The wide spread use of imaging examinations has increased the detection of CERCCs [17]. Our study showed that CERCC accounted for 7.6% of all localized RCC cases. Surgical removal of CERCCs is difficult and has a high incidence of postoperative complications. In contrast to previous studies that mainly focused on operative approaches, our study systematically compared the clinical, pathological, and prognostic features of CERCCs and NCERCCs, and elucidated that there were significant differences between CERCCs and NCERCCs in terms of tumor size, stage, and pathological type, suggesting that CERCC may be a special type of RCC.
The endogenous characteristics of CERCCs indicate that their diameter would not be large; otherwise, the renal mass would protrude beyond the outline of the kidney. Previous studies reported that the diameter of CERCCs ranged from 2–3 cm [6, 19, 20]. In our study, we found that the average tumor diameter of CERCC was 2.9 cm, which is consistent with previous studies. When comparing the size of CERCCs with NCERCCs, most studies have elucidated that the tumor diameter of CERCCs is smaller [3, 6, 11, 21]. Our study is in agreement with the results of these previous studies. However, one study reported that there was no significant difference in tumor size between CERCC and NCERCC [15]. Furthermore, Carbonara et al. compared the size of completely endogenous, intermediate, and exogenous renal tumors in patients undergoing RAPN and found that patients with complete endogenic renal masses had larger tumors [17]. The authors believed this could be because, with maturing experience, the surgeons at the participating centers tended to offer RAPN for larger and more endophytic masses [17]. However, this may be related to selection bias.
In terms of pathological staging, our study showed an earlier stage in CERCCs than in NCERCCs, which was consistent with previous studies [6, 21]. It is worth noting that in the CERCC group, although patients in the T1 stage accounted for 91.0%, the percentage of patients in the T3 stage was as high as 9.0%, which was slightly higher than that of patients in the T3 group in the NCERCC group (5.7%). Consistent with our research, previous studies also found that many CERCCs reached the T3 stage, suggesting that some CERCCs tend to invade the collecting system, renal sinus fat, or venous system [17, 21]. The guidelines of the European Association of Urology recommend PN as the standard treatment for T1 RCC [18]. PN is feasible for most CERCCs [1, 3, 6–11]. However, PN in patients with T3 stage CERCC may result in a positive margin and increase the risk of postoperative recurrence. In our study, all six patients with T3 stage CERCC underwent radical nephrectomy. A recent meta-analysis showed no difference in cancer-specific survival, OS, cancer-specific mortality, and recurrence-free survival between partial nephrectomy and radical nephrectomy in patients with pT3a RCC [22]. However, the safety and efficacy of partial nephrectomy in patients with T3 stage CERCCs need to be further confirmed by studies in the future with large sample sizes. Therefore, it is important to detect RCCs in the T3 stage before PN. Clinical manifestations and imaging examinations may help in making an accurate diagnosis. For instance, of the six patients with T3 stage CERCC in our study, 50% presented with symptoms such as hematuria and low back pain, and 50% showed collecting system or venous system involvement radiologically.
Previous studies have shown a correlation between growth patterns and pathological types of RCC [23, 24]. Exophytic renal tumors are more likely to be of the papillary RCC subtype than endophytic renal tumors [23]. Some studies have shown that ccRCC is less likely to be exogenous, whereas exophytic RCC is more likely to be non-clear cell RCC (nccRCC) [23, 24]. However, some other studies have found no significant difference in the distribution of pathological types between CERCCs and NCERCCs [6, 21]. Our study found no significant difference in the distribution of nccRCC and ccRCC between CERCC and NCERCC. However, when nccRCC was subdivided, there was a significant difference in the distribution of pathological types between the two groups. In our study, mucinous tubular and spindle cell carcinoma (MTSCC) accounted for 3% of the CERCC group, while MTSCC accounted for only 0.12% of the NCERCC group. MTSCC is a rare kidney cancer subtype with low malignant potential and a low risk of metastasis [25]. Geamizadeh et al. and Gaafar et al. reported three cases of MTSCC, all of which were endophytic renal tumors [26, 27]. Sahni et al. reported the imaging features of six cases of MTSCC and found that five were endophytic renal tumors [28]. Takahashi et al. reported the MRI features of 15 cases of MTSCC and found that endophytic tumors accounted for 40% of cases [29]. Therefore, despite its rarity, MTSCC should be considered in patients with CERCC.
In terms of tumor grade, Weld et al. found that 96.3% of exophytic tumors were grades 1 or 2, while only 75% of endophytic tumors were low-grade; however, this study was based on exophysis > 67% as the criterion for distinguishing exophytic and endophytic renal tumors [23]. Carbonara et al. found no significant difference between CERCC and NCERCC in terms of tumor pathological grade, which is consistent with our study [17]. However, our study found no patients with pathological grade IV CERCC. Mullerad et al. also found that no patients had pathological grade IV CERCC [13]. These results suggest that high pathological grade is relatively rare in patients with CERCC; however, this needs to be confirmed by studies with large sample sizes.
Previous studies mainly focused on surgical complications, renal function, and TRIFECTA outcomes after partial nephrectomy for CERCC with a short follow-up time [1, 3, 6–12]. Studies of the long-term prognosis of CERCC and NCERCC in terms of recurrence and survival are lacking. Mullerad et al. found that the local recurrence rate of patients with CERCC was higher than that of patients with NCERCC after partial nephrectomy, but there was no significant difference in the total survival time [13]. After a four-year follow-up, Komninos et al. and Zapala et al. found no significant difference in PFS and OS between patients with CERCC and NCERCC after robotic PN and open PN, respectively [15, 16]. A systematic review also showed no significant difference in recurrence and survival between patients with CERCC and NCERCC [3]. In our study, with a median follow-up time of 52 months, no significant differences were detected in PFS and OS between the two groups. However, the OS of patients with CERCC tended to be longer than that of patients with NCERCC, possibly because of the earlier stages of CERCC.
This study had several limitations. First, this study was retrospective; hence, recall errors may have occurred and affected the results. Second, owing to the long survival time of localized RCC, the follow-up time was relatively short, which affected the survival analysis. Third, compared with the sample size of patients with NCERCC, the number of patients with CERCC was smaller, which may have caused a selection bias. Fourth, the patients with CERCC and NCERCC included in this study were treated with partial nephrectomy and radical nephrectomy; these different surgical methods may have affected the prognosis.
In conclusion, compared to NCERCCs, CERCCs have smaller tumor sizes and earlier pathological stages. The distribution of the pathological types of CERCC is quite different from that of NCERCC. Although there was no significant difference in the pathological grade between the two groups, CERCC was less likely to be pathological grade IV. The prognosis of patients with CERCC tends to improve. Therefore, CERCC may be a special type of RCC, which needs to be treated differently in terms of treatment and clinical pathology.