were made on matched patients following 1:1 cardinality matching within individual multiply-imputed datasets. Matching variables used were radiotherapeutic treatment, years between primary and salvage treatments, European Association of Urology recurrence risk group, and presalvage age, prostate-specific antigen, prostate volume, grade group, T stage, and androgen-deprivation therapy use. Results A total of 923 patients were eligible for matching (419 undergoing sFT and 504 undergoing sRP). Of the patients undergoing sFT, 325 (77.6%) underwent HIFU and the remainder cryotherapy, with 241 (57.5%) treated with quadrant ablation. Of patients treated with sRP, 376 (74.6%) underwent open surgery and the remainder robot-assisted surgery. For sFT vs sRP, 10-year cancer-specific survival was 92% (95% CI, 86%-98%) vs 99% (95% CI, 97%-100%), with no statistically significant difference (restricted mean time lost, −0.09 years; 95% CI, −0.22 to 0.03 years; P = .15; subdistribution hazard ratio, 0.45; 95% CI, 0.05-4.00; P = .47). There was no statistically significant difference in 10-year overall survival (restricted mean survival time, −0.13 years; 95% CI, −0.86 to 0.60 years; P = .72). Undergoing sRP was associated with statistically significant higher odds of any complication (adjusted odds ratio, 24.20; 95% CI, 12.94-45.27; P < .001) and major complication (adjusted odds ratio, 9.31; 95% CI, 3.42-25.36; P < .001). Conclusions and Relevance In this cohort study, sFT and sRP were effective for treating localized radiorecurrent prostate cancer, while sFT was associated with fewer perioperative complications. sFT may provide a favorable therapeutic ratio for many patients with localized radiorecurrent prostate cancer.

Background: Lymph node invasion (LNI) represents a poor prognostic factor after primary radical prostatectomy (RP) for prostate cancer (PCa). However, the impact of LNI on oncologic outcomes in salvage radical prostatectomy (SRP) patients is unknown. Objective: To investigate the impact of lymph node dissection (LND) and pathological lymph node status (pNX vs. pN0 vs. pN1) on long-term oncologic outcomes of SRP patients. Patients and methods: Patients who underwent SRP for recurrent PCa between 2000 and 2021 were identified from 12 high-volume centers. Kaplan–Meier analyses and multivariable Cox regression models were used. Endpoints were biochemical recurrence (BCR), overall survival (OS), and cancer-specific survival (CSS). Results: Of 853 SRP patients, 87% (n = 727) underwent LND, and 21% (n = 151) harbored LNI. The median follow-up was 27 months. The mean number of removed lymph nodes was 13 in the LND cohort. At 72 months after SRP, BCR-free survival was 54% vs. 47% vs. 7.2% for patients with pNX vs. pN0 vs. pN1 (p < 0.001), respectively. At 120 months after SRP, OS rates were 89% vs. 81% vs. 41% (p < 0.001), and CSS rates were 94% vs. 96% vs. 82% (p = 0.02) for patients with pNX vs. pN0 vs. pN1, respectively. In multivariable Cox regression analyses, pN1 status was independently associated with BCR (HR: 1.77, p < 0.001) and death (HR: 2.89, p < 0.001). Conclusions: In SRP patients, LNI represents an independent poor prognostic factor. However, the oncologic benefit of LND in SRP remains debatable. These findings underline the need for a cautious LND indication in SRP patients as well as strict postoperative monitoring of SRP patients with LNI.

Purpose: Pelvic lymph node dissection is an important step during robotic radical prostatectomy. The collection of lymphatic fluid (lymphocele) is the most common complication with potentially severe impact; therefore, different strategies have been proposed to reduce its incidence. Materials and Methods: In this systematic review, EMBASE, MEDLINE, Cochrane Library, and NIH Registry of Clinical Trials were searched for articles including the following interventions: transperitoneal vs extraperitoneal approach, any reconfiguration of the peritoneum, the use of pelvic drains, and the use of different sealing techniques and sealing agents. The outcome evaluated was the incidence of symptomatic lymphocele. Randomized, nonrandomized, and/or retrospective studies were included. Results: Twelve studies were included (including one ongoing randomized clinical trial). Because of heterogeneity of included studies, no meta-analysis was performed. No significant impact was reported by different sealing techniques and agents or by surgical approach. Three retrospective, nonrandomized studies showed a potential benefit of peritoneal reconfiguration to maximize the peritoneal surface of reabsorption. Conclusion: Lymphocele formation is a multistep and multifactorial event; high-quality literature analyzing risk factors and preventive measures is rather scarce. Peritoneal reconfiguration could represent a reasonable option that deserves further evaluation; no other preventive measure is supported by current evidence.

AbstractBackgroundMetabolic syndrome (MetS) has a negative impact on functional recovery and complications after many surgical procedures.AimTo assess the role of Mets on functional outcomes and complications after radical prostatectomy (RP) for prostate cancer.Patients and MethodsComplete data were collected from 5758 patients, undergoing RP at a single referral centers in a 10‐year period and the presence of MetS before surgery was ascertained in 17.7% of them using a modified version of the IDF‐AHA/NHLBI criteria. Outcomes included 1‐year continence and potency rates, early (≤90 days) and late (>90 days) complications.ResultsPostoperative continence (no pads) was significantly less likely in MetS patients (75.4% vs 82.6%, P < .01), despite no difference in preoperative continence. Erections with or without therapy were reached in 55.8% of non‐MetS and 41.8% of MetS patients (P < .01), in this case a significant difference in preoperative function was seen. No differences in early and late complications, except for wound infections (5.8% vs 3.9%, P < .01) were observed.ConclusionsIn the present study RP was safe from the complications standpoint in MetS patients, but the presence of the syndrome was a significant risk factor for post‐RP incontinence and impotence.

Objectives To identify which patients with macroscopic bladder‐infiltrating T4 prostate cancer ( PC a) might have favourable outcomes when treated with radical cystectomy ( RC ). Materials and Methods We evaluated 62 patients with cT 4cN0–1 cM0 PC a treated with RC and pelvic lymph node dissection between 1972 and 2011. In addition to descriptive statistics, the Kaplan–Meier method and log‐rank tests were used to depict survival rates. Univariate and multivariate Cox regression analysis tested the association between predictors and progression‐free, PC a‐specific and overall survival. Results Of the 62 patients, 19 (30.6%) did not have clinical progression during follow‐up, two (3.2%) had local recurrence, and 32 (51.6%) had haematogenous and nine (14.5%) combined pelvic and distant metastasis. Forty patients (64.5%) died, 34 (54.8%) from PC a and six (9.7%) from other causes. The median (range) survival time of the 19 patients who were metastasis‐free at last follow‐up was 86 (1–314) months, 8/19 patients had a follow‐up of >5 years, and five patients survived metastasis‐free for >15 years. Patients without seminal vesicle invasion ( SVI ) had the best outcomes, with an estimated 10‐year PC a‐specific survival of 75% compared with 24% for patients with SVI . Conclusion For cT 4 PC a RC can be an appropriate treatment for local control and part of a multimodality‐treatment approach. Although recurrences are probable, these do not necessarily translate into cancer‐specific death. Men without SVI had a 75% 10‐year PC a‐specific survival. Although outcomes for patients with SVI are not as favourable, there can be good local control; however, these patients are at higher risk of progression and may need more aggressive systemic treatment.

BACKGROUNDA new prostate cancer (PCa) grading system (namely, Gleason score‐GS‐ ≤6 vs. 3 + 4 vs. 4 + 3 vs. 8 vs. ≥9) was recently proposed and assessed on biochemical recurrence (BCR) showing improved predictive abilities compared to the commonly used three‐tier system (GS ≤6 vs. 7 vs. ≥8). We assessed the predictive ability of the five‐tier grade group (GG) system on harder clinical endpoint, namely clinical recurrence (CR).METHODSBetween 2005 and 2014, 9,728 clinically localized PCa patients were treated with radical prostatectomy (RP) at two tertiary referral centers. Kaplan–Meier curves, multivariable Cox regression analyses, and concordance index (C‐index) were used to assess CR after treatment according to four Gleason grade classifications at biopsy and RP: Group 1: ≤6 versus 7 versus ≥8; Group 2: ≤6 versus 3 + 4 vs. 4 + 3 versus ≥8; Group 3: ≤6 versus 7 versus 8 versus ≥9; Group 4: ≤6 versus 3 + 4 versus 4 + 3 versus 8 versus ≥9. Same analyses were repeated in patients who had BCR (n = 1,624). Decision curve analyses were performed to evaluate and compare the net benefit associated with the use of the four Gleason grade classifications.RESULTSOverall, 443 (4.6%) patients had CR. The hazard ratio of the GS 3 + 4, 4 + 3, 8, and ≥9 relative to GS ≤6 were 3.63, 5.93, 11.44, 18.08 and 4.93, 9.99, 15.31 and 25.12 in the pre‐ and post‐treatment models, respectively. The C‐index of the five‐tier GG system was slightly higher relative to the other 3 Gleason grade classifications both in the pre‐ (range: 0.001–0.006) and post‐treatment models (range: 0–0.008). Similar findings were observed when we focused our analyses in patients with BCR after RP. The use of the five‐tier GG system did not result into higher net‐benefit relative to the other three Gleason grade classifications.CONCLUSIONSThe difference in accuracy between the five‐tier GG system and the other Gleason grade classifications, using CR as an endpoint, is clinically negligible. Current evidence suggests that the five‐tier GG system represents a simplified user‐friendly scheme available for patient counseling rather than a new histopathological diagnostic system that improves the prediction of CR. Prostate 77:263–273, 2017. © 2016 Wiley Periodicals, Inc.

Objective To investigate the long‐term utility of adjuvant therapy after radical prostatectomy ( RP ) for prostate cancer with seminal vesicle invasion ( SVI ; pT 3b), as the published data are conflicting. Patients and Methods Patients with SVI during RP and pelvic lymph node dissection at two major referral centres from 1986 to 2014 were included. Kaplan–Meier analyses and multivariable Cox regressions were used to determine if adjuvant radiotherapy ( aRT ) and adjuvant hormonal therapy ( aHT ) were predictors of biochemical recurrence ( BCR ), cancer‐specific mortality ( CSM ) and overall mortality ( OM ). Subset analyses were performed for pN 0 patients and pN + patients. Results Overall, 3 279 patients with prostate cancer and SVI were included with a median follow‐up of 148 months. Considering the whole SVI population, 1 387 (42%) received no adjuvant therapy, 1 179 (36%) received aHT , 461 (14.1%) received aRT , while 252 (7.7%) received both aHT and aRT . The 10‐year BCR , CSM , and OM rates were 64%, 14%, and 27%, respectively. In the overall population, aRT and aHT were predictors of BCR , CSM and OM (all P < 0.04). When only pT 3bN0 patients were considered, aHT was a significant multivariate predictor of BCR [hazard ratio ( HR ) 0.50, P < 0.001), CSM ( HR 0.62, P = 0.01) and OM ( HR 0.75, P = 0.004). Conversely, aRT was not associated with survival outcomes (all P > 0.05). When only the subgroup pT 3bN+ was considered, the use of aRT was related to an improvement in CSM ( HR 0.65, P = 0.03) and OM (HR 0.78, P = 0.03). Conclusions aHT + aRT seems to be effective in pT 3b patients. However, when stratified according to the presence of nodal metastases, aHT remains effective only in the node‐negative subgroup, while aRT remains effective only in the node‐positive subgroup. Further data including prospective trials are warranted to study the utility of adjuvant therapies in this setting.

Objective To evaluate the incidence, predictors and oncological outcomes of pT 0 prostate cancer ( PC a). Methods We conducted a retrospective analysis of 20 222 patients undergoing radical prostatectomy ( RP ) for PC a at the Mayo Clinic between 1987 and 2012. Disease recurrence was defined as follow‐up PSA >0.4 ng/mL or biopsy‐proven local recurrence. Systemic progression was defined as development of metastatic disease on imaging. Comparisons of baseline characteristics between pT 0 and non‐ pT 0 groups were carried out using chi‐squared tests. Recurrence‐free survival was estimated using the Kaplan–Meier method and compared using the log‐rank test. Results A total of 62 patients (0.3%) had pT 0 disease according to the RP specimen. In univariable analysis, pT 0 disease was significantly associated with older age ( P = 0.045), lower prostate‐specific antigen ( PSA ; P = 0.002), lower clinical stage ( P < 0.001), lower biopsy Gleason score ( P = 0.042), and receipt of preoperative transurethral resection, hormonal and radiation therapies (all P < 0.001). In multivariable analysis, lower PSA levels, lower Gleason score, and receipt of preoperative treatment were independently associated with pT 0 (all P < 0.05). Seven patients (11%) with pT 0 PC a developed disease recurrence over a median follow‐up of 10.9 years. All seven patients had preoperative treatment(s) and three had recurrence with a PSA doubling time of <9 months. Compared with non‐ pT 0 disease, pT 0 disease was associated with longer recurrence‐free survival ( P < 0.05). Only one (1.6%) patient with pT 0 disease developed systemic progression. Conclusions pT 0 stage PC a is a rare phenomenon and is associated with receipt of preoperative treatment and features of low‐risk PC a. Although pT 0 has a very favourable prognosis, some men, especially those who received preoperative treatment, experience a small but non‐negligible risk of disease recurrence and systemic progression.