Salvage treatments after focal therapy for prostate cancer - a comprehensive review.

OBJECTIVE: To review the literature on salvage treatments after focal therapy (FT) for prostate cancer (PCa). MATERIALS AND METHODS: A non-systematic literature review was conducted on PubMed, Scopus, and Web of Science up to March 15, 2024, for studies that assessed salvage treatment outcomes in patients with recurrent PCa after primary FT. Original prospective and retrospective studies with more than 10 patients were included. Reviews, editorial comments, conference abstracts, and studies focusing solely on whole-gland treatments were excluded. RESULTS: Twenty-one studies with a total of 1012 patients were included. The most reported salvage treatments were salvage radical prostatectomy followed by re-do ablation therapy. Only one study evaluated salvage radiation therapy. Except for one prospective study, all studies were retrospective. Oncological outcomes showed acceptable biochemical recurrence rates. Functional outcomes varied, with significant impacts observed on erectile function across modalities, though continence rates were less impacted. Complications were generally low across all treatment options. CONCLUSION: Salvage treatment post-primary FT is feasible, safe, and has reasonable oncologic outcomes. However, significant declines in sexual function are common, while continence is comparatively less affected. The literature primarily consists of retrospective studies; hence, future research should focus on large-scale prospective evaluations to better define treatment protocols and improve patient outcomes.

The role of androgen deprivation therapy prior to radical prostatectomy in high-risk prostate cancer: a systematic review.

INTRODUCTION: Patients with high-risk prostate cancer (HRPCa) are prone to have worse pathological features, resulting in early biochemical recurrence after radical prostatectomy (RP). There is an urgent need to develop novel treatment strategies for this group of patients to optimize their outcomes. The purpose of this study is to perform a systematic review of the role of neoadjuvant hormonal therapy (NHT) followed by RP in HRPCa patients. EVIDENCE ACQUISITION: We performed a systematic review of the following databases, MEDLINE (PubMed), EMBASE, Cochrane Library, and clinical Trial.gov; between January 2007 and August 2023, following the PRISMA guidelines. EVIDENCE SYNTHESIS: After screening and deduplication, we included ten studies from an initial pool of 1275. The risk of bias was low in observational studies but ranged from moderate to low in controlled trials. Five studies utilized traditional androgen deprivation treatments (ADT), revealing favorable pathological outcomes but inconsistency in evaluating oncological results. Additionally, four studies focused on RP combined with androgen receptor pathway inhibitors (ARPIs) in the NHT setting, all showing primarily positive pathological outcome, with no clear evidence of an oncological benefit. Limited long-term follow-up data and a shortage of randomized controlled trials were evident among all the studies included in this review, regardless of the type of hormonal treatment used. CONCLUSIONS: Different hormonal treatments, including traditional ADT and ARPIs, yield positive pathology outcomes. Oncological evidence remains limited, echoing older findings predating ARPIs. Definitive conclusions require longer follow-ups and precise patient selection. Currently, insufficient evidence support ARPIs' superiority over conventional therapy before RP.

Humoral complementomics - exploration of noninvasive complement biomarkers as predictors of renal cancer progression.

Despite the progress of anti-cancer treatment, the prognosis of many patients with solid tumors is still dismal. Reliable noninvasive biomarkers are needed to predict patient survival and therapy response. Here, we propose a Humoral Complementomics approach: a work-up of assays to comprehensively evaluate complement proteins, activation fragments, and autoantibodies targeting complement proteins in plasma, which we correlated with the intratumoral complement activation, and/or local production, focusing on localized and metastatic clear cell renal cell carcinoma (ccRCC). In two prospective ccRCC cohorts, plasma C2, C5, Factor D and properdin were elevated compared to healthy controls, reflecting an inflammatory phenotype that correlated with plasma calprotectin levels but did not associate with CRP or with patient prognosis. Conversely, autoantibodies against the complement C3 and the reduced form of FH (a tumor neo-epitope reported in lung cancer) correlated with a favorable outcome. Our findings pointed to a specific group of patients with elevated plasma C4d and C1s-C1INH complexes, indicating the initiation of the classical pathway, along with elevated Ba and Bb, indicating alternative pathway activation. Boostrapped Lasso regularized Cox regression revealed that the most predictive complement biomarkers were elevated plasma C4d and Bb levels at the time of surgery, which correlated with poor prognosis. In conclusion, we propose Humoral Complementomics as an unbiased approach to study the global state of the complement system in any pathological plasma sample and disease context. Its implementation for ccRCC revealed that elevated C4d and Bb in plasma are promising prognostic biomarkers, correlating with shorter progression-free survival.

Urinary Symptoms Change and Quality of Life After Robotic Radical Prostatectomy: A Secondary Analysis of a Randomized Controlled Trial.

OBJECTIVE: To present the patient-reported quality of life (QoL) outcomes from a prospective, randomized controlled trial comparing the use of pelvic floor muscle training (PFMT) and duloxetine after robot-assisted radical prostatectomy (RARP). METHODS: We identified 213 men with organ-confined disease having post-RARP urinary incontinence who were randomly assigned to received PFMT, duloxetine, combined PFMT-duloxetine and pelvic floor muscle home exercises. Urinary symptoms burden was measured by marked clinical important difference improvement (MCID) defined by using the International Prostate Symptom Score (IPSS) difference of - 8 points (ΔIPSS ≤-8). QoL was assessed according to Visual Analog Scale (VAS), King's Health Questionnaire (KQH), and International Index of Erectile Function (IIEF-5). Multivariable regression analyses aimed to predict MCID, burden of urinary symptoms (IPSS ≥8), and patients reporting to be satisfied (IPSS QoL ≤2) or comfortable (VAS ≤1) post-RARP. RESULTS: Moderate to severe urinary symptoms decreased from 48% preoperatively to 40%, 34%, and 23% at 3, 6, and 12months post-RARP. After surgery, MCID improvement was observed in 19% of patients, and deterioration in 3.3%. Large prostate was the only factor associated to MCID (OR 1.03 [95%CI 1.01-1.05], P = .005). At 6months, patients reached the same degree of preoperative satisfaction. Neurovascular bundle preservation was the only predictor of being comfortable regarding urinary symptoms postoperatively (OR 12.8 [CI95% 1.47-111.7], P = .02 at 3months) and was also associated to higher median postoperative IIEF-5. CONCLUSION: Despite urinary incontinence following RARP, patients with larger prostates experience a reduction of lower urinary tract symptoms within a year, which subsequently elevates QoL. Furthermore, nerve-sparing surgery augments erectile function and urinary outcomes, shaping postoperative QoL.

An updated model for predicting side-specific extraprostatic extension in the era of MRI-targeted biopsy.

PURPOSE: Accurate prediction of extraprostatic extension (EPE) is pivotal for surgical planning. Herein, we aimed to provide an updated model for predicting EPE among patients diagnosed with MRI-targeted biopsy. MATERIALS AND METHODS: We analyzed a multi-institutional dataset of men with clinically localized prostate cancer diagnosed by MRI-targeted biopsy and subsequently underwent prostatectomy. To develop a side-specific predictive model, we considered the prostatic lobes separately. A multivariable logistic regression analysis was fitted to predict side-specific EPE. The decision curve analysis was used to evaluate the net clinical benefit. Finally, a regression tree was employed to identify three risk categories to assist urologists in selecting candidates for nerve-sparing, incremental nerve sparing and non-nerve-sparing surgery. RESULTS: Overall, data from 3169 hemi-prostates were considered, after the exclusion of prostatic lobes with no biopsy-documented tumor. EPE was present on final pathology in 1,094 (34%) cases. Among these, MRI was able to predict EPE correctly in 568 (52%) cases. A model including PSA, maximum diameter of the index lesion, presence of EPE on MRI, highest ISUP grade in the ipsilateral hemi-prostate, and percentage of positive cores in the ipsilateral hemi-prostate achieved an AUC of 81% after internal validation. Overall, 566, 577, and 2,026 observations fell in the low-, intermediate- and high-risk groups for EPE, as identified by the regression tree. The EPE rate across the groups was: 5.1%, 14.9%, and 48% for the low-, intermediate- and high-risk group, respectively. CONCLUSION: In this study we present an update of the first side-specific MRI-based nomogram for the prediction of extraprostatic extension together with updated risk categories to help clinicians in deciding on the best approach to nerve-preservation.

Assessing the efficacy of pelvic floor muscle training and duloxetine on urinary continence recovery following radical prostatectomy: A randomized clinical trial.

BACKGROUND: Urinary incontinence (UI) can negatively impact quality of life (QoL) after robot-assisted radical prostatectomy (RARP). Pelvic floor muscle training (PFMT) and duloxetine are used to manage post-RARP UI, but their efficacy remains uncertain. We aimed to investigate the efficacy of PFMT and duloxetine in promoting urinary continence recovery (UCR) after RARP. METHODS: A randomized controlled trial involving patients with urine leakage after RARP from May 2015 to February 2018. Patients were randomized into 1 of 4 arms: (1) PFMT-biofeedback, (2) duloxetine, (3) combined PFMT-biofeedback and duloxetine, (4) control arm. PFMT consisted of pelvic muscle exercises conducted with electromyographic feedback weekly, for 3 months. Oral duloxetine was administered at bedtime for 3 months. The primary outcome was prevalence of continence at 6 months, defined as using ≤1 security pad. Urinary symptoms and QoL were assessed by using a visual analogue scale, and validated questionnaires. RESULTS: From the 240 patients included in the trial, 89% of patients completed 1 year of follow-up. Treatment compliance was observed in 88% (92/105) of patients receiving duloxetine, and in 97% (104/107) of patients scheduled to PFMT-biofeedback sessions. In the control group 96% of patients had achieved continence at 6 months, compared with 90% (p = 0.3) in the PMFT-biofeedback, 73% (p = 0.008) in the duloxetine, and 69% (p = 0.003) in the combined treatment arm. At 6 months, QoL was classified as uncomfortable or worse in 17% of patients in the control group, compared with 44% (p = 0.01), 45% (p = 0.008), and 34% (p = 0.07), respectively. Complete preservation of neurovascular bundles (NVB) (OR: 2.95; p = 0.048) was the only perioperative intervention found to improve early UCR. CONCLUSIONS: PFMT-biofeedback and duloxetine demonstrated limited impact in improving UCR after RP. Diligent NVB preservation, along with preoperative patient and disease characteristics, are the primary determinants for early UCR.

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.

Development, multi-institutional external validation, and algorithmic audit of an artificial intelligence-based Side-specific Extra-Prostatic Extension Risk Assessment tool (SEPERA) for patients undergoing radical prostatectomy: a retrospective cohort study.

BACKGROUND: Accurate prediction of side-specific extraprostatic extension (ssEPE) is essential for performing nerve-sparing surgery to mitigate treatment-related side-effects such as impotence and incontinence in patients with localised prostate cancer. Artificial intelligence (AI) might provide robust and personalised ssEPE predictions to better inform nerve-sparing strategy during radical prostatectomy. We aimed to develop, externally validate, and perform an algorithmic audit of an AI-based Side-specific Extra-Prostatic Extension Risk Assessment tool (SEPERA). METHODS: Each prostatic lobe was treated as an individual case such that each patient contributed two cases to the overall cohort. SEPERA was trained on 1022 cases from a community hospital network (Trillium Health Partners; Mississauga, ON, Canada) between 2010 and 2020. Subsequently, SEPERA was externally validated on 3914 cases across three academic centres: Princess Margaret Cancer Centre (Toronto, ON, Canada) from 2008 to 2020; L'Institut Mutualiste Montsouris (Paris, France) from 2010 to 2020; and Jules Bordet Institute (Brussels, Belgium) from 2015 to 2020. Model performance was characterised by area under the receiver operating characteristic curve (AUROC), area under the precision recall curve (AUPRC), calibration, and net benefit. SEPERA was compared against contemporary nomograms (ie, Sayyid nomogram, Soeterik nomogram [non-MRI and MRI]), as well as a separate logistic regression model using the same variables included in SEPERA. An algorithmic audit was performed to assess model bias and identify common patient characteristics among predictive errors. FINDINGS: Overall, 2468 patients comprising 4936 cases (ie, prostatic lobes) were included in this study. SEPERA was well calibrated and had the best performance across all validation cohorts (pooled AUROC of 0·77 [95% CI 0·75-0·78] and pooled AUPRC of 0·61 [0·58-0·63]). In patients with pathological ssEPE despite benign ipsilateral biopsies, SEPERA correctly predicted ssEPE in 72 (68%) of 106 cases compared with the other models (47 [44%] in the logistic regression model, none in the Sayyid model, 13 [12%] in the Soeterik non-MRI model, and five [5%] in the Soeterik MRI model). SEPERA had higher net benefit than the other models to predict ssEPE, enabling more patients to safely undergo nerve-sparing. In the algorithmic audit, no evidence of model bias was observed, with no significant difference in AUROC when stratified by race, biopsy year, age, biopsy type (systematic only vs systematic and MRI-targeted biopsy), biopsy location (academic vs community), and D'Amico risk group. According to the audit, the most common errors were false positives, particularly for older patients with high-risk disease. No aggressive tumours (ie, grade >2 or high-risk disease) were found among false negatives. INTERPRETATION: We demonstrated the accuracy, safety, and generalisability of using SEPERA to personalise nerve-sparing approaches during radical prostatectomy. FUNDING: None.

Unilateral Pelvic Lymph Node Dissection in Prostate Cancer Patients Diagnosed in the Era of Magnetic Resonance Imaging-targeted Biopsy: A Study That Challenges the Dogma.

PURPOSE: Bilateral extended pelvic lymph node dissection at the time of radical prostatectomy is the current standard of care if pelvic lymph node dissection is indicated; often, however, pelvic lymph node dissection is performed in pN0 disease. With the more accurate staging achieved with magnetic resonance imaging-targeted biopsies for prostate cancer diagnosis, the indication for bilateral extended pelvic lymph node dissection may be revised. We aimed to assess the feasibility of unilateral extended pelvic lymph node dissection in the era of modern prostate cancer imaging. MATERIALS AND METHODS: We analyzed a multi-institutional data set of men with cN0 disease diagnosed by magnetic resonance imaging-targeted biopsy who underwent prostatectomy and bilateral extended pelvic lymph node dissection. The outcome of the study was lymph node invasion contralateral to the prostatic lobe with worse disease features, ie, dominant lobe. Logistic regression to predict lymph node invasion contralateral to the dominant lobe was generated and internally validated. RESULTS: Overall, data from 2,253 patients were considered. Lymph node invasion was documented in 302 (13%) patients; 83 (4%) patients had lymph node invasion contralateral to the dominant prostatic lobe. A model including prostate-specific antigen, maximum diameter of the index lesion, seminal vesicle invasion on magnetic resonance imaging, International Society of Urological Pathology grade in the nondominant side, and percentage of positive cores in the nondominant side achieved an area under the curve of 84% after internal validation. With a cutoff of contralateral lymph node invasion of 1%, 602 (27%) contralateral pelvic lymph node dissections would be omitted with only 1 (1.2%) lymph node invasion missed. CONCLUSIONS: Pelvic lymph node dissection could be omitted contralateral to the prostate lobe with worse disease features in selected patients. We propose a model that can help avoid contralateral pelvic lymph node dissection in almost one-third of cases.

Diagnostic accuracy and clinical utility of micro-ultrasound guided biopsies in patients with suspected prostate cancer.

Introduction: New technologies to improve quality of prostate biopsies are appearing in clinical practice.We evaluate the performance of a micro-ultrasound device and the Prostate Risk Identification using MicroUltraSound (PRI-MUS) score in detecting clinically significant prostate cancer (csPCa). Material and methods: We retrospectively reviewed data of 139 biopsy- naïve patients with suspicion of prostate cancer, who underwent diagnostic MRI and micro-ultrasonography (microUS), followed by transrectal prostatic biopsy (systematic ±targeted) under local anesthetic. The main objective was to evaluate the performance of the Prostate Risk Identification using MicroUltraSound (PRI-MUS) score in detecting csPCa, defined as International Society of Urological Pathology (ISUP) ≥2. Results: Of all patients, 97 (70%) were found to have PCa, and 62 (45%) having csPCa.Among 100 patients with positive microUS (PRI-MUS score ≥3), 23 (23%) had ncsPCa and 57 (57%) were diagnosed with csPCa (ISUP ≥2); and in 39 patients with negative microUS, 12 (31%) were diagnosed with ncsPCa and 5 (13%) with csPCa.A PRI-MUS score ≥3 presented a sensitivity, specificity, positive predictive value and negative predictive value of 92%, 44%, 57% and 95%, respectively, for the detection of csPCa.The PRI-MUS score had higher areas under the curve than Prostate Imaging Reporting & Data System (PI-RADS) both for targeted (AUC 0.801 vs 0.733) and systematic + targeted (AUC 0.776 vs 0.694) biopsies for csPCa detection. Conclusions: In our cohort, microUS performed well as a diagnostic tool through an easily implementable scale. MicroUS presented similar sensitivity and higher specificity than MRI in detecting csPCa. Further multicenter prospective studies may clarify its role in prostate cancer diagnosis.

Accuracy of PET-choline in nodal staging of localized very high-risk prostate cancer.

OBJECTIVES: Localized very high-risk prostate cancer (VHR PCa) has long suffered from the inex-istence of good lymph node staging methods other than invasive surgery, as computed tomogra-phy has low sensitivity for nodal disease. With the rising use of positron emission tomography (PET), it is clinically meaningful to know its value for these patients. Our goal was to evaluate the real-life diagnostic accuracy of PET Choline in nodal staging, comparing it with the gold standard of extended pelvic lymph node dissection (ePLND). MATERIALS AND METHODS: We reviewed data from a high-volume center, including patients with VHR PCa according to current NCCN guidelines who underwent community 18F-fluorocholine PET/CT; followed by ro-botic assisted laparoscopic prostatectomy (RALP) and ePLND between 2010 and 2021. RESULTS: We included 44 patients and 88 lymph node regions. Among those, 14/44 (31.8%) patients and 20/88 (22.7%) regions had nodal disease present on definitive pathology. In comparison with ePLND, we found a sensitivity of 64.3% (95% CI, 39.2-89.4%), specificity of 83.3% (95% CI, 70.0- 96.7%), PPV of 64.3% (95% CI, 39.2-89.4%), and NPV of 83.3% (95% CI, 70.0-96.7%) for nodal disease on a patient-based analysis; and sensitivity of 35.0% (95% CI, 14.1-60.0%), specificity of 88.2% (95% CI, 80.6-95.9%), PPV of 46.7% (95% CI, 21.4-71.9%), and NPV of 82.2% (95% CI, 73.4-91.0%) on a region-based analysis. CONCLUSIONS: In our view 18F-fluorocholine PET/CT doesn't meet the criteria to be a standard exam for pre-operative staging for patients with VHR PCa, mostly due to its low sensitivity. However, other radiotracers should continue to be investigated in this setting.

Medium-term oncological outcomes of intermediate-risk prostate cancer treated with HIFU or cryotherapy. A single center 10-year experience.

OBJECTIVES: Focal therapies (FTs) are promising techniques for the treatment of localized prostate cancer. We assessed the medium-term oncological outcomes of intermediate-risk prostate cancer (PCa) treated with HIFU or cryotherapy. MATERIALS AND METHODS: One-hundred and fifty consecutive patients with intermediate-risk PCa, treated between 2009 and 2018 at a single center were included. Primary study outcome was failure-free survival (FFS), defined as absence of additional treatment, systemic progression or prostate cancer related death. RESULTS: Thirty-seven (25%) patients underwent cryotherapy and 113 (75%) HIFU. Median age was 69 (IQR 62-72) years, with 36 (24%) presenting palpable disease on rectal examination, and median total PSA of 7.85 (IQR 5.75-10.62) ng/mL. Patients were followed for a median of 61 (IQR 48-82) months. FFS at 2 and 4 years was of 75.6% and 53.6%, respectively. Survival from whole gland or systematic treatment at 2 and 4 years was of 78.9% and 53.9%, respectively. Patients with FFS presented lower total PSA nadir (1.89 vs 3.25 ng/mL, p < 0.001), higher % PSA reduction at 3 months (66.1% vs 49.3%, p < 0.001), and at nadir (75.5% vs 55.8%, p < 0.001). Other characteristics such has the treatment modality, age, prostate size, initial total PSA, cT stage, International Society of Urological Pathology (ISUP), tumor location and biopsy results by region did not differ between patients failing and not failing FT. Complications were uncommon (13%), with only onr (1%) patient having Clavien-Dindo grade > II. No deaths due to treatment were registered. CONCLUSIONS: At medium-term, FTs for intermediate-risk PCa presented good oncological results, with an excellent safety profile.

Focal High-Intensity Focused Ultrasound vs. Active Surveillance for ISUP Grade 1 Prostate Cancer: Medium-Term Results of a Matched-Pair Comparison.

INTRODUCTION/BACKGROUND: Only 1 randomized controlled trial has compared focal therapy and active surveillance (AS) for the low-risk prostate cancer (PCa). We investigated whether focal HIFU (fHIFU) yields oncologic advantages over AS for low-risk PCa. MATERIALS AND METHODS: We included 2 non-randomized prospective series of 132 (fHIFU) and 421 (AS) consecutive patients diagnosed with ISUP 1 PCa between 2008 and 2018. A matched pair analysis was performed to decrease potential bias. Study main outcomes were freedom from radical treatment (RT) or androgen-deprivation therapy (ADT), treatment-free survival (TFS), time to metastasis, and overall survival (OS). RESULTS: Median fHIFU follow-up was 50 months (interquartile range, 29-84 months). Among matched variables, no major differences were recorded except for AS having more suspicious digital rectal examination findings (P = .0074) and recent enrollment year (P = .0005). Five-year intervention-free survival from RT or ADT was higher for the fHIFU cohort (67.4% vs. 53.8%; P = .0158). Time to treatment was approximately 10 months shorter for AS than for fHIFU (time to RT, P = .0363; time to RT or ADT, P = .0156; time to any treatment, P = .0319). No differences were found in any-TFS (fHIFU, 61.4% vs. AS, 53.8%; P = .2635), OS (fHIFU, 97% vs. AS, 97%; P = .9237), or metastasis (n = 0 in fHIFU and n = 2 in AS; P = .4981). Major complications (≥ Clavien 3) were rare (n = 4), although 36.4% of men experienced complications. No relevant changes were noted in continence (P = .3949). CONCLUSION: At a 4-year median follow-up, fHIFU for mainly low-risk PCa (ISUP grade 1) is safe, may decrease the need for radical treatment or ADT and may allow longer time to treatment compared to AS. Nonetheless, no advantages are seen in PCa progression and/or death (OS).

Accuracy of the CUETO, EORTC 2016 and EAU 2021 scoring models and risk stratification tables to predict outcomes in high-grade non-muscle-invasive urothelial bladder cancer.

PURPOSE: Non-muscle-invasive bladder cancers (NMIBC) constitute 3-quarters of all primary diagnosed bladder tumors. For risk-adapted management of patients with NMIBC, different risk group systems and predictive models have been developed. This study aimed to externally validate EORTC2016, CUETO and novel EAU2021 risk scoring models in a multi-institutional retrospective cohort of patients with high-grade NMIBC who were treated with an adequate BCG immunotherapy. METHODS: The Kaplan-Meier estimates for recurrence-free survival and progression-free survival were performed, predictive abilities were assessed using the concordance index (C-index) and area under the curve (AUC). RESULTS: A total of 1690 patients were included and the median follow-up was 51 months. For the overall cohort, the estimates recurrence-free survival and progression-free survival rates at 5-years were 57.1% and 82.3%, respectively. The CUETO scoring model had poor discrimination for disease recurrence (C-index/AUC for G2 and G3 grade tumors: 0.570/0.493 and 0.559/0.492) and both CUETO (C-index/AUC for G2 and G3 grade tumors: 0.634/0.521 and 0.622/0.525) EAU2021 (c-index/AUC: 0.644/0.522) had poor discrimination for disease progression. CONCLUSION: Both the CUETO and EAU2021 scoring systems were able to successfully stratify risks in our population, but presented poor discriminative value in predicting clinical events. Due to the lack of data, model validation was not possible for EORTC2016. The CUETO and EAU2021 systems overestimated the risk, especially in highest-risk patients. The risk of progression according to EORTC2016 was slightly lower when compared with our population analysis.

Neoadjuvant chemotherapy does not increase peri-operative morbidity following radical cystectomy.

OBJECTIVE: To determine whether use of neoadjuvant chemotherapy (NAC) is associated with a higher risk of post-operative complications following radical cystectomy (RC) for bladder cancer (BCa). MATERIALS AND METHODS: We retrospectively reviewed records of patients undergoing RC for non-metastatic urothelial BCa at 13 tertiary care centres from 2007-2019. Patients who received NAC ('NAC + RC' group) were compared with those who underwent upfront RC ('RC alone' group) for intra-operative variables, incidence of post-operative complications as per the Clavien-Dindo classification (CDC) and rates of re-admission and re-intervention. Multivariable logistic regression analysis was performed to determine predictors of CDC overall and CDC major (grade III-V) complications. We also analysed the trend of NAC utilization over the study period. RESULTS: Of the 3113 patients included, 968 (31.1%) received NAC while the remaining 2145 (68.9%) underwent upfront RC for BCa. There was no significant difference between the NAC + RC and RC alone groups with regards to 30-day CDC overall (53.2% vs 54.6%, p = 0.4) and CDC major (15.5% vs 16.5%, p = 0.6) complications. The two groups were comparable for the rate of surgical re-intervention (14.6% in each group) and re-hospitalization (19.6% in NAC + RC vs 17.9% in RC alone, p = 0.2%) at 90 days. On multivariable regression analysis, NAC use was not found to be a significant predictor of 90-day CDC overall (OR 1.02, CI 0.87-1.19, p = 0.7) and CDC major (OR 1.05, CI 0.87-1.26, p = 0.6) complications. We also observed that the rate of NAC utilization increased significantly (p < 0.001) from 11.1% in 2007 to 41.2% in 2019, reaching a maximum of 48.3% in 2018. CONCLUSION: This large multicentre analysis with a substantial rate of NAC utilization showed that NAC use does not lead to an increased risk of post-operative complications following RC for BCa. This calls for increasing NAC use to allow patients to avail of its proven oncologic benefit.

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.

The Cancer of the Bladder Risk Assessment (COBRA) score accurately predicts cancer-specific survival after radical cystectomy: external validation and lymphovascular invasion assessment value to improve its performance.

The Cancer of the Bladder Risk Assessment (COBRA) score is a predictive tool for estimating Cancer Specific Survival (CSS) after Radical Cystectomy (RC) for urothelial carcinoma. COBRA score variables are: age at RC, Tumor stage and Lymph Node Density (LND). We sought to externally validate the COBRA score and to improve its performance in estimating CSS adding Lymphovascular Invasion (LVI) as a further variable (Modified COBRA score). Clinicopathological and survival data from 789 patients who underwent RC and Pelvic Lymph Node Dissection (PLND) between January 2007 and December 2020 in two European referral centers (Paris, France and Badalona, Spain) were analyzed. COBRA score was applied to our cohort and CSS Kaplan-Meier curves were performed. Univariable and Multivariable analysis was performed in order to identify risk factors for Cancer Specific Mortality (CSM) and a score was assigned for any statistically significant risk factor; afterward, c-index calculation was performed and CCS curves have been plotted for the model after having integrated LVI variable to the COBRA score. Finally, we compared both COBRA score and Modified COBRA score models with the established AJCC model. A total of 789 patients underwent RC during the observation period. Complete data were available for 731 patients with a median follow-up of 32 months (8-47). CSM was 27.6% (no. 218 patients) at follow-up. When COBRA score was applied to our cohort, c-index was 0.76. Regression COX analysis has shown HR 0.36, CI 95% (0.16-0.83), P = .016 for patients with COBRA score 1; HR 0, CI 95% (0-1.77), P =.94 for score 2; HR 0.51, CI 95% (0.39 -0.67), P =.001 for score 3; HR 1.67, CI 95% (1.23-2.27), P =.001 for score 4; HR 2.45, CI 95% (1.51-3.99), P =.001 for score 5; HR 2.01, CI 95% (1.42-2.85), P =.001 for score 6 and HR 0.66, CI 95% (0.09-4.73), P =.682 for score 7. When the LVI variable was added to the CSS predictive model the discriminatory power increased to a c-index of 0.78. COBRA score adequately identifies those patients with a higher risk of CSM, with a c-index of 0.76. Moreover, LVI variable further improves its predictive accuracy from c-index of 0.76 to c-index of 0.78. LVI variable could be integrated in the COBRA score to optimizing prognosis stratification for patients who undergo RC.

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.

Pelvic lymph node dissection in high-risk prostate cancer.

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.