In our recently published case report, we describe a 75-year-old man with node-positive upper tract urothelial carcinoma (cT4N2M0) who achieved a remarkable response to EVP therapy. After six cycles, radiographic evaluation demonstrated a partial response of the primary tumor and complete response of lymph node metastases. This deep response prompted a multidisciplinary discussion, and the patient subsequently underwent robot-assisted radical nephroureterectomy.
Notably, pathological examination revealed no residual viable carcinoma, confirming a pathologic complete response (pT0). This finding is particularly important, as imaging alone cannot reliably exclude microscopic residual disease. In this case, surgery not only served as a consolidative treatment but also provided definitive pathological confirmation of treatment response.
From a clinical perspective, an equally important aspect of this case is the management of treatment-related toxicity. The patient developed grade 2 skin rash early in the treatment course and later experienced peripheral neuropathy, which is well-recognized as a cumulative adverse event associated with EV. Given the patient’s strong oncologic response and increasing concern about worsening neuropathy, systemic therapy was discontinued after one additional postoperative cycle through shared decision-making.
As a result, the patient has remained recurrence-free without ongoing treatment, while also experiencing an improvement in QoL due to the resolution of treatment-related adverse events. This outcome highlights a key clinical dilemma in the era of highly effective systemic therapies: how to balance treatment efficacy with long-term tolerability.
This case provides several important clinical insights. First, EVP can induce deep responses, including pathologic complete response, even in patients with initially node-positive disease. Second, in selected patients who achieve a strong response, consolidative surgery may offer both therapeutic and diagnostic benefits. Third, incorporating surgery into the treatment strategy may allow for treatment discontinuation, thereby reducing cumulative toxicity and improving patient QoL.
Although current guidelines generally recommend continuing EVP until disease progression or unacceptable toxicity, they do not clearly define when treatment can be safely discontinued. Our experience suggests that a tailored, response-adapted approach—including the integration of surgery—may be a feasible strategy in carefully selected patients.
In conclusion, while EVP represents a powerful systemic therapy for la/mUC, its optimal duration remains uncertain. This case underscores the potential role of combining systemic therapy with surgery to achieve durable disease control while minimizing toxicity. Further prospective studies are warranted to establish criteria for patient selection, optimal timing of surgery, and safe treatment discontinuation strategies.
Written by:
- Yuki Kobari, MD, PhD, Tokyo Women’s Medical University Hospital, Tokyo, Japan
- Kayo Kikuchi, MD, Tokyo Women’s Medical University Hospital, Tokyo, Japan
- Toshio Takagi, MD,PhD, Tokyo Women’s Medical University Hospital, Tokyo, Japan