Primary Whole-gland Ablation for the Treatment of Clinically Localized Prostate Cancer: A Focal Therapy Society Best Practice Statement.

CONTEXT: Whole-gland ablation is a feasible and effective minimally invasive treatment for localized prostate cancer (PCa). Previous systematic reviews supported evidence for favorable functional outcomes, but oncological outcomes were inconclusive owing to limited follow-up. OBJECTIVE: To evaluate the real-world data on the mid- to long-term oncological and functional outcomes of whole-gland cryoablation and high-intensity focused ultrasound (HIFU) in patients with clinically localized PCa, and to provide expert recommendations and commentary on these findings. EVIDENCE ACQUISITION: We performed a systematic review of PubMed, Embase, and Cochrane Library publications through February 2022 according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. As endpoints, baseline clinical characteristics, and oncological and functional outcomes were assessed. To estimate the pooled prevalence of oncological, functional, and toxicity outcomes, and to quantify and explain the heterogeneity, random-effect meta-analyses and meta-regression analyses were performed. EVIDENCE SYNTHESIS: Twenty-nine studies were identified, including 14 on cryoablation and 15 on HIFU with a median follow-up of 72 mo. Most of the studies were retrospective (n = 23), with IDEAL (idea, development, exploration, assessment, and long-term study) stage 2b (n = 20) being most common. Biochemical recurrence-free survival, cancer-specific survival, overall survival, recurrence-free survival, and metastasis-free survival rates at 10 yr were 58%, 96%, 63%, 71-79%, and 84%, respectively. Erectile function was preserved in 37% of cases, and overall pad-free continence was achieved in 96% of cases, with a 1-yr rate of 97.4-98.8%. The rates of stricture, urinary retention, urinary tract infection, rectourethral fistula, and sepsis were observed to be 11%, 9.5%, 8%, 0.7%, and 0.8%, respectively. CONCLUSIONS: The mid- to long-term real-world data, and the safety profiles of cryoablation and HIFU are sound to support and be offered as primary treatment for appropriate patients with localized PCa. When compared with other existing treatment modalities for PCa, these ablative therapies provide nearly equivalent intermediate- to long-term oncological and toxicity outcomes, as well as excellent pad-free continence rates in the primary setting. This real-world clinical evidence provides long-term oncological and functional outcomes that enhance shared decision-making when balancing risks and expected outcomes that reflect patient preferences and values. PATIENT SUMMARY: Cryoablation and high-intensity focused ultrasound are minimally invasive treatments available to selectively treat localized prostate cancer, considering their nearly comparable intermediate- to long term cancer control and preservation of urinary continence to other radical treatments in the primary setting. However, a well-informed decision should be made based on one's values and preferences.

Age represents the main driver of surgical decision making in patients candidate to radical cystectomy.

BACKGROUND AND OBJECTIVES: Age might influence the choice of surgical approach, type of urinary diversion (UD) and lymph node dissection (LND) in patients candidate to radical cystectomy (RC) for urothelial bladder cancer (UBC). Similarly, age may enhance surgical morbidity and worsen perioperative outcomes. We tested the impact of age (octogenarian vs. younger patients) on surgical decision making and peri- and postoperative outcomes of RC. METHODS: Non-metastatic muscle-invasive UBC patients treated with RC at 18 high-volume European institutions between 2006 and 2021 were identified and stratified according to age (≥80 vs. <80 years). Intraoperative Complications Assessment and Reporting with Universal Standards and European Association of Urology guidelines recommendations were accomplished in collection and reporting of, respectively, intraoperative and postoperative complications. Multivariable logistic regression models (MVA) tested the impact of age on outcomes of interest. Sensitivity analyses after 1:3 propensity score matching were performed. RESULTS: Of 1955 overall patients, 251 (13%) were ≥80-year-old. Minimally invasive RC was performed in 18% and 40% of octogenarian and younger patients, respectively (p < 0.001). UD without bowel manipulation (ureterocutaneostomy, UCS) was performed in 31% and 7% of octogenarian and younger patients (p < 0.001). LND was delivered to 81% and 93% of octogenarian and younger patients (p < 0.001). At MVA, age ≥80 years independently predicted open approach (odds ratio [OR]: 1.55), UCS (OR: 3.70), and omission of LND (OR: 0.41; all p ≤ 0.02). Compared to their younger counterparts, octogenarian patients experienced higher rates of intraoperative (8% vs. 4%, p = 0.04) but not of postoperative complications (64% vs. 61%, p = 0.07). At MVA, age ≥80 years was not an independent predictor of length of stay, intraoperative or postoperative transfusions and complications, and readmissions (all p values >0.1). These results were replicated in sensitivity analyses. CONCLUSIONS: Age ≥80 years does not independently portend worse surgical outcomes for RC. However, octogenarians are unreasonably more likely to receive open approach and UCS diversion, and less likely to undergo LND.

Preoperative Risk-Stratification of High-Risk Prostate Cancer: A Multicenter Analysis.

Background: Cancer-specific survival (CSS) within high-risk non-metastatic prostate cancer varies dramatically. It is likely that within this heterogenous population there are subgroup(s) at extraordinary risk, burdened with an exaptational poor prognosis. Establishing the characteristics of these group(s) would have significant clinical implications since high quality preoperative risk stratification remains the cornerstone of therapeutic decision making to date. Objective: To stratify high-risk prostate cancer based on preoperative characteristics and evaluate cancer specific survival after radical prostatectomy. Method: The EMPaCT multi-center database offers an international population of non-metastatic high-risk prostate cancer. Preoperative characteristics such as age, biopsy Gleason score, PSA and clinical stage were subcategorized. A multivariate analysis was performed using predictors showing significant survival heterogeneity after stratification, as observed by a univariate analysis. Based upon the hazard ratios of this multivariate analysis, a proportional score system was created. The most ideal group distribution was evaluated trough different score cut-off's. The predictive value was tested by the herald C index. Results: An overall 5-years CSS of 94% was noted within the entire high-risk cohort (n = 4,879). Except for age, all preoperative risk factors showed a significantly differing CSS. Multivariate analysis indicated, T4 stage as being the strongest predictor of CSS (HR: 3.31), followed by ISUP grade 5 group (HR 3,05). A score system was created by doubling the hazard ratios of this multivariate analysis and rounding off to the nearest complete number. Multivariate analysis suggested 0, 4, 8, and 12 pts as being the most optimal group distribution (p-value: 0.0015). Five-years CSS of these groups were 97, 93, 87, and 70%, respectively. The calculated Herald C-index of the model was 0.77. Conclusion: An easy-to-use pre-operative model for risk stratification of newly diagnosed high-risk prostate cancer is presented. The heterogeneous CSS of high-risk non-metastatic prostate cancer after radical prostatectomy is illustrated. The model is clinically accessible through an online calculator, presenting cancer specific survival based on individualized patient characteristics.

Outcomes of European Basic Laparoscopic Urological Skills (EBLUS) Examinations: Results from European School of Urology (ESU) and EAU Section of Uro-Technology (ESUT) over 6 Years (2013-2018).

BACKGROUND: The European School of Urology (ESU) and EAU Section of Uro-Technology (ESUT) started hands-on-training (HOT) sessions in 2007 along with structured European Basic Laparoscopic Urological Skills (EBLUS) examinations in 2013. EBLUS includes an online theoretical course, HOT by expert tutors on a set of dry-lab exercises, and finally a standardised examination for skill assessment and certification. OBJECTIVE: To analyse the results and predictors of success from the EBLUS examinations that were conducted during the European Urology Residents Education Programme (EUREP) and other international and national dedicated ESU events. DESIGN, SETTING, AND PARTICIPANTS: ESU has been delivering EBLUS courses and examinations over the past 6 yr (2013-2018) in more than 40 countries worldwide. Trainees were asked about their laparoscopic background (procedures assisted/performed) and about the availability of HOT or simulator/box trainer in their facility. Apart from the online theoretical course, 4 HOT tasks [(1) peg transfer, (2) pattern cutting, (3) single knot tying, and (4) clip and cut] with its quality assessment of depth perception, bimanual dexterity, and efficiency were a part of the assessment and were considered critical to pass the EBLUS examination. RESULTS AND LIMITATIONS: A total of 875 EBLUS examinations were delivered (EUREP, n=385; other ESU events, n=490), with complete data available for 533 (61%) participants among which 295 (55%) passed the examinations. Pass rate increased on a yearly basis from 35% to 70% (p<0.001) and was similar between EUREP (56%) and other ESU/ESUT events (55%). The significant predictors of success were passing tasks 1 [odds ratio (OR): 869.9, 95% confidence interval (CI): 89.6-8449.0, p<0.001] and 2 (OR: 3045.0, 95% CI: 99.2-93 516.2, p<0.001) of the examinations. A limitation of EBLUS was its inability to provide more advanced training such as wet-lab or cadaveric training. CONCLUSIONS: Over the past few years more trainees have passed the European Basic Laparoscopic Urological Skills (EBLUS) examinations. Trainees who spend more time on laparoscopic procedures demonstrated a better performance and pass rate. We found almost no difference between the EBLUS results collected from EUREP and other ESU/ESUT events, which confirms the robustness of the training and examinations conducted worldwide. PATIENT SUMMARY: Training in laparoscopy helps trainees pass the European Basic Laparoscopic Urological Skills (EBLUS) examinations, reflected by an increase in the pass rate over the past 6 yr. Our results also confirm the robustness of EBLUS training and examinations worldwide.

Modified York Mason technique for repair of iatrogenic recto-urinary fistula: 20 years of the Montsouris experience.

PURPOSE: Iatrogenic recto-urinary fistulas are a disastrous complication of therapeutic interventions on the prostate. Many surgical approaches have been described to repair recto-urinary fistulas and no consensus has been reached regarding the better approach. The objective of this study is to present the results of our updated 20-year experience in the surgical management of recto-urinary fistula using a modified York Mason procedure. METHODS: We proceed to a retrospective single-institution review of surgically treated patients for iatrogenic recto-urinary fistulas between 1998 and 2017 by the modified York Mason technique. Descriptive analysis of our population was performed. Continuous and categorical variables were compared using Mann-Whitney and Fischer tests, respectively. All tests were two-sided with a significance level set at p value < 0.05. RESULTS: We included 30 consecutive patients treated for iatrogenic recto-urinary fistula. The median follow-up was 76 months (2-195). The median size of the fistula was 5 mm (2-20). Successful healing of the recto-urinary fistula was observed in 80, 97, and 100% of patients after 1, 2, or 3 York Mason procedure. During the study period, no one single case of acquired urinary incontinence or durable fecal incontinence has been observed. CONCLUSIONS: Our modified York Mason technique is a reliable and effective procedure with a 100% success rate for the repair of small iatrogenic recto-urinary fistulas in non-irradiated patients. It has a very low morbidity rate, and no case of postoperative urine or fecal incontinence has been observed.

The EMPaCT Classifier: A Validated Tool to Predict Postoperative Prostate Cancer-related Death Using Competing-risk Analysis.

BACKGROUND: Accurate prediction of survival after radical prostatectomy (RP) is important for making decisions regarding multimodal therapies. There is a lack of tools to predict prostate cancer-related death (PCRD) in patients with high-risk features. OBJECTIVE: To develop and validate a prognostic model that predicts PCRD combining pathologic features and using competing-risks analysis. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective multi-institutional observational cohort study of 5876 patients affected by high-risk prostate cancer. Patients were treated using RP and pelvic lymph node dissection (PLND) in a multimodal setting, with median follow-up of 49 mo. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: For PCRD prediction, a multivariate model with correction for competing risks was constructed to evaluate pathologic high-risk features (pT3b-4, Gleason score ≥8, and pN1) as predictors of mortality. All possible associations of the predictors were combined, and then subgroups with similar risk of PCRD were collapsed to obtain a simplified model encoding subgroups with significantly differing risk. Eightfold cross-validation of the model was performed. RESULTS AND LIMITATIONS: After applying exclusion criteria, 2823 subjects were identified. pT3b-4, Gleason score ≥8, and pN1 were all independent predictors of PCRD. The simplified model included the following prognostic groups: good prognosis, pN0 with 0-1 additional predictors; intermediate prognosis, pN1 with 0-1 additional predictors; poor prognosis, any pN with two additional predictors. The cross-validation yielded excellent median model accuracy of 88%. The retrospective design and the short follow-up could limit our findings. CONCLUSIONS: We developed and validated a novel and easy-to-use prognostic instrument to predict PCRD after RP+PLND. This model may allow clinicians to correctly counsel patients regarding the intensity of follow-up and to tailor adjuvant treatments. PATIENT SUMMARY: Prediction of mortality after primary surgery for prostate cancer is important for subsequent treatment plans. We present an accurate postoperative model to predict cancer mortality after radical prostatectomy for high-risk prostate cancer.

Impact of Lymph Node Burden on Survival of High-risk Prostate Cancer Patients Following Radical Prostatectomy and Pelvic Lymph Node Dissection.

AIM: To determine the impact of the extent of lymph node invasion (LNI) on long-term oncological outcomes after radical prostatectomy (RP). MATERIAL AND METHODS: In this retrospective study, we examined the data of 1,249 high-risk, non-metastatic PCa patients treated with RP and pelvic lymph node dissection (PLND) between 1989 and 2011 at eight different tertiary institutions. We fitted univariate and multivariate Cox models to assess independent predictors of cancer-specific survival (CSS) and overall survival (OS). The number of positive lymph node (LN) was dichotomized according to the most informative cutoff predicting CSS. Kaplan-Meier curves assessed CSS and OS rates. Only patients with at least 10 LNs removed at PLND were included. This cutoff was chosen as a surrogate for a well performed PNLD. RESULTS: Mean age was 65 years (median: 66, IQR 60-70). Positive surgical margins were present in 53.7% (n = 671). Final Gleason score (GS) was 2-6 in 12.7% (n = 158), 7 in 52% (n = 649), and 8-10 in 35.4% (n = 442). The median number of LNs removed during PLND was 15 (IQR 12-17). Of all patients, 1,128 (90.3%) had 0-3 positive LNs, while 126 (9.7%) had ≥4 positive LNs. Patients with 0-3 positive LNs had significantly better CSS outcome at 10-year follow-up compared to patients with ≥4 positive LNs (87 vs. 50%; p < 0.0001). Similar results were obtained for OS, with a 72 vs. 37% (p < 0.0001) survival at 10 years for patients with 0-3 vs. ≥4 positive LNs, respectively. At multivariate analysis, final GS of 8-10, salvage ADT therapy, and ≥4 (vs. <4) positive LNs were predictors of worse CSS and OS. Pathological stage pT4 was an additional predictor of worse CSS. CONCLUSION: Four or more positive LNs, pathological stage pT4, and final GS of 8-10 represent independent predictors for worse CSS in patients with high-risk PCa. Primary tumor biology remains a strong driver of tumor progression and patients having ≥4 positive LNs could be considered an enriched patient group in which novel treatment strategies should be studied.

Construct, content and face validity of the camera handling trainer (CHT): a new E-BLUS training task for 30° laparoscope navigation skills.

PURPOSE: Assessing construct, face and content validity of the camera handling trainer (CHT), a novel low-fidelity training device for 30° laparoscope navigation skills. METHODS: We developed a custom-designed box trainer with clinically based graphic targets. A total of 117 participants, stratified according to their previous experience (novice, competent, expert), took part to a CHT session and subsequently were asked to fill out a survey to assess the impact of the CHT on their 30° laparoscope navigation skills. Sixty of them were also studied for task performance during a 1-h session, with multiple time measurements. RESULTS: All participants, regardless of the previous experience, significantly improved their performance after the CHT session. Regarding construct validity, the mean task performance on the last measurement for novice group was found to be comparable to the mean first attempt of both competent (p = 0.12) and expert (p = 0.24) participants. All participants agreed that "the CHT is a valid training tool" and that "the CHT should be part of the regular dry laboratory training sessions", assessing both face and content validity. Limitations include the need for assessment of predictive validity. CONCLUSIONS: The CHT is a valid training tool for 30° laparoscope navigation and thus should be considered as one of the fundamental exercises during basic laparoscopic hands-on training sessions for urologists.

Positive surgical margins after minimally invasive radical prostatectomy in patients with pT2 and pT3a disease could be considered pathological upstaging.

OBJECTIVE: To assess the prognostic significance of positive surgical margins (PSMs) after minimally invasive radical prostatectomy (MIRP) in interaction with other established prognosis factors. PATIENTS AND METHODS: We retrospectively analysed data prospectively collected between 1998 and 2010 for 4628 consecutive patients who underwent MIRP for clinically localized prostate cancer. The impact of PSM on biochemical recurrence (BCR), defined as prostate-specific antigen (PSA) >0.2 ng/mL, was evaluated using multivariable Cox proportional hazards regression. Estimates of BCR-free survival were generated using the Kaplan-Meier method and compared among groups using the log-rank test. RESULTS: The median follow-up was 55 months. On multivariable analysis, PSM was an independent prognostic factor for BCR (adjusted hazard ratio: 2.14 for PSMs vs negative surgical margins (NSMs); 95% confidence interval [CI]: 1.86-2.45; P < 0.001). Other independent predictors for BCR were preoperative PSA, date of surgery, pT stage, Gleason score and lymph node involvement (all P < 0.001). The 5-year BCR-free probability was 80.6% (95% CI: 79-82.2) for NSMs vs 51% (95% CI: 47-55) for PSMs (log-rank P < 0.001). Patients with pT2 and pT3a PSMs had a similar prognosis to those with pT3a and pT3b NSMs, respectively (log-rank P ≥ 0.05). CONCLUSION: A PSM after MIRP is associated with 2.14-fold increased risk of BCR. In patients with pT2 and pT3a disease, a PSM could be considered a pathological upstaging.