Both neoadjuvant chemotherapy (NAC) and adjuvant chemotherapy (AC) are more effective than radical nephroureterectomy (RNU) alone in treating nonmetastatic upper tract urothelial carcinoma (UTUC), investigators confirm.
Joaquim Bellmunt, MD, of Beth Israel Deaconess Medical Center, Harvard Medical School, in Boston, Massachusetts, and colleagues conducted an updated systematic review and meta-analysis of 16 studies evaluating NAC and 29 studies evaluating AC published up to February 2020. The investigators found a pooled pathologic complete response rate of 11% and a partial response rate of 43% in patients who received NAC, according to study findings published in European Urology. The partial response rate should be interpreted cautiously, however, because it remains unclear whether some patients were overstaged at diagnosis, according to the investigators. Based on level 2 evidence (retrospective studies), NAC also yielded a significant overall survival (OS) benefit of 56% and a significant cancer-specific survival (CSS) benefit of 62% over RNU alone (both P <.001).
Based on both level 1 (randomized trials) and 2 evidence, AC yielded significant advantages in OS of 23% (P =.004), CSS of 21% (P =.001), and disease-free survival of 48% (P <.001).
In an accompanying editorial, Arlene Siefker-Radtke, MD, and colleagues from the University of Texas MD Anderson Cancer Center in Houston, Texas, commented that the latest meta-analysis reinforces “the growing support” for perioperative chemotherapy in the treatment of UTUC. But the type, timing, and doses of chemotherapy are still under investigation. Cisplatin-based chemotherapy hinges on adequate kidney function.
Study investigators noted that research on adjuvant immunotherapy thus far have been disappointing, but results from phase 2 trials of neoadjuvant immunotherapy seem promising. Both the study authors and editorialists noted that erdafitinib, a tyrosine kinase inhibitor, is effective in UTUC with certain fibroblast growth factor receptor (FGFR) alterations.
“We now understand that urothelial cancers comprise multiple diseases and may benefit from a more personalized strategy. The presence of mutations and other molecular signatures are now beginning to guide our therapy rather than proscribed limits of anatomy,” Dr Siefker-Radtke and her coauthors wrote.
Disclosure: One editorialist declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of disclosures.
Leow JJ, Chong YL, Chang SL, Valderrama BP, Powles T, Bellmunt J. Neoadjuvant and adjuvant chemotherapy for upper tract urothelial carcinoma: a 2020 systematic review and meta-analysis, and future perspectives on systemic therapy. Eur Urol. Published online September 10, 2020. doi:10.1016/j.eururo.2020.07.003
Andreev-Drakhlin A, Gao J, Siefker-Radtke A. Levelling the evidence: a comparison of neoadjuvant and adjuvant treatment for upper tract urothelial carcinoma. Eur Urol. Published online September 10, 2020. doi:10.1016/j.eururo.2020.08.033