UROSCAN and UROSCANSEQ: a large-scale multicenter effort towards translation of molecular bladder cancer subtypes into clinical practice – from biobank to RNA-sequencing in real time

Abstract

Background

Bladder cancer is molecularly one of the most heterogenous malignancies characterized by equally heterogenous clinical outcomes. Standard morphological assessment with pathology and added immunohistochemical analyses is unable to fully address the heterogeneity, but up to now treatment decisions have been made based on such information only. Bladder cancer molecular subtypes will likely provide means for a more personalized bladder cancer care.

Methods

To facilitate further development of bladder cancer molecular subtypes and clinical translation, the UROSCAN-biobank was initiated in 2013 to achieve systematic biobanking of preoperative blood and fresh frozen tumor tissue in a population-based setting. In a second phase, we established in 2018 a parallel logistic pipeline for molecular profiling by RNA-sequencing, to develop and validate clinical implementation of molecular subtyping and actionable molecular target identification in real-time.

Results

Until June 2021, 1825 individuals were included in the UROSCAN-biobank, of which 1650 (90%) had primary bladder cancer, 127 (7%) recurrent tumors, and 48 (3%) unknown tumor status. In 159 patients, multiple tumors were sampled, and metachronous tumors were collected in 83 patients. Between 2016 and 2020 the UROSCAN-biobanking included 1122/2999 (37%) of all primary bladder cancer patients in the Southern Healthcare Region. Until June 2021, the corresponding numbers subjected to RNA-sequencing and molecular subtyping was 605 (UROSCANSEQ), of which 52 (9%) samples were not sequenced due to inadequate RNA-quality (n = 47) or technical failure/lost sample (n = 5).

Conclusions

The UROSCAN-biobanking and UROSCANSEQ-infrastructure for molecular subtyping by real-time RNA-sequencing represents, to our knowledge, the largest effort of evaluating population-wide molecular classification of bladder cancer.

Keywords:

• Bladder cancer
• biobank
• RNA-sequencing
• molecular subtyping
• real-time

Acknowledgements

The authors thank the patients who have chosen to be part of the current effort and the Center for Translational Genomics, Lund University and Clinical Genomics Lund, SciLifeLab for providing sequencing service. The authors also thank the collaborators within urology, pathology, and clinical chemistry at the hospitals in Eksjö, Karlskrona, Växjö, Ljungby, Ängelholm, Helsingborg, Kristianstad, Landskrona, Ystad and Malmö for including patients and sampling tissue and blood and the Region Skåne Biobank for storage of samples and the Regional Cancer Center South for INCA data.

Disclosure satatement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The study was supported by Swedish Cancer Society [grant numbers CAN 2017/278, 2020/0709 and 2020/0710], Lund Medical Faculty (ALF), The Crafoord Foundation (ref 20130591 and 20140532), Skåne University Hospital Foundation, Gester Research Foundation, The Gorthon Foundation, Gyllenstierna Krapperup’s Foundation [KR2017-0031, KR2018-0050, KR2019-0019], Sten K Johnsson Foundation, Sigurd and Elsa Golje Foundation [LA2017-0222], Hjelm Foundation, Magnus Bergvall Foundation, Maud and Birger Gustavsson Foundation, Malmö General Hospital Cancer Foundation, Royal Physiographic Society of Lund, Skåne County Council’s Research and Development Foundation, The Swedish Research Council, Gunnar Nilsson Cancer Foundation, Gösta Jönsson Research Foundation, Foundation for Urological Research (Ove and Carin Carlsson bladder cancer donation), and Hillevi Fries Research Fund. The funding sources had no role in the study design, data analyses, interpretation of the results, or writing the manuscript.