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Abstract We aimed to evaluate the correlation between endoscopic papillary abnormalities (PA) and high renal papilla Hounsfield density (PHD) on CT scan in patients who underwent flexible ureteroscopic treatment (fURS) for renal stones. We retrospectively assessed patients from a prospectively collected database who were treated with fURS for renal stones between May 2016 and October 2020. PHD was measured on preoperative CT-scan by a radiologist blinded from the intraoperative aspect of the papillae. Correlation was examined between high PHD (≥ 43 HU) and PA described in fURS, stone composition, metabolic abnormalities, … Out of 159 consecutive cases, 131 were eligible for analysis with available preoperative CT-scan. Median age was 55 years (IQR 43–67) and median PHD was 40 (IQR 36–45). Eighty patients (61%) had PHD

Abstract Background Ureteral cancer is a rare cancer. This study aimed to provide an up-to-date and comprehensive analysis on the global trends of ureteral cancer incidence and its association with lifestyle and metabolic risk factors. Methods The incidence of ureteral cancer was estimated from the Cancer Incidence in Five Continents Plus and Global Cancer Observatory databases. We analyzed the (1) global incidence of ureteral cancer by region, country, sex, and age group by age-standardized rates (ASR); (2) associated risk factors on a population level by univariable linear regression with logarithm transformation; and (3) incidence trend of ureteral cancer by sex and age group in different countries by Average Annual Percentage Change (AAPC). Results The global age-standardized rate of ureteral cancer incidence in 2022 was 22.3 per 10,000,000 people. Regions with higher human development index (HDI), such as Europe, Northern America, and East Asia, were found to have a higher incidence of ureteral cancer. Higher HDI and gross domestic product (GDP) and a higher prevalence of smoking, alcohol drinking, physical inactivity, unhealthy dietary, obesity, hypertension, diabetes, and lipid disorder were associated with higher incidence of ureteral cancer. An overall increasing trend of ureteral cancer incidence was observed for the past decade, especially among the female population. Conclusions Although ureteral cancer was relatively rare, the number of cases reported was rising over the world. The rising trends among females were more evident compared with the other subgroups, especially in European countries. Further studies could be conducted to examine the reasons behind these epidemiological changes and confirm the relationship with the risk factors identified.

Background: Photodynamic diagnosis (PDD) during transurethral resection of bladder tumor (TURBT) is guideline recommended, as it improves bladder cancer detection rates. However, the extent to which PDD is implemented in everyday clinical practice has not been thoroughly assessed. We aimed to evaluate the current trends and major perioperative outcomes of TURBT with PDD. Methods: The present study evaluated the GeRmAn Nationwide inpatient Data (GRAND) from 2010 (the year when PDD started to be coded separately in Germany) to 2021, which were made available from the Research Data Center of the German Bureau of Statistics. We undertook numerous patient-level and multivariable logistic regression analyses. Results: Overall, 972,208 TURBTs [228,207 (23%) with PDD and 744,001 (77%) with white light] were performed. Patients offered PDD during TURBT were younger (p < 0.001), presented fewer comorbidities (p < 0.001) and were discharged earlier from hospital (p < 0.001). PDD was associated with additional costs of about EUR 500 compared to white-light TURBT (p < 0.001). The yearly TURBT cases remained relatively stable from 2010 to 2021, whereas utilization of PDD underwent a 2-fold increase. After adjusting for major risk factors in the multivariate regression analysis, PDD was related to lower rates of transfusion (1.4% vs. 5.6%, OR: 0.29, 95% CI: 0.28 to 0.31, p < 0.001), intensive care unit admission (0.7% vs. 1.4%, OR: 0.56, 95% CI: 0.53 to 0.59, p < 0.001) and 30-day in-hospital mortality (0.1% vs. 0.7%, OR: 0.24, 95% CI: 0.22 to 0.27, p < 0.001) compared to white-light TURBT. On the contrary, PDD was related to clinically insignificant higher rates of bladder perforation (0.6% versus 0.5%, OR: 1.3, 95% CI: 1.2 to 1.4, p < 0.001), and reoperation (2.6% versus 2.3%, OR: 1.2, 95% CI: 1.1 to 1.2, p < 0.001). Conclusions: The utilization of PDD with TURBT is steadily increasing. Nevertheless, the road toward the establishment of PDD as the standard of care for TURBT is still long, despite of the advantages of PDD.

Background: Follow-up after radical cystectomy (RC) for bladder cancer can be divided into oncological and functional surveillance. It remains unclear how follow-up after RC should ideally be scheduled. The aim of this report was to gain insight into the organization of follow-up after RC in Europe, for which we conducted a roundtable inventory within the EAU Young Academic Urologists Urothelial Cancer working group. Methods: An inventory semi-structured survey was performed among urologists of the EAU Young Academic Urologists Urothelial Cancer working group to describe the organization of follow-up. The surveys were analyzed using a deductive approach. Similarities and differences in follow-up after RC for bladder cancer were described. Results: The survey included 11 urologists from six different European countries. An institutional follow-up scheme was used by six (55%); three (27%) used a national or international guideline, and two (18%) indicated that there was no defined follow-up scheme. Major divergent aspects included the time points of follow-up, the frequency, and the end of follow-up. Six centers (55%) adopted a risk-adapted follow-up approach tailored to (varying) patient and tumor characteristics. Laboratory tests and CT scans were used in all cases; however, the intensity and frequency varied. Functional follow-up overlapped with oncological follow-up in terms of frequency and duration. Patient-reported outcome measures were only used by two (18%) urologists. Conclusions: Substantial variability exists across European centers regarding the follow-up after RC for bladder cancer. This highlights the need for an international analysis focusing on its organization and content as well as on opportunities to improve patients’ needs during follow-up after RC.

Background: There are currently no guideline recommendations regarding the treatment of cisplatin-ineligible, clinically lymph node–positive (cN+) bladder cancer (BCa). Objective: To investigate the oncological efficacy of gemcitabine/carboplatin induction chemotherapy (IC) in comparison to cisplatin-based regimens in cN+ BCa. Design, setting, and participants: This was an observational study of 369 patients with cT2–4 N1–3 M0 BCa. Intervention: IC followed by consolidative radical cystectomy (RC). Outcome measurements and statistical analysis: The primary endpoints were the pathological objective response (pOR; ypT0/Ta/Tis/T1 N0) rate and the pathological complete response (pCR; ypT0N0) rate. We applied 3:1 propensity score matching (PSM) to reduce selection bias. Overall survival (OS) and cancer-specific survival (CSS) were compared across groups using the Kaplan-Meier method. Associations between the treatment regimen and survival endpoints were tested in multivariable Cox regression analyses. Results and limitations: After PSM, a cohort of 216 patients was available for analysis, of whom 162 received cisplatin-based IC and 54 gemcitabine/carboplatin IC. At RC, 54 patients (25%) had a pOR and 36 (17%) had a pCR. The 2-yr CSS was 59.8% (95% confidence interval [CI] 51.9–69%) for patients who received cisplatin-based IC versus 38.8% (95% CI 26–57.9%) for those who received gemcitabine/carboplatin. For the pOR (p = 0.8), ypN0 status at RC (p = 0.5), and cN1 BCa subgroups (p = 0.7), there was no difference in CSS between cisplatin-based IC and gemcitabine/carboplatin. In the cN1 subgroup, treatment with gemcitabine/carboplatin was not associated with shorter OS (p = 0.2) or CSS (p = 0.1) on multivariable Cox regression analysis. Conclusions: Cisplatin-based IC seems to be superior to gemcitabine/carboplatin and should be the standard for cisplatin-eligible patients with cN+ BCa. Gemcitabine/carboplatin may be an alternative treatment for selected cisplatin-ineligible patients with cN+ BCa. In particular, selected cisplatin-ineligible patients with cN1 disease may benefit from gemcitabine/carboplatin IC. Patient summary: In this multicenter study, we found that selected patients with bladder cancer and clinical evidence of lymph node metastasis who cannot receive standard cisplatin-based chemotherapy before surgery to remove their bladder may benefit from chemotherapy with gemcitabine/carboplatin. Patients with a single lymph node metastasis may benefit the most.

Background: Skeletal muscle loss (sarcopenia) has been linked to cancer cachexia and can predict survival in several tumors, including advanced genitourinary malignancies. Objective: To investigate the predictive and prognostic role of sarcopenia in patients with T1 high grade (HG) non-muscle invasive bladder cancer (NMIBC) treated with adjuvant intravesical Bacillus Calmette-Guerin (BCG). Design, setting, and participants: Oncological outcomes were evaluated for 185 patients with T1 HG NMIBC treated with BCG at two European referral centers. Sarcopenia, identified from computed tomography scans performed within 2 mo after surgery, was defined as a skeletal muscle index of

Abstract The aim of our study was to determine the clinical utility of neutrophil-to-lymphocyte ratio (NLR) in predicting presence and prognosis of nodal involvement in patients treated with radical prostatectomy (RP) due to prostate cancer. This single-centre retrospective study included 205 patients treated with RP and lymphadenectomy between 2012 and 2018. Logistic regression and Kaplan–Meier analyses were performed to evaluate the prognostic value of preoperative NLR in terms of nodal spread and survival. Patients staged pN1 presented lower mean NLR (2.53 vs 3.86; p = 0.0025) compared to pN0 patients. On multivariable analysis of different haematological markers, only NLR exceeding the median (≥ 2.7) predicted pN1 (OR = 0.38; p = 0.0367) independently of biopsy grading and PSA. In internal validation (n = 31 pN1, n = 174 pN0) on the bootstrapped dataset using a spare cutoff of NLR ≥ 4.1 would allow sparing lymphadenectomy in 22.09% pN0 patients, missing 6.45% pN1 (NPV 92.66%; 95% CI 84.91–100%). Noticeably, in pN1 patients NLR ≥ 2.7 correlated with shorter overall survival (p = 0.0196), despite its association with reduced risk of pN1. High pre-prostatectomy NLR was negatively associated with pN1, yielding high NPV in internal validation. Simultaneously, high NLR in pN1 patients was associated with shorter survival.

In non-muscle invasive bladder cancer, Bacillus Calmette–Guérin (BCG) responders benefit from strong Th1-type inflammatory and T cell responses mediating tumor rejection. However, the corresponding lack of anti-inflammatory Th2-type immunity impairs tissue repair in the bladder wall and facilitates the development of cystitis, causing urinary pain, urgency, incontinence, and frequency. Mechanistically, the leakage of the glycosaminoglycan (GAG) layer enables an influx of potassium ions, bacteria, and urine solutes towards the underlying bladder tissue, promoting chronic inflammation. Treatments directed towards re-establishing this mucopolysaccharide-based protective barrier are urgently needed. We discuss the pathomechanisms, as well as the therapeutic rationale of how chondroitin and hyaluronic acid instillations can reduce or prevent BCG-induced irritative bladder symptoms. Moreover, we present a case series of five patients with refractory BCG-induced cystitis successfully treated with combined chondroitin and hyaluronic acid instillations.

BCG is the most efficient adjuvant therapy for high-risk, non-muscle-invasive bladder cancer (NMIBC). Both innate and adaptive immune responses have been implicated in BCG-mediated effects. BCG vaccination can boost innate immune responses via trained immunity (TI), resulting in an increased resistance to respiratory viral infections. Here we evaluated for the first time whether intravesical application of BCG triggers increased immunity against SARS-CoV-2 in patients with high-risk NMIBC. Serum and peripheral blood mononuclear cells (PBMCs) from heparinized whole blood samples of 11 unvaccinated SARS-CoV-2-naïve high-risk NMIBC patients were collected at baseline and during BCG treatment in a pre-COVID-19 era. To examine B-cell or T cell-dependent adaptive immunity against SARS-CoV-2, sera were tested for the presence of SARS-CoV-2 neutralizing antibodies. Using a SARS-CoV-2 peptide pool, virus-specific T cells were quantified via IFNγ ELISpot assays. To analyze innate immune responses, mRNA and protein expression levels of pro- and anti-inflammatory cytokines were measured after a 24-hour stimulation of PBMCs with either BCG or SARS-CoV-2 wildtype. ATAC- sequencing was performed to identify a potential epigenetic reprogramming in immune cells. We neither identified SARS-CoV-2 neutralizing antibodies nor SARS-CoV-2- reactive T cells, indicating that intravesical BCG did not induce adaptive immunity against SARS-CoV-2. However, a significant increase in mRNA as well as protein expression of IL-1β, IL-6 and TNFα, which are key cytokines of trained immunity, could be observed after at least four intravesical BCG instillations. Genomic regions in the proximity of TI genes (TLR2, IGF1R, AKT1, MTOR, MAPK14, HSP90AA1) were more accessible during BCG compared to baseline. Although intravesical BCG did not induce adaptive immune responses, repetitive intravesical instillations of BCG induced circulating innate immune cells that produce TI cytokines also in response to SARS-CoV-2.

Background: Evidence-based medicine (EBM) was introduced as a concept in the early 1990s as an integration of the best available evidence with clinical expertise and patient values. Objective: To evaluate the current status of EBM training and EBM perception, attitudes, and self-perceived skills among European urology residents. Design, setting, and participants: Our online open survey comprised 28 multiple-choice items, including ten questions with responses on a five-point Likert scale ranging from 1 = strongly disagree to 5 = strongly agree. The survey was distributed via the mailing lists and social media accounts of the European Society of Residents in Urology, German Society of Residents in Urology, French Society of Urologists in Training, Spanish Urology Residents Working Group, Italian Society of Residents in Urology, and the Urology Social Media Working Group in two rounds (May–July 2019 and July 2020). We excluded responses from non-European countries. Outcome measurements and statistical analysis: The online open survey comprised 28 multiple-choice items. These included ten questions with answers on a five-point Likert scale with response items ranging from strongly disagree (score of 1) to strongly agree (score of 5). Results and limitations: We received 210 responses, of which 181 from 23 European countries were eligible. Approximately three-quarters (73.7%) of the respondents were male, with a mean age of 31 yr. Only 28.2% reported EBM training as part of their urology curriculum and 19.3% felt that the training they received was sufficient to guide their daily practice. An overwhelming majority (91.5%) stated that they would be interested in more formalized EBM training or additional training. There was a strong level of agreement (median score 5, interquartile range 4–5) that EBM is important for daily medical and surgical practice and that it improves patient care. Overall, the mean self-perceived understanding of basic EBM concepts was good. Limitations include concerns about generalizability given its internet-based format, the inability to calculate a response rate, poor representation from some European regions, and limited sample size. Conclusions: Our survey suggests that European urology residents receive a limited amount of EBM training despite considerable appreciation, interest, and self-perceived deficits for more advanced concepts. Formal integration of EBM teaching in all European residency programs should be considered. Patient summary: We performed an online survey of urology residents in Europe. We found that residents have positive perceptions of and attitudes to evidence-based medicine but most programs lack formal training in this area.

Social Media (SoMe) platforms are widely used by urologists with over 99% using SoMe and 63% of young urologists rating the influence of SoMe on knowledge acquisition as moderate to high. The urology community is abreast with the SoMe revolution in many ways but several new methods of SoMe dissemination remain to be explored. These provide an exciting future for SoMe enthusiasts in urology and beyond. In this article, the European Association of Urology Dissemination Committee explores these novel methods of SoMe dissemination while discussing the importance of maintaining quality, ethics, and reliability in SoMe and the role EAU plays in it.

Background: There might be differential sensitivity to neoadjuvant chemotherapy (NAC) in patients with primary muscle-invasive bladder cancer (MIBC) in comparison to patients with secondary MIBC after a history of non–muscle-invasive disease. Objective: To investigate pathologic response rates and survival associated with primary versus secondary MIBC among patients treated with cisplatin-based NAC for cT2–4N0M0 MIBC. Design, setting, and participants: Oncologic outcomes were compared for 350 patients with primary MIBC and 64 with secondary MIBC treated with NAC and radical cystectomy between 1992 and 2021 at 11 academic centers. Genomic analyses were performed for 476 patients from the Memorial Sloan Kettering/The Cancer Genome Atlas cohort. Outcome measurements and statistical analysis: The outcome measures were pathologic objective response (pOR; ≤ypT1 N0), pathologic complete response (pCR; ypT0 N0), overall mortality, and cancer-specific mortality. Results and limitations: The primary MIBC group had higher pOR (51% vs 34%; p = 0.02) and pCR (33% vs 17%; p = 0.01) rates in comparison to the secondary MIBC group. On multivariable logistic regression analysis, primary MIBC was independently associated with both pOR (odds ratio [OR] 0.49, 95% confidence interval [CI] 0.26–0.87; p = 0.02) and pCR (OR 0.41, 95% CI 0.19–0.82; p = 0.02). However, on multivariable Cox regression analysis, primary MIBC was not associated with overall mortality (hazard ratio 1.70, 95% CI 0.84–3.44; p = 0.14) or cancer-specific mortality (hazard ratio 1.50, 95% CI 0.66–3.40; p = 0.3). Genomic analyses revealed a significantly higher ERCC2 mutation rate in primary MIBC than in secondary MIBC (12.4% vs 1.3%; p

Context: Active surveillance (AS) of biopsy-proven renal oncocytomas may reduce overtreatment. However, on biopsy, the risk of misdiagnosis owing principally to entities with peculiar hybrids and overlap morphology, and phenotypes argues for early intervention. Objective: To assess the benefit and harm of AS in biopsy-proven renal oncocytoma. Evidence acquisition: A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). We systematically searched PubMed, Scopus, and Web of Science databases from September 26 up to October 2021, for studies that analyzed the outcomes of AS in patients with biopsy-proven renal oncocytoma. Evidence synthesis: A total of ten studies with 633 patients met our inclusion criteria and were included for analysis. After a median follow-up of 34.5 mo (95% confidence interval [CI] 30.6–38.4), the overall definitive treatment rate from AS to definitive treatment was 17.3% (n = 75/433, six studies). The pooled pathological agreement between the initial renal mass biopsy and the surgical pathology report was 91.1%. The main indications for surgery during follow-up were rapid tumor growth and patient request. The pooled median growth rate was 1.55 mm/yr (95% CI 0.9–2.2). No metastasis or death related to renal oncocytoma was reported. Conclusions: Annual tumor growth of biopsy-proven renal oncocytoma is low. AS is oncologically safe, with favorable compliance of patients. Crossover to definitive treatment revealed a strong concordance between biopsy and final pathology. Further studies on the long-term outcomes of AS are needed. Patient summary: In this study, we examined the benefit and harm of active surveillance (AS) in biopsy-proven oncocytoma. Based on the available data, AS appears oncologically safe and may represent a promising alternative to immediate treatment. Patients should be included in AS decision discussions.

Background: Radical cystectomy (RC) is indicated in primary or secondary muscle-invasive bladder cancer (primMIBC, secMIBC) and in primary or recurrent high- or very high-risk non–muscle-invasive bladder cancer (primHR-NMIBC, recHR-NMIBC). The optimal timing for RC along the disease spectrum of nonmetastatic urothelial carcinoma remains unclear. Objective: To compare outcomes after RC between patients with primHR-NMIBC, recHR-NMIBC, primMIBC, and secMIBC. Design, setting, and participants: This retrospective, multicenter study included patients with clinically nonmetastatic bladder cancer (BC) treated with RC. Outcome measurements and statistical analysis: We assessed oncological outcomes for patients who underwent RC according to the natural history of their BC. primHR-NMIBC and primMIBC were defined as no prior history of BC, and recHR-NMIBC and secMIBC as previously treated NMIBC that recurred or progressed to MIBC, respectively. Log-rank analysis was used to compare survival outcomes, and univariable and multivariable Cox and logistic regression analyses were used to identify predictors for survival. Results and limitations: Among the 908 patients included, 211 (23%) had primHR-NMIBC, 125 (14%) had recHR-NMIBC, 404 (44%) had primMIBC, and 168 (19%) had secMIBC. Lymph node involvement and pathological upstaging were more frequent in the secMIBC group than in the other groups (p

Background: Some health care systems have set up referral trauma centers to centralize expertise to improve trauma management. There is scant and controversial evidence regarding the impact of provider’s volume on the outcomes of trauma management. Objective: To evaluate the impact of hospital volume on the outcomes of renal trauma management in a European health care system. Design, setting, and participants: A retrospective multicenter study, including all patients admitted for renal trauma in 17 French hospitals between 2005 and 2015, was conducted. Intervention: Nephrectomy, angioembolization, or nonoperative management. Outcome measurements and statistical analysis: Four quartiles according to the caseload per year: low volume (eight or fewer per year), moderate volume (nine to 13 per year), high volume (14–25/yr), and very high volume (≥26/yr). The primary endpoint was failure of nonoperative management defined as any interventional radiology or surgical procedure needed within the first 30 d after admission. Results and limitations: Of 1771 patients with renal trauma, 1704 were included. Nonoperative management was more prevalent in the very-high- and low-volume centers (p = 0.02). In a univariate analysis, very high hospital volume was associated with a lower risk of nonoperative management failure than low (odds ratio [OR] = 0.54; p = 0.05) and moderate (OR = 0.48; p = 0.02) hospital volume. There were fewer nephrectomies in the high- and very-high-volume groups (p = 0.003). In a multivariate analysis, very high volume remained associated with a lower risk of nonoperative management failure than low (OR = 0.48; p = 0.04) and moderate (OR = 0.42; p = 0.01) volume. Study limitations include all the shortcomings inherent to its retrospective multicenter design. Conclusions: In this multicenter study, management of renal trauma varied according to hospital volume. There were lower rates of nephrectomy and failure of nonoperative management in very-high-volume centers. These results raise the question of centralizing the management of renal trauma, which is currently not the case in our health care system. Patient summary: In this study, management of renal trauma varied according to hospital volume. Very-high-volume centers had lower rates of nephrectomy and failure of nonoperative management.

Acute scrotal pain (ASP) requiring surgical exploration is common in the pediatric population, but little has been reported on this subject with regard to the adult population. The aim of this study was to investigate the demographic and clinical characteristics and outcomes of scrotal explorations performed on adult patients. Patients over 21 years of age who underwent surgical exploration for ASP with suspected testicular torsion (TT) at 14 French hospitals between January 2005 and December 2019 were included in this study. The main outcome measures were demographic characteristics, pathology found during scrotal exploration, and perioperative outcomes. Logistic regression was used to perform univariate and multivariate analyses to identify predictors of TT. Data for 1329 men were analyzed. The median age was 30 (interquartile range [IQR]: 25–35; range: 21–89) years. Regarding the clinical examination, 867 (65.2%) patients presented with an elevation of the testicle, 613 (46.1%) patients with scrotal edema or erythema, and 211 (15.9%) patients with nausea or vomiting. Operative findings identified TT in only 684 (51.5%) patients, epididymo-orchitis in 112 (8.4%) patients, a tumor in 16 (1.2%) patients, and no causes in 475 (35.7%) patients. Orchiectomy for nonviable testes was required in 101 (7.6%) patients. In multivariate analysis, an elevation of the testicle, erythema/swelling, and the presence of nausea/vomiting were found to be associated with the occurrence of TT. Testicular torsion is not exclusive to children and adolescents, so must be considered in males of any age with acute scrotal findings. However, one-third of scrotal explorations in adults did not lead to a diagnosis.

Background: For non-muscle-invasive bladder cancer (NMIBC) requiring radical surgery, limited data are available comparing robotic-assisted radical cystectomy with intracorporeal urinary diversion (iRARC) to open radical cystectomy (ORC). The objective of this study was to compare the two surgical techniques. Methods: A multicentric cohort of 593 patients with NMIBC undergoing iRARC or ORC between 2015 and 2020 was prospectively gathered. Perioperative and pathologic outcomes were compared. Results: A total of 143 patients operated on via iRARC were matched to 143 ORC patients. Operative time was longer in the iRARC group (p = 0.034). Blood loss was higher in the ORC group (p < 0.001), with a consequent increased post-operative transfusion rate in the ORC group (p = 0.003). Length of stay was longer in the ORC group (p = 0.007). Post-operative complications did not differ significantly (all p > 0.05). DFS at 60 months was 55.9% in ORC and 75.2% in iRARC with a statistically significant difference (p = 0.033) found in the univariate analysis. Conclusion: We found that iRARC for patients with NMIBC is safe, associated with a lower blood loss, a lower transfusion rate and a shorter hospital stay compared to ORC. Complication rates were similar. No significant differences in survival analyses emerged across the two techniques.

BackgroundCurrent guidelines recommend assessing the prognosis in high-risk upper tract urothelial carcinoma patients (UTUC) after surgery. However, no specific method is endorsed. Among the various prognostic models, nomograms represent an easy and accurate tool to predict the individual probability for a specific event. Therefore, identifying the best-suited nomogram for each setting seems of great interest to the patient and provider.ObjectivesTo identify, summarize and compare postoperative UTUC nomograms predicting oncologic outcomes. To estimate the overall performance of the nomograms and identify the most reliable predictors. To create a reference tool for postoperative UTUC nomograms, physicians can use in clinical practice.DesignA systematic review was conducted following the recommendations of Cochrane’s Prognosis Methods Group. Medline and EMBASE databases were searched for studies published before December 2021. Nomograms were grouped according to outcome measurements, the purpose of use, and inclusion and exclusion criteria. Random-effects meta-analyses were performed to estimate nomogram group performance and predictor reliability. Reference tables summarizing the nomograms’ important characteristics were created.ResultsThe systematic review identified 26 nomograms. Only four were externally validated. Study heterogeneity was significant, and the overall Risk of Bias (RoB) was high. Nomogram groups predicting overall survival (OS), recurrence-free survival (RFS), and intravesical recurrence (IVR) had moderate discrimination accuracy (c-Index summary estimate with 95% confidence interval [95% CI] and prediction interval [PI] > 0.6). Nomogram groups predicting cancer-specific survival (CSS) had good discrimination accuracy (c-Index summary estimate with 95% CI and PI > 0.7). Advanced pathological tumor stage (≥ pT3) was the most reliable predictor of OS. Pathological tumor stage (≥ pT2), age, and lymphovascular invasion (LVI) were the most reliable predictors of CSS. LVI was the most reliable predictor of RFS.ConclusionsDespite a moderate to good discrimination accuracy, severe heterogeneity discourages the uninformed use of postoperative prognostic UTUC nomograms. For nomograms to become of value in a generalizable population, future research must invest in external validation and assessment of clinical utility. Meanwhile, this systematic review serves as a reference tool for physicians choosing nomograms based on individual needs.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=282596, identifier PROSPERO [CRD42021282596].

Introduction: Lymph node (LN) involvement is a crucial determinant of prognosis for patients with bladder cancer, and an accurate staging is of utmost importance to better identify timely and appropriate therapeutic strategies. To improve the accuracy of LN detection, as an alternative to traditional methods such as CT or MRI, 18F-FDG PET/CT has been increasingly used. 18F-FDG PET/CT is also used in post-treatment restaging after neoadjuvant chemotherapy. The aim of this narrative literature review is to provide an overview of the current evidence on the use of 18F-FDG PET/CT in the diagnosis, staging, and restaging of bladder cancer, with a particular focus on its sensitivity and specificity for the detection of LN metastasis. We aim to provide clinicians with a better understanding of 18F-FDG PET/CT’s potential benefits and limitations in clinical practice. Materials and Methods: We designed a narrative review starting from a wide search in the PubMed/MEDLINE and Embase databases, selecting full-text English articles that have examined the sensibility and specificity of PET/CT for nodal staging or restaging after neoadjuvant therapy in patients with bladder cancer. The extracted data were analyzed and synthesized using a narrative synthesis approach. The results are presented in a tabular format, with a summary of the main findings of each study. Results: Twenty-three studies met the inclusion criteria: fourteen studies evaluated 18F-FDG PET/CT for nodal staging, six studies examined its accuracy for restaging after neoadjuvant therapy, and three studies evaluated both applications. To date, the use of F-18 FDG PET/TC for detection of LN metastasis in bladder cancer is controversial and uncertain: some studies showed low accuracy rates, but over the years other studies have reported evidence of high sensitivity and specificity. Conclusions: 18F-FDG PET/CT provides important incremental staging and restaging information that can potentially influence clinical management in MIBC patients. Standardization and development of a scoring system are necessary for its wider adoption. Well-designed randomized controlled trials in larger populations are necessary to provide consistent recommendations and consolidate the role of 18F-FDG PET/CT in the management of bladder cancer patients.

Background: In an era of Bacillus of Calmette-Guérin (BCG) shortages, the comparative efficacy from different adjuvant intravesical BCG strains in non-muscle invasive bladder cancer (NMIBC) has not been clearly elucidated. We aim to compare, through a systematic review and meta-analysis, the cumulative BC recurrence rates and the best efficacy profile of worldwide available BCG strains over the last forty years. Methods: PubMed, Scopus, Web of Science, Embase, and Cochrane databases were searched from 1982 up to 2022. A meta-analysis of pooled BC recurrence rates was stratified for studies with ≤3-y vs. >3-y recurrence-free survival (RFS) endpoints and the strain of BCG. Sensitivity analysis, sub-group analysis, and meta-regression were implemented to investigate the contribution of moderators to heterogeneity. A random-effect network meta-analysis was performed to compare BCG strains on a multi-treatment level. Results: In total, n = 62 series with n = 15,412 patients in n = 100 study arms and n = 10 different BCG strains were reviewed. BCG Tokyo 172 exhibited the lowest pooled BC recurrence rate among studies with ≤3-y RFS (0.22 (95%CI 0.16–0.28). No clinically relevant difference was noted among strains at >3-y RFS outcomes. Sub-group and meta-regression analyses highlighted the influence of NMIBC risk-group classification and previous intravesical treated categories. Out of the n = 11 studies with n = 7 BCG strains included in the network, BCG RIVM, Tice, and Tokyo 172 presented with the best-predicted probability for efficacy, yet no single strain was significantly superior to another in preventing BC recurrence risk. Conclusion: We did not identify a BCG stain providing a clinically significant lower BC recurrence rate. While these findings might discourage investment in future head-to-head randomized comparison, we were, however, able to highlight some potential enhanced benefits from the genetically different BCG RIVM, Tice, and Tokyo 172. This evidence would support the use of such strains for future BCG trials in NMIBCs.

Objectives: To identify correlates of survival and perioperative outcomes of upper tract urothelial carcinoma (UTUC) patients undergoing open (ORNU), laparoscopic (LRNU), and robotic (RRNU) radical nephroureterectomy (RNU). Methods: We conducted a retrospective, multicenter study that included non-metastatic UTUC patients who underwent RNU between 1990–2020. Multiple imputation by chained equations was used to impute missing data. Patients were divided into three groups based on their surgical treatment and were adjusted by 1:1:1 propensity score matching (PSM). Survival outcomes per group were estimated for recurrence-free survival (RFS), bladder recurrence-free survival (BRFS), cancer-specific survival (CSS), and overall survival (OS). Perioperative outcomes: Intraoperative blood loss, hospital length of stay (LOS), and overall (OPC) and major postoperative complications (MPCs; defined as Clavien–Dindo > 3) were assessed between groups. Results: Of the 2434 patients included, 756 remained after PSM with 252 in each group. The three groups had similar baseline clinicopathological characteristics. The median follow-up was 32 months. Kaplan–Meier and log-rank tests demonstrated similar RFS, CSS, and OS between groups. BRFS was found to be superior with ORNU. Using multivariable regression analyses, LRNU and RRNU were independently associated with worse BRFS (HR 1.66, 95% CI 1.22–2.28, p = 0.001 and HR 1.73, 95%CI 1.22–2.47, p = 0.002, respectively). LRNU and RRNU were associated with a significantly shorter LOS (beta −1.1, 95% CI −2.2–0.02, p = 0.047 and beta −6.1, 95% CI −7.2–5.0, p < 0.001, respectively) and fewer MPCs (OR 0.5, 95% CI 0.31–0.79, p = 0.003 and OR 0.27, 95% CI 0.16–0.46, p < 0.001, respectively). Conclusions: In this large international cohort, we demonstrated similar RFS, CSS, and OS among ORNU, LRNU, and RRNU. However, LRNU and RRNU were associated with significantly worse BRFS, but a shorter LOS and fewer MPCs.

Background: The efficacy of intravesical chemotherapy maintenance for patients with non-muscle invasive bladder cancer (NMIBC) is inferior compared to intravesical bacillus Calmette–Guerin (BCG). How intravesical chemohyperthermia (CHT) compares with BCG is under investigation.Objective: To compare the oncological outcomes and safety profile between intravesical CHT and BCG treatment for intermediate- and high-risk NMIBC.Methods: We performed a systematic review and meta-analysis of clinical studies comparing CHT with BCG for intermediate- and high-risk NMIBC patients. A comprehensive literature search on OVID MEDLINE, EMBASE, and Cochrane Library was conducted. Risk of bias was assessed by the Cochrane RoB tool and ROBINS-I. Certainty of evidence was rated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology.Results: A total of 2,375 articles were identified and five studies were finally included. Among them, four randomised trials comprising 327 patients (CHT group: 156 patients; BCG group: 171 patients) were included in the meta-analysis. There were no significant differences in the 24–36 months recurrence rates (CHT: 29.5%, BCG: 37.4%; RR: 0.83, 95% CI 0.61–1.13; moderate certainty of evidence) and the 24–36 months progression rates (CHT: 4.4%, BCG: 7.6%, RR = 0.62, 95% CI 0.26–1.49; low certainty of evidence). There were also no significant differences in grade 1–2 adverse events (CHT group: 59.9%, BCG group 54.5%; RR = 1.10, 95% CI 0.93–1.30; moderate certainty of evidence) and grade 3 or above adverse events (CHT group: 23.2%, BCG group 22.5%; RR = 0.99, 95% CI 0.69–1.43; low certainty of evidence).Conclusions: Intravesical CHT had equivalent oncological outcomes and similar safety profile when compared to BCG maintenance therapy for patients with intermediate- and high-risk NMIBC. CHT is a possible alternative treatment in the times of BCG shortage.

Objective:. To propose a standardized methodology for estimating the embodied carbon footprint (CF) of disposable minimally-invasive surgical devices (MISDs) and their application in new benign prostatic hyperplasia (BPH) MISDs. Summary of Background Data:. The estimation of the CO2e emissions of disposable surgical devices is central to empowering the healthcare supply chain. Methods:. The proposed methodology relied on a partial product lifecycle assessment and was restricted to a specific part of scope 3, which comprised the manufacturing of surgical device- and non–device-associated products (NDAPs), including packaging and user manual. The process-sum inventory method was used, which involves collecting data on all the component processes underpinning disposable MISDs. The seven latest disposable MISDs used worldwide for transurethral prostatic surgery were dismantled, and each piece was categorized, sorted into the appropriate raw material group, and weighed. The CF was estimated according to the following formula: activity data (weight of raw material) × emission factors of the corresponding raw material (kg CO2e/kg). Results:. The total weights of disposable packaging and user manuals ranged from 0.062 to 1.013 kg. Plastic was the most common and least emissive raw material (2.38 kg CO2e/kg) identified. The estimated embodied CF of MISDs ranged from 0.07 to 3.3 kg CO2e, of which 9% to 86% was attributed to NDAPs. Conclusions:. This study described a simple and independent calculation method for estimating the embodied CF of MISDs. Using this method, our results showed a wide discrepancy in the estimated CO2 emissions of the most recent disposable MISDs for transurethral BPH surgery. Thus, the lack of CF information should be of major concern in the development of future MISDs.

Background: Transurethral resection of the prostate (TURP) is the gold-standard treatment for benign prostatic hyperplasia (BPH). However, laser surgery techniques (e.g., photoselective vaporization of the prostate (PVP), holmium laser, thulium laser enucleation of the prostate (HoLEP or ThuLEP)), and minimally invasive treatment options (e.g., UroLift) are increasingly replacing TURP. This study seeks to report the annual incidence, management trends, and costs of BPH procedures in the U.S. Methods: Data analyses of U.S. health insurance claims from 2004 to 2017, collected from the de-identified Optum Clinformatics Claims Database, were performed to determine the number of BPH patients and the treatment selected. Results: A total of 51,448 patients underwent BPH procedures from 2004 to 2017. There was a significant increase in the annual rate from 770 in 2004 to 6571 in 2017. The mean patient age (±SD) increased from 67.6 years old (±8.4) in 2004 to 73.4 years old (±8.4) in 2017. More than 60% of patients underwent cystourethroscopy and a post-void residual urine check for workup prior to surgical management. TURP was the most-common, and PVP was the second-most-common BPH procedure. Medical and total treatment costs increased, while the detection rate of prostate cancer after BPH surgery gradually decreased from 19.87% in 2004 to 5.78% in 2017. Conclusions: Our study demonstrates a recent trend in BPH management that replaces the traditional TURP technique with alternative methods. Due to rising costs, future studies should assess whether these newer methods are cost effective over the long term.

Background: we aimed to characterize the financial needs expressed through online crowdfunding for urologic cancers. Methods: the data used in this study came from the online crowdfunding platform GoFundMe.com. Using an automated software method, we extracted data for campaigns related to urologic cancers. Subsequently, four independent investigators reviewed all extracted data on prostate, bladder, kidney and testicular cancer. We analyzed campaigns’ basic characteristics, goals, fundraising, type of treatment and factors associated with successful campaigns. Results: in total, we identified 2126 individual campaigns, which were related to direct treatment costs (34%), living expenses (17%) or both (48%). Median fundraising amounts were greatest for testicular cancer. Campaigns for both complementary and alternative medicine (CAM) (median $11,000) or CAM alone (median $8527) achieved higher fundraising totals compared with those for conventional treatments alone (median $5362) (p < 0.01). The number of social media shares was independently associated with campaign success and highest quartile of fundraising. Conclusions: using an automated web-based approach, we identified and characterized online crowdfunding for urologic cancer care. These findings indicated a diverse range of patient needs related to urologic care and factors related to campaigns’ success.

Prostate Imaging-Reporting and Data System (PI-RADS) has been widely implemented as a diagnostic tool for significant prostate cancer (PCa); less is known about its prognostic value, especially in the setting of primary radiotherapy. We aimed to analyze the association between PI-RADS v. 2.1 classification and risk of metastases, based on a group of 152 patients treated with ultra-hypofractionated stereotactic CyberKnife radiotherapy for localized low or intermediate risk-group prostate cancer. We found that all distant failures (n = 5) occurred in patients diagnosed with a PI-RADS score of 5, and axial measurements of the target lesion were associated with the risk of developing metastases (p < 0.001). The best risk stratification model (based on a combination of greatest dimension, the product of multiplication of PI-RADS target lesion axial measurements, and age) achieved a c-index of 0.903 (bootstrap-validated bias-corrected 95% CI: 0.848–0.901). This creates a hypothesis that PI-RADS 5 and the size of the target lesion are important prognostic factors in early-stage PCa patients and should be considered as an adverse prognostic measure for patients undergoing early treatment such as radiation or focal therapy.

Background: Measuring quality of care indicators is important for clinicians and decision making in health care to improve patient outcomes. Objective: The primary objective was to identify quality of care indicators for patients with upper tract urothelial carcinoma (UTUC) and to validate these in an international cohort treated with radical nephroureterectomy (RNU). The secondary objective was to assess the factors associated with failure to validate the pentafecta. Design: We performed a retrospective multicenter study of patients treated with RNU for EAU high-risk (HR) UTUC. Outcome measurements and statistical analysis: Five quality indicators were consensually approved, including a negative surgical margin, a complete bladder-cuff resection, the absence of hematological complications, the absence of major complications, and the absence of a 12-month postoperative recurrence. After multiple imputations and propensity-score matching, log-rank tests and a Cox regression were used to assess the survival outcomes. Logistic regression analyses assessed predictors for pentafecta failure. Results: Among the 1718 included patients, 844 (49%) achieved the pentafecta. The median follow-up was 31 months. Patients who achieved the pentafecta had superior 5-year overall- (OS) and cancer-specific survival (CSS) compared to those who did not (68.7 vs. 50.1% and 79.8 vs. 62.7%, respectively, all p < 0.001). On multivariable analyses, achieving the pentafecta was associated with improved recurrence-free survival (RFS), CSS, and OS. No preoperative clinical factors predicted a failure to validate the pentafecta. Conclusions: Establishing quality indicators for UTUC may help define prognosis and improve patient care. We propose a pentafecta quality criteria in RNU patients. Approximately half of the patients evaluated herein reached this endpoint, which in turn was independently associated with survival outcomes. Extended validation is needed.

Background: Intravesical immunotherapy with bacillus Calmette–Guerin (BCG) is the standard therapy for high-risk non-muscle invasive bladder cancer (NMIBC). The superiority of any BCG strain over another could not be demonstrated yet. Methods: Patients with NMIBCs underwent adjuvant induction ± maintenance schedule of intravesical immunotherapy with either BCG TICE or RIVM at two high-volume tertiary institutions. Only BCG-naïve patients and those treated with the same strain over the course of follow-up were included. One-to-one (1:1) propensity score matching (PSM) between the two cohorts was utilized to adjust for baseline demographic and tumor characteristics imbalances. Kaplan–Meier estimates and multivariable Cox regression models according to high-risk NMIBC prognostic factors were implemented to address survival differences between the strains. Sub-group analysis modeling of the influence of routine secondary resection (re-TUR) in the setting of the sole maintenance adjuvant schedule for the two strains was further performed. Results: 852 Ta-T1 NMIBCs (n = 719, 84.4% on TICE; n = 133, 15.6% on RIVM) with a median of 53 (24–77) months of follow-up were reviewed. After PSM, no differences at 5-years RFS, PFS, and CSS at both Kaplan–Meier and Cox regression analyses were detected for the whole cohort. In the sub-group setting of full adherence to European/American Urology Guidelines (EAU/NCCN), BCG TICE demonstrated longer 5-years RFS compared to RIVM (68% vs. 43%, p = 0.008; HR: 0.45 95% CI 0.25–0.81). Conclusion: When routinely performing re-TUR followed by a maintenance BCG schedule, TICE was superior to RIVM for RFS outcomes. However, no significant differences were detected for PFS and CSS, respectively.

The aim of this study was to assess the predictive value of pre-biopsy blood-based markers in patients undergoing a fusion biopsy for suspicious prostate magnetic resonance imaging (MRI). We identified 365 consecutive patients who underwent MRI-targeted and systematic prostate biopsy for an MRI scored Prostate Imaging–Reporting and Data System Version (PI-RADS) ≥ 3. We evaluated the neutrophil/lymphocyte ratio (NLR), derived neutrophil/lymphocyte ratio (dNLR), platelet/lymphocyte ratio (PLR), systemic immune inflammation index (SII), lymphocyte/monocyte ratio (LMR,) de Ritis ratio, modified Glasgow Prognostic Score (mGPS), and prognostic nutrition index (PNI). Uni- and multivariable logistic models were used to analyze the association of the biomarkers with biopsy findings. The clinical benefits of biomarkers implemented in clinical decision-making were assessed using decision curve analysis (DCA). In total, 69% and 58% of patients were diagnosed with any prostate cancer and Gleason Grade (GG) ≥ 2, respectively. On multivariable analysis, only high dNLR (odds ratio (OR) 2.61, 95% confidence interval (CI) 1.23–5.56, p = 0.02) and low PNI (OR 0.48, 95% CI 0.26–0.88, p = 0.02) remained independent predictors for GG ≥ 2. The logistic regression models with biomarkers reached AUCs of 0.824–0.849 for GG ≥ 2. The addition of dNLR and PNI did not enhance the net benefit of a standard clinical model. Finally, we created the nomogram that may help guide biopsy avoidance in patients with suspicious MRI. In patients with PI-RADS ≥ 3 lesions undergoing MRI-targeted and systematic biopsy, a high dNLR and low PNI were associated with unfavorable biopsy outcomes. Pre-biopsy blood-based biomarkers did not, however, significantly improve the discriminatory power and failed to add a clinical benefit beyond standard clinical factors.

Introduction: The increasing efficiency of the different lasers and the improved performance of endoscopic devices have led to smaller stone fragments that impact the accuracy of microscopic evaluation (morphological and infrared). Before the stone destruction, the urologist has the opportunity to analyze the stone and the papillary abnormalities endoscopically (endoscopic papillary recognition (EPR) and endoscopic stone recognition (ESR)). Our objective was to evaluate the value for those endoscopic descriptions. Methods: The MEDLINE and EMBASE databases were searched in February 2021 for studies on endoscopic papillary recognition and endoscopic stone recognition. Results: If the ESR provided information concerning the main crystallization process, EPR provided information concerning the origin of the lithogenesis and its severity. Despite many actual limitations, those complementary descriptions could support the preventive care of the stone formers in improving the diagnosis of the lithogenesis mechanism and in identifying high-risk stone formers. Conclusion: Until the development of an Artificial Intelligence recognition, the endourologist has to learn EPSR to minimize the distortion effect of the new lasers on the stone analysis and to improve care efficiency of the stone formers patients.

Background: Cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) with pelvic lymph-node dissection is the standard treatment for cT2-4a cN0 cM0 muscle-invasive bladder cancer (MIBC). Despite the significant improvement of primary-tumor downstaging with NAC, up to 50% of patients are eventually found to have advanced residual disease (pT3–T4 and/or histopathologically confirmed nodal metastases (pN+)) at RC. Currently, there is no established standard of care in such cases. The aim of this systematic review and meta-analysis was to assess differences in survival rates between patients with pT3–T4 and/or pN+ MIBC who received NAC and surgery followed by adjuvant chemotherapy (AC), and patients without AC. Materials and Methods: A systematic search was conducted in accordance with the PRISMA statement using the Medline, Embase, and Cochrane Library databases. The last search was performed on 12 November 2020. The primary end point was overall survival (OS) and the secondary end point was disease-specific survival (DSS). Results: We identified 2124 articles, of which 6 were selected for qualitative and quantitative analyses. Of a total of 3096 participants in the included articles, 2355 (76.1%) were in the surveillance group and 741 (23.9%) received AC. The use of AC was associated with significantly better OS (hazard ratio (HR) 0.84, 95% confidence interval (CI) 0.75–0.94; p = 0.002) and DSS (HR 0.56, 95% CI 0.32–0.99; p = 0.05). Contrary to the main analysis, in the subgroup analysis including only patients with pN+, AC was not significantly associated with better OS compared to the surveillance group (HR 0.89, 95% CI 0.58–1.35; p = 0.58). Conclusions: The administration of AC in patients with MIBC and pT3–T4 residual disease after NAC might have a positive impact on OS and DSS. However, this may not apply to N+ patients.

Background: Bacillus Calmette-Guérin (BCG) immunotherapy, the standard adjuvant intravesical therapy for some intermediate and most high-risk non-muscle invasive bladder cancers (NMIBCs), suffers from a heterogenous response rate. Molecular markers to help guide responses are scarce and currently not used in the clinical setting. Methods: To identify novel biomarkers and pathways involved in response to BCG immunotherapy, we performed a genome-wide DNA methylation analysis of NMIBCs before BCG therapy. Genome-wide DNA methylation profiles of DNA isolated from tumors of 26 BCG responders and 27 failures were obtained using the Infinium MethylationEPIC BeadChip. Results: Distinct DNA methylation patterns were found by genome-wide analysis in the two groups. Differentially methylated CpG sites were predominantly located in gene promoters and gene bodies associated with bacterial invasion of epithelial cells, chemokine signaling, endocytosis, and focal adhesion. In total, 40 genomic regions with a significant difference in methylation between responders and failures were detected. The differential methylation state of six of these regions, localized in the promoters of the genes GPR158, KLF8, C12orf42, WDR44, FLT1, and CHST11, were internally validated by bisulfite-sequencing. GPR158 promoter hypermethylation was the best predictor of BCG failure with an AUC of 0.809 (p-value < 0.001). Conclusions: Tumors from BCG responders and BCG failures harbor distinct DNA methylation profiles. Differentially methylated DNA regions were detected in genes related to pathways involved in bacterial invasion of cells or focal adhesion. We identified candidate DNA methylation biomarkers that may help to predict patient prognosis after external validation in larger, well-designed cohorts.

Background: To compare overall survival (OS) outcomes in pN1-3 disease at the time of radical cystectomy (RC) for muscle invasive bladder according to the neoadjuvant chemotherapy (NAC) status. Materials and Methods: This multicenter study included 450 consecutive patients undergoing RC for muscle-invasive urothelial bladder cancer with pN1-3 pM0 disease from 2010 to 2019. NAC consisted in platinum-based chemotherapy. The primary endpoint was the comparison between NAC and non-NAC in terms of death from any cause. OS was assessed using the Kaplan–Meier method and multivariate Cox proportional hazards regression was used to estimate adjusted hazard ratios. Results: Median age was 69 years. Patients receiving NAC were younger (p = 0.051), and more likely had downstaging to non-muscle invasive disease (10.7% versus 4.3%, p = 0.042). Median OS was 26.6 months. NAC patients had poorer OS compared with those who did receive NAC (Hazard ratio (HR) 1.6; p = 0.019). The persistence of muscle-invasive bladder in RC specimens was also significantly associated with OS (HR 2.40). In the NAC cohort, the two factors independently correlated with OS were the number of positive lymph nodes (p = 0.013) and adjuvant chemotherapy (AC) (HR 0.31; p = 0.015). Conclusions: Persistent nodal disease in RC specimens after NAC was associated with poor prognosis and lower OS rates compared with pN1-3 disease after upfront RC. In this sub-group of NAC patients, AC was independently associated with better OS.