Perioperative chemotherapy for upper tract urothelial cancer

Abstract

Upper tract urothelial cancer (UTUC) is an aggressive disease associated with significant morbidity and mortality. Radical nephroureterectomy (RNU) with bladder cuff removal is considered the standard of care for most invasive UTUCs but distant relapses after surgery for locally advanced, high-grade disease are common. Although multimodality treatment with perioperative chemotherapy has been investigated thoroughly in recent years, adjuvant chemotherapy has primarily been analyzed in small retrospective uncontrolled studies and a clear benefit for this treatment modality is yet to be established. It is likely that the high incidence of renal insufficiency after surgery substantially limits the applicability of adjuvant chemotherapy with cisplatin-based regimens. Neoadjuvant cisplatin-based chemotherapy has several practical advantages over adjuvant therapy, including better patient tolerance in the preoperative setting when a patient has two kidneys rather than one and the obtainment of prognostic information from pathological downstaging. Although, some academic centers have adopted neoadjuvant chemotherapy as a de facto treatment standard for patients with high-grade locally advanced UTUC, this treatment approach has not been prospectively validated or adopted in general urologic practice. A multicenter trial of neoadjuvant chemotherapy for locally advanced high-grade UTUC could further define the role of neoadjuvant chemotherapy in treating UTUC.

Significance of HER2 expression in patients with upper tract urothelial carcinoma: A meta-analysis

“…Little progress is noted in treating advanced UC compared with other types of malignancies, even with chemotherapy, 25,26 although some small series showed a promising sensitivity to everolimus in bladder cancer with tuberous sclerosis complex 1 mutation. 27 Recent genomic studies demonstrated that diverse genomic aberrations existed in bladder UC, 28,29 and that bladder cancers split into three pan-cancer subtypes.…”

Radical nephroureterectomy for pathologic T4 upper tract urothelial cancer: can oncologic outcomes be improved with multimodality therapy?

“…There is a solid clinical rationale to utilize neoadjuvant rather than adjuvant chemotherapy for appropriately selected patients with UTUC, as the decline in renal function after nephrectomy may hinder effective chemotherapy dosing in an adjuvant setting (12)(13)(14). Moreover, a significant number of UTUC patients may already have a degree of renal insufficiency at the time of diagnosis (13,14).…”

“…Moreover, a significant number of UTUC patients may already have a degree of renal insufficiency at the time of diagnosis (13,14). Recent reports have shown rates of up to 14% and 53% for complete response and down staging, after utilization of neoadjuvant chemotherapy in patients with locally advanced UTUC (12,15).…”

Rationale and timing of perioperative chemotherapy for upper-tract urothelial carcinoma

“…When administering chemotherapy for urothelial carcinoma, cisplatin-containing regimens are superior to carboplatin-based therapy with respect to patient survival outcomes [30]. In patients with metastatic urothelial cancer, multiple studies have shown that carboplatin-based regimens are less toxic compared with cisplatin-based therapy [31].…”

“…Unlike bladder cancer, where more accurate staging can be achieved with adequate transurethral resection, our current staging modalities for UTUC are less consistent in their ability to accurately identify invasive carcinoma. This raises the possibility of overtreatment in some patients without pathologically proven muscle invasive disease [30,45,46]. In a large retrospective multi-institutional review, Hellenthal et al found that only 39% of UTUC patients who underwent RNU actually had high-risk features ( ‡pT3 or ‡pN1) on final pathology, thus potentially risking overtreatment in 61% of patients [47].…”