Papillary urothelial neoplasm of low malignant potential (PUN-LMP): Still a meaningful histo-pathological grade category for Ta, noninvasive bladder tumors in 2019?

Hentschel, A. E.; van Rhijn, B. W. G.; Brundl, J.; Comperat, E. M.; Plass, K.; Rodriguez, O.; Henriquez, J. D. S.; Hernandez, V.; de la Pena, E.; Alemany, I.; Turturica, D.; Pisano, F.; Soria, F.; Capoun, O.; Bauerova, L.; Pesl, M.; Bruins, H. M.; Runneboom, W.; Herdegen, S.; Breyer, J.; Brisuda, A.; Scavarda-Lamberti, A.; Calatrava, A.; Rubio-Briones, J.; Seles, M.; Mannweiler, S.; Bosschieter, J.; Kusuma, V. R. M.; Ashabere, D.; Huebner, N.; Cotte, J.; Mertens, L. S.; Cohen, D.; Lunelli, L.; Cussenot, O.; Sheikh, S. E.; Volanis, D.; Cote, J. -F.; Roupret, M.; Haitel, A.; Shariat, S. F.; Mostafid, A. H.; Nieuwenhuijzen, J. A.; Zigeuner, R.; Dominguez-Escrig, J. L.; Hacek, J.; Zlotta, A. R.; Burger, M.; Evert, M.; Hulsbergen-van de Kaa, C. A.; van der Heijden, A. G.; Kiemeney, L. A. L. M.; Soukup, V.; Molinaro, L.; Gontero, P.; Llorente, C.; Algaba, F.; Palou, J.; N'Dow, J.; Babjuk, M.; van der Kwast, T. H.; Sylvester, R. J.

doi:10.1016/j.urolonc.2019.10.002

Background: Papillary urothelial neoplasm of low malignant potential (PUN-LMP) was introduced as a noninvasive, noncancerous lesion and a separate grade category in 1998. Subsequently, PUN-LMP was reconfirmed by World Health Organization (WHO) 2004 and WHO 2016 classifications for urothelial bladder tumors. Objectives: To analyze the proportion of PUN-LMP diagnosis over time and to determine its prognostic value compared to Ta-LG (low-grade) and Ta-HG (high-grade) carcinomas. To assess the intraobserver variability of an experienced uropathologist assigning (WHO) 2004/2016 grades at 2 time points. Materials and methods: Individual patient data of 3,311 primary Ta bladder tumors from 17 hospitals in Europe and Canada were available. Transurethral resection of the tumor was performed between 1990 and 2018. Time to recurrence and progression were analyzed with cumulative incidence functions, log-rank tests and multivariable Cox-regression stratified by institution. Intraobserver variability was assessed by examining the same 314 transurethral resection of the tumorslides twice, in 2004 and again in 2018. Results: PUN-LMP represented 3.8% (127/3,311) of Ta tumors. The same pathologist found 71/314 (22.6%) PUN-LMPs in 2004 and only 20/314 (6.4%) in 2018. Overall, the proportion of PUN-LMP diagnosis substantially decreased over time from 31.3% (1990–2000) to 3.2% (2000–2010) and to 1.1% (2010–2018). We found no difference in time to recurrence between the three WHO 2004/2016 Ta-grade categories (log-rank, P = 0.381), nor for LG vs. PUN-LMP (log-rank, P = 0.238). Time to progression was different for all grade categories (log-rank, P < 0.001), but not between LG and PUN-LMP (log-rank, P = 0.096). Multivariable analyses on recurrence and progression showed similar results for all 3 grade categories and for LG vs. PUN-LMP. Conclusions: The proportion of PUN-LMP has decreased to very low levels in the last decade. Contrary to its reconfirmation in the WHO 2016 classification, our results do not support the continued use of PUN-LMP as a separate grade category in Ta tumors because of the similar prognosis for PUN-LMP and Ta-LG carcinomas.