Available evidence on HIFU for focal treatment of prostate cancer: a systematic review

ABSTRACT Purpose: Prostate cancer (PCa) is the second most common oncologic disease among men. Radical treatment with curative intent provides good oncological results for PCa survivors, although definitive therapy is associated with significant number of serious side-effects. In modern-era of medicine tissue-sparing techniques, such as focal HIFU, have been proposed for PCa patients in order to provide cancer control equivalent to the standard-of-care procedures while reducing morbidities and complications. The aim of this systematic review was to summarise the available evidence about focal HIFU therapy as a primary treatment for localized PCa. Material and methods: We conducted a comprehensive literature review of focal HIFU therapy in the MEDLINE database (PROSPERO: CRD42021235581). Articles published in the English language between 2010 and 2020 with more than 50 patients were included. Results: Clinically significant in-field recurrence and out-of-field progression were detected to 22% and 29% PCa patients, respectively. Higher ISUP grade group, more positive cores at biopsy and bilateral disease were identified as the main risk factors for disease recurrence. The most common strategy for recurrence management was definitive therapy. Six months after focal HIFU therapy 98% of patients were totally continent and 80% of patients retained sufficient erections for sexual intercourse. The majority of complications presented in the early postoperative period and were classified as low-grade. Conclusions: This review highlights that focal HIFU therapy appears to be a safe procedure, while short-term cancer control rate is encouraging. Though, second-line treatment or active surveillance seems to be necessary in a significant number of patients.

Pelvic lymph node dissection in high-risk prostate cancer

ABSTRACT Introduction: The therapeutic role of pelvic lymph node dissection (PLND) in prostate cancer (PCa) is unknown due to absence of randomized trials. Objective: to present a critical review on the therapeutic benefits of PLND in high risk localized PCa patients. Materials and Methods: A search of the literature on PLND was performed using PubMed, Cochrane, and Medline database. Articles obtained regarding diagnostic imaging and sentinel lymph node dissection, PLND extension, impact of PLND on survival, PLND in node positive "only" disease and PLND surgical risks were critically reviewed. Results: High-risk PCa commonly develops metastases. In these patients, the possibility of presenting lymph node disease is high. Thus, extended PLND during radical prostatectomy may be recommended in selected patients with localized high-risk PCa for both accurate staging and therapeutic intent. Although recent advances in detecting patients with lymph node involvement (LNI) with novel imaging and sentinel node dissection, extended PLND continues to be the most accurate method to stage lymph node disease, which may be related to the number of nodes removed. However, extended PLND increases surgical time, with potential impact on perioperative complications, hospital length of stay, rehospitalization and healthcare costs. Controversy persists on its therapeutic benefit, particularly in patients with high node burden. Conclusion: The impact of PLND on biochemical recurrence and PCa survival is unclear yet. Selection of patients may benefit from extended PLND but the challenge remains to identify them accurately. Only prospective randomized study would answer the precise role of PLND in high-risk pelvis confined PCa patients.

Does mpMRI guidance improve HIFU partial gland ablation compared to conventional ultrasound guidance? Early functional outcomes and complications from a single center

ABSTRACT Background Focal therapy (FT) for localized prostate cancer (PCa) treatment is raising interest. New technological mpMRI-US guided FT devices have never been compared with the previous generation of ultrasound-only guided devices. Materials and Methods We retrospectively analyzed prospectively recorded data of men undergoing FT for localized low- or intermediate-risk PCa with US- (Ablatherm®-2009 to 2014) or mpMRI-US (Focal One®-from 2014) guided HIFU. Follow-up visits and data were collected using internationally validated questionnaires at 1, 2, 3, 6 and 12 months. Results We included n=88 US-guided FT HIFU and n=52 mpMRI-US guided FT HIFU respectively. No major baseline differences were present except higher rates of Gleason 3+4 for the mpMRI-US group. No major differences were present in hospital stay (p=0.1), catheterization time (p=0.5) and complications (p=0.2) although these tended to be lower in the mpMRI-US group (6.8% versus 13.2% US FT group). At 3 months mpMRI-US guided HIFU had significantly lower urine leak (5.1% vs. 15.9%, p=0.04) and a lower drop in IIEF scores (2 vs. 4.2, p=0.07). Of those undergoing 12-months control biopsy in the mpMRI-US-guided HIFU group, 26% had residual cancer in the treated lobe. Conclusion HIFU FT guided by MRI-US fusion may allow improved functional outcomes and fewer complications compared to US- guided HIFU FT alone. Further analysis is needed to confirm benefits of mpMRI implementation at a longer follow-up and on a larger cohort of patients.

Clinical and surgical assistance in prostate cancer during the COVID-19 Pandemic: implementation of assistance protocols

ABSTRACT Purpose: Propose an approach of prostate cancer (PCa) patients during COVID-19 pandemic. Material and Methods: We conducted a review of current literature related to surgical and clinical management of patients during COVID-19 crisis paying special attention to oncological ones and especially those suffering from PCa. Based on these publications and current urological guidelines, a manual to manage PCa patients is suggested. Results: Patients suffering from cancer are likely to develop serious complications from COVID-19 disease together with an increased risk of postoperative morbidity and mortality. Therefore, the management of oncological patients should be taken into special consideration and most of the treatments postponed. In case the procedure is not deferrable, it should be adapted to the current situation. While the shortest radiotherapy (RT) regimens should be applied, surgical procedures must undergo the following recommendations proposed by main surgical associations. PCa prognosis is generally favourable and therefore one can safely delay most of the biopsies up to 6 months without interfering with survival outcomes in the vast majority of cases. In the same way, most of the localised PCa patients are suitable for active surveillance (AS) or hormonal therapy until local definitive treatment could be reconsidered. In metastatic as well as castration resistant PCa stages, adding androgen receptor targeted agents (abiraterone, apalutamide, darolutamide or enzalutamide) to androgen-deprivation therapy (ADT) could be considered in high risk patients. On the contrary, chemotherapy, immunotherapy and Radium-223 must be avoided with regard to the consequence of hematologic toxicity and risk of COVID-19 infection because of immunodepression. Conclusions: Most of the biopsies should be delayed while AS is advised in those patients with low risk PCa. ADT allows us to defer definitive local treatment in many cases of intermediate and high risk PCa. In regard to metastatic and castration resistant PCa, combination therapies with abiraterone, apalutamide, darolutamide or enzalutamide could be considered. Chemotherapy, Radium-223 and immunotherapy are discouraged.

HRQOL related to urinary diversion in Radical Cystectomy: a systematic review of recent literature

ABSTRACT Introduction: The health-related QoL is a patient-centered evaluation covering several aspects. This evaluation seems to be particularly important in patients submitted to radical cystectomy (RC) and urinary diversion with ileal conduit (IC) or a neobladder (NB). Objective: Review all recent data comparing QoL outcomes after radical cystectomy with NB and IC diversions. Evidence Acquisition: A systematic search in PubMed/Medline, Embase, and Cochrane databases was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement in December 2018. All articles published from January 01, 2012 to December 31, 2018, were included. A study was considered relevant if it compared QoL outcomes using validated questionnaires (EORTC QLQ C30, FACT-G, FACT-BL, FACT-VCI, and BCI). Evidence Synthesis: In 11 included studies, a total of 1389 participants were accounted (730 NB and 659 IC cases). The studies were conducted in 8 different countries, two were prospective, and none was randomized. There were two studies favoring results with a neobladder, 3 with incontinent diversion and 6 with no differences. The EORTC-QLQ-C30 was the most used instrument (5 studies) followed by FACT VCI and BCI (3 studies each). Given the heterogeneity of data and lack of prospective studies, a meta-analysis was not performed. Conclusion: No superiority of one urinary diversion was characterized. It seems that the choice must be individualized with an extensive preoperative orientation of the patient and their relatives. That will probably influence how the patient accepts the new condition.

Biochemical recurrence after radical prostatectomy: what does it mean?

ABSTRACT Background Radical prostatectomy (RP) has been used as the main primary treatment for prostate cancer (PCa) for many years with excellent oncologic results. However, approximately 20-40% of those patients has failed to RP and presented biochemical recurrence (BCR). Prostatic specific antigen (PSA) has been the pivotal tool for recurrence diagnosis, but there is no consensus about the best PSA threshold to define BCR until this moment. The natural history of BCR after surgical procedure is highly variable, but it is important to distinguish biochemical and clinical recurrence and to find the correct timing to start multimodal treatment strategy. Also, it is important to understand the role of each clinical and pathological feature of prostate cancer in BCR, progression to metastatic disease and cancer specific mortality (CSM). Review design A simple review was made in Medline for articles written in English language about biochemical recurrence after radical prostatectomy. Objective To provide an updated assessment of BCR definition, its meaning, PCa natural history after BCR and the weight of each clinical/pathological feature and risk group classifications in BCR, metastatic disease and CSM.

Focal therapy with high-intensity focused ultrasound for prostate cancer in the elderly: a feasibility study with 10 years follow-up

PURPOSE: To evaluate the long-term efficacy of prostate cancer control and complication rates, in the elderly, after focal therapy with high-intensity focused ultrasound (HIFU). MATERIALS AND METHODS: Between June 1997 and March 2000, patients with localized prostate cancer were included into a focal therapy protocol. Inclusion criteria were: PSA < 10 ng/mL, < 3 positive biopsies with only 1 lobe involved, clinical stage < T2a, Gleason score < 7 (3+4), negative CT scan and bone scan. Hemi-ablation of the prostate was performed with the Ablatherm(R) device. Survival, complication rates and urinary continence were evaluated. Control biopsies were performed at 1 year. Treatment failure was defined as a positive biopsy or need for salvage therapy. RESULTS: Twelve patients with a mean age 70 years were included. Median follow-up was 10 years. Control prostate biopsies were negative in 11/12 (91 percent) patients. Overall survival was 83 percent (10/12) and cancer specific survival was 100 percent at 10 years. Two patients died from other causes. Recurrence free survival was 90 percent (95 percent CI; 0.71-1) at 5 years, and 38 percent (95 percent CI; 0.04-0.73) at 10 years. Five patients had salvage therapy with repeat HIFU (n = 1) or hormonal therapy (n = 4) and all salvage patients were alive at 10 years. No patients developed lymph node or bone metastasis. No patients suffered from urinary incontinence. International Prostate Symptom Score was stable at 1 year. Complications included two urinary tract infections and one episode of acute urinary retention. CONCLUSIONS: Hemi-prostate ablation with HIFU can be safely performed in selected elderly patients with adequate long-term cancer control and low complication rates. Results from larger prospective studies using improved imaging techniques and extensive biopsy protocols are awaited.

Current status of natural orifice trans-endoscopic surgery (NOTES) and laparoendoscopic single site surgery (LESS) in urologic surgery

Laparoendoscopic single site surgery (LESS) and natural orifice transluminal endoscopic surgery (NOTES) represent novel approaches in urological surgery. To perform a review of the literature in order describe the current status of LESS and NOTES in Urology. References for this manuscript were obtained by performing a review of the available literature in PubMed from 01-01-02 to 15-05-09. Search terms included single port, single site, NOTES, LESS and single incision. A total of 412 manuscripts were initially identified. Out of these, 64 manuscripts were selected based in their urological content. The manuscript features subheadings for experimental and clinical studies, as NOTES-LESS is a new surgical technique and its future evolution will probably rely in initial verified feasibility. A subheading for reviews presents information regarding common language and consensus for the techniques. The issue of complications published in clinical series and the future needs of NOTES-LESS, are also presented.

Radical prostatectomy: evolution of surgical technique from the laparoscopic point of view: [review]

PURPOSE: To review the literature and present a current picture of the evolution in radical prostatectomy from the laparoscopic point of view. MATERIALS AND METHODS: We conducted an extensive Medline literature search. Articles obtained regarding laparoscopic radical prostatectomy (LRP) and our experience at Institut Montsouris were used for reassessing anatomical and technical issues in radical prostatectomy. RESULTS: LRP nuances were reassessed by surgical teams in order to verify possible weaknesses in their performance. Our basic approach was to carefully study the anatomy and pioneer open surgery descriptions in order to standardized and master a technique. The learning curve is presented in terms of an objective evaluation of outcomes for cancer control and functional results. In terms of technique-outcomes, there are several key elements in radical prostatectomy, such as dorsal vein control-apex exposure and nerve sparing with particular implications in oncological and functional results. Major variations among the surgical teams' performance and follow-up prevented objective comparisons in radical prostatectomy. The remarkable evolution of LRP needs to be supported by comprehensive results. CONCLUSIONS: Radical prostatectomy is a complex surgical operation with difficult objectives. Surgical technique should be standardized in order to allow an adequate and reliable performance in all settings, keeping in mind that cancer control remains the primary objective. Reassessing anatomy and a return to basics in surgical technique is the means to improve outcomes and overcome the difficult task of the learning curve, especially in minimally access urological surgery.

Cirugía y tratamiento sistémico en cáncer de vejiga invasor / Surgery and systemic treatment for invasive bladder cancer

El tratamiento del cáncer vesical de células transicionales con invasión muscular sigue siendo difícil, debido a los múltiples patrones de comportamiento biológico que muestra esta enfermedad. Existe controversia en cuanto a la aplicación de tratamiento sistémico en cáncer invasor vesical y el tiempo ideal de indicación de la quimioterapia perioperatoria. Se presenta una visión general de la terapia sistémica en cáncer invasor vesical.

Defining adequate therapy in every patient with invasive transitional cell carcinoma remains difficult, because multiple biologic behavior patterns can be found in this disease. There is controversy regarding the use of systemic treatment in invasive bladder carcinoma and the momentum for chemotherapy deployment. We present an overview of current trends for systemic treatment in bladder carcinoma.