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Purpose: The purpose of this study is to compare perioperative and oncological outcomes of upfront vs. delayed early radical cystectomy (eRC) for high-risk non-muscle-invasive bladder cancer (HR-NMIBC). Methods: All consecutive HR-NMIBC patients who underwent eRC between 2001 and 2020 were retrospectively included and divided into upfront and delayed groups, according to the receipt or not of BCG. Perioperative outcomes were evaluated and the impact of upfront vs. delayed eRC on pathological upstaging, defined as ≥pT2N0 disease at final pathology, was assessed using multivariable logistic regression. Recurrence-free (RFS), cancer-specific (CSS) and overall survival (OS) were compared between upfront and delayed eRC groups using inverse probability of treatment weighting (IPTW)-adjusted Cox model. Results: Overall, 184 patients received either upfront (n = 87; 47%) or delayed (n = 97; 53%) eRC. No difference was observed in perioperative outcomes between the two treatment groups (all p > 0.05). Pathological upstaging occurred in 55 (30%) patients and upfront eRC was an independent predictor (HR = 2.65; 95% CI = (1.23–5.67); p = 0.012). In the IPTW-adjusted Cox analysis, there was no significant difference between upfront and delayed eRC in terms of RFS (HR = 1.31; 95% CI = (0.72–2.39); p = 0.38), CSS (HR = 1.09; 95% CI = (0.51–2.34); p = 0.82) and OS (HR = 1.19; 95% CI = (0.62–2.78); p = 0.60). Conclusion: our results suggest similar perioperative outcomes between upfront and delayed eRC, with an increased risk of upstaging after upfront eRC that did impact survival, as compared to delayed eRC.

Simple Summary Transurethral resection of bladder tumours may be technically challenging. Complexity was defined by consensus from the literature by a panel of ten senior urologists as “any TURBT/En-bloc dissection that results in incomplete resection and/or prolonged surgery (>1 h) and/or significant (Clavien-Dindo ≥ 3) perioperative complications”. Patient and tumour’s characteristics that suggested to by the panel to relate to complex surgery were collected and then ranked by Delphi consensus. They were tested in the prediction of complexity in 150 clinical scenarios. After univariate and logistic regression analyses, significant characteristics were organized into a checklist that predicts complexity. Receiver operating characteristics (ROC) curves of the regression model and the corresponding calibration curve showed adequate discrimination (AUC = 0.916) and good calibration. The resulting Bladder Complexity Checklist can be used to deliver optimal preoperative information and personalise the organisation of surgery. Abstract Ten senior urologists were interrogated to develop a predictive model based on factors from which they could anticipate complex transurethral resection of bladder tumours (TURBT). Complexity was defined by consensus. Panel members then used a five-point Likert scale to grade those factors that, in their opinion, drove complexity. Consensual factors were highlighted through two Delphi rounds. Respective contributions to complexity were quantitated by the median values of their scores. Multivariate analysis with complexity as a dependent variable tested their independence in clinical scenarios obtained by random allocation of the factors. The consensus definition of complexity was “any TURBT/En-bloc dissection that results in incomplete resection and/or prolonged surgery (>1 h) and/or significant (Clavien-Dindo ≥ 3) perioperative complications”. Logistic regression highlighted five domains as independent predictors: patient’s history, tumour number, location, and size and access to the bladder. Receiver operating characteristic (ROC) analysis confirmed good discrimination (AUC = 0.92). The sum of the scores of the five domains adjusted to their regression coefficients or Bladder Complexity Score yielded comparable performance (AUC = 0.91, C-statistics, p = 0.94) and good calibration. As a whole, preoperative factors identified by expert judgement were organized to quantitate the risk of a complex TURBT, a crucial requisite to personalise patient information, adapt human and technical resources to individual situations and address TURBT variability in clinical trials.

Prostate cancer (PCa) is the second most common cancer of men and is typically slow-growing and asymptomatic. The use of blood PSA as a screening method has greatly improved PCa diagnosis, but high levels of false positives has raised much interest in alternative biomarkers. We used next-generation sequencing (NGS) to elucidate the urinary transcriptome of whole urine collected from high-stage and low-stage PCa patients as well as from patients with the confounding diagnosis of benign hyperplasia (BPH). We identified and validated five differentially expressed protein-coding genes (FTH1 BRPF1, OSBP, PHC3, and UACA) in an independent validation cohort of small-volume (1 mL) centrifuged urine (n = 94) and non-centrifuged urine (n = 84) by droplet digital (dd)PCR. These biomarkers were able to discriminate between BPH and PCa patients and healthy controls using either centrifuged or non-centrifuged whole urine samples, suggesting that the urinary transcriptome is a valuable source of non-invasive biomarkers for PCa that warrants further investigation.

Upfront MRI is taking the lead in the diagnosis of clinically significant prostate cancer, while few image-guided biopsies (IGBs) fail to demonstrate clinically significant prostate cancer. The added value of innovative biomarkers is not confirmed in this context. We analysed SelectMDx-v2 (MDx-2) in a cohort of upfront MRI and image-guided biopsy patients. Participants included patients who received a trans-rectal elastic-fusion registration IGB on the basis of DRE, PSA, PCA3, and PCPT-2.0 risk evaluation. Pre-biopsy MRI DICOM archives were reviewed according to PI-RADS-v2. Post-massage first-void urine samples stored in the institutional registered bio-repository were commercially addressed to MDxHealth to obtain MDx-2 scores. Univariate and multivariate analyses were conducted with the detection on IGB of high-grade (ISUP 2 and higher) as the dependent variable. High-grade cancer was demonstrated in 32/117 (27.4%) patients (8/2010&ndash, 8/2018). Age, prostate volume, biopsy history, MDx-2, and PI-RADS-v2 scores significantly related to the detection of high-grade cancer. MDx-2 scores and the clinical variables embedded into MDx-2 scores were analysed in multivariate analysis to complement PI-RADS-v2 scores. The two combinations outperformed PI-RADS-v2 alone (AUC-ROC 0.67 vs. 0.73 and 0.80, respectively, p &lt, 0.05) and calibration curves confirmed an adequate prediction. Similar discrimination (C-statistics, p = 0.22) was observed in the prediction of high-grade cancer, thereby questioning the respective inputs and added values of biomarkers and clinical predictors in MDx-2 scores. Based on the results of this study, we can conclude that instruments of prediction developed for systematic prostate biopsies, including those that incorporate innovative biomarkers, must be reassessed and eventually confirmed in the context of upfront MRI and IGB.