Prostate Cancer Lab #22: Brian McCloskey’s Tissue and Testing

“I want to use the biopsy of my tumor tissue to do a couple things: (1) to make sure that I get greater depth of understanding regarding my cancer, and (2) to inform my treatment decisions.” – Brian McCloskey

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“The Issue is tissue” – getting tumor tissue for potential tests which can guide treatment is a recurring challenge in making personalized cancer treatment decisions. Advanced prostate cancer patient Brian McCloskey is going to get a tissue biopsy which he can use for tests. How should he allocate this scarce resource to increase his understanding of his disease and prioritize the many treatment decisions he is considering?

Brian was diagnosed with prostate cancer in 2016. He has had 9 rounds of treatment, including a prostatectomy, chemotherapy, radiation, and various rounds of androgen deprivation drugs, as his PSA has cycled up and down. In 2020 they found six metastatic lesions in his peritoneum (the lining of his abdomen). He had surgery to remove as much of them as they could, but they knew they didn’t get it all. Recent scans found three metastatic lesions. His PSA is rising, so androgen deprivation therapy may be becoming ineffective. He has found 21 options for his next lines of treatment, which he has whittled down to a shortlist of five or so options through conversations with his oncologist.

Through our meetings at Prostate Cancer Lab, Brian has learned about many potential ways to use the tissue from his upcoming biopsy in tests, including whole exome sequencing, IHC (immunohistochemistry), proteomics, spatial phenotyping, and functional testing. He needs a plan to work with his oncologist, addressing the tests that he should consider, the amount of tissue each one needs, the type of tissue in terms of preservation, and anything else that he should consider before the biopsy.

Here are highlights from the discussion of testing options:

• Whole exome sequencing: Brian will get this test, which can, among other things, be used to develop a personalized cancer vaccine. Tempus XE is one option, with experts liking BostonGene’s new test and Exact Sciences’ test.
• Immunohistochemistry (IHC): Brian will get this common test that uses antibodies to check for certain antigens (markers) in a tissue sample, usually highlighted by a fluorescent dye. It helps visualize the distribution and localization of specific cellular components within cells and their context.
• Proteomics: A proteomics test could allow Brian to analyze the concentrations of 72 different proteins, beyond knowing which proteins are present, which could help predict therapy effectiveness, such as chemotherapy sensitivity, effectiveness of drugs, such as antibody drug conjugates, and immune system dynamics. For example, Brian has elevated levels of a biomarker (TDO2) which creates an immune suppressive environment.
• Functional testing: While functional tests that try out drugs on fresh tumor tissue “ex vivo” could provide confidence in choosing drugs that perform well, including drug combinations, Brian’s oncologist doesn’t trust these tests.
• Spatial analysis: Brian’s oncologist is unenthusiastic.

Brian is looking to align with his oncologist on these tests, or find another physician, to push the envelope in trying innovative tests.