Introduction:

Recurrence following nephrectomy for kidney cancer remains a major contributor to kidney cancer-specific mortality. In 2021, pembrolizumab, a monoclonal antibody against programmed cell death receptor-1, became the first, and remains the only FDA-approved adjuvant therapy to reduce recurrence risk after high-risk nephrectomy for clear cell renal cell carcinoma (ccRCC); Mature outcome data published in 2024 also implies a significant overall survival benefit for adjuvant pembrolizumab compared to placebo after high-risk nephrectomy. Despite its approval and data suggesting improvements in both recurrence-free survival and overall survival, real-world data on its clinical adoption and reasons for non-receipt remain limited.

Methods:

We conducted a retrospective cohort study of consecutive patients who underwent nephrectomy for high-risk (pathologic stage T2 with grade 4 or sarcomatoid features, stage ≥T3, regional lymph node involvement), ccRCC at a multi-hospital academic health system between January 2022 and May 2025. We assessed the proportion of patients offered adjuvant pembrolizumab, compared baseline characteristics between those who received versus did not receive therapy, and identified reasons for non-receipt. 

Results:

Among 128 patients referred to medical oncology after high-risk nephrectomy for ccRCC, 118 (92.1%) completed a consultation, and 108 (91.5%) were offered adjuvant pembrolizumab. The most common reasons for not offering therapy were medical comorbidities (n=5) and delayed initiation post-surgery (n=3). Of 108 patients offered therapy, 77 (71.3%) initiated treatment, 25 (23.1%) did not, and 6 (5.6%) had unknown treatment status. Patients who received adjuvant pembrolizumab were significantly younger (median age 66.0, IQR 59.8-70.7) than those who did not (median age 70.0, IQR 62.5-77.0, p=0.04), and had higher histologic grades (p=0.003). There was no significant difference in sex, tumor staging or presence of sarcomatoid features between groups. Patient preference (n=23) was the most common reason for non-receipt, followed by concern for cost (n=1), and development of metastatic disease (n=1).

Conclusion:

Following FDA approval, adjuvant pembrolizumab is being routinely offered after high-risk nephrectomy for ccRCC in our academic health system, with patients receiving pembrolizumab tending to be younger and having higher grade disease. However, approximately a quarter of all eligible patients do not receive treatment, most commonly due to personal preference. Adoption patterns may improve as overall survival data for adjuvant pembrolizumab after high-risk nephrectomy have recently become mature.

Funding: N/A