How are metastatic and node-positive urothelial tumors of the renal pelvis and ureters treated?

Updated: Aug 07, 2020
  • Author: Kyle A Richards, MD, FACS; Chief Editor: Bradley Fields Schwartz, DO, FACS  more...
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Answer

As noted above, gemcitabine with cisplatin has replaced MVAC, which was the historical standard treatment. However, no strong evidence supports the use of systemic chemotherapy in metastatic disease. This is attributed to the relative rarity of metastatic upper tract TCC and the absence of prospective trials. [32] Furthermore, approximately 50% of patients with metastatic urothelial carcinoma are not candidates for cisplatin-based therapy. [38]

Exclusion criteria for cisplatin-based chemotherapy are as follows:

  • Eastern Cooperative Oncology Group (ECOG) performance status ≥2

  • Creatinine clearance < 60 mL/min

  • Grade 2 audiometric hearing loss

  • Grade 2 or higher peripheral neuropathy

  • New York Heart Association class III heart failure

In patients with limited renal function, chemotherapy options are limited but can consist of the following:

  • Gemcitabine and carboplatin [39] – Overall response rate, 41.2%; median survival, 9.3 months

  • Methotrexate, carboplatin, and vinblastine [39] – Overall response rate, 30.3%; median survival, 8.1 months

  • Gemcitabine and cisplatin given every 2 weeks (split dose) [40] – Partial response, 39%; stable disease, 31%; median progression-free survival of 3.5 months and overall survival of 8.5 months

De Santis et al randomized patients to gemcitabine and carboplatin versus methotrexate, carboplatin, and vinblastine and found statistically similar outcomes. [39]

A retrospective study by Huang et demonstrated the benefit of aljuvant chemotherapy in the setting of pT3 disease. The study included 171 patients with pT3N0M0 disease treated with nephroureterectomy between 2004 and 2014. Median followup was 35.8 months. Patients who received adjuvant therapy (n=60) had statistically signifcantly better 5-year cancer-specific survival, compared with those treated with surgery alone (n=111); (80.5% vs 57.6%, P = 0.010), as well as better recurrence-free survival (74.4% vs 52.9%, P = 0.026). [41]

Although there was no statistically significant difference in overall survival (71.9% vs 49.0%, P = 0.072), there was a trend toward better overall survival in the patients who received postoperative chemotherapy. On multivariable analysis age (P = 0.018), tumor location (P = 0.003) and adjuvant chemotherapy (P = 0.001) were predictors of cancer-specific survival. [41]

A retrospective study by Lucca et al in 263 patients who underwent radical nephroureterectomy for lymph node–positive upper tract urothelial carcinoma, 107 (41%) of whom received three to six cycles of adjuvant chemotherapy, the use of adjuvant chemoterapy had no significant impact on cancer-related mortality, on univariable (P = 0.49) and multivariable (P = 0.11) analysis. However a stratified analysis showed a 34% reduction of cancer-related mortality with adjuvant chemotherapy in the subgroup with pT3-4 with lymph node positivity (P = 0.019). [42]

Non–cisplatin-based chemotherapy has been tried as a less toxic alternative. However, a comprehensive search of the literature did not find benefit from it. [43]


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