Currently, there are no reliable prognostic factors to determine which upper tract urothelial carcinoma (UTUC) patients will progress after radical nephroureterectomy (RNU). We aim to evaluate whether liquid-biopsy-based biomarkers (circulating tumor cells (CTCs), cell-free DNA (cfDNA), and circulating tumor DNA (ctDNA)) were able to predict clinical outcomes in localized UTUC patients undergoing RNU. Twenty patients were prospectively enrolled between 2021 and 2023. Two blood samples were collected before RNU and three months later. CTCs and cfDNA were isolated and evaluated using the IsoFlux system and Quant-iT PicoGreen dsDNA kit, respectively. Droplet digital PCR was performed to determine ctDNA status. Cox regression analysis was performed on CTCs, cfDNA, and ctDNA at two different follow-up time points to examine their influence on tumor progression and cancer-specific survival (CSS). During a median follow-up of 18 months, seven (35%) patients progressed and three (15%) died. Multivariate analysis demonstrated that cfDNA levels three months after RNU are a significant predictor of tumor progression (HR = 1.085; p = 0.006) and CSS (HR = 1.168; p = 0.029). No associations were found between CTC enumeration and ctDNA status with any of the clinical outcomes evaluated. The evaluation of cfDNA levels in clinical practice could improve the disease management of UTUC patients.

Objectives: We aimed to compare Bosniak III and IV cystic renal masses (CRM) using Bosniak classification version 2005 (BC-v2005) versus BC-v2019 and analyze radiological findings and patterns of benignity and malignancy. Methods: We retrospectively reviewed all Bosniak III-IV CRMs using BC-v2005 at our center with four-phase CT confirmed pathology, between January 2014 and June 2019. Two radiologists independently re-evaluated each lesion using both BCs, including findings of benignity and malignancy. Bosniak III-IV CRMs were classified in four radiological patterns: inflammatory (CRM-IP), cystic nephroma (CRM-CNP), papillary (CRM-PP), and clear cell (CRM-CCP). Characteristics of patterns were compared. Results: Out of 97 patients, 57 Bosniak III-IV CRMs met the inclusion criteria. Twenty-four (42.10%) lesions were reclassified as solid tumours using BC-v2019. Any lesion was downgraded to IIF or lower. Nine (15.78%) lesions were upgraded to Bosniak III-IV CRMs by BC-v2019, despite benign lesions. The presence of acute-angle nodules was the only statistically significant sign of malignancy ( p < 0.01). All benign lesions, not considered solid, were included in the two patterns of benignity, characterized by thickened septa and/or wall and without acute-angle nodules. All malignant CRMs presented two patterns of malignancy, proposed as acute-angle nodules. All clear cell carcinomas presented with hyperenhancing acute-angle nodules in the arterial phase. Pattern classification was better for BC-v2005 and BC-v2029, differentiating benign and malignant CRM. Conclusion: The proposed four radiological patterns improved performance than BC-v2019 in classifying benign lesions (CRM-IP and CRM-CNP) and malignant ones (CRM-PP and CRM-CCP), with wall and septa thickening and acute-angle nodules as relevant biomarkers.

Background and Objective: The role of urine cytology during follow-up for low-grade (LG) non-muscle-invasive bladder cancer (NMIBC) is not well established, although cytology has low sensitivity in detecting LG recurrences. Our study aims to evaluate the impact of urine cytology as a complementary method to cystoscopy during follow-up for LG NMIBC. Methods: Patients diagnosed with primary LG TaT1 bladder cancer (BC) between 2010 and 2020 were included. Patients were stratified according to the EAU NMIBC scoring model. Urine cytology was performed during follow-up cystoscopy. The outcomes of the study were BC recurrence and upgrading to high-grade (HG). Cytology utility was established by assessing whether its result led to management change. Results: We included 337 patients with LG TaT1 BC. EAU risk group distribution was low in 262 (77.7%), intermediate in 57 (16.9%), and high-risk in 18 (5.3%) cases. With a median follow-up of 5 years, 166 (49.3%) patients experienced recurrence. Cystoscopy was positive in 154 (92.8%) and suspicious in 12 (7.2%) cases. Urine cytology was positive in 33 (19.9%) cases but only changed management in 3 (0.89%), all with suspicious cystoscopy. Positive cytology at first recurrence was associated with higher risk of upgrading during follow-up (HR 2.781, p = 0.006) and lower upgrading-free survival (p = 0.001). Conclusions: The role of urine cytology to detect first recurrences during follow-up for primary LG TaT1 NMIBC might be limited to patients with non-conclusive lesions in the cystoscopy. A positive cytology at first recurrence is associated with a higher risk of upgrading to HG BC during follow-up.

Background/Objectives: Currently, the prediction of disease recurrence after radical prostatectomy (RP) in localized prostate cancer (PCa) relies on clinicopathological parameters, which lack accuracy in predicting clinical outcomes. This study focused on evaluating the utility of cfDNA levels and fragmentation patterns as prognostic biomarkers in progressive prostate-specific antigen (PSA) patients, including those with persistent PSA and biochemical recurrence (BR), after primary treatment in localized PCa patients. Methods: Twenty-nine high-risk localized PCa patients were enrolled in the study between February 2022 and May 2023. Blood samples were obtained before robotic RP. cfDNA concentration and fragment size were quantified using the Quant-it PicoGreen dsDNA Assay kit and Agilent 2200 TapeStation System, respectively. Results: The mean PSA value at diagnosis was 9.4 ng/mL. Seven patients (24.1%) had stage pT2 and 22 (75.9%) pT3. Nine patients (31%) had detectable PSA at the first PSA control six weeks after surgery, and four patients (20%) had BR during a mean follow-up of 18.4 months. No associations were found between cfDNA levels or fragmentation patterns and clinicopathological data. Although not statistically significant, patients with detectable PSA levels post-surgery exhibited higher cfDNA levels and shorter fragments compared with those with undetectable PSA. Conclusions: Our study indicated a tendency toward more fragmented cfDNA levels in PCa patients with persistent PSA. Strikingly, biochemical recurrent PCa patients exhibited similar cfDNA levels and fragmentation patterns compared to non-recurrent patients. Further studies exploring liquid biopsy-derived biomarkers in localized PCa patients are needed to elucidate their clinical utility in predicting PSA persistence.

Bacillus Calmette-Guérin (BCG) remains the cornerstone of therapy for high-risk non–muscle-invasive bladder cancer (NMIBC). However, up to 40% of patients develop BCG-unresponsive disease, where radical cystectomy remains the gold standard but is often unfeasible. During the past few years, multiple novel intravesical therapies have been developed, reshaping the management of BCG-unresponsive disease. The FDA approvals of pembrolizumab, nadofaragene firadenovec, BCG combined with the IL-15 superagonist N‑803, and the recently approved drug-delivery device TAR-200, alongside promising results of the oncolytic agent CG0070, mark a new era in bladder-sparing management. These therapies demonstrate clinically relevant efficacy with limited toxicity, redefining the treatment algorithm for BCG-unresponsive NMIBC.