Limited Clinical Value of PRCC Subtyping in Advanced Kidney Cancer Treatment

What is it about?

This study investigated the clinical significance of subtyping (type 1 vs 2) of papillary renal cell carcinoma (PRCC) in patients treated with targeted therapy and the concordance, sensitivity, and positive predictive value (PPV) of local review pathology review. The study found that the prevalence of individual subtypes varied by local or central review and that individual cases were frequently reclassified. The sensitivity and PPV of local review were estimated and outcomes [objective response rate (ORR), progression-free survival (PFS)] were summarized for treatment groups stratified by subtypes by central review. The study concluded that the PRCC subtype assignment did not identify a subset of patients with greater clinical benefit from cabozantinib, with significant discordance between local and central review. The findings confirm the limited clinical value of pathological subtyping of metastatic PRCC, in line with the recent World Health Organisation 2022 guidelines.

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Why is it important?

The study highlights the limited clinical value of pathological subtyping of metastatic PRCC, as the concordance, sensitivity, and positive predictive value of local review pathology review were found to be low, and there was significant discordance between local and central review. The findings confirm the recent World Health Organisation 2022 guidelines, which recommend against the use of PRCC subtype as a predictive biomarker for targeted therapy. The study demonstrates the importance of using central review pathology in clinical trials and highlights the need for standardization of pathology review to ensure accurate and reliable results. Key Takeaways: 1. The prevalence of individual subtypes varied by local or central review in the 147 patients reviewed, with significant discordance between local and central review. 2. Compared to sunitinib, cabozantinib demonstrated improved PFS for both type 1 and type 2 PRCC subgroups and higher ORR. 3. The PRCC subtype assignment did not identify a subset of patients with greater clinical benefit from cabozantinib. 4. The study supports a potential prognostic role of PRCC subtype classification with lower PFS in the type 2 subtype compared to type 1, but it did not enrich for patients likely to benefit from cabozantinib.