title: Chromophobe renal cell carcinoma (RCC): oncological outcomes and prognostic factors in a large multicentre series.
abstract: Study Type - Outcomes (cohort) Level of Evidence 2b What's known on the subject? and What does the study add? About 80% of RCCs have clear cell histology, and consistent data are available about the clinical and histological characteristics of this histological subtype. Conversely, less attention has been dedicated to the study of non-clear cell renal tumours Specifically, published data show that chromophobe RCC (ChRCC) have often favourable pathological stages and better nuclear grades as well as a lower risk of metastasizing compared with clear cell RCC (ccRCC). Patients with ChRCC were shown to have significantly higher cancer-specific survival (CSS) probabilities compared with ccRCC. However, an independent prognostic role of RCC histotype was not confirmed in some large multicenter series and only a few studies have focused on the oncological outcomes of ChRCC. The present study is one of the few to evaluate cancer-related outcomes of ChRCC and represents to our knowledge the largest series of ChRCCs. Consequently, the present findings may assist in elucidating the natural history of surgically treated ChRCC. The present study confirms that ChRCCs have good prognosis and a low tendency to progress and metastasize. Only 1.3% of patients presented with distant metastases at diagnosis, and the 5- and 10-year CSS were 93% and 88.9%, respectively. However, although ChRCCs are generally characterised by an excellent prognosis, we observed that patients with locally advanced or metastatic cancers as well as those with sarcomatoid differentiation have a poor outcome. The study also investigated prognostic factors for recurrence-free survival (RFS) and CSS for this RCC histotype. The definition of outcome predictors can be useful for patient counselling, planning of follow-up strategies, and patient selection for clinical trials. In the present study, gender, clinical T stage, pathological T stage, and presence of sarcomatoid differentiation were significantly associated with RFS and CSS at multivariable analysis. We also identified N/M stage as an independent predictor of CSS. Notably, as Fuhrman grade was not an independent predictor of cancer-related outcomes, the present study confirms that this histological variable is not a reliable prognostic factor for ChRCC.
  
  
  OBJECTIVE
  To investigate cancer-related outcomes of chromophobe renal cell carcinoma (ChRCC) in a large multicentre dataset. To determine prognostic factors for recurrence-free survival (RFS) and cancer-specific survival (CSS) for this RCC histological type.
  
  
  METHODS
  In all, 291 patients with ChRCC were identified from a multi-institutional retrospective database including 5463 patients who were surgically treated for RCC at 16 Italian academic centres between 1995 and 2007. Univariable and multivariable Cox regression models were used to identify prognostic factors predictive of RFS and CSS after surgery for ChRCC.
  
  
  RESULTS
  At a median follow-up of 44 months, 25 patients (8.6%) had disease recurrence and 18 patients (6.2%) died from disease. The 5-year RFS and CSS rates were 89.3% and 93%, respectively. Gender (P= 0.014), clinical T stage (P= 0.017), pathological T stage (P= 0.003), and sarcomatoid differentiation (P= 0.032) were independent predictors of RFS at multivariable analysis. For CSS, there was an independent prognostic role for gender (P= 0.032) and T stage (P= 0.019) among the clinical variables and for T stage (P= 0.016), N/M stage (P= 0.023), and sarcomatoid differentiation (P= 0.015) among the pathological variables.
  
  
  CONCLUSIONS
  Patients with ChRCC have a low risk of tumour progression, metastasis, and cancer-specific death. Patient gender, clinical and pathological tumour stage, and sarcomatoid differentiation are significant predictors of RFS and CSS for ChRCC.
authors: University of Eastern Piedmont, Novara, Italy.
authors: Alessandro
authors: A
authors: Volpe
authors: Giacomo
authors: G
authors: Novara
authors: Alessandro
authors: A
authors: Antonelli
authors: Roberto
authors: R
authors: Bertini
authors: Michele
authors: M
authors: Billia
authors: Giorgio
authors: G
authors: Carmignani
authors: Sergio Cosciani
authors: SC
authors: Cunico
authors: Nicola
authors: N
authors: Longo
authors: Guido
authors: G
authors: Martignoni
authors: Andrea
authors: A
authors: Minervini
authors: Vincenzo
authors: V
authors: Mirone
authors: Alchiede
authors: A
authors: Simonato
authors: Carlo
authors: C
authors: Terrone
authors: Filiberto
authors: F
authors: Zattoni
authors: Vincenzo
authors: V
authors: Ficarra
mesh_terms: D002292:Carcinoma, Renal Cell / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009392:Nephrectomy; D011379:Prognosis