APCCC 2021: The Role of Somatic Tumor Testing – Implications for Treatment With PARP Inhibitors

(UroToday.com) In this session, Dr. Hussain discussed somatic testing in prostate cancer. Tumor genomic profiling is central to successful implementation of personalized for men diagnosed with prostate cancer.

The era of precision medicine in prostate cancer began in 2017 when Pembrolizumab received FDA approval for patients with high microsatellite instability (MSI-high) or mismatch repair deficient (MMRd) solid tumors. Abida et al subsequently demonstrated that these alterations are present in only 3% of men with mCRPC. In May 2020 olaparib and rucaparib both received FDA approval for men with homologous recombination deficient (HRd) prostate cancer. As such, current NCCN Guidelines recommend somatic tumor testing for MSI-h, MMRd, and HRd alterations. The NCCN Guidelines recommend molecular tumor analysis for patients with metastatic prostate and suggest it should be considered for those with node-positive disease. The AUA/ASTRO/SUO 2020 Guidelines state the following as expert opinion: “In patients with mCRPC, clinicians should offer germline and somatic tumor genetic testing to identify DNA repair deficiency mutations and microsatellite instability status that may inform prognosis and counseling regarding family risk as well as potential targeted therapy.”

 

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There are several important considerations in what and how somatic testing should be performed. Dr. Hussain reported results of an analysis of samples from the PROfound study that found a higher success rate (samples passing quality control metrics) for new samples compared to older samples. Success rates dropped from 71% for samples less than one year old to 47% in those greater than ten years old. Newly collected samples performed better than archived samples. There were also notable differences by site of tissue. Notoriously challenging to work with for molecular analysis, bone biopsies were successfully analyzed 43% of the time compared to 56% for prostate samples, and 75% for lymph node specimens.

 

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Dr. Hussain concluded by summarizing lessons learned from the PROfound study that are important to consider when planning somatic tumor testing:

  • Testing success rates were higher in newly collected tissue compared to archival tissue
  • “Younger” archival samples, less than five years old perform better than older samples
  • Metastatic samples have higher success rate than primary samples, which may be due to higher cellularity and tumor content or that they are more likely to be newly collected
  • Methods of collecting and processing are important – core needle biopsies are preferable to needle aspiration samples
  • Finally, it is critical to avoid strong decalcification of bone biopsies – for newly collected bone samples, it is recommended that decalcification not be performed

 

Presented by: Maha Hussain, MD, FACP, FASCO, Genevieve Teuton Professor of Medicine in the Division of Hematology Oncology, Department of Medicine, and the Deputy Director at the Robert H. Lurie Comprehensive Cancer Center of the Northwestern University Feinberg School of Medicine

Written by: Jacob Berchuck, MD, Genitourinary Medical Oncologist, Dana-Farber Cancer Institute (Twitter: @jberchuck) during the 2021 Advanced Prostate Cancer Consensus Conference, Saturday, October 9, 2021.


References:
  1. Abida W, et al. Analysis of the Prevalence of Microsatellite Instability in Prostate Cancer and Response to Immune Checkpoint Blockade. JAMA Oncol. 2019 Apr 1;5(4):471-478.

 

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