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Lymphadenectomy may not add benefit in high-risk renal cell carcinoma
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Patients with high-risk renal cell carcinoma who undergo surgery may not benefit from lymphadenectomy, according to a secondary analysis of the randomized ASSURE trial.
Benjamin T. Ristau, MD, MHA, assistant professor of surgery and urologic oncology in the division of urology at UConn Health in Farmington, Conn., and colleagues in the ECOG-ACRIN cancer research group aimed to determine whether lymphadenectomy affected OS, DFS and surgical parameters among a cohort of 1,943 patients with fully resected disease.
Slightly more than one-third of the cohort (36.1%) in the ASSURE trial (ECOG-ACRIN E2805) underwent lymphadenectomy at surgeon discretion. Patients with clinically node-positive disease were significantly more likely to undergo lymphadenectomy than patients with CN0 disease (99.4% vs. 30.1%; P < .001).
In the lymphadenectomy group, the rate of lymph node positivity was 23.4%.
Results showed no significant OS benefit for lymphadenectomy. Among those who underwent lymphadenectomy and were found to have positive lymph nodes, adjuvant therapy conferred no OS or DFS benefit compared with placebo.
HemOnc Today spoke with Ristau about the study, the potential implications of the results, and what still must be confirmed in subsequent research.
Question: What prompted this analysis?
Answer: Lymphadenectomy is standard practice for many urologic malignancies, including prostate and bladder cancers. Kidney cancer is the third most common urologic malignancy in the United States; however, the utility of routine lymph node dissection (LND) for patients with kidney cancer had not been established. Similarly, the use of adjuvant systemic therapy for patients with high-risk kidney cancer is controversial because randomized trials have provided conflicting evidence of benefit. Our objectives were to assess whether LND affected OS and whether LND may help improve selection of patients for adjuvant therapy. This trial randomly assigned patients with fully resected, high-risk, nonmetastatic renal cell carcinoma to adjuvant sorafenib (Nexavar, Bayer), sunitinib (Sutent, Pfizer) or placebo. We performed the secondary analysis to better understand the effect of LND on OS in this patient population.
Q: How did you conduct the analysis?
A: The trial included patients with high-risk renal cell carcinoma. High risk was defined as pT1b G3-4 N0 (or pNX with cN0) M0 to T (any) G (any) N+ M0. Patients with clinically node-positive disease were required to undergo complete resection. We compared OS between patients who underwent lymph node dissection and those who did not. Secondary objectives included examining differences in DFS conferred by LND, the oncologic benefit of adjuvant therapy for patients with node-positive disease who underwent LND, the extent of LND performed, factors that predicted LND, and complications associated with LND.
Q. What did you find?
A. Slightly more than one-third of the patients in the trial (36.1%) underwent LND, with a median three lymph nodes removed (interquartile range, 1-8). We observed no difference in OS between patients who underwent LND and those who did not (HR = 1.14; 95% CI, 0.93-1.39). Among patients who underwent LND and had positive lymph nodes on pathologic analysis, we observed no difference in DFS or OS between those who received adjuvant systemic therapy and those who received placebo. We also found no difference in postoperative complications between patients who underwent LND and those who did not (14.2% vs. 13.4%).
Q: The author of an editorial that accompanied the study emphasized that lymph node management was at surgeon discretion, and that surgeons were likely to resect grossly positive nodes but not resect normal-appearing nodes. He said it is not surprising that patients who underwent such limited lymph node sampling did not achieve improved OS or DFS. How would you respond?
A. This was a trial of adjuvant systemic therapy vs. placebo, not a trial of LND vs. no LND. Therefore, our analysis was limited to the confines of the study protocol, which required removal of all clinically suspicious nodes but did not mandate LND for patients with normal-appearing lymph nodes. Although this secondary analysis gives us some insight into whether LND is beneficial in high-risk kidney cancer, we agree that a prospective, randomized trial of LND vs. no LND would be the best way to answer this question.
Q. Should lymphadenectomy not be performed for this patient population?
A. There is no clear-cut answer to whether LND should be performed for patients with high-risk kidney cancer. Our recent work, combined with research done by Gershman and colleagues, suggest that routine LND is unlikely to provide a significant survival benefit. Most urologic oncologists would advocate removing clinically suspicious lymph nodes when technically feasible.
Q. How likely is it that a prospective randomized trial of lymphadenectomy at the time of radical nephrectomy will be performed?
A. The gold standard to guide evidence-based practice is the randomized controlled trial. There is appropriate equipoise to conduct this trial given the uncertain benefit of LND for patients with high-risk renal cell carcinoma and the lack of difference in complications associated with LND. The ideal scenario would be for a multi-institutional group to work collaboratively to answer this important question. – by Rob Volansky
References:
Gershman B, et al. Eur Urol. 2017;doi:10.1016/j.eururo.2016.09.019.
Ristau BT, et al. J Urol. 2018;doi:10.1016/j.juro.2017.07.042.
For more information:
Benjamin T. Ristau, MD, can be reached at Urology, UConn Health, 263 Farmington Ave., Farmington, CT 06030; email: benristaumd@gmail.com.
Disclosure: Ristau reports no relevant financial disclosures.