Clinical and Genomic Predictors of Pathologic Upstaging in Newly Diagnosed High-grade T1 Non-Muscle Invasive Bladder Cancer

By GU Oncology Now Editors - Last Updated: January 19, 2022

There are factors that can be used to risk stratify patients with high-grade T1 non-muscle invasive bladder cancer (NMIBC) and thus direct treatment, according to the latest findings from a study presented by Carissa Chu, MD, Urology Fellow in The David Solit Lab, Memorial Sloan Kettering Cancer Center (MSKCC), New York, The study has been looking at potential clinical and genomic predictors of upstaging on immediate radical cystectomy.

High-grade NMIBC is associated with high rates of being understaged on pathology obtained during initial transurethral resection as well as high risk of progression, evidence that supports early radical cystectomy rather than intravesical BCG in these patients. Dr Chu noted that current clinical and pathologic factors do not reliably risk stratify patients to radical cystectomy versus bladder-sparing approaches. This study aimed to identify clinical, histologic, and genomic predictors in patients who underwent immediate radical cystectomy for high-grade T1 NMIBC.

Dr Chu and her colleagues at MSKCC collected data from patients diagnosed with high-grade T1 NMIBC between 2010 and 2020 who underwent immediate radical prostatectomy without any prior intravesical therapy. All patients underwent restaging transurethral resection of bladder tumor (TURBT) with pathology review. Patients clinically upstaged by bimanual exam or cross-sectional imaging (CT or MRI) were excluded from the study. Variables collected included general demographics such as age at diagnosis, sex, and ethnicity and clinical characteristics such as smoking history, comorbidities, date of diagnosis, prior recurrences, imaging findings, time to re-resection, tumor multifocality, depth of invasion, presence of variant histology, time to radical cystectomy, and follow-up time. The primary outcome of interest was pathologic upstaging to pT2+ and/or the presence of nodal positive disease (pN+). In addition, Dr Chu and her colleagues looked at a targeted exome sequencing panel of up to 468 cancer genes. Secondary outcomes included overall survival and the development of recurrence or metastases during follow-up.

Over the 10-year period, 829 patients were diagnosed with clinical high-grade T1 bladder cancer, 174 of whom underwent immediate radical cystectomy. Targeted exome sequencing was available for 60 patients, of whom 25 (41%) were pathologically upstaged to pT2+ and/or pN+ at the time of radical cystectomy.

At a median follow-up time of 26 months, 7 (11%) had local or nodal recurrence and 4 (6%) had distant metastases 23% of the upstaged group vs 13% of the non- upstaged group). Variant histology was identified in 18 (28%) and was in it of itself significantly associated with upstaging (P<0.01). Tumor mutational burden was higher among patients who were upstaged compared with those who were not (P<0.01). There were notable differences in genomic alterations between upstaged and non-upstaged patients and in those who experienced recurrence or progression after radical cystectomy.

The MSKCC researchers have concluded that for patients with high-grade T1 NMIBC, who are known to be at high risk of progression and upstaging at time of immediate radical prostatectomy, variant histology and tumor mutational burden are associated with upstaging. The unique genomic alterations observed highlight the divergent tumor biology, Dr Chu noted. This study is continuing to examine oncogenic drivers and biomarkers in the expanding patient cohort.



Chu C, De Jesus Escano M, Jiang S, et al. Clinical and genomic predictors of pathologic upstaging in newly diagnosed high grade T1 non-muscle invasive bladder cancer treated with immediate radical cystectomy. Poster #42 presented at the 22nd Annual Meeting of the Society of Urologic Oncology (SUO), December 103, 2021, Orlando, FL.