Most previous studies reported the role of age as a prognostic factor in RCC patients with all subtypes and all stages, telling conflicting conclusions [7,11–20]. Of these studies, some have claimed that the prognosis of RCC in younger patients did not differ from that in older patients [13–15]. The most recent multicenter study including 5,178 patients who underwent surgery for RCC showed no significant difference in CSS among three age groups (< 40 years, ≥ 40 and < 60 years, ≥60 years) [15]. However, more studies reported better CSS rates in young RCC patients than in older ones [16–20]. Although clear cell cancer is the predominant pathological subtype, these studies conclusions can not simply extrapolate to the pT2N0M0 ccRCC setting. Because above studies had limited pT2N0M0 ccRCC cases or no further stratified by stage I and II, or included other subtypes. As we know, because of differences in the prognosis among RCC subtypes, the prognostic implications of age can vary among RCC subtypes. Hence the statistics power is weak.
Several studies exploring the role of age as a prognostic factor in localized RCC (stage I and II) patients suggested that age was a significant predictor of survival [9,12,21–23]. These patient populations also included other subtypes or had relatively few proportion of pT2N0M0 RCC cases (9.7–27%), or no further stratified by stage I and II. So the role of age as a prognostic factor in pT2N0M0 ccRCC is unclear.
In the present SEER-based study, our analysis demonstrated for the first time that age is a powerful independent prognostic factor for OS and CSS in pT2N0M0 ccRCC patient population. Age is the only risk factor for overall survival in multivariable analyses and also the most powerful predictor for CSS (Table 2). We found that old age was associated with worse OS and CSS, especially for≥70 years old patients. There are many possibilities to explain this. First, the elderly patients were more likely to have complications either after radical nephrectomy or after partial nephrectomy, which confers worse survival [24]. Second,increasing age companies progressive decline in immune function, which may account for poor survival in elderly RCC patients [25]. Third, majority of pT2N0M0 ccRCC patients received radical nephrectomy (Table 1), which seems to be risk factors associated with a poor outcome if renal function insufficiency happens [26]. Fourth, the old age group had more widowed patients than the other age groups (P<0.001, Table 1), which confers a worse survival [27].
We also found that marital status, tumor size and grade were also independent prognostic factors for CSS in both univariate and multivariate analysis, which is consistent with previous studies [27–29]. With respect to tumor size, our study is not consistent with previous study by Scoll BJ et al who revealed that age was not a significant predictor of relative survival for patients with large (greater than 7 cm) tumors in localized renal cell carcinoma [10]. However, above study sample was from 1988 to 1997, part of the cases with large (greater than 7 cm) tumors was T3 or T4 stage according to modern TNM stage. Besides, its study end point is relative survival instead of CSS.
Our study represents the largest series of pT2N0M0 ccRCC published to date with assessment of the prognostic impact of age in this patient population. Combined with the conclusions from previous studies [8–9], we can confirm that age is a powerful predictor for survival in pT1–2N0M0 ccRCC, so previous conflicting results may be partially explained by the small sample size or the heterogeneity of the study cohort by incorporation of other subtypes and all stages.
Several limitations of the present study should be noted. First, SEER does not collect performance status data, which might be a predictor of CSS in a previous study [35]. Second, SEER does not distinguish sporadic ccRCC from familial cases such as Von Hippel-Lindau disease (VHL). However,VHL disease is the most common cause of hereditary renal cell carcinoma and comprises only about 2–3% of the total RCC incidence. RCCs tend to be multifocal and bilateral in the setting of VHL disease [30]. In this settings, we had excluded cases of bilaterality, so the bias is small.