Decisional and prognostic impact of diagnostic ureteroscopy in high-risk upper tract urothelial carcinoma: A multi-institutional collaborative analysis (ROBUUST collaborative group).

BACKGROUND: Diagnostic ureteroscopy (URS) with or without biopsy remains a subject of contention in the management of upper tract urothelial carcinoma (UTUC), with varying recommendations across different guidelines. The study aims to analyse the decision-making and prognostic role of diagnostic ureteroscopy (URS) in high-risk UTUC patients undergoing curative surgery. MATERIALS AND METHODS: In this retrospective multi-institutional analysis of high-risk UTUC patients from the ROBUUST dataset, a comparison between patients who received or not preoperative URS and biopsy before curative surgery was carried out. Logistic regression analysis evaluated differences between patients receiving URS and its impact on treatment strategy. Survival analysis included 5-year recurrence-free survival (RFS), metastasis-free survival (MFS), cancer-specific survival (CSS) and overall survival (OS). After adjusting for high-risk prognostic group features, Cox proportional hazard model estimated significant predictors of time-to-event outcomes. RESULTS: Overall, 1,912 patients were included, 1,035 with preoperative URS and biopsy and 877 without. Median follow-up: 24 months. Robot-assisted radical nephroureterectomy was the most common procedure (55.1%), in both subgroups. The 5-year OS (P = 0.04) and CSS (P < 0.001) were significantly higher for patients undergoing URS. The 5-year RFS (P = 0.6), and MFS (P = 0.3) were comparable between the 2 groups. Preoperative URS and biopsy were neither a significant predictor of worse oncological outcomes nor of a specific treatment modality. CONCLUSIONS: The advantage in terms of OS and CSS in patients undergoing preoperative URS could derive from a better selection of candidates for curative treatment. The treatment strategy is likely more influenced by tumor features than by URS findings.

Race has no impact on prostate cancer-specific mortality, when comparing patients with similar risk of other-cause mortality: An analysis of a population-based cohort.

BACKGROUND: Other-cause mortality (OCM) can serve as a surrogate for access-to-care. The authors sought to compare prostate cancer-specific mortality (PCSM) in Black versus White men matched based on their calculated OCM risk. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was queried for Black and White men diagnosed with prostate cancer between 2004 to 2009, to collect long-term follow-up. A Cox regression was used to calculate the OCM risk using all available covariates. This calculated OCM risk was used to construct a 1:1 propensity score matched (PSM) cohort. Then, a competing-risks multivariable tested the impact of race on PCSM. RESULTS: A total of 94,363 patients were identified, with 19,398 Black men and 74,965 White men. The median (IQR) follow-up was 11.3 years (9.8-12.8). In the unmatched-cohort at 10-years, PCSM and OCM were 5.5% versus 3.5% and 13.8% versus 8.4% in non-Hispanic Black (NHB) versus non-Hispanic White (NHW) patients (all p < .0001). The standardized mean difference was <0.15 for all covariates, indicating a good match. In the matched cohort at 10-years, OCM was 13.6% and 10.0% in NHB versus NHW (p < .0001), whereas the PCSM was 5.3% versus 4.7% (p < .01). On competing-risks multivariable analysis on PCSM, Black men had a hazard ratio of 1.08 (95% confidence interval, 0.98-1.20) compared to White men with a p = .13. CONCLUSIONS: The results of this study showed similar PCSM in Black and White patients, when matched with their calculated OCM risk. This report is the first to indicate at a population-based level that race has no impact on PCSM. PLAIN LANGUAGE SUMMARY: Prostate cancer is a very common cancer among men and it is associated with health disparities that disproportionately impact Black men compared to White men. There is an on-going discussion of whether disparities between these two groups stem from genetic or environmental factors. This study sought to examine if matching based on overall health status, a proxy for the impact of social determinants of health, mitigated significant differences in outcomes. When matched using risk of death from any cause other than prostate cancer, Black and White men had no significant differences in prostate cancer death.

Adequacy of prostate cancer prevention and screening recommendations provided by an artificial intelligence-powered large language model.

PURPOSE: We aimed to assess the appropriateness of ChatGPT in providing answers related to prostate cancer (PCa) screening, comparing GPT-3.5 and GPT-4. METHODS: A committee of five reviewers designed 30 questions related to PCa screening, categorized into three difficulty levels. The questions were formulated identically for both GPTs three times, varying the prompts. Each reviewer assigned a score for accuracy, clarity, and conciseness. The readability was assessed by the Flesch Kincaid Grade (FKG) and Flesch Reading Ease (FRE). The mean scores were extracted and compared using the Wilcoxon test. We compared the readability across the three different prompts by ANOVA. RESULTS: In GPT-3.5 the mean score (SD) for accuracy, clarity, and conciseness was 1.5 (0.59), 1.7 (0.45), 1.7 (0.49), respectively for easy questions; 1.3 (0.67), 1.6 (0.69), 1.3 (0.65) for medium; 1.3 (0.62), 1.6 (0.56), 1.4 (0.56) for hard. In GPT-4 was 2.0 (0), 2.0 (0), 2.0 (0.14), respectively for easy questions; 1.7 (0.66), 1.8 (0.61), 1.7 (0.64) for medium; 2.0 (0.24), 1.8 (0.37), 1.9 (0.27) for hard. GPT-4 performed better for all three qualities and difficulty levels than GPT-3.5. The FKG mean for GPT-3.5 and GPT-4 answers were 12.8 (1.75) and 10.8 (1.72), respectively; the FRE for GPT-3.5 and GPT-4 was 37.3 (9.65) and 47.6 (9.88), respectively. The 2nd prompt has achieved better results in terms of clarity (all p < 0.05). CONCLUSIONS: GPT-4 displayed superior accuracy, clarity, conciseness, and readability than GPT-3.5. Though prompts influenced the quality response in both GPTs, their impact was significant only for clarity.

Testing the external validity of the POUT III trial (adjuvant platnium-based chemotherapy in upper tract urothelial carcinoma) in a North American cohort.

OBJECTIVE: The European POUT III randomized controlled trial provided level-one evidence that adjuvant platinum-based chemotherapy is the standard of care following nephroureterectomy (RNU) for locally invasive or node-positive upper tract urothelial carcinoma. We aim to assess this European randomized controlled trial's generalizability (external validity) to a North American cohort, using a nationwide database. MATERIALS AND METHODS: To compare trial patients with those seen in real-world practice, we simulated the trial inclusion criteria using data from the National Cancer Database (NCDB). We identified patients with histologically confirmed transitional cell carcinoma who underwent RNU. The available demographic characteristics of the NCDB cohort were compared with the POUT III trial cohort using Chi-squared test. RESULTS: The NCDB cohort (n = 3,380) had a significantly higher proportion of older patients (age ≥ 80: 23.5% vs. 5%), and more males (68% vs. 56.2%) than the POUT cohort (Table 1, both p < 0.001). Additionally, the rate of advanced nodal disease was higher in the NCDB (N1 9.6%, N2 9.3%) than in the POUT (N1 6%, N2 3%) cohort (p < 0.001). A more extensive lymph node dissection was performed in NCDB vs. POUT patients (node≥10 10.9% vs. 3%, p < 0.001). Sensitivity analysis removing all subjects with a Charlson Comorbidity Index > 0 did not change the significance of any results. CONCLUSIONS: While the primary disease stage was similar, the rate of advanced nodal disease was significantly higher in NCDB, which might be explained partially by the more extensive lymph node dissection performed in the latter. These differences warrant caution when applying the POUT III findings to North American patients.

Impact of low-intensity extracorporeal shockwave therapy on vascular parameters and sexual function in patients with arteriogenic erectile dysfunction.

ABSTRACT: Previous published studies have shown an improvement of penile hemodynamic parameters after low-intensity extracorporeal shockwave therapy (Li-ESWT). However, the clinical significance of these findings remains unclear, and definitive selection criteria for Li-ESWT based on preexisting comorbidities have yet to be established. This was an observational study of 113 patients with ED, evaluated between January 2019 and December 2021 in Andrology Unit at the Department of Urology and Renal Transplantation, University of Foggia (Foggia, Italy). Penile dynamic Doppler was performed to evaluate vascular parameters and 5-item version of the International Index of Erectile Dysfunction (IIEF-5) questionnaire was administered to assess the severity of ED. This was repeated 1 month after treatment. Patients with a peak systolic velocity (PSV) <30 cm s-1 were considered eligible for Li-ESWT. Our protocol consisted of 8 weekly sessions with 1500 strokes distributed in 5 different locations along the penis. After treatment, a significant mean (±standard deviation [s.d.]) PSV increase of 5.0 (±3.4) cm s-1 was recorded and 52/113 (46.0%) patients reached a PSV >30 cm s-1 at posttherapeutic penile dynamic Doppler. A clinically significant IIEF-5 score improvement was observed in 7 patients, 21 patients, and 2 patients with mild-to-moderate, moderate, and severe pretreatment ED, respectively. No different outcomes were assessed based on smoking habits, previous pelvic surgery, or use of oral phosphodiesterase-5 inhibitor (PDE5i). On the other side, only 1 (6.7%) in 15 patients with diabetes mellitus showed an IIEF-5 score improvement after Li-ESWT. Shockwave treatment determined a significant increase in PSV and correlated IIEF-5 improvement in ED patients. This advantage seemed particularly evident for moderate ED and was not affected by smoking habits, previous pelvic surgery, and use of PDE5i. Conversely, diabetic patients did not benefit from the treatment.

Comparison of patient background between a real-world North American cohort and the Göteborg-2 trial.

OBJECTIVES: To analyze the generalizability of the Göteborg-2 findings to a North American cohort. METHODS: We replicated the Göteborg-2 inclusion criteria in our Henry Ford Health (HFH) cohort, by identifying all patients 50-60 years old who had a PSA test from 2013 to 2018. The first PSA within the study period was considered PSA at entry, and included in the analysis. Chi-square test was used to compare categorical variables between the Göteborg-2 and HFH cohort, with a particular focus on Black men, who were also analyzed separately. RESULTS: The HFH patients included in the cohort were 49 456, of which 8562 were Black. In patients within the entire HFH cohort, HFH Black cohort, Göteborg Reference cohort, and Göteborg Experimental cohort, the rate of PSA ≥3 ng/mL was, respectively, 6.8%, 10.2%, 6.8%, and 6.6%. The rate of biopsy performed was, respectively, 1.8%, 4.1%, 5.8%, and 2.5%. PCa was found in, respectively, 1.4%, 3.0%, 2.3%, and 1.5%; Gleason score 3 + 3 in, respectively, 0.5%, 0.8%, 1.2%, and 0.6%; Gleason score > 3 + 3 in, respectively, 0.9%, 2.2%, 1.1%, and 0.9%. CONCLUSIONS: Our cohort had a lower biopsy rate and a lower incidence of non-csPCa diagnosis than both Göteborg cohorts, while still maintaining the same incidence of csPCa. This implies that the benefits of reducing non-csPCa diagnosis, as observed in the Experimental Göteborg cohort, are not necessarily replicable in U.S. "real-world practice" patients. Also noteworthy, we had a significantly higher percentage of Black men, who showed more aggressive disease.

Admission Rates, Healthcare Utilization, and Inpatient Cost of Radiation Cystitis in the United States.

OBJECTIVE: To assess the incidence, cumulative healthcare burden, and financial impact of inpatient admissions for radiation cystitis (RC), while exploring practice differences in RC management between teaching and nonteaching hospitals. METHODS: We focused on 19,613 patients with a diagnosis of RC within the National Inpatient Sample (NIS) from 2008 to 2014. ICD-9 diagnosis and procedure codes were used. Complex-survey procedures were used to study the descriptive characteristics of RC patients and the procedures received during admission, stratified by hospital teaching status. Inflation-adjusted cost and cumulative annual cost were calculated for the study period. Multivariable logistic regression was used to study the impact of teaching status on the high total cost of admission. RESULTS: Median age was 76 (interquartile range 67-82) years. Most of the patients were males (73%; P < .001). 59,571 (61%) patients received at least one procedure, of which, 24,816 (25.5%) received more than one procedure. Median length of stay was 5days (interquartile range 2-9). Female patients and patients with a higher comorbidity score were more frequently treated at teaching hospitals. A higher proportion of patients received a procedure at a teaching hospital (64% vs 59%; P < .001). The inflation-adjusted cost was 9207 USD and was higher in teaching hospitals. The cumulative cost of inpatient treatment of RC was 63.5 million USD per year and 952.2 million USD over the study period. CONCLUSION: The incidence of RC-associated admissions is rising in the US. This disease is a major burden to US healthcare. The awareness of the inpatient economic burden and healthcare utilization associated with RC may have funding implications.

Impact of lymphovascular invasion on survival in surgically treated upper tract urothelial carcinoma: a nationwide analysis.

OBJECTIVES: To assess the prognostic ability of lymphovascular invasion (LVI) in upper tract urothelial carcinoma (UTUC) as a predictor of overall survival (OS) using a large North American cohort. PATIENTS AND METHODS: Our cohort included 5940 patients with clinical M0 UTUC who underwent a radical nephroureterectomy (RNU), between 2010 and 2016, within the National Cancer Database. The main variable of interest was LVI status, and its interaction with pathological nodal (pN) status. Kaplan-Meier curves were used to depict the OS also stratifying patients on LVI status. Cox regression analysis tested the impact of LVI status on OS after accounting for the available covariates. RESULTS: The median (interquartile range [IQR]) age at diagnosis was 71 (63-78) years and most patients had pathological T1 stage disease (48.6%). Nodal status was pN0, pN1 and pNx in 45.8%, 6.3% and 47.9%, respectively. Overall, 22.1% had LVI. The median (IQR) follow-up time was 32.6 (16.0-53.3) months. At the 5-year postoperative follow-up, the estimated OS rate was 28% in patients with LVI vs 66% in those without LVI (P < 0.001). When patients were stratified based on nodal status those rates were 32% vs 68% in pN0 patients (P < 0.001), 23% vs 30% in pN1 patients (P = 0.8), and 28% vs 65% in pNx patients (P < 0.001). On multivariable analysis, the presence of LVI was associated with less favourable OS (hazard ratio 1.79, 95% confidence interval 1.60-1.99; P < 0.001). CONCLUSION: Our study assessed the impact of LVI on OS in patients with UTUC in a large North American nationwide cohort. Our series, as the largest to date, indicate that LVI is associated with less favourable survival outcomes in patients with UTUC after RNU, and this variable could be used in counselling patients about their prognosis and might be a useful tool for future trials to risk-stratify patients.

Diagnosis of prostate cancer with magnetic resonance imaging in men treated with 5-alpha-reductase inhibitors.

PURPOSE: The primary aim of this study was to evaluate if exposure to 5-alpha-reductase inhibitors (5-ARIs) modifies the effect of MRI for the diagnosis of clinically significant Prostate Cancer (csPCa) (ISUP Gleason grade ≥ 2). METHODS: This study is a multicenter cohort study including patients undergoing prostate biopsy and MRI at 24 institutions between 2013 and 2022. Multivariable analysis predicting csPCa with an interaction term between 5-ARIs and PIRADS score was performed. Sensitivity, specificity, and negative (NPV) and positive (PPV) predictive values of MRI were compared in treated and untreated patients. RESULTS: 705 patients (9%) were treated with 5-ARIs [median age 69 years, Interquartile range (IQR): 65, 73; median PSA 6.3 ng/ml, IQR 4.0, 9.0; median prostate volume 53 ml, IQR 40, 72] and 6913 were 5-ARIs naïve (age 66 years, IQR 60, 71; PSA 6.5 ng/ml, IQR 4.8, 9.0; prostate volume 50 ml, IQR 37, 65). MRI showed PIRADS 1-2, 3, 4, and 5 lesions in 141 (20%), 158 (22%), 258 (37%), and 148 (21%) patients treated with 5-ARIs, and 878 (13%), 1764 (25%), 2948 (43%), and 1323 (19%) of untreated patients (p < 0.0001). No difference was found in csPCa detection rates, but diagnosis of high-grade PCa (ISUP GG ≥ 3) was higher in treated patients (23% vs 19%, p = 0.013). We did not find any evidence of interaction between PIRADS score and 5-ARIs exposure in predicting csPCa. Sensitivity, specificity, PPV, and NPV of PIRADS ≥ 3 were 94%, 29%, 46%, and 88% in treated patients and 96%, 18%, 43%, and 88% in untreated patients, respectively. CONCLUSIONS: Exposure to 5-ARIs does not affect the association of PIRADS score with csPCa. Higher rates of high-grade PCa were detected in treated patients, but most were clearly visible on MRI as PIRADS 4 and 5 lesions. TRIAL REGISTRATION: The present study was registered at ClinicalTrials.gov number: NCT05078359.

Oncological outcomes of whole-gland cryoablation in patients with prostate cancer and high risk of lymph node invasion.

Purpose: Prostate cryoablation has been proposed as an alternative to radical prostatectomy for men with localized prostate cancer (PCa); however, it is limited by the lack of data regarding oncological outcomes and the impossibility of performing a lymph node dissection. The aim of this study was to assess if whole-gland cryoablation is oncologically safe, especially for patients in whom pelvic lymph node dissection would be necessary. Materials and Methods: After institutional review board approval, we identified 102 patients who underwent whole-gland prostate cryoablation between 2013 and April 2019. Lymph node invasion (LNI) probability was computed using Briganti nomogram, and a 5% cutoff probability was used to stratify the population in two groups. Biochemical recurrence after procedure was assessed using Phoenix criteria. Multiparametric magnetic resonance imaging, (CT), and bone scan or choline positron-emission tomography/CT were performed for the detection of distant metastases. Results: Seventeen (17%) patients were treated for a low-risk PCa, 48 (47%) patients were at intermediate-risk PCa, and 37 (36%) patients were at high-risk PCa. Patients with a probability of LNI >5% (n = 46) exhibited higher prostate-specific antigen (PSA), PSA density, ISUP Grade Group, CT stage, and european association of urology (EAU) risk. Recurrence-free survival rates at 3 years' follow-up were 93%, 82%, and 72%, respectively for low-, intermediate-, and high-risk patients. At a median follow-up of 37 months (17-62), additional treatment and metastasis-free survival were 84% and 97%, respectively. No differences in oncological outcomes were found in patients with a probability of LNI above and below 5%. Conclusions: Prostate whole-gland cryoablation can be considered a safe procedure with acceptable outcomes in low- and intermediate-risk patients. A high preoperative risk of nodal involvement could not be considered an exclusion criterion to perform cryoablation. Further studies are required.

Bladder Cancer and Risk Factors: Data from a Multi-Institutional Long-Term Analysis on Cardiovascular Disease and Cancer Incidence.

Background: Bladder cancer (BCa) is a heterogeneous disease with a variable prognosis and natural history. Cardiovascular disease (CVD), although completely different, has several similarities and possible interactions with cancer. The association between them is still unknown, but common risk factors between the two suggest a shared biology. Materials and Methods: This was a retrospective study that included patients who underwent transurethral resection of bladder tumor at two high-volume institutions. Depending on the presence of a previous history of CVD or not, patients were divided into two groups. Results: A total of 2050 patients were included, and 1638 (81.3%) were diagnosed with bladder cancer. Regarding comorbidities, the most common were hypertension (59.9%), cardiovascular disease (23.4%) and diabetes (22.4%). At univariate analysis, independent risk factors for bladder cancer were age and male sex, while protective factors were cessation of smoking and presence of CVD. All these results, except for ex-smoker status, were confirmed at the multivariate analysis. Another analysis was performed for patients with high-risk bladder cancer and, in this case, the role of CVD was not statistically significant. Conclusions: Our study pointed out a positive association between CVD and BCa incidence; CVD was an independent protective factor for BCa. This effect was not confirmed for high-risk tumors. Several biological and genomics mechanisms clearly contribute to the onset of both diseases, suggesting a possible shared disease pathway and highlighting the complex interplay of cancer and CVD. CVD treatment can involve different drugs with a possible effect on cancer incidence, but, to date, findings are still inconclusive.

Conservative treatment for high-risk NMIBC failing BCG treatment: who benefits from adding electromotive drug administration (EMDA) of mitomycin C (MMC) to a second BCG induction cycle?

PURPOSE: Radical cystectomy (RC) is the standard treatment for high-risk non muscle-invasive bladder cancer (NMIBC) failing first BCG treatment. A second BCG course is an option for those patients who refuse RC or are not eligible for it, but its success rate is quite low. Aim of the present study was to determine whether the addition of intravesical electromotive drug administration of mytomicin-C (EMDA-MMC) improved the efficacy of second BCG course. METHODS: Patients with high-risk NMIBC having failed first BCG treatment and having refused RC were offered a second BCG induction course either alone (group A) or combined with EMDA-MMC (group B). Recurrence-free survival (RFS), progression-free survival (PFS) and cancer-specific survival (CSS) were tested. RESULTS: Of the 80 evaluable patients, 44 were in group A and 36 in group B; median follow-up was 38 months. RFS was significantly worse in group A whereas there was no difference in PFS and CSS between the two groups. Stratifying by disease stage, Ta patients receiving combined treatment had statistically better RFS and PFS survival than those receiving BCG only; this difference did not apply to T1 patients. Multivariable analysis confirmed that combined treatment was a significant predictor of recurrence and was close to predict progression. No tested variable was predictive of recurrence or progression in T1 tumours. Among those who underwent RC, CSS was 61.5% in those who had progression and 100% in those who remained with NMIBC. CONCLUSION: Combined treatment improved RFS and PFS only in patients with Ta disease.

Treatment of localized prostate cancer in elderly patients: the role of partial cryoablation.

PURPOSE: To evaluate oncological outcomes of partial gland cryoablation (PGC) for localized prostate cancer (PCa) in a cohort of elderly patients who required an active treatment. METHODS: Data from 110 consecutive patients treated with PGC for localized PCa were collected. All patients underwent the same standardized follow-up with serum-PSA level and digital rectal examination. Prostate MRI and eventual re-biopsy were performed at twelve months after cryotherapy or in case of suspicion of recurrence. Biochemical recurrence was defined according to Phoenix criteria (PSA nadir + 2 ng/ml). Kaplan-Meier curves and Multivariable Cox Regression analyses were used to predict disease progression, biochemical recurrence- (BCS) and additional treatment-free survival (TFS). RESULTS: Median age was 75 years (IQR 70-79). PGC was performed in 54 (49.1%) patients with low-risk PCa, 42 (38.1%) with intermediate risk and 14 (12.8%) high risk. At a median follow-up of 36 months, we recorded a BCS and TFS of 75 and 81%, respectively. At 5 years, BCS was 68.5% and CRS 71.5%. High-risk prostate cancer was associated with lower TFS and BCS curves when compared with low-risk group (all p values < .03). A PSA reduction < 50% between preoperative level and nadir resulted as an independent failure predictor for all outcomes evaluated (all p values < .01). Age was not associated with worse outcomes. CONCLUSIONS: PGC could be a valid treatment for low- to intermediate PCa in elderly patients, when a curative approach is suitable in terms of life expectancy and quality of life.

The Accuracy of Transurethral Bladder Resection in Detecting Bladder Cancer Histological Variants and Their Prognostic Value at Radical Cystectomy.

OBJECTIVES: to investigate the accuracy of transurethral resection of bladder tumours (TURBT) in detecting histological variants (BHV) at radical cystectomy (RC) and to evaluate the impact of TURBT before cystectomy on oncological outcomes. METHODS: Data of 410 consecutive RCs were assessed. Positive and negative predictive values were used to assess the accuracy of TURBT in detecting BHV. Cohen's Kappa coefficient was used to calculate the agreement grade. Logistic regression analysis predicted features based on the presence of BHV at TURBT. Multivariable backward conditional Cox regression analysis was used to estimate oncological outcomes. RESULTS: A total of 73 patients (17.8%) showed BHV at TURBT as compared to 108 (26.3%) at RC. A moderate agreement in histological diagnosis was found between TURBT and RC (0.58). However, sensitivity and specificity in detecting BHV were 56% and 96%, respectively. Furthermore, positive predictive value (PPV) was 84.7% and negative predictive value (NPV) was 84.6%. Presence of BHV at TURBT was an independent predictor for pathologic upstage, albeit not a predictor for positive nodes or positive surgical margins. However, at multivariable analysis adjusted for all confounders, presence of BHV at TURBT was an independent predictor for recurrence after RC, but not for survival. Conversely, the presence of BHV at RC was an independent predictor for both recurrence and survival. CONCLUSION: There was a moderate agreement between TURBT and RC histopathological findings. TURBT, alone, could not provide an accurate and definitive histological diagnosis. Detection of BHV in TURBT specimens is not an independent predictor of oncological outcomes; indeed, only pathological features at RC are associated with worse survival. However, BHV presence in cystectomy specimens resulted as an independent predictor of both cancer-specific and overall mortality.

Oncological outcomes of concomitant carcinoma in situ at radical cystectomy in pure urothelial bladder cancer and in histological variants.

INTRODUCTION: The presence of carcinoma in situ at transurethral resection is known to increase the risk of recurrence and progression to invasive disease. However, the evidence regarding the prognostic role of concomitant carcinoma in situ after radical cystectomy due to bladder cancer is controversial. Moreover, concomitant carcinoma in situ was found to be significantly associated with bladder histological variants. The aim of our study is to evaluate whether the presence of concomitant carcinoma in situ at radical cystectomy, impacts on recurrence and survival outcomes in pure urothelial bladder cancer, compared to histological variants. METHODS: We evaluated 410 consecutive patients diagnosed with non-metastatic bladder cancer and treated with radical cystectomy at a single tertiary referral centre between January 2009 and May 2019. Patients were stratified according to the presence of carcinoma in situ. The Kaplan-Meier method was used to compare recurrence free, cancer specific and overall survival in pure urothelial and histological variants. Cox proportional hazards regression analyses model was used to predict recurrence, cancer specific and overall mortality in pure urothelial and histological variants bladder cancer, according to pathological stage. RESULTS: Median age was 71 years. 340 patients (82%) were male. At a median follow-up of 32 months, disease recurrence, cancer specific mortality and overall mortality were, 37% (155 patients), 32.9% (135 patients) and 46.6% (191 patients), respectively. Concomitant and pure carcinoma in situ were found in 39% and 19% of radical cystectomy specimens, respectively. Concomitant carcinoma in situ was more frequent in patients with histological variants (50.9%) compared to pure urothelial bladder cancer (35.4%) (P-value <.001) and was associated with worst pathological features (lymphovascular invasion, lymph node involvement and non-organ confined disease). Recurrence free survival at Kaplan-Meyer analyses was significantly higher in patients with pure carcinoma in situ compared to those with concomitant or no carcinoma in situ (all P <.001), similarly for patients without carcinoma in situ compared with those with concomitant Cis (P =.02) at radical cystectomy. Cancer specific and overall survival were significantly higher in patients with pure carcinoma in situ compared to those with concomitant or no carcinoma in situ (all P <.001). Conversely no significant difference was found between patients without carcinoma in situ and with concomitant carcinoma in situ (P>0.1) at radical cystectomy Moreover, concomitant carcinoma in situ at radical cystectomy in histological variants is associated with higher free recurrence rate compared to the other groups. At multivariate Cox proportional hazards regression analyses the presence of carcinoma in situ at radical cystectomy was not associated with any survival effect or recurrence (all P > .05) in the overall population and when patients are stratified according to histology. However, concomitant carcinoma in situ represents an independent predictor of recurrence in the subgroup of patients with organ confined disease in case of urothelial bladder cancer and histological variants. CONCLUSION: Concomitant carcinoma in situ should be considered a proxy of aggressiveness in bladder cancer after radical cystectomy. Based on its prognostic implications, concomitant carcinoma in situ should be considered for strict follow-up in patients with organ confined disease which may deserve adjuvant treatment both in pure urothelial bladder cancer and histological variants.

The impact of histological variants on outcomes after open radical cystectomy for muscle-invasive urothelial bladder cancer: results from a single tertiary referral centre.

OBJECTIVES: To evaluate the impact of histological variants on oncological outcomes of patients with muscle-invasive bladder cancer treated with open radical cystectomy and furthermore to determine any association between survival and each histotype of bladder cancer. MATERIALS AND METHODS: Data from 525 consecutive patients with muscle-invasive bladder cancer treated with radical cystectomy between January 2008 and May 2019 were collected retrospectively. The Kaplan-Meier curves and multivariable analysis addressed the role of histological variants in recurrence, cancer-specific and overall mortality between all subgroups. RESULTS: Of 525 patients, 131 (25.0%) showed a histological variant at radical cystectomy. With a median follow-up of 31 months, 209 (39.8%) recurrences, 184 (35.0%) cancer-related deaths and 260 (49.5%) overall deaths were reported. The presence of histological variant was associated with advanced tumour stage, the presence of concomitant carcinoma in situ, lymph node metastasis, lymphovascular invasion and positive surgical margins compared to pure urothelial bladder cancer (all p values < .008) and resulted as an independent risk factor for cancer-specific mortality (p = 0.001). Patients with a histological variant were at significantly higher risk for recurrence, cancer-specific mortality and overall mortality (all p values ≤ .001). Micropapillary, sarcomatoid or small cell differentiation was associated with reduced survival. CONCLUSION: The presence of histological variants at radical cystectomy seems to be weakly associated with reduced survival compared to pure urothelial bladder cancer paired for pathologic stage. The association of histological variants with advanced and biologically aggressive tumours suggests the need for attention on the overall management of these patients, in particular for micropapillary, sarcomatoid and small cell differentiation.