Sophia Bhalla

Purpose: Bladder cancer is one of the most common malignancies worldwide with over 614,000 new cases and 220,000 deaths annually. Five percent of newly diagnosed patients have metastatic disease. Metastatic urothelial carcinoma (mUC) is primarily treated with cisplatin-based chemotherapy, immunotherapy, targeted therapy, or combinations. Cure from disease is rarely achieved, with the overall survival being between 12 and 15 months, and the 5-year survival in the range of 5–15%. Historically, mUC has been deemed surgically incurable. There are limited data available to assess survival benefit with surgical extirpation of the primary site or metastases. In this review, we summarize findings from previous studies regarding the role of surgery in patients with clinically node-positive bladder cancer or metastatic urothelial carcinoma, focusing on cytoreductive radical cystectomy (RC) and distant metastasectomy. Materials and Methods: A literature search was conducted on The Medical Literature Analysis and Retrieval System Online (Medline), Excerpta Medica dataBASE (Embase), preprints, and ClinicalTrials.gov for studies that discussed the role of surgery in patients with clinically node-positive bladder cancer or mUC, focusing on cytoreductive radical cystectomy (RC) and distant metastasectomy. The keywords used included transitional cell carcinoma, urothelial carcinoma, bladder cancer, bladder carcinoma, bladder metastasis, bladder tumor, lymph node metastasis, metastasis, and muscle-invasive bladder cancer. Results: The final analysis included 21 studies, including 17 retrospective reviews, 2 prospective phase II trials, and 2 meta-analyses. Of the studies that assessed patients with urothelial carcinoma (UC) with nodal involvement, 15 of 17 showed improved survival with chemotherapy followed by radical cystectomy (RC). To our knowledge, few studies have solely assessed surgery in patients with distant metastases. Most studies include patients with both UC with local LN involvement and patients with distant sites of metastasis. Of these studies, 12 of 13 indicated improved survival with metastasectomy. Conclusions: While it remains to be seen whether metastasectomy will have a role in patients with mUC, patient selection is an important factor when assessing the survival benefits. Patient characteristics correlated with improved survival include good performance status, good response to chemotherapy, and single site of metastasis. Further studies of mUC patients are required to clearly assess the survival impact of cytoreductive surgery.

Bladder cancer (BC) is one of the most common malignancies in the United States, with over 80,000 new cases and 16,000 deaths each year. Urothelial carcinoma (UC) is the most common histology and accounts for 90% of cases. BC management is complicated by recurrence rates of over 50% in both muscle-invasive and non-muscle-invasive bladder cancer. As such, the American Urological Association (AUA) recommends that patients undergo close surveillance during and after treatment. This surveillance is in the form of cystoscopy or imaging tests, which can be invasive and costly tests. Considering this, there have been recent pushes to find complements to bladder cancer surveillance. Cell-free DNA (CfDNA), or DNA released from dying cells, and circulating tumor DNA (ctDNA), or mutated DNA released from tumor cells, can be analyzed to detect and characterize the molecular characteristics of tumors. Research has shown promising results for ctDNA use in the BC care realm. A PubMed literature review was performed finding studies discussing cfDNA and ctDNA in BC detection, prognostication, and monitoring for recurrence. Keywords used included bladder cancer, cell-free DNA, circulating tumor DNA, urothelial carcinoma, and liquid biopsy. Studies show that ctDNA can serve as prognostic indicators of both early- and late-stage BC, aid in risk stratification prior to major surgery, assist in detection of disease progression and metastatic relapse, and can assess patients who may respond to immunotherapy. The benefit of ctDNA is not confined to BC, as studies have also suggested its promise as a biomarker for neoadjuvant chemotherapy in upper-tract UC. However, there are some limitations to ctDNA that require improvements in ctDNA-specific detection methods and BC-specific mutations before widespread utilization can be achieved. Further prospective, randomized trials are needed to elucidate the true potential ctDNA has in advancements in BC care.