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This is a 78 year old woman with high-grade T1 urothelial bladder cancer with repeat TURBT showing pTa disease with lower ureter involved. The retroperitoneal lymphadenopathy (LN) is suspicious for metastatic disease. I would complete staging to assess the lung with a CT chest. Assuming no other suspicious lesions, I would biopsy the retroperitoneal LN to guide therapy (a PET scan may inform this decision although I prefer a definitive biopsy given the probability an elderly patient may concurrently have a low grade lymphoma causing lymphadenopathy).
Assuming the LN is proven metastatic, the next question is- is she cisplatin-eligible? If cisplatin-eligible, I would advise gemcitabine-cisplatin (GC) or dose dense MVAC, given the potential for cure. If the patient is not a candidate for cisplatin but has proven metastasis in the LN, I would suggest carboplatin (I personally prefer split dose weekly cisplatin if CrCl 40 to <60) plus gemcitabine. Following 4-6 cycles of platinum-based chemotherapy, I would offer switch maintenance Avelumab if she exhibits stable/responding disease, which is established by a phase III trial (Javelin Bladder-100). If cisplatin-ineligible, first-line pembrolizumab or atezolizumab may be considered if tumor PD-L1 expression is high. However, the first-line PD1/L1 inhibitor approach does not have phase III trial data to support it.
Given the oligometastatic clinical picture, I would consider SBRT (stereotactic body radiotherapy) to the LN metastasis after completing the chemotherapy and before Avelumab starts. I would also consider radiating the bladder with curative intent potentially with concurrent chemotherapy (following the chemotherapy and before Avelumab initiation) if the patient exhibits a satisfactory performance status and is willing to pursue an aggressive approach.
The role of radical surgery in this setting of metastatic disease is unproven. However, in a young and fit patient, I would consider radical surgery (instead of radiation to the bladder mentioned above).
Tumor genomic profiling should be performed in patients with metastatic disease to guide future therapy, especially with erdafitinib, an FGFR inhibitor.
If the retroperitoneal LN is not metastatic urothelial carcinoma, I would pursue neoadjuvant cisplatin-based combination chemotherapy followed by radical surgery (probably radical cystectomy + ureterectomy/nephroureterectomy). Following surgery, if high-risk muscle-invasive disease is seen, I would offer adjuvant nivolumab, which is supported by improved DFS seen in the CHECKMATE274 trial leading to US FDA approval.
Clinical trials should be strongly considered at every stage of the disease.
Pending Moderator approval.
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