Prostate Cancer Lab #34: Review of Eric Hall’s Case

“The medical oncologist and the radiation oncologist were really against the PSMA. They were transparent, and said they thought he would be high volume based on the Gleason 10 and PSA of 146. If we did the PSMA, it would show high volume, and that would essentially take radiation off the table in their opinion. We disagreed with them that if it was high volume, we wanted to know that it’s high volume, and if that did take radiation off the table, then it did, but not to say we didn’t lose a lot of sleep about that decision.” – Stephanie Hall

“My big question is: what is the value for me to skip over the standard of care things of surgery and radiation and try to go straight to one of these more targeted drug approaches?” – Eric Hall

Eric Hall is a prostate cancer patient, currently on his first line of treatment of androgen (hormone) deprivation therapy and facing a decision on what to do for his next step of treatment. Eric’s situation is unique because from his initial diagnosis he was faced with a very aggressive cancer which didn’t fit well with the standard approaches codified in the “standard of care” (the NCCN guidelines).

The community we have built in the Prostate Cancer Lab has discussed the cases of several advanced prostate patients. The community is a diverse crowd composed mostly of engaged and educated advanced prostate cancer patients, and also including molecular biologists, bioinformaticians, and clinicians. We call this patient case review a “hackathon”. Eric shared his medical history, treatment options, strategic considerations, and leanings, and solicited feedback.

What is Eric Hall’s medical situation?

Eric was diagnosed with “de novo” (at diagnosis) “oligo-metastatic” (cancer cells have traveled from the original or primary prostate tumor site to form a small number of new tumors in one or two other sites) prostate cancer in July 2022 at age 50. Eric’s cancer was very unique. The cancer was advanced, as measured by a PSA (prostate specific antigen, the biomarker that measures prostate cancer activity) of 146, and “Gleason” 10. (The lowest Gleason score is 6, which is a low-grade cancer. A Gleason score of 7 is a medium-grade cancer, and a score of 8, 9, or 10 is a high-grade cancer.) His cancer has spread beyond the prostate capsule, but not out of the pelvic area. His tumor measured 4×5 cm, abutted the rectum and pelvic floor, and involved the soft tissues. Eric’s doctors were hesitant about getting a scan to look at the spread of his cancer, assuming that it would show widespread metastasis, given his high PSA and Gleason scores, but relented. They were quite surprised to not see more metastatic sites. His medical diagnosis is “oligo-metastatic; nodally advanced; locally advanced.” It’s metastatic (has spread beyond the prostate), but not too far, which is a rare in-between condition.

In terms of biomarkers, Eric has an “ALK fusion (ALK:DTNB)”. ALK is anaplastic lymphoma kinase, and a fusion is a chromosome mutation. This ALK fusion is extremely rare in prostate cancer, yet is common in other cancers, especially non-small-cell lung cancer. Further testing revealed additional biomarkers: a CHEK2 mutation and high expression for AR and FOLH1 (PSMA) proteins.

Since his diagnosis four months ago, Eric has started two types of androgen deprivation therapy (Orgovyx – Relugolix and Zytiga – Abiraterone) along with a steroid (Prednisone). In addition to medical treatments, Eric has been very active in researching and implementing many lifestyle changes to heal his cancer, boost his immune system, and detoxify his body, including switching to a vegan diet with fresh-pressed vegetable juices and intermittent fasting, taking several supplements, such as mushroom powders, TUDCA, melatonin, and CBG, and cutting out alcohol and soda. He has increased his exercise.

What treatment options is Eric considering?

Eric is considering two categories of treatment options: standard of care physical treatments (surgery and radiation) and targeted drugs.

Since Eric got the PSMA scan and his recent MRI scan which showed relatively local containment of his cancer, surgery and radiation are treatment options. (Had Stephanie and Eric not pushed to get the PSMA scan, the surgery and radiation options would have been off the table – another example of the importance of active patient and caregiver engagement in testing and treatment decisions.) Under standard of care treatment options, Eric is considering:

• Surgery followed by targeted radiation (IMRT – Intensity-Modulated Radiation Therapy)
• High-Dose-Rate (HDR) brachytherapy (radiated rods placed near the tumors for about ten minutes) followed by targeted radiation (IMRT)
• Open surgery followed by wait and see

As with other patients who are actively engaged with the Prostate Cancer Lab, Eric has received targeted drug recommendations from his medical team (Mayo), Massive Bio, CureMatch, and Cancer Commons. Under targeted drug options, Eric is considering:

• Drugs targeting his ALK fusion (such as ceritinib, alectinib, and brigatinib) – which would need to be delivered off-label since Eric is not metastatic, which is a requirement for existing clinical trials
• Functional testing of drugs (which requires live tissue)
• Drug combinations, such as a triplet therapy (e.g., Lupron, chemo, and abiraterone)
• Three clinical trials (from Massive Bio), of which two are for metastatic castrate resistant patients, so not exactly a fit, and the third one is a phase one and two trial, so early in the trial process.

What thoughts did the Prostate Cancer Lab community have for Eric’s treatment decision?

Eric’s main questions were whether he should (1) skip the surgery and radiation options and go straight to one of the targeted drug approaches, and (2) which of the two preferred physical treatment options, surgery plus IMRT or HDR brachy plus IMRT, is better.

The discussion exposed many tradeoffs, which came down to a judgment call depending on Eric’s (and his wife Stephanie’s) intent. He would like to choose a treatment that has a good chance of resulting in a cure now versus a treatment option that is not as effective now but could provide guidance for future treatment options.

Surgery is attractive. With more treatment, his tumor might shrink even more. Surgery may have fewer consequences than radiation to his prostate. Surgery can remove the tumor tissue and get tissue for functional testing. There was an endorsement of getting functional testing, if adequate fresh tissue is available, and using multiple functional testing sources (e.g., SEngine, Nagourney, Tempus).

But surgery is less effective than high-dose-rate brachytherapy plus IMRT, according to research and anecdotal success stories from patients. Choosing the brachytherapy option now has the best chance at a durable response, and if the cancer recurs and tissue is needed for a targeted therapy, Eric can get tissue from where it recurs.

The targeted drug combinations and clinical trials have access, efficacy, and dosing issues.