We aimed to clarify the clinical characteristics and oncological outcomes of upper tract urothelial carcinoma (UTUC) patients who developed muscle-invasive bladder cancer (MIBC) after radical nephroureterectomy (RNU). We identified 966 pTa-4N0-2M0 UTUC patients who underwent RNU and clarified the risk factors for MIBC progression after initial intravesical recurrence (IVR). We also identified 318 primary pT2-4N0-2M0 MIBC patients to compare the oncological outcomes with those of UTUC patients who developed or progressed to MIBC. Furthermore, immunohistochemical examination of p53 and FGFR3 expression in tumor specimens was performed to compare UTUC of MIBC origin with primary MIBC. In total, 392 (40.6%) patients developed IVR after RNU and 46 (4.8%) developed MIBC at initial IVR or thereafter. As a result, pT1 stage on the initial IVR specimen, concomitant carcinoma in situ on the initial IVR specimen, and no intravesical adjuvant therapy after IVR were independent factors for MIBC progression. After propensity score matching adjustment, primary UTUC was a favorable indicator for cancer-specific death compared with primary MIBC. Subgroup molecular analysis revealed high FGFR3 expression in NMIBC and MIBC specimens from primary UTUC, whereas low FGFR3 but high p53 expression was observed in specimens from primary MIBC. In conclusion, our study demonstrated that UTUC patients who develop MIBC recurrence after RNU exhibit the clinical characteristics of subsequent IVR more than those of primary UTUC. Of note, MIBC subsequent to UTUC may have favorable outcomes, probably due to the different molecular biological background compared from primary MIBC.
Cancer science. 2020 Dec 25 [Epub ahead of print]
Keisuke Shigeta, Kazuhiro Matsumoto, Koichiro Ogihara, Tetsushi Murakami, Tadatsugu Anno, Kota Umeda, Mizuki Izawa, Yuto Baba, Tansei Sanjo, Kazunori Shojo, Nobuyuki Tanaka, Toshikazu Takeda, Takeo Kosaka, Ryuichi Mizuno, Shuji Mikami, Eiji Kikuchi, Mototsugu Oya
Department of Urology, Keio University School of Medicine, Tokyo, Japan., Department of Urology, Saitama City Hospital, Saitama, Japan., Department of Urology, Kawasaki Municipal Hospital, Kanagawa, Japan., Department of Urology, International University of Health and Welfare Mita Hospital, Tokyo, Japan., Department of Urology, Isehara Kyodo Hospital, Kanagawa, Japan., Department of Urology, Tokyo Dental College, Ichikawa General Hospital, Chiba, Japan., Division of Diagnostic Pathology, Keio University School of Medicine, Tokyo, Japan., Department of Urology, St. Marianna University School of Medicine, Kanagawa, Japan.