IO Improves Survival for Patients With mRCC, Sarcomatoid Features After Cytoreductive Nephrectomy

According to study results presented at the 2024 American Urological Association Annual Meeting, immune checkpoint inhibitors (ICIs), a type of immunotherapy (IO), significantly improve survival for patients with metastatic renal cell carcinoma (mRCC) and sarcomatoid features who undergo cytoreductive nephrectomy (CN), regardless of the timing of surgery.

It is rare for mRCC tumors to have sarcomatoid dedifferentiation, and sarcomatoid features are known to be associated with poor survival outcomes.

Daniel D. Shapiro, MD, and colleagues designed a study to compare survival outcomes among patients with mRCC and sarcomatoid features who were treated with either targeted therapy or ICIs. Researchers sought to determine whether the sequence of CN and systemic therapy is associated with survival.

A total of 1421 patients with mRCC who underwent CN from 2006 to 2022 were sampled from 8 institutions, 309 of whom had sarcomatoid features identified on surgical pathology. Patients were categorized into 4 cohorts by the systemic therapy they received and the sequence of treatments:

• Upfront IO plus deferred CN (7%)
• Upfront targeted therapy plus deferred CN (14%)
• Upfront CN plus deferred IO (19%)
• Upfront CN plus deferred targeted therapy (60%)

Researchers utilized multivariable Cox regression to evaluate variables associated with overall survival (OS). The median age was 68 years, and most (77%) patients had clear cell RCC.

After a median follow-up of 37 months, researchers found that patients with sarcomatoid features had significantly shorter OS (median, 15 months vs 37 months, respectively; P<.001) than a cohort of 1112 patients without sarcomatoid features who underwent CN.

Additionally, they reported that patients treated with IO at any time had significantly improved OS compared with patients not treated with IO (median, 40 months vs 13 months, respectively; P=.0001). The sequence of systemic therapy and CN was not found to be associated with survival in these patients (P=.7).

Furthermore, researchers noted that among patients receiving targeted therapy, upfront CN was associated with reduced mortality (hazard ratio, 0.6; 95% CI, 0.4-0.9; P=.03).

“ICIs have significantly improved survival for mRCC patients with sarcomatoid features treated with CN, regardless of timing of surgery,” study authors concluded.