Safety and quality of cystectomy and pelvic lymph node dissection after neoadjuvant durvalumab and cisplatin/gemcitabine.

OBJECTIVE: To report on the surgical safety and quality of pelvic lymph node dissection (PLND) in patients treated with radical cystectomy (RC) and PLND for muscle-invasive bladder cancer (MIBC) after neoadjuvant chemo-immunotherapy. PATIENTS AND METHODS: The Swiss Group for Clinical Cancer Research (SAKK) 06/17 was an open-label single-arm phase II trial including 61 cisplatin-fit patients with clinical stage (c)T2-T4a cN0-1 operable urothelial MIBC or upper urinary tract cancer. Patients received neoadjuvant cisplatin/gemcitabine and durvalumab followed by surgery. Prospective quality assessment of surgeries was performed via central review of intraoperative photographs. Postoperative complications were assessed using the Clavien-Dindo Classification. Data were analysed descriptively. RESULTS: A total of 50 patients received RC and PLND. All patients received neoadjuvant chemo-immunotherapy. The median (interquartile range) number of lymph nodes removed was 29 (23-38). No intraoperative complications were registered. Grade ≥III postoperative complications were reported in 12 patients (24%). Complete nodal dissection (100%) was performed at the level of the obturator fossa (bilaterally) and of the left external iliac region; in 49 patients (98%) at the internal iliac region and at the right external iliac region; in 39 (78%) and 38 (76%) patients at the right and left presacral level, respectively. CONCLUSION: This study supports the surgical safety of RC and PLND following neoadjuvant chemo-immunotherapy in patients with MIBC. The extent and completeness of protocol-defined PLND varies between patients, highlighting the need to communicate and monitor the surgical template.

A Phase 1/2 Single-arm Clinical Trial of Recombinant Bacillus Calmette-Guérin (BCG) VPM1002BC Immunotherapy in Non-muscle-invasive Bladder Cancer Recurrence After Conventional BCG Therapy: SAKK 06/14.

BACKGROUND: VPM1002BC is a genetically modified Mycobacterium bovis bacillus Calmette-Guérin (BCG) strain with potentially improved immunogenicity and attenuation. OBJECTIVE: To report on the efficacy, safety, tolerability and quality of life of intravesical VPM1002BC for the treatment of non-muscle-invasive bladder cancer (NMIBC) recurrence after conventional BCG therapy. DESIGN, SETTING, AND PARTICIPANTS: We designed a phase 1/2 single-arm trial (NCT02371447). Patients with recurrent NMIBC after BCG induction ± BCG maintenance therapy and intermediate to high risk for cancer progression were eligible. INTERVENTION: Patients were scheduled for standard treatment of six weekly instillations with VPM1002BC followed by maintenance for 1 yr. Treatment was stopped in cases of recurrence. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was defined as the recurrence-free rate (RFR) in the bladder 60 wk after trial registration. The sample size was calculated based on the assumption that ≥30% of the patients would be without recurrence at 60 wk after registration. RESULTS AND LIMITATIONS: After exclusion of two ineligible patients, 40 patients remained in the full analysis set. All treated tumours were of high grade and 27 patients (67.5%) presented with carcinoma in situ. The recurrence-free rate in the bladder at 60 wk after trial registration was 49.3% (95% confidence interval [CI] 32.1-64.4%) and remained at 47.4% (95% CI 30.4-62.6%] at 2 yr and 43.7% (95% CI 26.9-59.4%) at 3 yr after trial registration. At the same time, progression to muscle-invasive disease had occurred in three patients and metastatic disease in four patients. Treatment-related grade 1, 2, and 3 adverse events (AEs) were observed in 14.3%, 54.8%, and 4.8% of the patients, respectively. No grade ≥4 AEs occurred. Two of the 42 patients did not tolerate five or more instillations during induction. Limitations include the single-arm trial design and the low number of patients for subgroup analysis. CONCLUSIONS: At 1 yr after treatment start, almost half of the patients remained recurrence-free after therapy with VPM100BC. The primary endpoint of the study was met and the therapy is safe and well tolerated. PATIENT SUMMARY: We conducted a trial of VPM100BC, a genetically modified bacillus Calmette-Guérin (BCG) strain for treatment of bladder cancer not invading the bladder muscle. At 1 year after the start of treatment, almost half of the patients with a recurrence after previous conventional BCG were free from non-muscle-invasive bladder cancer (NMIBC). The results are encouraging and VPM1002BC merits further evaluation in randomised studies for patients with NMIBC.

Substaging of pT1 Urothelial Bladder Carcinoma Predicts Tumor Progression and Overall Survival.

INTRODUCTION: Limitations in tumor staging and the heterogeneous natural evolution of pT1 urothelial bladder carcinoma (UBC) make the choice of treatment challenging. We evaluated if histopathological substaging (pT1a, pT1b, and pT1c) helps predict disease recurrence, progression, and overall survival following transurethral resection of the bladder (TURB). METHODS: We included 239 consecutive patients diagnosed with pT1 UBC at TURB in a single institution since 2001. Each sample was interpreted by our specialized uropathologists trained to subclassify pT1 stage. Three groups were distinguished according to the degree of invasion: T1a (up to the muscularis mucosae [MM]), T1b (into the MM), and T1c (beyond the MM). RESULTS: T1 substaging was possible in 217/239 (90%) patients. pT1a, b, and c occurred in 124 (57), 59 (27), and 34 (16%), respectively. The median follow-up was 3.1 years, with a cumulative recurrence rate of 52%, progression rate of 20%, and survival rate of 54%. Recurrence was not significantly associated with tumor substage (p = 0.61). However, the Kaplan-Meier survival analysis showed a significantly higher progression rate among T1b (31) and T1c (26%) tumors than T1a (13%) (log-rank test: p = 0.001) stages. In a multivariable model including gender, age, ASA score, smoking, tumor grade, and presence of carcinoma in situ, T1 substage was the single variable significantly associated with progression-free survival (HR 1.7, p = 0.005). Nineteen patients (9%) needed radical cystectomy; among them, 12/19 (63%) had an invasive tumor. Overall survival was significantly associated with tumor substaging (p = 0.001). CONCLUSION: Histopathological substaging of pT1 UBC is significantly associated with tumor progression and overall survival and therefore appears to be a useful prognostic tool to counsel patients about treatment options.

A novel nomogram provides improved accuracy for predicting biochemical recurrence after radical prostatectomy.

BACKGROUND: Various prediction tools have been developed to predict biochemical recurrence (BCR) after radical prostatectomy (RP); however, few of the previous prediction tools used serum prostate-specific antigen (PSA) nadir after RP and maximum tumor diameter (MTD) at the same time. In this study, a nomogram incorporating MTD and PSA nadir was developed to predict BCR-free survival (BCRFS). METHODS: A total of 337 patients who underwent RP between January 2010 and March 2017 were retrospectively enrolled in this study. The maximum diameter of the index lesion was measured on magnetic resonance imaging (MRI). Cox regression analysis was performed to evaluate independent predictors of BCR. A nomogram was subsequently developed for the prediction of BCRFS at 3 and 5 years after RP. Time-dependent receiver operating characteristic (ROC) curve and decision curve analyses were performed to identify the advantage of the new nomogram in comparison with the cancer of the prostate risk assessment post-surgical (CAPRA-S) score. RESULTS: A novel nomogram was developed to predict BCR by including PSA nadir, MTD, Gleason score, surgical margin (SM), and seminal vesicle invasion (SVI), considering these variables were significantly associated with BCR in both univariate and multivariate analyses (P < 0.05). In addition, a basic model including Gleason score, SM, and SVI was developed and used as a control to assess the incremental predictive power of the new model. The concordance index of our model was slightly higher than CAPRA-S model (0.76 vs. 0.70, P = 0.02) and it was significantly higher than that of the basic model (0.76 vs. 0.66, P = 0.001). Time-dependent ROC curve and decision curve analyses also demonstrated the advantages of the new nomogram. CONCLUSIONS: PSA nadir after RP and MTD based on MRI before surgery are independent predictors of BCR. By incorporating PSA nadir and MTD into the conventional predictive model, our newly developed nomogram significantly improved the accuracy in predicting BCRFS after RP.

Long-term Oncologic Impact of Positive Anterior and Posterior Surgical Margins After Radical Prostatectomy.

OBJECTIVE: The objective of this study was to evaluate the impact of the anterior/posterior status of positive surgical margin (PSM) on long-term outcomes after radical prostatectomy for prostate cancer. PATIENTS AND METHODS: We included 391 consecutive PSM patients after radical prostatectomy between 1993 and 2007 excluding cases with multiple location PSM or lack of anterior/posterior status data. The oncologic impact of anterior-PSM and posterior-PSM were examined by Kaplan-Meier analysis and the Cox proportional hazards model. RESULTS: There were 115 cases (29.4%) with apex-PSM, 257 cases (65.7%) with peripheral PSM, and 19 cases (4.9%) with bladder neck PSM. Among the 257 peripheral PSM cases, 58 cases (22.6%) were with anterior-PSM, 174 cases (67.7%) were with posterior-PSM, and 25 cases (9.7%) were with both anterior and posterior PSM. Over a median follow-up of 12.6 years, patients with anterior-PSM, especially those with low to intermediate Gleason score (≤7), showed a biochemical recurrence (BCR) prognosis similar to those with apex-PSM. In contrast, patients with posterior-PSM showed significantly higher BCR risk on both univariate and multivariate analyses when compared with those with apex-PSM. No impact on metastasis-free survival or overall survival was observed. CONCLUSIONS: In our study, we found that prostate cancer patients with anterior-PSM showed a more favorable BCR prognosis similar to those with apex-PSM when comparing to patients with posterior-PSM. Our study results may help physicians to choose different treatment options for patients diagnosed with different PSM status including considering further adjuvant treatment for patients with posterior-PSM.

Quantification of perineural invasion focus after radical prostatectomy could improve predictive power of recurrence.

Perineural invasion (PNI) after radical prostatectomy (RP) is a common feature of prostate cancer (PCa) and has been associated with unfavorable tumor characteristics. However, its prognostic relevance is controversial. In this study, we evaluated the impact of both PNI status (PNI+ versus PNI-) and quantified number of PNI focus on the long-term prognosis of biochemical recurrence (BCR) after RP. After reevaluating PNI of a total of 721 patients with localized PCa who underwent RP at our institution between 2000 and 2002, we examined associations between PNI status or PNI focus number and clinicopathological factors including tumor stage, Gleason score, margin status, tumor location, preoperative prostate specific antigen, age, prostate weight as well as BCR outcome. PNI was present in 530 of 721 cases (73.5%) of the RP specimens and was associated with more aggressive disease. BCR occurred in 19.4% of all patients within a median follow-up period of 8.5 years. PNI+ status was associated with poor BCR prognosis in univariate analysis but lost in multivariate analysis. Based on the number of PNI focus, PNI was further divided into 2 distinct group: PNI+ a (≤3) and PNI+ b (>3). In a multivariate Cox regression model, PNI+ b (>3) was identified as an independent BCR prognostic factor. Quantification of PNI focus number beside the dichotomized status recording will not only provide more detailed information but also be a novel prognostic indicator for risk stratification. Further external validation will be needed for an optimal cut-off value of the PNI focus number. Our findings will help further research on the relevance of PNI in the pretreatment setting and support ongoing efforts to understand its role of cancer progression.

Results of the phase I open label clinical trial SAKK 06/14 assessing safety of intravesical instillation of VPM1002BC, a recombinant mycobacterium Bacillus Calmette Guérin (BCG), in patients with non-muscle invasive bladder cancer and previous failure of conventional BCG therapy.

Background: VPM1002BC is a modified mycobacterium Bacillus Calmette Guérin (BCG) for the treatment of non-muscle invasive bladder cancer (NMIBC). The genetic modifications are expected to result in better immunogenicity and less side effects. We report on patient safety and immunology of the first intravesical application of VPM1002BC in human. Methods: Six patients with BCG failure received a treatment of 6 weekly instillations with VPM1002BC. Patients were monitored for adverse events (AE), excretion of VPM1002BC and cytokines, respectively. Results: No DLT (dose limiting toxicity) occurred during the DLT-period. No grade ≥3 AEs occurred. Excretion of VPM1002BC in the urine was limited to less than 24 hours. Plasma levels of TNFα significantly increased after treatment and blood-derived CD4+ T cells stimulated with PPD demonstrated significantly increased intracellular GM-CSF and IFN expression. Conclusion: The intravesical application of VPM1002BC is safe and well tolerated by patients and results in a potential Th1 weighted immune response.

[Evolution and miniaturization of percutaneous nephrolithotomy]. / Évolution et miniaturisation de la néphrolithotomie percutanée.

Percutaneous nephrolithotomy (PCNL) was at first indicated for larger renal stones. Technological progress allowed a significant improvement of the available equipment, mostly to miniaturize the devices. However, this should not affect the stone clearance. Many different techniques arised aiming to reduce the complications of PCNL, in particular the risk of haemorrhage. As it becomes less invasive, the indications are greatly expanded, and a growing number of patients will benefit from it in the future. This explains the significance of knowing this procedure in continual development in greater detail.

La néphrolithotomie percutanée (NLPC) était initialement indiquée pour les calculs rénaux de grande taille. Les progrès technologiques ont permis une amélioration significative du matériel disponible, principalement dans le sens de la miniaturisation des instruments. Ceci ne doit cependant pas se faire au détriment de la plus grande clairance possible des calculs. Une multitude de techniques sont apparues sur le marché dans l'optique de diminuer les complications possibles des NLPC, en particulier le risque hémorragique. L'invasivité de cette intervention étant réduite, ses indications s'en trouvent considérablement élargies et un nombre croissant de patients vont en bénéficier à l'avenir. Ceci explique l'intérêt de connaître un peu mieux cette technique chirurgicale en constante évolution.

Impact of Multifocality and Multilocation of Positive Surgical Margin After Radical Prostatectomy on Predicting Oncological Outcome.

OBJECTIVE: To assess the impact of focality and location of positive surgical margins (PSM) on long-term outcomes after radical prostatectomy (RP) for prostate cancer (PCa), including biochemical recurrence (BCR), metastasis and overall mortality. PATIENTS AND METHODS: From a total of 2796 cases of RP between 1993 and 2007 in our single hospital, 476 cases with PSMs were identified and included in this study. PSM location was categorized into apex, peripheral, and bladder neck. Survival was estimated using the Kaplan-Meier method. Cox proportional hazard regression models were used to analyze the impact of PSM focality and location status on oncologic survival. RESULTS: Of these 476 cases with PSMs, 335 (70.4%) cases were with single focal (sF) PSMs and 141 (29.6%) cases were with multifocal (mF) PSMs. Furthermore, 406 (85.3%) cases were found to have single location (sL) PSMs, and 70 (14.7%) cases were with multilocation (mL) PSMs. The median follow-up was 12.9 years. mF-PSMs and mL-PSMs showed significant impact on increased BCR risk on univariate analysis, and mL-PSMs remained significant on multivariate analysis (P = .048). Furthermore, the combination of multifocality and multilocation showed added prognostic value on predicting BCR-free survival, but not on metastasis-free survival or overall survival. CONCLUSION: The presence of mF-PSMs and mL-PSMs, and especially the combination of both, demonstrated significant impact on BCR prognosis. Patients with apex sLsF-PSMs were less likely to have BCR when compared with all those with non-apex sLsF-PSMs. These results should be considered when evaluating patients for adjuvant therapy.

[Augmented reality in urology : present and future]. / Réalité augmentée en urologie : actualité et avenir.

Minimally invasive surgery has recently gained popularity. This paradigm shift involves a series of potential difficulties from the surgeon's perspective. With recent developments these obstacles are gradually being overcomed. Recent navigation systems offer major improvements in the way information is acquired, displayed, and integrated into the surgical workflow through augmented reality. Finally, the progress of robotics has helped to improve the minimally invasive dexterity and competence of the surgeon. This article sumarizes the main and most recent developments in the areas mentionned above, analyzes the current limits that still need to be addressed, and suggests possible future directions.

La réalité augmentée en urologie a gagné en popularité ces dernières années. Des systèmes de navigation récents offrent des améliorations majeures en termes d'information acquise, qui est affichée et intégrée dans le flux de travail chirurgical, grâce à la réalité augmentée. De même, le progrès de la robotique a contribué à améliorer la dextérité et la compétence mini-invasives du chirurgien. Cet article résume les principaux et les plus récents développements dans les domaines susmentionnés, analyse les limites actuelles qui doivent encore être abordées et suggère des orientations futures possibles.

80-W GreenLight Laser Vaporization Versus Transurethral Resection of the Prostate for Treatment of Benign Prostatic Obstruction: 5-Year Outcomes of a Single-center Prospective Randomized Trial.

OBJECTIVE: To assess long term functional and safety follow-up data after 80-W GreenLight photoselective vaporization (GL PV) of the prostate and transurethral resection of the prostate (TURP). MATERIALS AND METHODS: Prospective randomized trial at a single tertiary referral center (Geneva, Switzerland). Patients were recruited in the outpatient clinic if they met the criteria for surgical treatment of benign prostatic obstruction. At baseline, 238 patients were treated either with the 80-W GL PV or monopolar TURP. After 5 years, data were available from 105 patients: 44 GL PV patients and 61 TURP patients. The primary outcome measure was the International Prostate Symptom Score (IPSS). Secondary outcome measures included maximum urinary flow rate (Qmax), postvoidal residual (PVR) and reoperation rate. Statistical analyses were performed using Stata 14 (StataCorp). RESULTS: After 5 years of follow-up, mean improvements in International Prostate Symptom Score, postvoidal residual and maximum urinary flow rate were similar in both groups. The re-treatment rate was 14.3% in the GL PV group vs 11.9% in the TURP group (P = .9). CONCLUSION: Noninferiority of the GL PV to TURP was confirmed in all functional and safety outcomes at 5-year follow-up. GL-PV could be a safe surgical alternative for patients suffering from benign prostatic obstruction.

[Intravesical microwave thermo-chemotherapy for the treatment of non-invasive bladder cancer]. / Thermo-chimiothérapie intravésicale par radiofréquence pour le traitement du cancer non invasif de la vessie.

Non-invasive urothelial carcinoma of the bladder is known for its significant rate of recurrence after transurethral resection (TURB) even after adjuvant intravesical chemotherapy or immunoprophylaxis. Therefore, new and more effective approaches for the management of non-invasive bladder tumors have been developed and are progressively introduced in clinical practice. Recently, the endovesical administration of a combined regimen using a cytostatic agent and microwave-induced hyperthermia appears to be highly efficient and possibly superior to intravesical chemotherapy alone for none invasive bladder cancer.

Le carcinome urothélial non invasif de la vessie (n'envahissant pas le détrusor) est grevé d'un risque de récidive significatif malgré les instillations endovésicales adjuvantes avec des agents chimio- ou immunothérapeutiques suite à la résection endoscopique de la tumeur vésicale. Dans ce contexte, de nouvelles approches thérapeutiques potentiellement plus efficaces ont été récemment développées et sont progressivement introduites dans la pratique clinique courante. L'une de ces dernières est la combinaison d'une hyperthermie endovésicale à l'instillation intravésicale d'agents chimiothérapeutiques classiquement administrés lors de la prise en charge des cancers non invasifs. Ce nouveau traitement apparaît être d'une efficacité supérieure à celle de l'instillation simple d'agents chimiothérapeutiques endovésicaux.

[Laparoscopic cystectomy-urinary diversion with robotic assistance : which future ?] / Cystectomie-dérivation par laparoscopie robot-assistée : quel avenir ?

Known for its significant morbidity, radical cystectomy must improve minimally invasively. Rapidly but sporadically initiated at the beginning of the robotic era 15 years ago, laparoscopic cystectomy-urinary diversion has slowly progressed technically. It is actually optimally standardized to be entirely performed intra-corporealy. Its technical difficulty remaining high, robotic cystectomy should remain in expert hands with a significant recruitement to remain performant.

Connue pour sa morbidité significative, la cystectomie radicale se doit d'évoluer vers des techniques mini-invasives. Rapidement initiée sporadiquement, au début de l'ère robotique il y a 15 ans, la cystectomie-dérivation par laparoscopie sous assistance robotisée a lentement progressé dans sa mise au point technique, actuellement standardisée de manière optimale pour être réalisée intégralement intracorporellement. Sa difficulté technique restant élevée, la cystectomie robotisée doit donc rester en mains expertes disposant d'un recrutement suffisant pour demeurer performantes.

Impact of the Level of Urothelial Carcinoma Involvement of the Prostate on Survival after Radical Cystectomy.

OBJECTIVE: Urothelial prostatic involvement (UPI) at the time of radical cystoprostatectomy (RCP) was found associated with worse survival outcomes by several previous reports. Our aim is to evaluate the impact of different levels of UPI on survival outcomes using a large series of male patients treated with RCP. METHODS: Whole step section specimens from 995 male BCa patients were assessed for UPI defined as: no involvement vs. prostatic urethral carcinoma in situ (CIS) vs. lamina propria involvement vs. ductal CIS vs. prostate stromal involvement. Primary end point of the study was predictors of prostatic involvement at RCP and its impact on overall survival after surgery. RESULTS: Prostatic involvement was recorded in 307 (30.9%) patients: 28% with prostatic urethral CIS, 12% with lamina propria involvement, 13% with ductal CIS and 47% with stromal involvement. Median follow-up was 70 months. Patients with stromal involvement had a worse 5-year survival (12%) than those with prostatic urethra CIS (40%), lamina propria involvement (36%), and ductal CIS (35%). Considering predictors of prostatic involvement, multifocal tumor (Odds Ratio [OR]: 6.60, p < 0.001), lymphovascular invasion (OR: 2.61, p < 0.001), lymph node metastases (OR: 2.02, p < 0.001) and CIS (OR: 2.02, p < 0.001) were found associated. Similar predictors were found assessing stromal involvement. CONCLUSIONS: Approximately one third of RCP patients harbor prostatic involvement of urothelial carcinoma. While all UPI are associated with worse overall survival, stromal involvement confers the worst outcome supporting its classification as T4 in the TNM staging.

Post-kidney Transplant Robot-assisted Laparoscopic Ureteral (Donor-receiver) Anastomosis for Kidney Graft Reflux or Stricture Disease.

OBJECTIVE: To report our experience with robot-assisted ureteral anastomosis for kidney graft. Kidney graft complex ureteral strictures or symptomatic vesicoureteral reflux may require complex reconstruction. This is classically done through an open surgical access, which adds to the morbidity of kidney transplantation. The da Vinci robot enables performance of complex laparoscopic procedures and may hence be used for such reconstructions. PATIENTS AND METHODS: We retrospectively reviewed all patients undergoing robotic surgical revision for stricture or reflux disease over a 3-year period. Contemporary patients who underwent open surgery were used as a control group. RESULTS: Ten patients underwent a robotic attempt, of whom 4 needed conversion to open surgery. Seven patients underwent an open surgery. Preoperative demographics were similar in both groups. The median operative time was 293 minutes, with a shorter operative time in the open group. The group of patients who could be completed robotically had a significantly lower postoperative length of stay (5 vs 9 days), quicker return to normal food intake (postoperative day 1 vs 3), and quicker control of pain without opiates (postoperative day 1 vs 4) than the converted or open group. Morbidity was comparable with 1 late Clavien IIIb complication in each subgroup (open, converted, and robotic group). After a median follow-up of 43 months, renal function was stable and there were no recurrent graft infections. CONCLUSION: Robotic ureteral reconstruction for kidney graft patients is feasible and efficient, and offers the classical advantages of minimally invasive surgery with outcomes comparable with open series.

Characterization of Late Recurrence After Radical Cystectomy in a Large Multicenter Cohort of Bladder Cancer Patients.

OBJECTIVE: To investigate the characteristics and outcomes of late recurrence (LR) in patients with bladder cancer (BCa) treated with radical cystectomy (RC) and to identify clinicopathologic predictors of LR and postrecurrence survival. MATERIALS AND METHODS: This multicenter study included 1652 BCa patients. LR was defined as occurring more than 5 years after RC. Differences in postrecurrence overall survival according to the timing of disease recurrence and the location of recurrence were calculated using the log-rank test. A logistic regression model was used to identify predictors of LR, and Cox regression models were used to evaluate variables associated with postrecurrence overall survival (OS). RESULTS: Overall, 548 patients experienced disease recurrence. Of these, 67 patients (12.2%) experienced LR, with a median time to recurrence of 86 months (interquartile range 70.5-107.2). LR was more likely to be located in the urothelium (P = .005). On multivariable analysis, younger age (P = .008) and non-organ confined disease (P = .03) were found to be predictors of LR. Postrecurrence 5-year OS was worse in patients who experienced early recurrence compared with those with LR (12% vs 25%, P = .02) and in those with nonurothelial recurrence compared to those with disease recurrence in the remaining urothelium (12% vs 51%, P < .001). Older age (P < .001), non-organ confined disease at RC (P = .02), and nonurothelial recurrence site (P = .002) were independently associated with postrecurrence OS. CONCLUSION: LR after RC is an uncommon but non-negligible event that harbors unique characteristics. LR is associated with better OS compared to early recurrence. Our findings reinforce the need for lifelong follow-up of BCa patients after RC.

HER2 overexpression is associated with worse outcomes in patients with upper tract urothelial carcinoma (UTUC).

PURPOSE: The aim of our study was to evaluate the expression pattern of HER2 overexpression in patients with upper tract urothelial carcinoma (UTUC) and to evaluate its association with clinical outcomes. METHODS: This multicenter retrospective study included 732 patients treated with radical nephroureterectomy for UTUC. HER2 expression was assessed using immunohistochemistry and scored according to the HercepTest: Scores of 0 or 1 were considered negative and 2 or 3 as positive. To qualify for 2 scoring, complete membrane staining of more than 10 % of tumor cells at a moderate intensity had to be observed. RESULTS: HER2 was overexpressed in 262 (35.8 %) patients. It was associated with pathologic characteristics such as more advanced T stage (p < 0.001), presence of lymph node metastasis (p = 0.006), high-grade tumor (p < 0.001), tumor necrosis (p = 0.01) and lymphovascular invasion (p = 0.02). Patients with HER2 overexpression had a 1.66-fold increased risk of experiencing disease recurrence (95 % CI 1.24-2.24, p = 0.001), 1.55-fold increased risk of death (95 % CI 1.21-1.99, p = 0.001) and 1.81-fold increased risk of cancer-specific death (95 % CI 1.33-2.48, p < 0.001). On multivariable analysis that adjusted for the effects of standard clinicopathologic variables, HER2 overexpression remained associated with disease recurrence (p = 0.04), overall (p = 0.02) and cancer-specific mortality (p = 0.02). CONCLUSIONS: Approximately, one-third of UTUC patients overexpressed HER2. HER2 overexpression was associated with features of clinically and biologically aggressive disease as well as prognosis. HER2 may represent a good marker for therapeutic risk stratification and potentially a target for therapy in some UTUC tumors.

Validation of Preoperative Risk Grouping of the Selection of Patients Most Likely to Benefit From Neoadjuvant Chemotherapy Before Radical Cystectomy.

INTRODUCTION: The aim of this study was to validate the value of preoperative patient characteristics in prognosticating survival after radical cystectomy (RC) to guide treatment decisions regarding neoadjuvant systemic treatment. METHODS: We evaluated a single cohort of 449 consecutive patients treated with RC for bladder cancer. Patients treated with neoadjuvant therapy were excluded from the study cohort (n = 24). Patients were stratified based on preoperative characteristics into 2 risk groups. The high-risk group included patients harboring clinically non-organ-confined disease (≥ cT3), hydroureteronephrosis, lymphovascular invasion, or variant histology (micropapillary, neuroendocrine, sarcomatoid, or plasmacytoid variants on transurethral resection). The low-risk group included patients with cT2 disease without any of the aforementioned features. Survival expectancies after surgery were evaluated using competing risk and Kaplan-Meier analyses. RESULTS: We identified 153 (44.6%) low-risk and 190 (55.4%) high-risk patients. The majority of high-risk patients had only 1 high-risk feature (n = 111; 58.4%); the most common high-risk feature was preoperative hydroureteronephrosis (n = 107; 56.3%). The majority of low-risk patients were upstaged at time of RC (n = 118; 70.6%), whereas a pathologic downstage occurred only in 27 high-risk patients (14.2%). Cancer-specific mortality-free rates at 5 years after RC were 77.4% versus 64.4% for low-risk versus high-risk patients, respectively. CONCLUSIONS: We confirm that preoperative risk features can stratify patients with muscle-invasive bladder cancer into differential risk groups regarding survival. Decision-making regarding neoadjuvant systemic therapy administration is likely to be improved by integrating clinical stage, lymphovascular invasion, variant histology, and hydroureteronephrosis.

Transrectal Ultrasound-Guided Prostate Biopsy for Cancer Detection: Performance of 2D-, 3D- and 3D-MRI Fusion Targeted Techniques.

INTRODUCTION: The study aimed to evaluate 3 different modalities of transrectal ultrasound (TRUS)-guided prostate biopsies (PBs; 2D-, 3D- and targeted 3D-TRUS with fusion to MRI - T3D). Primary end point was the detection rate of prostate cancer (PC). Secondary end point was the detection rate of insignificant PC according to the Epstein criteria. PATIENTS AND METHODS: Inclusion of 284 subsequent patients who underwent 2D-, 3D- or T3D PB from 2011 to 2015. All patients having PB for initial PC detection with a serum prostate-specific antigen value ≤20 ng/ml were included. Patients with T4 and/or clinical and/or radiological metastatic disease, so as these under active surveillance were excluded. RESULTS: Patients with T3D PB had a significantly higher detection rate of PC (58 vs. 19% for 2D and 38% for 3D biopsies; p = 0.001), with no difference in Gleason score distribution (p = 0.644), as well as detection rate of low-risk cancers (p = 0.914). Main predictive factor for positive biopsies was the technique used, with respectively a 3- and 8-fold higher detection rate in the 3D- and T3D group. For T3D-PB, there was a significant correlation between radiological cancer suspicion (Prostate Imaging Reporting and Data System Score) and cancer detection rate (p = 0.02). CONCLUSIONS: T3D PB should be preferred over 2D PB and 3D PB in patients with suspected PC as it improves the cancer detection rate.