Multiple Patterns of Perirenal Fat Invasion Are Associated With a Poorer Prognosis Compared With Isolated Invasion: A Proposal for a Revision of T3aN0M0 TNM Staging System

Abstract

Objectives: Currently, renal cell carcinoma (RCC) presenting with perisinus fat invasion (PSI) and/or perinephric fat invasion (PFI) is merged as one entity, pathological T3a (pT3a); however, the combination of PFI and PSI (PFI+PSI) may not be associated with equivalent prognosis compared with either PFI or PSI alone (PFI/PSI). Here, we analyzed the prognostic significance of PFI+PSI vs. PFI/PSI in pT3aN0-1M0-1 RCC.Method: We identified 5,290 patients with pT3aN0-1M0-1 RCC, treated by nephrectomy, from the Surveillance, Epidemiology and End Results database, between 2010 and 2016. Cox proportional hazards regression and Fine and Gray competing risks regression were fitted to assess risks of survival outcomes, respectively. 1:1 propensity score method was used to minimize differences in the covariates' distributions.Results: Among all patients, 746 patients (14.1%), 2,569 patients (48.5%) and 1,975 patients (37.3%) experienced PFI+SI, PFI, and PSI, respectively, and 3,952 patients (74.7%) without diseases of lymphnode (N1) and/or distant metastasis (M1). PFI alone compared with PSI alone showed a comparable overall survival (OS) and cancer-special survival (CSS), either PFI or PSI alone experienced a better OS and CSS than PFI+PSI. In patients with pT3aN0M0 RCC, PFI+PSI compared with the PFI/PSI was significantly associated with worse OS with hazard ratio (HR) [95% confidence interval (CI)]: 1.38 [1.12-1.69], p = 0.002 and 1.41 [1.06-1.87], p = 0.017 for unmatched data and matched data, respectively, and higher RCC-special mortality (HR [95%CI]: 1.55 [1.21-1.99], p = 0.001 and 1.70 [1.19-2.43], p = 0.004 for unmatched data and matched data, respectively). However, in pT3aN1/M1 RCC patients, PFI+PSI was not significantly associated with RCC-special mortality (HR [95%CI]: 1.02 [0.85-1.23], p = 0.800 and 0.99 [0.79-1.24], p = 0.920 for unmatched data and matched data, respectively) in comparison with PFI/PSI. In addition, invasion type was not an independent risk factor for patient's prognostication in the pT3a RCC with diseases of N1 and/or M1 (all p > 0.5).Wang et al. Stage's Revision of Renal CancerConclusion: Multiple invasion patterns (PFI+PSI) are associated with inferior survival relative to PFI/PSI alone in patients with pT3aN0M0 RCC; however, these effects are masked in patients with metastatic disease. These results warrant consideration in the development of the next edition of the tumor-node-metastasis staging system, to improve risk stratification.

The critical impact of tumor size in predicting cancer special survival for T3aM0M0 renal cell carcinoma: A proposal of an alternative T3aN0M0 stage

“…We further conducted a sensitivity analysis including the data of T3aNanyMany and found that stratification for T3a RCC with a cutoff of 4 cm and 7 cm still showed a good predictive accuracy (c‐index: 0.781, data not shown). Another study by our group showed that multiple patterns of perirenal fat invasion are associated with a poorer prognosis than isolated invasion, which was consistent with previous studies 15 . Therefore, there is a need to further refine the reclassification for T3a RCC to increase the ability to predict prognosis and integrate tumor size and perirenal fat invasion types in future investigations.…”

“…The current definition of T3a RCC is tumor grossly extends into the renal vein or its segmental (muscle‐containing) branches or tumor invades perirenal and/or renal sinus fat (peripelvic fat), but not beyond Gerota fascia. The three types of T3a infiltration (renal vein infiltration, perirenal fat, and renal sinus fat infiltration) may have their prognostic differences, and there are some pieces of evidence to prove this point 14‐16 . One of the most classic studies is from Shah's research, 14 they found that the presence of multiple patterns of extrarenal extension (renal vein infiltration, perirenal fat, and renal sinus fat infiltration) is associated with a higher risk of disease progression and RCC‐related death after RN compared to isolated involvement of the renal vein infiltration, perirenal fat, and renal sinus fat infiltration.…”

“…One of the most classic studies is from Shah's research, 14 they found that the presence of multiple patterns of extrarenal extension (renal vein infiltration, perirenal fat, and renal sinus fat infiltration) is associated with a higher risk of disease progression and RCC‐related death after RN compared to isolated involvement of the renal vein infiltration, perirenal fat, and renal sinus fat infiltration. Because the information on this aspect in the SEER database is lacking, or only a small part of the information about fat infiltration around the kidney and renal sinus infiltration is recorded, and there is no vascular infiltration, 15 so it cannot guarantee high‐quality regression analysis. In all, our conclusions can only be based on the results of the current eighth edition AJCC TNM RCC staging system.…”

Radical Nephrectomy Provides a Worse Prognosis Than Partial Nephrectomy in T3aN0M0 Renal Cancer of Small (≤4 cm) Size and No Invasion of Perisinus Fat

“…Invasion into perirenal fat has been shown to not increase RCC-speci c mortality. Conversely, invasion into sinus fat portends a worse prognosis than perirenal-fat invasion even though both are classi ed as T3aN0M0 [23][24][25]. We found that RCC presenting with sinus/perisinus-fat invasion could not bene t from PN regardless of tumor size.…”

Oncological Outcomes of Patients With Different Pathological Features of pT3a Renal Tumor: A Systematic Review and Quantitative Synthesis

“…Our understanding of the heterogeneous behavior of renal tumors has been well advanced. The increasing interest in adjuvant treatment, immunotherapy and targeted therapies has prompted the need for more accurate staging of renal tumors (5)(6)(7)(8)(9). In the clinical context, some pT3a renal tumors are confirmed by postoperative pathology, and their incidence is usually underestimated.…”