Determining the impact of histology on the incidence, pattern, and timing of recurrences in patients with renal cell carcinoma: a pooled analysis from the SORCE and ASSURE Trials

Background and objective: Outcomes after nephrectomy for intermediate- and high-risk renal cell carcinoma (RCC) according to histological subtype are poorly characterised. This study aims to determine the value of RCC histology in predicting survival and to inform on surveillance strategies in relation to patterns of first recurrence.0
Methods: We pooled data from phase 3 trials: SORCE (n = 1689) and ASSURE (n = 1853). Of 3542 patients, 2881 had clear-cell RCC (ccRCC), 269 had papillary RCC (pRCC), 201 had chromophobe RCC (chRCC), and 191 had sarcomatoid RCC (sRCC). Relapse rates, median time to relapse (TTR), and first relapse sites were reported. Multivariable Cox regression models evaluated overall survival by histology, adjusting for initial relapse location and other important clinical factors.
Key findings and limitations: Patients with pRCC and ccRCC had similar overall survival (log-rank p = 0.1). The median TTR for those with pRCC was 1.34 yr (interquartile range [IQR] 0.76, 2.59) compared with 1.78 yr (IQR 0.96, 3.38) for ccRCC patients (p = 0.012). Patients with chRCC had a median TTR of 2.72 yr (IQR 0.91, 4.11), and those with sRCC had a median TTR of 0.74 yr (IQR 0.50, 1.55). For sRCC patients, relapsing in the chest was associated with a lower risk of death than those relapsing in the abdomen (hazard ratio [HR] 0.5, confidence interval [CI]: 0.3, 0.88; p = 0.06). A similar trend was shown for pRCC (HR 0.5, CI: 0.2, 1.3; p = 0.1). Recurrence patterns for World Health Organization 2020 molecularly classified RCCs were not included. Despite pooling phase three datasets, small event numbers led to imprecise estimates, particularly for chRCC.
Conclusions and clinical implications: Patients with intermediate and high-risk pRCC relapse earlier than those with ccRCC. Papillary RCC and sRCC first recurring in the abdomen exhibit poor prognosis, warranting consideration of additional abdominal imaging to enhance early relapse detection. ChRCC exhibits favourable prognosis and could avoid image-based surveillance until year 2. Patient summary This study evaluates pooled data from large phase 3 trials to precisely delineate relapse patterns for patients with intermediate- and high-risk cell renal cell carcinoma (RCC) according to their histology. The site and timing of first relapse provide useful information to support histology-specific RCC surveillance after nephrectomy. Development of genetic and molecular signatures corresponding to relapses at poor prognosis sites for each histology will individualise follow-up and is the next step.