Urachal cancer (UrC) is a rare disease which is mostly diagnosed late due to symptoms caused by its local invasion to the urinary bladder. Given the lack of clinical trials and guideline recommendations for systemic treatment, a molecularly informed precision oncology approach is a viable option for UrC already in the early lines of systemic treatment. While single case experiences may provide valuable reference for later decision-making, well-documented clinical experience with off-label targeted treatments is limited to a few patients. Here, we report a case of a 31-year-old female UrC patient who underwent intensive therapy with three surgeries and five lines of systemic treatments, including chemo-, checkpoint inhibitor and tyrosine kinase inhibitor therapies. In addition, next-generation sequencing (NGS) analysis and an ex vivo drug-screening analysis were performed on patient-derived tumor cells and the results were implemented into the therapeutic decision-making. Finally, serum carcinoembryonic antigen (CEA) levels proved to be helpful for therapy monitoring during the whole follow-up period.

Lymph node (LN) status is the most significant prognostic factor for invasive urothelial bladder cancer (UBC); however, the optimal extent of LN dissection (LND) is debated. We assessed circulating matrix metalloproteinase-7 (MMP-7) as a prognostic factor and decision-making marker for the extent of LND. Preoperative serum MMP-7 levels were determined in two independent UBC cohorts (n = 188; n = 68) and in one control cohort (n = 97) by using the ELISA method. A systematic review and meta-analysis on the prognostic role of circulating pretreatment MMP-7 levels were performed. Serum MMP-7 levels were higher in patients compared to controls (p < 0.001) with the highest levels in LN-positive cases. Half of LN-positive UBC patients had low MMP-7 levels, whereas the survival of LN-negative patients with high serum MMP-7 findings was poor. MMP-7 levels were independently associated with poor survival in both cohorts (p = 0.006, p < 0.001). Accordingly, our systematic review of six eligible publications revealed a 2.5-fold higher mortality risk in patients with high MMP-7 levels. In conclusion, preoperative MMP-7 level is a validated and independent prognostic factor in urothelial cancer. It cannot be used to decide between regional or extended LND but may be useful in identifying LN-negative high-risk patients with potentially undetected metastases.

Small-cell bladder cancer (SCBC) is an aggressive and rare malignancy for which there is no clear optimal treatment strategy. This systematic review and meta-analysis aimed to compare the median overall survival (OS) of patients with limited-stage (LS) SCBC treated with either cystectomy-based multimodal therapy (CBMMT) or radiation-based multimodal therapy (RBMMT). A comprehensive search of PUBMED, Embase, and Scopus databases was performed for studies published before January 2024 according to the PRISMA guidelines. Studies have assessed LS-SCBC disease and provided survival data for subgroups of patients undergoing radical surgery or bladder-preserving approaches to be deemed eligible. Data extraction and quality assessment were independently conducted by 2 authors. Five studies comprising 1041 patients were analyzed. The pooled median OS for patients receiving RBMMT was 34.6 months (95% CI, 25.5-43.7), compared to 29.7 months (95% CI, 18.2-41.1) for those undergoing CBMMT. The main limitations are the retrospective nature of the included studies and the potential bias. This meta-analysis indicates that RBMMT may provide comparable outcomes to CBMMT in LS-SCBC patients, supporting the consideration of bladder-preserving approaches in selected cases. RBMMT may offer a potential clinical benefit in terms of organ preservation for appropriately selected patients, although survival differences were not statistically significant.

Perioperative platinum-based chemotherapy remains the standard systemic treatment for nonmetastatic muscle-invasive bladder cancer (MIBC). Adjuvant chemotherapy (AC) is recommended for patients with pT3/4 (stage IIIA) or lymph node-positive (LN+, stage IIIB) disease following radical cystectomy (RC). However, not all patients benefit equally, highlighting the need for predictive biomarkers. Lymphovascular invasion (LVI) is a known risk-factor in several cancers, including MIBC, but its predictive value for AC benefit remains unclear. Therefore, we aimed to assess whether LVI can predict response to platinum-based AC in MIBC. We conducted a retrospective cohort study involving MIBC patients who underwent RC between 2005 and 2023 at two academic centers. Inclusion criteria were pT3/T4M0 or LN+ disease, with available LVI status and survival data. Patients were divided into a treatment (AC) and a control group (RC without AC). Overall survival (OS) was the primary endpoint; cancer-specific survival (CSS) was secondary. Statistical analysis was performed using Kaplan-Meier estimates, Cox proportional hazards models, and propensity score matching (PSM) to adjust for potential confounders. A total of 345 patients fulfilled the inclusion criteria of whom 92 (27%) received and 253 (73%) did not receive AC. LVI-positive patients demonstrated significantly improved OS and CSS when treated with AC (both P < .001), while no significant OS or CSS benefit was observed for AC-treated LVI-negative patients (P = .146 for OS, P = .975 for CSS). Results remained similar after PSM correction revealing survival benefit for AC treatment in LVI-positive but not in LVI-negative patients. This study demonstrates, for the first time, LVI status as a predictor of treatment benefit from platinum-based AC. Our results suggest that LVI status is an easily assessable biomarker to identify those patients who derive greater benefit from the treatment, while LVI-negative patients might be spared unnecessary chemotherapy and its associated toxicity.