Issues and Controversies in Upper Tract Urothelial Carcinoma
Ureteroscopy (URS) is the standard diagnostic tool and is being used with different technologies: narrow band imaging (increased detection rate by 23%), SPIES and hexvix; the diagnosis is challenging secondary to tangential viewing angle. Two studies differ about its findings of bladder recurrence after URS previous to Radical Nephroureterectomy (RNU), the first found that URS >5 days previous to RNU was an independent predictor for recurrence and the second did not show a difference.
The indication for conservative management UTUC is low grade: unifocal disease, tumor size <2 cm, low-grade cytology, low-grade URS biopsy and no invasive aspect on CTU (EAU guidelines 2018). Second Look after endoscopic treatment should be performed 2 months later; is the strongest prognostic factor for recurrence, progression and improvement of the oncologic outcomes.
Upper tract instillations of BCG or MMC showed no benefit for UTUC in a 30-year experience including 141 patients (Motamedinia, J Endourol016). MitoGel trial (temperature sensitive water-soluble gel formulation of mitomycin C), for low-grade tumors and small volume, reported improved outcomes; preliminary results in 33 patients with complete response (57%) at 6 weeks, Kassouf stated that this could change the way we treat this disease.
The POUT trial data indicates that peri-operative chemotherapy after RNU (pT2-pT4) has a better metastasis-free survival (photo). Neoadjuvant chemotherapy improves survival in patients with UTUC (n=107 controls, n=43 neoadjuvant HG, 25% reduction ≥pT2, 42% reduction, CR 14% - Porten, Cancer 2014). When considering neoadjuvant chemotherapy, Kassouf suggests following these factors to help in counseling patients: high grade on biopsy grade, sessile tumor, large tumor burden, local invasion on radiographic studies and adequate renal function (cisplatin-based regimens).
There is no doubt in patients with hilar/regional adenopathy, they should be treated upfront with chemotherapy (metastatic disease).
Bladder instillation with mitomycin C post-OP should be a standard treatment according to a RCT of 248 patients, which showed decreased bladder recurrence (1 year: 16% VS 27%, p=0.03, MMC given 7-10 post-OP).
The evidence on the benefit of extended lymphadenectomy is very weak (retrospective). Kassouf in his practice does lymphadenectomy of para-aortic nodes (left tumor) and para-caval nodes (right tumor), but not extended because of morbidity and questionable benefit.
The lecture concluded with the next take-home messages: the role of NBI is uncertain, intracavitary instillation remains unclear (BCG appears to work best for CIS, emerging therapies as Mitogel may change paradigm) and the therapeutic benefit on extended lymphadenectomy remains unclear.
Presented by: Wassim Kassouf, MD, CM, FRCSC, Professor of Urology, McGill University Health Center, Montreal, QC - Canada.
Written by: Eduardo Gonzalez-Cuenca, MD, Urology Resident, Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”, Mexico City and Ashish M. Kamat, MD, Professor of Urologic Oncology, MD Anderson Cancer Center, Houston, TX at the 2018 Congreso de la Asociación Mexicana de Urología Oncológica – July 25-28, 2018, Acapulco, GRO México