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Identification of reliable molecular biomarkers that can complement clinical practice represents a fascinating challenge in any cancer field. Renal tumors are usually asymptomatic and incidentally identified during imaging studies undertaken for unrelated causes. However, in 25% to 30% of patients the first diagnosis is accompanied by symptoms and associated with distant metastasis. Thus, early diagnosis may reduce the risk of disease progression also avoiding side effects of inadequate treatments. Moreover, the ability to categorize patients' risk of recurrence after radical treatment, or even predict benefit from a target therapy, represents a compelling challenge. Here we review the current state-of-the-art on RCC biomarkers, particularly focusing on the new approaches of genomics, liquid biopsy, proteomics, and metabolomics.

Purpose: To evaluate the risk factors associated with positive surgical margins' (PSMs) location and their impact on disease-specific survival (DSS) in patients with bladder cancer (BCa) undergoing radical cystectomy (RC). Methods: We analyzed a large multi-institutional cohort of patients treated with upfront RC for non-metastatic (cT1-4aN0M0) BCa. Multivariable binomial logistic regression analyses were used to assess the risk of PSMs at RC for each location after adjusting for clinicopathological covariates. The Kaplan–Meier method was used to estimate DSS stratified by margins’ status and location. Log-rank statistics and Cox’ regression models were used to determine significance. Results: A total of 1058 patients were included and 108 (10.2%) patients had PSMs. PSMs were located at soft-tissue, ureter(s), and urethra in 57 (5.4%), 30 (2.8%) and 21 (2.0%) patients, respectively. At multivariable analysis, soft-tissue PSMs were independently associated with pathological stage T4 (pT4) (Odds ratio (OR) 6.20, p < 0.001) and lymph-node metastases (OR 1.86, p = 0.04). Concomitant carcinoma-in-situ (CIS) was an independent risk factor for ureteric PSMs (OR 6.31, p = 0.003). Finally, urethral PSMs were independently correlated with pT4-stage (OR 5.10, p = 0.01). The estimated 3-years DSS rates were 58.2%, 32.4%, 50.1%, and 40.3% for negative SMs, soft-tissue-, ureteric- and urethral PSMs, respectively (log-rank; p < 0.001). Conclusions: PSMs’ location represents distinct risk factors’ patterns. Concomitant CIS was associated with ureteric PSMs. Urethral and soft-tissue PSM showed worse DSS rates. Our results suggest that clinical decision-making paradigms on adjuvant treatment and surveillance might be adapted based on PSM and their location.

Background Literature lacks clear evidence regarding the optimal treatment for non–muscle-invasive micropapillary bladder cancer (MPBC) due to its rarity and the presence of only small sample size and single-centre studies. Objective To assess cancer-specific mortality (CSM) and overall mortality (OM) between immediate radical cystectomy (RC) and conservative management among T1 high-grade (HG) MPBC. Design, setting, and participants We retrospectively analysed a multicentre dataset including 119 T1 HG MPBC patients treated between 2005 and 2019 at 15 tertiary referral centres. The median follow-up time was 35 mo (interquartile range: 19–64). Intervention Patients underwent immediate RC versus conservative management with bacillus Calmette-Guerin. Outcomes measurements and statistical analysis Cumulative incidence functions and Kaplan-Meier methods were applied to estimate survival outcomes. Multivariable Cox analyses were performed to assess independent predictors of disease recurrence and disease progression after conservative management; covariates consisted of pure MPBC, concomitant lymphovascular invasion (LVI), and carcinoma in situ at initial diagnosis. Results and limitations Immediate RC and conservative management were performed in 27% and 73% of patients, respectively. CSM and OM did not differ significantly among patient treated with immediate RC versus conservative management (Pepe-Mori test p = 0.5 and log-rank test p = 0.9, respectively). Overall, 66.7% and 34.5% of patients experienced disease recurrence and disease progression after conservative management, respectively. At multivariable Cox analyses, concomitant LVI was an independent predictor of disease recurrence (p = 0.01) and progression (p = 0.03), while pure MPBC was independently associated with disease progression (p = 0.03). The absence of a centralised re-review and the retrospective design represent the main limitations of our study. Conclusions Conservative management could achieve satisfactory results among T1 HG MPBC patients with neither pure MPBC nor LVI at initial diagnosis. Patient summary Bacillus Calmette-Guerin seems to be an effective therapy for T1 micropapillary bladder cancer patients with neither pure micropapillary disease nor lymphovascular invasion at initial diagnosis.

We describe the case of a 71-yr-old woman with locally advanced muscle-invasive bladder cancer and stage III chronic kidney disease due to an obstructed nonfunctional left kidney. She was started on neoadjuvant immunotherapy, but had to stop treatment because of acute worsening of renal function. Radical cystectomy was then performed uneventfully, revealing pT3aN1 urothelial carcinoma of the bladder. Adjuvant chemotherapy in high-risk locally advanced bladder cancer after radical cystectomy currently poses several challenges, especially for cisplatin-ineligible candidates. Recent data on adjuvant immunotherapy trials suggest a disease-free survival advantage for this subgroup of patients. The current and future role of immuno-oncology agents in this setting is discussed. PATIENT SUMMARY: Patients with advanced bladder cancer might benefit from further chemotherapy or immunotherapy following bladder removal, but it is still unclear which patients benefit the most from this strategy. Measurement of biomarkers and scans to show urinary function will probably help in optimising patient selection for this treatment in the near future.

Renal cell carcinoma (RCC) incidence has been increasing in recent years, and it now represents the sixth most common cancer diagnosis in men and the tenth in women. Although this is partly due to in-creased detection of incidental small renal masses on unrelated imaging, advanced RCC continues to be diagnosed in a significant portion of patients, with more than 15% presenting with distant metasta-ses. Biomarkers can be a cost-effective tool to identify high-risk patients and institute appropriate indi-vidualised therapies. While the literature in this field is nascent, this paper focuses on several bi-omarkers that have been extensively investigated in the diagnosis and prognosis of RCC, as well as in predicting its response to treatments, particularly the newer immuno-oncology drugs.