Radiation & P53 Mutation

[Stickingaround1]

Quick recap. dx in February, 2017. PSA 8.8, Gleason 8, and 11 of 12 cores positive. Left Seminal vesicle invasion, two mets, one in left femur, and one in hip, not to mention one questionable lesion in the left pelvic region and a small number of “suspicious” lymph nodes in the pelvic area. Went on Lupron and Casodex end of March 2017 and Abiraterone in September, 2017 and omitted Casodex. My PSA has been undetectable since early June, 2017. I had both a decipher and Foundation report taken of the prostate and it came back with TMPRSS and a P53 mutation. With news of the P53 mutation, I felt it would make the most sense to have an RP since, to me, the ADT would not have as much, or any impact of the mutation: therefore, remove as much cancer as I could. The goal was not to exercise all of the cancer, but simply to debulk. This was my idea, not my chemical oncologist (although he supported the path I decided to take). I had the RP the end of January, 2017, and the report came back with no lymph node involvement of the 28 that were removed, no seminal vesical involvement, but half of the margins were not clear and there was a possibility of vascular and neurologic involvement. The prostate itself still had a “decent amount of cancer,” but was 70% smaller than at dx. The surgeon, was confident that he removed 99% of the cancer, which was more than I had expected. My thoughts are, since my PSA is still undetectable, the cancer that remained must be the P53 mutated cells. One thing that is strange, almost immediately after having the RP, I felt so much better (no chills or feeling cold when I shouldn’t). It is almost intangible, but, my quality of life is a whole lot better. I am so happy I took the RP path. During my last scan, (July, 2018), there was no evidence of any cancer in my soft tissue area (pelvic region), and almost complete resolution of the mets in femur and hip. I decided it would make sense to talk with a radiologist to see if that may be an option. He mentioned that I should go off ADT until the cancer would reach .2, as the ADT will not reveal what may truly be lurking, and to radiate while the cancer is still being suppressed, the likelihood would be potentially high that something could be missed while being controlled by ADT. Shortly after, I had a meeting with my chemical uro/onco, and he brought my case to the tumor board. They felt that radiation to the entire prostate bed as well as the two mets in femur and hip, and stay on ADT until radiation is completed would be the proper course of action. I met with the radiologist, and we are ready to start mid-month and will be having my CT scan to create the template this week. The two questions that I could really use help with is, first, I have read, that there is possibly evidence that radiation can actually help proliferate cancer cells that are P53 mutated, so does anyone know what the risk may be with radiation, or would this be the right course of action (my goal is to cure the incurable)? The second part is, should I begin radiation now while the activity is low (cancer), or should I go off ADT, and let my PSA rise until I hit .2, to potentially eliminate the possibility of missing some areas that are lying dormant due to the ADT? This is a little different path than staying on ADT as my uro/onco had me on when I was dx, but I am doing my best to buy a whole lot more time, and so far, I think it is working. Thank you all my friends!

[Stickingaround1]

Sorry, meant had RP January 2018!

[Tall_Allen]

To your two questions, my thoughts are:

(1) P53 is one of the most common mutations in prostate cancer metastases. My understanding is that mutations can confer radiosensitivity or radioresistance, depending on the mutation.. A functional P53 (without mutation) confers radioresistance on prostate cancer cells; however, when mutated, it can actually INCREASE the radiosensitivity of the tumor (it's repair function is sometimes destroyed by the mutation).

cancerres.aacrjournals.org/...

All you can do is take a sufficient dose - maybe 72 Gy to to the prostate bed and SBRT to the mets.

(2) I think it is very risky, and a self-fulfilling prophecy, to wait for your PSA to rise just so the mets become detectable. The ADT is keeping your micro-mets from becoming macro-mets. What is the point of taking the brakes off and allowing the cancer to proliferate? With known bone mets, you cannot be cured. But it is possible that you can slow it down (jury is still out as to whether that's possible).

[Stickingaround1 in reply to Tall_Allen]

I really appreciate your insight and reply Tall_Allen. To me, I would rather radiate with ADT, than just ADT alone. Going form "inoperable" according to my MO initially, to having surgery 11 months after dx, and radiation more than a year and a half after dx, is definitely out of the facility's standard of care, as I believe they have not followed this course before. I will keep posting how things are going. Thanks so very much again. You have no idea (maybe you do) how much help you are, and have been to me!