Enfortumab vedotin as a salvage option as 5th line therapy for metastatic urothelial bladder cancer.

A 67-year-old female patient with a muscle-invasive, non-metastatic urothelial bladder cancer (UC) (pT2 G3 cN0 cM0) developed metachronous metastases within 6 months after radical cystectomy with ileal conduit urinary diversion. After a good primary response to platinum-based chemotherapy, treatment was switched to the immune checkpoint inhibitor (ICI) pembrolizumab due to progressive disease. Subsequently the patient underwent selective internal radiotherapy (SIRT) of the liver and received vinflunine as well as a re-challenge with pembrolizumab. Two years after the initial diagnosis, rapid disease progression ultimately led to a switch to 5th line therapy with enfortumab vedotin (EV), which had only been approved in the United States at that time. The antibody-drug conjugate was well tolerated by the patient after dose reduction to 1.0 mg/ kg body weight. Simultaneous irradiation of newly occurring precardiac, hepatic and cerebral metastases were necessary. After 10 months of therapy with EV, tumour regression was observed accompanied with good symptom control. The presented case illustrates the efficacy and tolerability of EV in a heavily pre-treated patient with metastatic UC (mUC).

Enfortumab Vedotin in Metastatic Urothelial Carcinoma: Survival and Safety in a European Multicenter Real-world Patient Cohort.

Background: Treatment options for patients with urothelial cancer (UC) refractory to platinum and immunotherapy are limited and survival is short. Enfortumab vedotin (EV) is a monoclonal anti-NECTIN4 antibody conjugated to monomethyl auristatin. It was recently approved because of superior survival in comparison to standard-of-care (SOC) chemotherapy. Real-world patients, however, often have worse characteristics than patients included in clinical trials. Objective: To analyze the efficacy and safety of EV in a cohort of real-world patients. Design setting and participants: Retrospective data were collected from 23 hospitals and private practices for patients with metastatic and previously treated UC who received EV either when reimbursed by their insurance company before European Medicines Agency (EMA) approval, within a compassionate use program, or as SOC treatment after EMA approval. Imaging and therapy management were in accordance with local standards. Outcome measurements and statistical analysis: Adverse events (AEs) were reported according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 criteria. Objective responses were evaluated according to Response Evaluation Criteria in Solid Tumors version 1.1. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Results and limitations: The median age for the 125 eligible patients was 66 yr (range 31-89). The Eastern Cooperative Oncology Group performance status (ECOG PS) was 0-1 for 76.0%, 2-4 for 13.6%, and unknown for 10.4% of patients. EV was administered in the fourth or later line for 44.8% of patients. The overall response rate was 41.6% (partial response 39.2%, complete response 2.4%). Median OS was 10.0 months (mo) (95% confidence interval 7.20-12.80) and median PFS was 5.0 mo (95% confidence interval 4.34-5.67). For patients with ECOG PS of 0-1, median OS was 14 mo. Any-grade AEs were observed in 67.2% and CTCAE grade ≥3 AEs in 30.4%. The most common AEs were peripheral sensory neuropathy and skin toxicity. Three fatal events (pneumonia, pneumonitis) occurred. Limitations include the retrospective design and short follow-up. Conclusions: Administration of EV for real-world patients was feasible with an acceptable toxicity profile. No new safety signals were reported. Antitumor activity in our cohort was comparable to data previously reported for trials. In summary, our results support the use of EV in patients with metastatic UC. Patient summary: Enfortumab vedotin is a medication that improved the survival of patients with bladder cancer in comparison to standard chemotherapy in clinical trials. However, patients included in clinical trials are highly selected and results for toxicities and improvements in survival do not always transfer to the real-world setting. We analyzed data for 125 patients who were treated with enfortumab vedotin. Our results are comparable to the outcomes from clinical trials regarding the safety and efficacy of this treatment.

RLC score (R status, lymphovascular invasion, C-reactive protein) predicts survival following radical cystectomy for muscle-invasive bladder cancer.

BACKGROUND: CRP-based scoring systems were found to correlate with survival in patients with urooncologic diseases. Our retrospective single-centre study aimed to confirm CRP as a prognostic parameter in patients with bladder cancer (BCa) undergoing radical cystectomy (RC) and, based on the findings, to develop our own outcome score for muscle-invasive bladder cancer (MIBC) patients undergoing RC in order to identify patients with a high risk of mortality. MATERIAL AND METHODS: A total of 254 patients who underwent RC at Hanover Medical School between 1996 and 2007 were reviewed with a follow-up until autumn 2013. The clinicopathologic parameters assessed included age, co-morbidities, pre-/postoperative serum levels of CRP, leukocytes, haemoglobin, creatinine, urinary diversion, tumour grading, staging, lymph node status, lymph node density (LND), lymphovascular invasion (LVI), metastases, and resection margin status. The Chi-square test was used for univariate analyses. Kaplan-Meier estimates and the log-rank test were used for survival analyses. Regarding outcome, overall survival (OS) was assessed. RESULTS: The multivariate analysis excluding lymph node (LN)-positive and metastatic patients at time of RC showed a significant association of R status (R; p < 0.001), LVI (L; p = 0.021) and preoperative CRP level > 5 mg/l (C; p = 0.008) with OS. Based on these parameters, the RLC score was developed. The median OS in the intermediate, high-risk and very high-risk groups according to the RLC score was 62, 22, and 6.5 months, respectively. The score had a high predictive accuracy of 0.752. CONCLUSION: The RLC score identifies BCa patients at a higher risk of overall mortality after RC. Overall, our study supports the role of CRP in prognostic score models for BCa.

Impact of double J stenting or nephrostomy placement during transurethral resection of bladder tumour on the incidence of metachronous upper urinary tract urothelial cancer.

BACKGROUND: Whether or not double J (DJ) stenting during transurethral resection of a bladder tumour (TURBT) harms patients with regard to possible metachronous upper urinary tract urothelial cancer (UUTUC) development remains controversial. This study evaluated the impact of DJ compared to nephrostomy placement during TURBT for bladder cancer (BCa) on the incidence of metachronous UUTUCs. METHODS: We retrospectively analysed 637 patients who underwent TURBT in our department between 2008 and 2016. BCa, UUTUC and urinary drainage data (retrograde/anterograde DJ and percutaneous nephrostomy) were assessed, along with the prevalence of hydronephrosis, and mortality. Chi-square and Fisher's exact test was performed for univariate analyses. Survival analysis was performed by the Kaplan-Meier method and log-rank tests. RESULTS: UUTUC was noted in 28 out of 637 patients (4.4%), whereas only eight (1.3%) developed it metachronously to BCa. Out of these, four patients received DJ stents, while four patients received no urinary drainage of the upper urinary tract. Placement of urinary drainage significantly correlated with UUTUC (50.0% vs. 17.9%; p = 0.041). DJ stenting significantly correlated with UUTUC (50.0% vs. 11%; p <  0.01), while no patient with a nephrostomy tube developed UUTUC. UUTUC-free survival rates were significantly lower for patients with DJ stents than for all other patients (p = 0.001). Patients with or without DJ stents had similar overall survival (OS) rates (p = 0.73), whereas patients with nephrostomy tubes had significantly lower OS rates than all other patients (p <  0.001). CONCLUSIONS: Patients with DJ stenting during TURBT for BCa might have an increased risk of developing metachronous UUTUC. This study indicated advantages in placing nephrostomy tubes rather than DJ stents; however, confirmation requires investigation of a larger cohort. Even so, the increased mortality rate in the nephrostomy group reflected hydronephrosis as an unfavourable prognostic factor.