Stesura Seveso Archivio Italiano di Urologia e Andrologia 2023; 95, 2 57 ORIGINAL PAPER was a significant risk factor (7, 8). However, the results of multivariable analyses assessing the prognostic signifi- cance of type2 pRCC histological subtype are incoherent (9, 10). In this context, outcomes may vary depending on the pRCC type and tumor stage. The aim of this study was to compare OS, CSS and RFS of patients diagnosed with pRCC and ccRCC and define the factors affecting survival in the patient population with localized disease. MATERIALS AND METHODS Patients with renal cell carcinoma (RCC), who underwent radical or partial nephrectomy due to renal tumors, whose data were obtained from a series of 5300 patients with kidney tumors included in the Urologic Cancer Database - Kidney (UroCaD-K) of Turkish Urooncology Association (TUOA) were evaluated retrospectively. Pathological stage and grade were determined according to the 2002 Union Internationale Contre le Cancer TNM Classification, and Fuhrman classification (G1-G4), respectively. Tumor size was measured using the computed tomography (CT) and taking the largest diameter. Histological subtypes were classified according to the Heidelberg classification (1): ccRCC, pRCC, chromo- phobe, Bellini duct, and unclassified RCC. Patients from UroCaD-K database, who had pathological T1-T2 ccRCC and pRCC were evaluated in the study. According to the two histological subtype, recurrence and mortality status, recurrence free survival (RFS), overall survival (OS) and cancer-specific survival (CSS) data were analyzed. The fol- low-up protocol of the patients was arranged according to the EAU-RCC guideline. Statistical analysis Analyses were performed by the using of Statistical Package for the Social Sciences (SPSS) version 22.0. Chi- Objectives: To compare overall survival (OS), recurrence free survival (RFS), and cancer-specific survival (CSS) in the long-term follow-up of T1 and T2 clear-cell-Renal Cell Carcinoma (ccRCC) and papillary Renal Cell Carcinoma (pRCC) patients, as well as to determine the risk factors for recurrence and overall mortality. Material and method: Data of patients with kidney tumors obtained from the Urologic Cancer Database - Kidney (UroCaD-K) of Turkish Urooncology Association (TUOA) were evaluated retrospectively. Out of them, patients who had patho- logical T1-T2 ccRCC and pRCC were included in the study. According to the two histological subtype, recurrence and mor- tality status, RFS, OS and CSS data were analyzed. Results: RFS, OS and CSS of pRCC and ccRCC were found to be similar. Radiological local invasion was shown to be a risk fac- tor for recurrence in pRCC, and age was the only independent factor affecting overall mortality. Conclusions: There were no differences in survivals (RFS, OS and CSS) of patients with localized papillary and clear cell RCC. While age was the only factor affecting overall mortality, radiological local invasion was a risk factor for recurrence in papillary RCC. KEY WORDS: Kidney cancer; Renal cell carcinoma; Clear cell RCC; Papillary type RCC; Recurrence, Survival. Submitted 26 January 2023; Accepted 17 February 2023 INTRODUCTION Almost twenty years ago the Heidelberg classification sys- tem recognized the histological subtypes of Renal Cell Carcinoma (RCC) as clear cell (cc)-RCC, with a frequency of 70-88% in most series, papillary (p)-RCC accounting for 10-15% and other RCC accounting for less than 10% (1, 2). Several studies have uniformly reported that a pRCC his- tology is associated with a favorable prognosis compared with clear cell RCC (ccRCC) (3-6). In other studies, pRCC Oncological outcomes of papillary versus clear cell renal cell carcinoma in pT1 and pT2 stage: Results from a contemporary Turkish patient cohort Taha Cetin 1, Serdar Celik 1, Sinan Sozen 2, Bulent Akdogan 3, Volkan Izol 4, Guven Aslan 5, Evren Suer 6, Yildirim Bayazit 4, Nihat Karakoyunlu 7, Haluk Ozen 3, Sumer Baltaci 6, Fatih Gokalp 8, Ilker Tinay 9, Members of Turkish Urooncology Association 1 Izmir Bozyaka Research and Training Hospital Urology Department, Izmir, Türkiye; 2 Gazi University Faculty of Medicine Urology Department, Ankara, Türkiye; 3 Hacettepe University Faculty of Medicine Urology Department, Ankara, Türkiye; 4 Cukurova University Faculty of Medicine Urology Department, Adana, Türkiye; 5 Dokuz Eylul University Faculty of Medicine Urology Department, Izmir, Türkiye; 6 Ankara University Faculty of Medicine Urology Department, Ankara, Türkiye; 7 University of Health Sciences Dıskapi Yildirim Beyazit Research and Training Hospital Urology Department, Ankara, Türkiye; 8 Mustafa Kemal University Tayfur Ata Sokmen Medicine Faculty Urology Department, Hatay, Türkiye; 9 Marmara University Faculty of Medicine Urology Department, Istanbul, Türkiye. DOI: 10.4081/aiua.2023.11218 Summary Archivio Italiano di Urologia e Andrologia 2023; 95, 2 T. Cetin, S. Celik, S. Sozen, et al. 58 square and Student t-tests were used to compare categor- ical and continuous data, respectively. The relationship between tumor size and histological subtype was ana- lyzed with logistic regression models. The Kaplan-Meier method was used to estimate tumor specific survival, and comparison was performed by the log-rank test. Multivariate Cox proportional hazard models were used to detect independent variables with a p < 0.05 consid- ered to indicate statistical significance. RESULTS The clinical, pathological and oncological data of the patients are shown in Table 1. Among 5300 patients, 2129 patients who had pathological T1-T2 ccRCC and pRCC were included in the study. The mean age was 57.7 ± 11.8 years and two-thirds of the patients were male. There were 1700 patients with ccRCC, while the pRCC was observed in 429 patients. Patients in the ccRCC group were younger and had a higher BMI. (p values were < 0.001 and 0.004, respectively). Radiological tumor size was statistically found to be smaller in pRCC than ccRCC group (mean size were 4.7 cm vs 5cm, p = 0.001). We detected that radiologically < 4 cm tumors were more frequent in the pRCC group that ccRCC (p = 0.034). The finding of radiological local invasion was also more common in ccRCC, but there was no statistically difference (5.4% vs 3.5%). There was no statistically difference between the groups when we evaluated them in terms of pathological tumor size and Fuhrman grade. Considering the postoperative follow-up periods, the mean follow-up time for ccRCC and pRCC were 25.2 months and 26.1 months, respectively (p = 0.613). Pathological T stage and radiological local inva- sion were found to be risk factors for recurrence in ccRCC. Age, radiological local invasion and Fuhrman grade 3-4 were found to be independ- ent risk factors affecting overall mortality in patients with ccRCC. In pRCC patients, radio- logical local invasion was found to be an inde- pendent risk factor for recurrence and age was a risk factor for overall mortality (Table 2). In addition, RFS, OS and CSS were not statisti- cally different between the groups (Figure 1). DISCUSSION We aimed to discuss OS, CSS and RFS of patients diagnosed with pRCC and ccRCC and define the factors affecting survival in patient population with pT1 and pT2 disease. It was observed that ccRCC was seen in younger patients and in patients with higher BMI, and that pRCC was more common in males. Papillary type pathology was radiologically smaller and was more frequently evaluated as pT1a than clear cell type. Radiological local inva- sion and age were found to be independent risk factors for recurrence and overall mortality, respectively for both groups. Pathological stage was also a risk factor for recurrence in ccRCC. In addition, during the follow-up, OS, CSS and RFS were not statistically different for both groups in pT1 and pT2 disease. The two most important factors determining the outcome of RCC are nuclear grade and tumor stage (11). According to some authors, apart from these two factors, histological subtype was also an independent prognostic factor (12). Table 1. Clinical, pathological and oncological data of the patients. ccRCC (n = 1700) pRCC (n = 429) P Age (year) 56.7 ± 12 59.6 ± 11.8 < 0.001 Sex, n (%) Female 641 (37.9) 72 (16.8) < 0.001 Male 1048 (62.1) 356 (83.2) BMI (kg/m2) 28.3 ± 5 27 ± 4 0.004 Radiological tumor size (cm) 5 ± 3 4.7 ± 3 0.001 Tumor diameter, n (%) < 4 cm 787 (46.4) 226 (52.6) 0.034 4-7 cm 626 (36.8) 126 (29.4) 7-10 cm 209 (12.3) 55 (12.8) > 10 cm 77 (4.5) 22 (5.2) Radiological Organ confined, n (%) Localized 1609 (94.6) 414 (96.5) 0.114 Locally invasive 91 (5.4) 15 (3.5) Pathological tumor size (cm) 5±2.8 5.2±3.2 0.155 Pathological T stage, n (%) T1a 806 (37.1) 216 (43.4) 0.05 T1b 606 (28.4) 129 (25.7) T2a 214 (10.9) 55 (11.6) T2b 74 (4.1) 29 (6.3) Fuhrman Grade, n (%) 1-2 986 (70.4) 177 (67.8) 0.385 3-4 413 (29.6) 70 (32.2) Relapse, n (%) 33 (1.94) 10 (2.33) 0.608 Overall mortality, n (%) 37 (2.17) 11 (2.6) 0.629 Cancer specific mortality, n (%) 10 (0.6) 2 (0.5) 0.556 Mean follow-up time (months) 25.2 ± 30.3 26.1 ± 30.7 0.613 Table 2. Factors affecting recurrence and overall mortality in ccRCC and pRCC groups. Histologic subtype Recurrence Overall mortality Univariate Multivariate Univariate Multivariate P value OR (CI) P value OR (CI) ccRCC • Age 0.958 - 0.002 1.056 (1.023-1.090) • Sex 0.370 - 0.084 - • BMI 0.279 - 0.471 - • Pathological tumor size 0.071 - 0.105 - • Pathological stage 0.044 1.447 (1.006-2.081) 0.091 - • Radiological local inv. 0.007 4.136 (1.663-10.287) 0.044 - • Fuhrman 3-4 0.952 - 0.033 - pRCC • Age 0.444 - 0.026 1.066 (1.009-1.127) • Sex 0.069 - 0.128 - • BMI 0.270 - 0.131 - • Pathological tumor size 0.776 - 0.275 - • Pathological stage 0.423 - 0.474 - • Radiological local inv. 0.044 7.808(1.507-40.450) 0.673 - • Fuhrman 3-4 0.406 - 0.681 - Archivio Italiano di Urologia e Andrologia 2023; 95, 2 59 Papillary clear cell carcinoma outcomes Type 1 pRCC is associated with MET alteration or tri- somy of chromosome 7 where the MET gene is located, while Type2 pRCC shows allelic imbalance on chromo- somes 1p, 3p, 5, 6, 8, 9p, 10, 11, 15, 18 and 22 (13, 14). According to the study shared by Waldert et al. 5-year CSS was 94% in type 1 pRCC and 74% in type 2 pRCC (p = 0.027). During the follow-up, the overall CSS for M0 patients with pRCC and ccRCC (90% vs 84% respective- ly) was not significantly different). Steffens et al. evaluated long-term survival of pRCC versus ccRCC. In this series, patients with pRCC had significantly higher 5-yr CSS rate (85.1% vs 76.3%; p = 0.001). Notably, at multivariable analysis, the papillary subtype was significantly associat- ed with favorable oncologic outcome in localized RCC but was an independent negative prognostic factor in metastatic patients. These results could be evaluated separately for papillary type 1 and type 2, but this was not evaluated in the study (14). In addition, authors have shown that type 1 and type 2 RCC have similar clinical and histopathological features, but lymphovascular invasion (LVI) in type 2 pRCC wors- ened CSS rate, compared to type1 pRCC (5). In a multicenter study involving more than four thousand patients from eight international centers, patients with pRCC had better 5-year CSS than patients with ccRCC in univariate analysis (73% versus 79% respectively). In multivariate analysis, the histological subtype was not an independent prognostic factor (15). Five studies with 32.158 patients indicated that pRCC had a better prognosis than ccRCC (3, 6, 16-18), while other 5 studies including 3674 patients showed that pRCC was an independent predictor of poor outcomes (4, 7, 8, 19, 20). According to the results of the meta- analysis including these studies, pRCC was associated with better outcomes than ccRCC in patients with non- metastatic disease, but not in patients with metastatic dis- ease. Type 2 pRCC had worse prognosis than ccRCC, but no significant difference was found with type 1 pRCC. In this study, it was observed that the tumor size was smaller in pRCC. In the study of Waldert et al. tumor size was also smaller in pRCC (mean 4.5 cm) compared to ccRCC (mean 5.5 cm) (p = 0.013) (14). Traditionally, p-RCC is divided into 2 types: type 1 is characterized by a basophilic cytoplasm and is classified as a low-grade tumor, while type 2 displays a bulky eosinophilic cytoplasm and pseudostratified tumor cell nuclei and is considered a high-grade tumor (3). Compared to type 1 p-RCC, type 2 p-RCC presents more frequently as a locally advanced disease and is associated with more aggressive clinicopathologic features and sig- nificantly worse outcome (9, 10, 14, 21). Our study had some limitations. Most important limita- tions are the retrospective analysis and the multi-centered design with pathological evaluation not performed in a single centre. Evaluation of the patients by experts in uro- oncology may reduce the disadvantage of multi-center data analysis. 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Correspondence Taha Cetin, MD, FEBU (Corresponding Author) tahacetin88@gmail.com Serdar Celik, MD serdarcelik84@hotmail.com Izmir Bozyaka Research and Training Hospital Urology Department, Izmir, Türkiye Sinan Sozen, MD sinansozen@usa.net Gazi University Faculty of Medicine Urology Department, Ankara, Türkiye Bulent Akdogan, MD blntakdogan@yahoo.com Haluk Ozen, MD drhalukozen@gmail.com Hacettepe University Faculty of Medicine Urology Department, Ankara, Türkiye Volkan Izol, MD volkanizol@yahoo.com Yildirim Bayazit, MD ybayazit@yahoo.com Cukurova University Faculty of Medicine Urology Department, Adana, Türkiye Guven Aslan, MD drguvenaslan@gmail.com Dokuz Eylul University Faculty of Medicine Urology Department, Izmir, Türkiye Evren Suer, MD drevrensuer@gmail.com Sumer Baltaci, MD baltacisumer@gmail.com Ankara University Faculty of Medicine Urology Department, Ankara, Türkiye Nihat Karakoyunlu, MD nkarakoyunlu@gmail.com University of Health Sciences Dıskapi Yildirim Beyazit Research and Training Hospital Urology Department, Ankara, Türkiye Fatih Gokalp, MD fatihgokalp85@gmail.com Mustafa Kemal University Tayfur Ata Sokmen Medicine Faculty Urology Department, Hatay, Türkiye Ilker Tinay, MD ilker_tinay@yahoo.com Marmara University Faculty of Medicine Urology Department, Istanbul, Türkiye Conflict of interest: The authors declare no potential conflict of interest.