To evaluate the clinical significance of subtyping (type 1 vs 2) of papillary renal cell carcinoma (PRCC) in patients treated with targeted therapy, as well as the concordance, sensitivity and positive predictive value (PPV) of local review pathology review.
Patients with advanced refractory PRCC were randomised to receive sunitinib or cabozantinib, crizotinib or savolitinib, stratified by PRCC subtype (type 1, type 2, or not otherwise specified [NOS]/mixed) by local review. Central review was retrospectively conducted by three expert genitourinary pathologists who independently reviewed cases. The sensitivity and PPV of local review were estimated and outcomes [objective response rate (ORR), progression-free survival (PFS)] were summarised for treatment groups stratified by subtypes by central review.
Amongst the 147 patients reviewed, the prevalence of individual subtypes varied by local or central review (type 1: 17.7% vs 29.3%; type 2: 53.1% vs 45.6%; NOS/mixed: 29.3% vs 25.2%), respectively. Individual cases were frequently reclassified and local pathology review demonstrated low sensitivity (type 1: 48%, 95% confidence interval [CI] 33, 65; type 2: 67%, 95% CI 55, 78; NOS/mixed: 43%, 95% CI 27, 61). The PPVs of local review were 80%, 57.7% and 37% for type 1, 2 and NOS/mixed, respectively. Compared to sunitinib, cabozantinib demonstrated improved PFS for both type 1 and type 2 PRCC subgroups (7.4 vs 9.0 and 2.9 vs 5.6 months, respectfully) as well as higher ORR.
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. Our findings confirm the limited clinical value of pathological subtyping of metastatic PRCC, in line with the recent World Health Organisation 2022 guidelines.
In this study, categorising papillary renal cell carcinoma into type 1 or 2 subtypes showed limited concordance between central and local pathological review and did not enrich for patients more likely to benefit from cabozantinib in the S1500 PAPMET trial.
BJU international. 2024 Jul 16 [Epub ahead of print]
Abhishek Tripathi, Catherine M Tangen, Melissa Plets, Xiaochen Li, Maria Tretiakova, Peter A Humphrey, Adebowale Adeniran, Pedro C Barata, Shuchi Gulati, Cristiane D Bergerot, Deepak K Pruthi, Ian M Thompson, Primo N Lara, Seth P Lerner, Sumanta K Pal, Brian M Shuch
City of Hope Comprehensive Cancer Center, Duarte, CA, USA., SWOG Statistics and Data Management Center, Seattle, WA, USA., Department of Biostatistics, City of Hope Comprehensive Cancer Center, Duarte, CA, USA., University of Washington, Seattle, WA, USA., Yale University, New Haven, CT, USA., University Hospitals Seidman Cancer Center, Cleveland, OH, USA., University of California Davis Comprehensive Cancer Center, Sacramento, CA, USA., Oncoclinicas DF, BrasÃlia, DF, Brazil., UT Health San Antonio, San Antonio, TX, USA., Children's Hospital of San Antonio, San Antonio, TX, USA., Baylor College of Medicine, Dan L Duncan Cancer Center, Houston, TX, USA., UCLA Institute of Urologic Oncology, Los Angeles, CA, USA.