Retrospective Data Show Metastasectomy Plus Nephrectomy Improves Survival in Non–ccRCC

Findings from a retrospective cohort study showed that patients with metastatic non–clear cell renal cell carcinoma (ccRCC) who underwent metastasectomy and radical nephrectomy experienced improved progression-free survival (PFS) and overall survival (OS) compared with those who received radical nephrectomy alone, particularly in patients without liver metastases and those with metachronous metastases.

Data published in the World Journal of Urology demonstrated that patients who underwent metastasectomy (n = 20) achieved a median PFS of 27.1 months compared with 14.0 months for those who did not receive metastasectomy (n = 100; HR, 0.277; 95% CI, 0.086-0.895; P = .032). The median OS was 67.3 months for the metastasectomy group vs 24.0 months for the non- metastasectomy group (HR, 0.300; 95% CI, 0.094-0.963; P = .043).

Additionally, patients with metachronous metastases who underwent metastasectomy and radical nephrectomy (n = 11) experienced a benefit in PFS (HR, 0.103; 95% CI 0.014-0.784; P = .028) and OS (HR, 0.250; 95% CI, 0.059-0.965; P = .043) vs those who underwent nephrectomy alone (n = 44). Benefits in PFS (HR, 0.256; 95% CI, 0.061-0.974; P = .043) and OS (HR, 0.152; 95% CI, 0.021-0.989; P = .032) were also observed for those without liver metastases who received metastasectomy (n = 16) vs those who did not (n = 85).

“Metastasectomy may serve as a viable treatment option for patients with metastatic non-ccRCC. Individuals with metachronous metastases and those without liver metastases may benefit from metastasectomy. However, these findings require further exploration through extensive prospective cohort studies,” lead study author Jindong Dai, MMS, of the Department of Urology at the Institute of Urology of West China Hospital, Sichuan University, in Chengdu, China, and colleagues wrote.

Study authors also noted that the optimal management of metastatic non-ccRCC is largely unknown, and although metastasectomy could be a viable option for this patient population, there is no available evidence demonstrating a survival benefit with this approach.

The cohort study was designed to evaluate the efficacy of metastasectomy in patients with metastatic non-ccRCC. Investigators retrospectively identified patients at least 18 years of age from the West China Hospital metastatic RCC database. To enroll, patients needed to have been diagnosed with pathologically confirmed non-ccRCC between September 2008 and July 2021, and the study included patients harboring metastases with clear radiological or pathological diagnoses.

Investigators excluded patients diagnosed before 2008 due to incomplete information. Other exclusion criteria included metastatic non-ccRCC treated with nephrectomy plus systemic therapy, including TKIs, mTOR inhibitors, as well as combination regimens consisting of TKIs and immune checkpoint or mTOR inhibitors.

The median age was 36.0 years (range, 31.0-49.5) in the metastasectomy group and 45.0 years (range, 31.0-52.0) in the non-metastasectomy group. The majority of patients in both arms were male (60.0% for metastasectomy; 60.0% for non-metastasectomy), had an ECOG performance status of less than 2 (90.0%; 77.0%), had an International Metastatic RCC Database Consortium intermediate risk score (75.0%; 50.0%), did not have synchronous metastases (55.0%; 55.0%), and had at least 2 metastatic sites (60.0%; 63.0%).

Metastatic sites in the metastasectomy group included lung (15%), bone (25.0%), liver (20%), lymph node (75.0%), and other (65%). In the non-metastasectomy group, metastatic sites were comprised of lung (27.0%), bone (25.0%), liver (15.0%), brain (1.0%), lymph node (36.0%), and other (36.0%).

All patients received primary systemic therapy, which consisted of a TKI (metastasectomy group, 65.0%; non-metastasectomy group, 69.0%); a TKI plus immune checkpoint inhibitor (35.0%; 26.0%); a TKI plus mTOR inhibitor (0%; 2.0%); an mTOR inhibitor (0%; 1.0%); and immune checkpoint inhibitor (0%; 2.0%). The median time from diagnosis to metastasis was 15.2 months (range, 4.5-118.0) in the metastasectomy group and 12.2 months (range, 7.6-114.6) in the non-metastasectomy group.

Among patients who underwent metastasectomy, the median duration of the operation was 100.0 minutes (range, 73.0-132.5), and the median perioperative blood loss was 30.0 mL (range, 13.75-50). Notably, the median hospital stay was 6.5 days (range, 6-8). Postoperative fever occurred in 10.0% of patients, and 25.0% of patients experienced pain following the procedure. Surgical site infection occurred in 1 patient. No serious grade 3 or higher perioperative complications were reported, per Clavien-Dindo Classification.

“However, it is important to consider the technical intricacies and safety of surgery, in addition to therapeutic outcomes when implementing metastasectomy,” study authors wrote. “A retrospective study indicated that among 1102 patients who underwent metastasectomy, 27.5% experienced major complications [Clavien grade ≥3], and liver metastasectomy [was] associated with a higher incidence of overall complications compared to procedures performed at other sites.”

Study authors noted the retrospective analysis was limited by a relatively small patient population, making data prone to possible selection bias. They also noted that the findings may be influenced by unexamined confounders and neglected values.

Reference

Dai J, He B, Zhang Y, et al. The survival benefit of metastasectomy for metastatic non-clear cell renal cell carcinoma: a retrospective cohort study. World J Urol. 2024;42(1):259. doi:10.1007/s00345-024-04973-8