Metric substage according to micro and extensive lamina propria invasion improves prognostics in T1 bladder cancer

Elisabeth E Fransen van de Putte; Wolfgang Otto; Arndt Hartmann; Simone Bertz; Roman Mayr; Johannes Bründl; Johannes Breyer; Quentin Manach; Eva M Compérat; Joost L Boormans; Judith Bosschieter; Michael A S Jewett; Robert Stoehr; Geert J L H van Leenders; Jakko A Nieuwenhuijzen; Alexandre R Zlotta; Kees Hendricksen; Morgan Rouprêt; Maximilian Burger; Theo H van der Kwast; Bas W G van Rhijn

doi:10.1016/j.urolonc.2018.05.007

Metric substage according to micro and extensive lamina propria invasion improves prognostics in T1 bladder cancer

Urol Oncol. 2018 Aug;36(8):361.e7-361.e13. doi: 10.1016/j.urolonc.2018.05.007. Epub 2018 Jun 5.

Authors

Elisabeth E Fransen van de Putte¹, Wolfgang Otto², Arndt Hartmann³, Simone Bertz³, Roman Mayr², Johannes Bründl², Johannes Breyer², Quentin Manach⁴, Eva M Compérat⁵, Joost L Boormans⁶, Judith Bosschieter⁷, Michael A S Jewett⁸, Robert Stoehr³, Geert J L H van Leenders⁹, Jakko A Nieuwenhuijzen¹⁰, Alexandre R Zlotta¹¹, Kees Hendricksen¹, Morgan Rouprêt⁴, Maximilian Burger², Theo H van der Kwast¹², Bas W G van Rhijn¹³

Affiliations

¹ Department of Surgical Oncology (Urology), Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
² Department of Urology, Caritas St. Josef Medical Centre, University of Regensburg, Regensburg, Germany.
³ Department of Pathology, University of Erlangen, Erlangen, Germany.
⁴ Academic Department of Urology, Pitié-Salpétrière Hospital, Assistance-Publique Hôpitaux de Paris, Pierre et Marie Curie Medical School, Sorbonne University, Paris, France.
⁵ Department of Pathology, Hôpital Tenon, HUEP, UPMC Paris VI, Paris, France.
⁶ Department of Urology, Erasmus MC Cancer Institute, Erasmus MC, Rotterdam, The Netherlands.
⁷ Department of Surgical Oncology (Urology), Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands; Department of Urology, VU University Medical Centre, Amsterdam, The Netherlands.
⁸ Department of Surgical Oncology (Urology), University Health Network, Princess Margaret Cancer Center, University of Toronto, Toronto, Canada.
⁹ Department of Pathology, Erasmus MC Cancer Institute, Erasmus MC, Rotterdam, The Netherlands.
¹⁰ Department of Urology, VU University Medical Centre, Amsterdam, The Netherlands.
¹¹ Department of Surgical Oncology (Urology), University Health Network, Princess Margaret Cancer Center, University of Toronto, Toronto, Canada; Department of Urology, Mount Sinai Hospital, University of Toronto, Toronto, Canada.
¹² Department of Pathology, Erasmus MC Cancer Institute, Erasmus MC, Rotterdam, The Netherlands; Department of Pathology, University Health Network, Princess Margaret Cancer Center, University of Toronto, Toronto, Canada.
¹³ Department of Surgical Oncology (Urology), Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands; Department of Urology, Caritas St. Josef Medical Centre, University of Regensburg, Regensburg, Germany; Department of Urology, Erasmus MC Cancer Institute, Erasmus MC, Rotterdam, The Netherlands; Department of Surgical Oncology (Urology), University Health Network, Princess Margaret Cancer Center, University of Toronto, Toronto, Canada. Electronic address: basvanrhijn@hotmail.com.

PMID: 29880460
DOI: 10.1016/j.urolonc.2018.05.007

Abstract

Background: Reliable prognosticators for T1 bladder cancer (T1BC) are urgently needed.

Objective: To compare the prognostic value of 2 substage systems for T1BC in patients treated by transurethral resection (TUR) and adjuvant bacillus Calmette-Guérin therapy.

Design, setting, and participants: The slides of 601 primary T1BCs from four institutes were reviewed by 2 uropathologists and substaged according to 2 classifications: metric substage according to T1 microinvasive (T1m-lamina propria invasion <0.5mm) and T1 extensive invasive (pT1e-invasion ≥ 0.5mm), and according to invasion of the muscularis mucosae (MM) (T1a-invasion above or into MM/T1b).

Outcome measurements and statistical analysis: Multivariable analyses for progression-free (PFS) and cancer-specific survival (CSS) were performed including substage, size, multiplicity, carcinoma in situ, sex, age, WHO-grade 1973, and WHO-grade 2004 as variables.

Results: Median follow-up was 5.9 years (interquartile range: 3.3-9.0). Progression to T2BC was observed in 148 (25%) patients and 94 (16%) died of BC. The MM was not present at the invasion front in 135 (22%) of tumors. Slides were substaged as follows: 213 T1m and 388 T1e and 281 T1a and 320 T1b. On multivariable analysis, T1m/e substage and WHO 1973 grade were the strongest prognosticators for PFS (hazard ratio [HR] = 3.8 and HR = 1.8) and CSS (HR = 2.7 and HR = 2.6), respectively. Other prognostic factors for CSS were age (HR = 1.03), and tumor size (HR = 1.8). Substage according to MM-invasion was not significant. Our study was limited by its retrospective design and that standard re-TUR was not performed if TUR was macroscopically complete and muscularis propria was present in resected specimens.

Conclusions: Metric substaging of T1BC was possible in all cases of 601 T1BC patients and it was a strong independent prognosticator of both PFS and CSS.

Keywords: Bladder cancer; Grade; Prognosis; Stage; T1; Urothelial, Substage; WHO.

MeSH terms

Aged
Disease Progression
Female
Humans
Male
Mucous Membrane / physiopathology*
Neoplasm Staging
Prognosis
Urinary Bladder Neoplasms / physiopathology*