Recently the European Association of Urology met to attempt to develop a consensus statement but acknowledged the challenges in doing so with the lack of high-quality data. Locally recurrent urothelial cancer is defined as recurrence following cystectomy that lies within the surgical bed or regional pelvic lymph nodes and is associated with a poor prognosis regardless of treatment. Therefore, we aimed to review the literature to guide management in these challenging conditions.1
Unfortunately, most studies identified were limited to single-center and retrospective data with multiple confounders, thus managing these cancers requires an interdisciplinary approach. In almost all patients, systemic therapy was a component of care, but the modality of chemotherapy differed between studies as well as the timing of it (e.g. before or after metastases-directed treatment). Additionally, there is no published data on the role of immunotherapy which has become the standard of care in the setting of advanced disease based on recent trials (JAVELIN Bladder 100, EV-302).2,3 For metastases-directed localized therapy in the oligometastatic setting, patients appear to have better survival outcomes from metastasectomy, although this may be biased because candidates for surgery have a better functional status and prognosis. Radiation therapy has had less toxicity in comparison with surgery and may be preferred in patients who desire a less aggressive intervention. In locally recurrent urothelial cancers, most patients in the studies received a combination of localized and systemic therapy making it difficult to assess the independent impact of each, partly because these patients frequently have metastatic disease at other sites.4
Several ongoing trials may clarify the future treatment landscape. For example, in NCT04428554, the impact of radiotherapy on oligometastatic bladder cancer will be assessed in the context of patients on maintenance avelumab, and NCT05259319 is an ongoing early-phase clinical trial evaluating the role of immunotherapy with radiotherapy in patients with oligometastatic solid cancers. Additionally, NCT01050504 plans to use DNA sequencing and genetic profiling in patients with urothelial cancer to identify relevant biomarkers to guide management in patients with locally recurrent disease. Further prospective studies and clinical trials will be essential to establishing the best treatment approach for both oligometastatic and locally recurrent urothelial cancer.
Written by:
- Jennifer W. Li, MD, Department of Medicine, Warren Alpert Medical School of Brown University, Providence, RI
- Karie Runcie, MD, Division of Hematology and Oncology, Columbia University Irving Medical Center, New York, NY
- Liu MA, Li JW, Runcie K. Management of Oligometastatic and Locally Recurrent Urothelial Carcinoma. Curr Oncol Rep. 2024. doi: 10.1007/s11912-024-01523-8.
- Powles T, Park SH, Voog E, Caserta C, Valderrama BP, Gurney H, et al. Avelumab Maintenance Therapy for Advanced or Metastatic Urothelial Carcinoma. N Engl J Med. 2020;383(13):1218-30. doi: 10.1056/NEJMoa2002788.
- Powles TB, Perez Valderrama B, Gupta S, Bedke J, Kikuchi E, Hoffman-Censits J, et al. LBA6 EV-302/KEYNOTE-A39: Open-label, randomized phase III study of enfortumab vedotin in combination with pembrolizumab (EV+P) vs chemotherapy (Chemo) in previously untreated locally advanced metastatic urothelial carcinoma (la/mUC). Annals of Oncology. 2023;34:S1340. doi: 10.1016/j.annonc.2023.10.106.
- Westney OL, Pisters LL, Pettaway CA, Tu SM, Pollack A, Dinney CP. Presentation, methods of diagnosis, and therapy for pelvic recurrence following radical cystectomy for transitional cell carcinoma of the bladder. J Urol. 1998;159(3):792-5.