[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.

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.

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.

Midterm oncological outcomes of laparoscopic vs open radical prostatectomy (RP).

OBJECTIVE: To compare the midterm risks of biochemical recurrence (BCR) and salvage radiation therapy (SRT) after laparoscopic (LRP) and open retropubic radical prostatectomy (RRP). Strong evidence that these techniques are comparable to the 'gold standard' of open RRP is lacking, as most comparative studies are limited by short follow-up or rely on historical controls. PATIENTS AND METHODS: We studied 1000 consecutive patients concurrently treated by either LRP or RRP between 2001 and 2005. LRPs were performed by a single surgeon and RRP by four surgeons. Primary outcomes were BCR and SRT. Survival analysis included relevant clinical and pathological variables. RESULTS: Of 844 included patients, 244 underwent LRP and 600 RRP. Clinical and pathological characteristics were similar in both groups. Most patients had Gleason 6 tumours (68%) and pT2 disease (86%). The median follow-up was 6.1 years and median time to recurrence 3.4 years. Overall, BCR occurred in 14% of patients: 13.1% after LRP and 14.7% after RRP. SRT was performed in 10.7% of patients both after LRP and RRP. In uni- and multivariate Cox regression models, surgical technique was not a significant predictor of BCR or SRT. CONCLUSION: Our results suggest that in high-volume centres, LRP provides equivalent oncological control to RRP.

A close surgical margin after radical prostatectomy is an independent predictor of recurrence.

PURPOSE: The term close surgical margin refers to a tumor extending to the inked margin of the specimen without reaching it. Current guidelines state that a close surgical margin should simply be reported as negative. However, this recommendation remains controversial and relies on limited evidence. We evaluated the impact of close surgical margins on the long-term risk of biochemical recurrence after radical prostatectomy. MATERIALS AND METHODS: We identified 1,195 consecutive patients who underwent radical prostatectomy and lymphadenectomy for localized prostate cancer at our institution from 1993 to 1999. In 894 of these patients associations between margin status and location, Gleason score, pathological stage, preoperative prostate specific antigen, prostate weight and age with the risk of biochemical recurrence were examined. RESULTS: Of these 894 patients 644 (72%) had negative margins and of these patients 100 (15.5%) had close surgical margins. In the group with prostate specific antigen failure, median time to recurrence was 3.5 years. In the group without recurrence median followup was 9.9 years. Cumulative recurrence-free survival differed significantly among positive, negative and close surgical margins (p <0.001). On multivariate analysis a close surgical margin constituted a significant, independent predictor of recurrence (HR 2.1, 95% CI 1.04-4.33). Gleason score and positive margins were the strongest prognostic factors. CONCLUSIONS: In this cohort close surgical margins were independently associated with a twofold risk of postoperative biochemical recurrence. Further evaluation of the clinical significance of close surgical margins is indicated as they might be an indicator of local recurrence and of relevance when considering salvage therapy.

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.

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.

Advances in the management of blunt traumatic bladder rupture: experience with 36 cases.

OBJECTIVE: To assess how advances in urology, radiology and orthopaedics are changing the current management of bladder ruptures, by reviewing patients treated for bladder ruptures after blunt trauma. PATIENTS AND METHODS: Our database was screened for patients admitted with bladder ruptures between 1980 and 2008. Charts were reviewed for demographics, clinical variables, diagnostics, treatment and outcome. RESULTS: Thirty-six patients with extraperitoneal (EPR, 61%) and intraperitoneal (IPR) or combined ruptures (39%) were identified; 81% of them presented pelvic-ring fractures. Diagnosis relied on computed tomography cystography (CT-C), which has replaced plain-film cystography. The sensitivity of either type of cystography was > 90%. However, three bladder ruptures (11%) were missed on CT-C performed with insufficient bladder distension. All 14 patients with IPRs had immediate surgical repair, four of them by laparoscopy. Twelve of 22 EPRs (55%) were sutured during concomitant orthopaedic/visceral surgery or because of the urologist's apprehension of infection. Only eight of 22 patients with EPR (36%) completed conservative treatment. CONCLUSIONS: Diagnosis relies increasingly on CT-C, allowing simultaneous assessment of multiple organ systems. However, only specific CT-C guarantees an adequate sensitivity. Orthopaedists increasingly use open reductions and fixation of pelvic-ring fractures, prompting urologists to suture EPRs simultaneously. Our data indicate that this proactive management reduces infectious complications, and we have adopted it as the standard of care in our institution. Laparoscopic suture is an advantageous treatment of isolated IPR.

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.

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.

Tissue microarrays of human tumor xenografts: characterization of proteins involved in migration and angiogenesis for applications in the development of targeted anticancer agents.

As new target-directed anticancer agents emerge, preclinical efficacy studies need to integrate target-driven model systems. This approach to drug development requires rapid and reliable characterization of the new targets in established tumor models, such as xenografts and cell lines. Here, we have applied tissue microarray technology to patient-derived, re-growable human tumor xenografts. We have profiled the expression of five proteins involved in cell migration and/or angiogenesis: vascular endothelial growth factor (VEGF), matrix metalloproteinase 1 (MMP1), protease activated receptor (PAR1), cathepsin B, and beta1 integrin in a panel of over 150 tumors and compared their expression levels to available patient outcome data. For each protein, several target overexpressing xenografts were identified. They represent a subset of tumor models prone to respond to specific inhibitors and are available for future preclinical efficacy trials. In a "proof of concept" experiment, we have employed tissue microarrays to select in vivo models for therapy and for the analysis of molecular changes occurring after treatment with the anti-VEGF antibody HuMV833 and gemcitabine. Whereas the less angiogenic pancreatic cancer PAXF736 model proved to be resistant, the highly vascularized PAXF546 xenograft responded to therapy. Parallel analysis of arrayed biopsies from the different treatment groups revealed a down-regulation of Ki-67 and VEGF, an altered tissue morphology, and a decreased vessel density. Our results demonstrate the multiple advantages of xenograft tissue microarrays for preclinical drug development.

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.

Prostatic Utricle Cyst as the Most Likely Cause in a Case of Recurrent Episodes of Hematospermia.

Hematospermia is a clinical symptom that raises anxiety in patients and has various causes, benign and malignant. We report a case of hematospermia for which appropriate multidisciplinary expertise favored a conservative management of a benign prostatic cyst, namely, a prostatic utricle cyst. A cystic lesion found by transrectal ultrasound in the context of hematospermia related to masturbation in a young virgin male patient was investigated with a high-field magnetic resonance imaging (MRI) and an endorectal coil. The association of high-field MRI and endorectal coil leads to high quality images.

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.

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.

Preoperative anemia is associated with disease recurrence and progression in patients with non-muscle-invasive bladder cancer.

PURPOSE: To evaluate the effect of preoperative anemia (PA) on oncological outcomes in a multicenter cohort of patients with non-muscle-invasive bladder cancer (NMIBC) treated with transurethral resection of the bladder (TURB) and adjuvant intravesical therapies. We hypothesize that PA represents a marker of disease aggressiveness and could be used to improve the discrimination of prognostic tools for the prediction of disease recurrence and progression. METHODS: This multicenter retrospective study included 1,117 patients from 4 different centers. The presence of PA was assessed according to the World Health Organization classification as a preoperative hemoglobin level of≤13g/dl in men and≤12g/dl in women. PA evaluation was done at each institution, generally 1 to 3 days before surgery. Multivariable Cox regression models were performed to evaluate the prognostic effect of PA on survival outcomes. RESULTS: Overall, 381 (34%) patients with NMIBC treated with TURB, had PA. Median follow-up for patients alive at last follow-up was 62.7 months (interquartile range: 25-110.7). On multivariable Cox regression analyses that accounted for the effect of standard clinicopathologic prognosticators, PA was independently associated with recurrence-free survival (P = 0.045) and progression-free survival (P = 0.01). Adding PA to a model for the prediction of disease recurrence and progression improved the discrimination of the prognostic models marginally from 69.8% to 70.3% and from 71.6% to 73.1%, respectively. CONCLUSIONS: PA was found in more than one-third of patients with NMIBC treated with TURB. PA was associated with poor oncological outcomes and was an independent predictor of intravesical disease recurrence and progression. However, the additional prognostic information provided by PA remains limited.

The effect of HER2 status on oncological outcomes of patients with invasive bladder cancer.

PURPOSE: The aim of this study was to evaluate the overexpression of human epidermal growth factor receptor 2 (HER2) in patients with bladder cancer (BCa) and to assess its association with oncological outcomes. METHODS: This retrospective single-center study included 354 patients with BCa treated with radical cystectomy (RC). HER2 status was assessed with immunohistochemistry and scored according to HercepTest. Conditional survival and competing risk regression were performed to assess the association between HER2 expression and survival outcomes. RESULTS: HER2 was overexpressed in 36% of patients. HER2 overexpression was associated with features of tumor aggressiveness such as lymph-node metastases (P = 0.002). At a median follow-up of 123 months (interquartile range: 79-180), 160 patients (45%) experienced disease recurrence, 263 patients (74%) died and 157 (44%) died of cancer. On multivariable analyses, HER2 overexpression was not significantly associated with any oncological outcomes. Adding HER2 status to a model for the prediction of survival outcomes did not change the accuracy of the model for any of the outcomes. Interestingly, HER2 status significantly affected late disease recurrence (P = 0.05 for conditional survival at 24 months). CONCLUSIONS: More than one third of RC patients overexpress HER2 in their tumors. HER2 overexpression was associated with features of biological and clinical aggressiveness. HER2 did not add prognostic significance to the standard established predictors of survival outcomes after RC. However, due to the high overexpression rate, it could represent a target for therapy in select advanced BCa tumors.