APCCC 2021: Summary of Panel Responses Regarding Tumor Molecular Testing

(UroToday.com) The third and final session of the Advanced Prostate Cancer Consensus Conference 2021 which was hosted virtually in the context of the COVID-19 pandemic focused on molecular characterization of both tissue and blood, with a focus on implications for treatment with PARP inhibitors and beyond. Following the conference presentations, Dr. Matthew Smith and Dr. Nicholas Mottet led a discussion of the consensus panel responses to questions relating to the role of tumor molecular testing.

First addressing question #87 in which there are insufficient genetic counselors, 80% of respondents suggested that it would be appropriate for physicians to order germline testing without pre-test counseling.


Next, Dr. Smith reviewed results of question #91 which showed that just over half (54%) of respondents would endorse the use of genetic counseling and germline testing for patients with intraductal/cribriform histology.


With respect to question #95 regarding the source of tissue for somatic genomic testing, there was a widespread of responses though 57% favored the use of the most recent archival tumor tissue with a new biopsy preferred by just over one-quarter of respondents (26%). Notably, only 3% of respondents preferred to use primary tumor archival tissue and 14% would prefer to use a circulating tumor DNA test.


Question #96, which addressed the question of tests to include in somatic genomic testing for patients with metastatic prostate cancer, provided a very mixed result without any clear preference or consensus from the group: 46% of panelists recommended comprehensive panel testing, 34% recommending BRCA1/2, mismatch repair evaluation, and additional DDR genes, and 20% recommending only BRCA1/2 and mismatch repair evaluation. Polling the audience, there was a similar lack of consensus.



Following a discussion of these results, Dr. Smith moved to question #101 which addresses the timing of PARP inhibitor treatment in patients with known BRCA1/2 aberrations. Here, the consensus panel was relatively closely split between those who recommended use after one line of androgen receptor pathway inhibitor (55%) and after one line of androgen receptor pathway inhibitor plus one line of chemotherapy (41%). The audience panel similarly was split between these two options.



Moving to question #103 which examined patients with known pathogenic BRCA1/2 mutations who are progressing on a PARP inhibitor after first-line androgen-pathway inhibitors, the majority of panel members (53%) preferred the use of docetaxel chemotherapy while a platinum-taxane chemotherapy combination was the second-most-popular choice (25%). The remaining treatment options were supported by a small number of respondents.



Dr. Smith then discussed question #105: among patients with pathogenic genomic ATM alterations, do you recommend treatment with a PARP inhibitor. Responses to this question were split with 33% of panelists saying yes, 29% saying yes if loss of protein function (by immunohistochemistry) or positive HRD score is noted; and 38% saying no. Notably, the audience response to this question had a large proportion of members abstaining.


Finally, Dr. Smith discussed the results of question #109 what assessed the role of platinum-based chemotherapy in patients with confirmed pathogenic aberrations in BRCA1/2 where there is no access to a PARP inhibitor. Here, 61% of respondents recommended use of platinum-based chemotherapy but only after at least one line of androgen receptor targeting agents and one line of taxane-based chemotherapy.

This concluded the discussion of the consensus panel responses in the context of the PARP inhibitors and beyond: Molecular characterization of tissue and blood session.

Presented by: Matthew R. Smith, MD, Ph.D., Professor of Medicine, Harvard Medical School, Assistant in Medicine, Hematology/Oncology, Massachusetts General Hospital, Boston, Massachusetts, USA.

Nicolas Mottet, MD, PhD, Head of the Urology Department at Centre Hospitalier Universitaire de Saint-√Čtienne, and Professor of Surgery at Universit√© Jean Monnet in Saint-Etienne, France

Written by: Christopher J.D. Wallis, University of Toronto, Twitter: @WallisCJD during the 2021 Advanced Prostate Cancer Consensus Conference, Saturday, October 9, 2021.