ASCO GU 2020: Germline DNA Copy Number Polymorphism to Predict the Efficacy of BCG Therapy for Non-Muscle Invasive Bladder Cancer

San Francisco, CA (UroToday.com) Bacillus Calmette-Guerin (BCG) intravesical instillation is the most effective immunotherapy for non-muscle-invasive bladder cancer (NMIBC), however, there are few reliable markers to elucidate the efficacy of BCG therapy. Germline copy number polymorphisms are expected to affect various diseases including human malignancies, but the significance of copy number polymorphisms in NMIBC patients treated with BCG therapy remains unclear. FAM81A located on chromosome 15q22.2 was previously reported as one of tumor-associated shared target genes in prostate cancer. Also, PCSK6 located on chromosome 15q26.3 was reported to regulate proliferation and tumor progression in several cancers. At the bladder cancer session at GU ASCO 2020, Dr. Yoshiaki Yamamoto and colleagues from Japan presented results of their study assessing the prognostic value of copy number polymorphisms for NMIBC treated with BCG therapy.

For this study, array comparative genomic hybridization was performed to search for candidate whole genome-wide copy number polymorphisms related to NMIBC susceptibility. Next, the investigators used quantitative real-time polymerase chain reaction to evaluate the effect of BCG therapy for 57 Japanese patients with NMIBC treated with BCG intravesical instillation.

There were 11 copy number polymorphisms associated with NMIBC risk in array comparative genomic hybridization. FAM81A and PCSK6 copy number according to those copy number polymorphisms examined showed significant relationship with disease progression in NMIBC treated with BCG. The means of the relative copy numbers of patients with copy number polymorphisms and those without it were 1.58 and 2.10 for FAM81A (p < 0.0001), and 1.06 and 1.80 for PCSK6 (p < 0.0001). Univariate Cox proportional hazards regression analysis showed that FAM81A (p = 0.0022), and PCSK6 (p = 0.0147) copy number had a significant effect on progression-free survival. In multivariate analyses, FAM81A copy number was an independent prognostic factor for progression-free survival (RR 7.59, 95% CI 1.07–153.42, p = 0.0419,). The combination of FAM81A or PCSK6 copy number polymorphisms was the most significant prognostic biomarker to predict the efficacy of BCG therapy for NMIBC (p = 0.0002). The Kaplan Meier curves for PFS for FAM81A, PCSK6 and the combination of FAM81A/PCSK6 are as follows:

ASCO GU 2020 fig 2 PFS 3 graphs

Dr. Yamamoto concluded this presentation with several summary take-home messages:

  • Eleven copy number polymorphisms were associated with NMIBC risk
  • FAM81A and PCSK6 copy number showed a significant relationship with recurrence and disease progression in NMIBC
  • FAM81A and PCSK6 copy number according to those copy number polymorphisms examined showed a significant relationship with disease progression in NMIBC patients treated with BCG therapy
  • The combination of FAM81A and PCSK6 copy number polymorphisms was the most significant prognostic biomarker to predict the efficacy of BCG therapy for NMIBC
  • These data suggest that germline DNA copy number polymorphisms may be a potential new biomarker for estimating the efficacy of BCG therapy in Japanese patients with NMIBC
  • To the investigator’s knowledge, this is the first report to confirm copy number polymorphisms as a potential biomarker for assessing the efficacy of immunotherapy


Presented by: Yoshiaki Yamamoto, MD, Yamaguchi University, Yamaguchi, Japan

Written by: Zachary Klaassen, MD, MSc – Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, Twitter: @zklaassen_md  at the 2020 Genitourinary Cancers Symposium, ASCO GU #GU20, February 13-15, 2020, San Francisco, California
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