Viability of Cytoreductive Nephrectomy Followed by Active Surveillance in mRCC Upheld

Performing cytoreductive nephrectomy (CRN) followed by active surveillance (AS) in patients with metastatic renal cell carcinoma (mRCC) continues to be an alternate option to immediate systemic therapy for select patients, according to retrospective data presented during the 2021 International Kidney Cancer Symposium: North America.¹

“While this study was not designed to identify features of patients who would best benefit from surveillance rather than systemic therapy following CRN, we did note that for those patients who underwent CRN followed by surveillance, patients with favorable Rini criteria had much longer intervention-free survival [IFS] and cancer-specific survival [CSS] than those with unfavorable Rini criteria,” Sari Khaleel, MD MSc told Targeted Oncology™, in an interview.

According to Khaleel, experts who treat mRCC debate about the role CRN plays in modern management of the disease. There are multiple systemic combinations available to treat mRCC like nivolumab (Opdivo) plus ipilimumab (Yervoy) with a 5-year survival rate of 48%, or atezolizumab (Tecentriq) plus bevacizumab (Avastin) with a median overall survival of 7.7 months. But Khaleel noted during his presentation that immunotherapy can lead to grade 3 or 4 adverse events (AEs) in 40% to 50% of patients, and VEGF inhibitor combinations had a >50% rate of grade 3/4 AEs.

In a phase 2 study of 73 patients with mRCC published in 1988, patients were only treated if they developed disease progression and 90% progressed at 12 months. Another study published in 2006 showed that in 15 patients with mRCC who were treated by CRN followed by AS, 80% progressed a median follow-up of 18 months.

In a prospective phase 2 trial for which data were published in 2016, a subset of patients was able to be surveilled without systemic treatment. The time until initiation of systemic therapy in the study was 14.9 months (95% CI, 10.6-25.0), warranting further exploration of the disease management approach.²

Based on this earlier research, Khaleel et al set out to determine if CRN followed by AS was still a valid option for patients.¹

A total of 508 patients were evaluated retrospectively. The entire cohort was previously untreated with systemic therapy and underwent CRN followed by AS between August 1989 to January 2020. The primary end point of the study was IFS, and the secondary CSS and overall survival. The efficacy results of the management strategy in this study were compared with the results from Rini et al.

Of the 508 patients who underwent CRN, 80% had residual disease. A total of 97 patients were actively surveilled following CRN while the other 256 were sent on to receive systemic therapy. Within the 97 patients who had CRN followed by AS, the median age was 66.72 (range, 59.03-71.63), and the median baseline tumor size in patients was 8.50 cm (range, 6.00-10.50). In terms of other disease characteristics, 20.6% had sarcomatoid features, 23.7% had stage T1/T2 tumors, 76.3% had stage T3/T4 tumors, 21.6% had nodal metastases. 19.6% had bone metastases, and 69/1% had pulmonary metastases.

In comparison, for those who received systemic therapy following their CRN, the median age was 59.69 years (range, 51.62-66.66), and the median tumor size was 9.50 cm (range, 7.00-12.30). Sarcomatoid features were present in 49.2% of the CRN plus systemic therapy cohort. In terms of disease stage, 13.6% had T1/T2 disease, and 86.1% had T3/T4 disease. Nodal metastases were present in 47.1% of patients, while 31.9% had bone metastases, and 64.1% had pulmonary metastases.

At a median follow-up of 31.8 months, the median IFN was 11.6 months in the overall study population of which only 59.8% had received systemic therapy. The OS result in the overall population was 52.3 months (95% CI, 46.1-66.7), and the CSS was 56.5 months (95% CI, 41.0-74.2).

Looking at the study outcomes according to Rini risk stratification criteria, patients with favorable risk were defined as those with ≤ 1 International Metastatic RCC Database Consortium (IMDC) risk factors and ≤ 2 metastatic organ sites. Those with unfavorable risk were those with > 1 IMDC risk factors or > 2 metastatic organ sites.

Having favorable-risk disease was associated with a significantly prolonged IFS compared with unfavorable disease. The median IFS in the favorable-risk group was 17.1 months (95% CI, 11.8-26.6) versus 8.9 months (95% CI, 6.4-13.5) in the unfavorable-risk group (HR, 0.60; 95% CI, 0.38-0.95; P =.026). Having favorable-risk mRCC was also associated improvement CSS at 71.4 months (95% CI, 66.7-74.2) versus 50.4 months (95% CI, 35.6 -74.2) in the unfavorable-risk group (HR 0.51; 95% CI, 0.27-0.99; P =.041).

There was no correlation between disease risk and improvement in OS. The median OS in the favorable-risk population was 66.7 months (95% CI, 51.2-92.3) in the favorable-risk population compared with 46.1 months (95% CI, 35.6-57.7) in patients with unfavorable risk (P =.12).

“This supports current evidence for primary CRN plus AS as a reasonable alternative to primary or additional ST in the management of mRCC, avoiding the morbidity of deferrable adjuvant interventions. Prognostic criteria proposed by Rini et al for patients undergoing CRN plus AS were predictive of intervention-free and cancer-specific survival in our CRN plus AS cohort, suggesting that they could aid in selecting patients most appropriate for this approach, as well as patients on CRN plus AS who are likely to require additional focal or systemic therapies,” said Sari Khaleel, MD MSc, during his presentation.

_References:

_{Rini BI, Dorff TB, Elson P, et al. Active surveillance in metastatic renal-cell carcinoma: a prospective, phase 2 trial. Lancet Oncol. 2016;17(9):1317-24. doi: 10.1016/S1470-2045(16)30196-6}