Bladder cancer with extravesical extension and involvement of the distal ureter poses significant therapeutic challenges, especially in patients ineligible for cisplatin-based chemotherapy. We report a case of cT4N0M0 muscle-invasive bladder cancer (MIBC) with intraluminal distal ureteral extension that achieved a pathological complete response (pCR) following neoadjuvant therapy with enfortumab vedotin (EV), enabling radical surgery.

A 75-year-old man presented with gross hematuria and urinary frequency. Contrast-enhanced CT performed at a local clinic suggested a bladder mass, prompting referral to our department. Cystoscopy revealed a broad-based papillary tumor extending from the left lateral bladder wall to the bladder neck and prostatic urethra. The left ureteral orifice was not visible. MRI and PET-CT indicated a primary lesion originating near the left ureteral orifice, with intraluminal progression into the distal ureter and evidence of prostatic invasion. No lymph node or distant metastases were detected, and the clinical staging was cT4N0M0. Transurethral resection of the bladder tumor (TURBT) confirmed high-grade urothelial carcinoma. The patient was diagnosed with muscle-invasive urothelial carcinoma of the bladder (cT4N0M0) with distal ureter involvement. Given his renal function and performance status, he underwent one cycle of neoadjuvant gemcitabine and carboplatin (GCa). This resulted in a partial response with a 40% reduction in tumor volume. However, ground-glass opacities suspicious for interstitial pneumonitis emerged on chest CT, necessitating discontinuation of GCa. Given the risk of progression and lack of contraindications, neoadjuvant treatment with EV was initiated under the close supervision of respiratory medicine. After three cycles of EV, the patient developed grade 3 fatigue, leading to treatment interruption. Although a reduced-dose regimen was proposed, the patient opted to discontinue EV entirely. MRI at this point showed almost complete resolution of the primary tumor with no evidence of metastasis.

The patient subsequently underwent open total cystectomy and left nephroureterectomy. Final pathological examination revealed no residual tumor (ypT0) and no lymph node involvement (ypN0), indicating a pathological complete response. At the 9-month postoperative follow-up, the patient remains recurrence-free with no evidence of metastasis.

This case demonstrates that enfortumab vedotin may serve as an effective neoadjuvant therapy for patients with locally advanced MIBC, especially those ineligible for cisplatin-based regimens. The achievement of pCR allowed for successful curative-intent surgery. EV holds promise not only in the metastatic setting but potentially as part of multimodal therapy for locally advanced urothelial carcinoma. Further investigation is warranted to define its role in neoadjuvant treatment.