Triplet then RP or RP then triplet?

[Cold77]

I was diagnosed a month ago with Stage 4 (one lymph and one sit bone met) and a 50g prostate tumor with Gleason 9. PSA was 32.5 on Nov 6 (17.2 in May). Got a 30 day shot for ADT on the same day. Then the two mets were treated with 5 sessions of SBRT about 2 weeks ago.

PSA today is 3.2 after a month of ADT and the SBRT.

I would like to get the prostate removed and get triplet treatment afterwards, because RP first seems like a good way to reduce the total PC load and so slow spread (or is that a misconception?)

But maybe that surgery would mean putting off triplet therapy until healed from the surgery (and I don't know how long that might be...4-6 weeks?)

My question is, what order is best in others' opinions?

RP then triplet, or triplet then RP?

And the PC Newsletter says: "Both the TITAN trial of Erleada (apalutamide) and the ENZAMET trial of Xtandi (enzalutamide) showed no benefit for the advanced hormone therapy when docetaxel had been used previously. Timing is important! When chemo or advanced hormone therapy is used as monotherapy, protective mechanisms (like cellular senescence) kick in soon afterward. It protects the cancer cells from destruction by the other medicine. They have to be used together or wait until the first drug stops working."

I'm on ADT, and expect to continue, but my MO is planning to give me another ADT injection + darolutamide.

So the take-way from the newsletter is with the drugs it's "all or nothing"?

Surely, someone has sliced and diced the data with those who had an RP and triple treatment before or after?

But I'd like to hear from others about the conceptual underpinning to the order

Thanks in advance.....

[Tall_Allen]

There is no evidence that RP is beneficial for oligometastatic PCa. There is evidence that radiation of the prostate is beneficial for oligometastatic PCa. You have to get triplet therapy from the start, and it has to be used simutaneously, not sequentially.

[Cold77 in reply to Tall_Allen]

Thanks for the quick reply.

[IKNY]

FWIW, my prostate was fully involved, Mets to lymph’s only and I went ahead with the RAPL as scheduled and bilateral Lymphectomy as it was progressing rather quickly.

Unfortunately, the extent of metastasis was unknown due to a failed PSMA/PET scan and an unwillingness of my Urologist to look at the imaging provided by a cancer center of excellence.

Post surgery PSA went town from 6.8 to 1.7, cancer was G9 (4+5) and I immediately moved my care to Boston MGH, I was started on Lupron which dropped PSA to .7, then Abiraterone was added which brought PSA to <.01.

I was on this treatment for 4 months, then followed up with EBRT to the prostate fossa bed and the remaining involved para-Aortic lymph node.

One benefit of the RAPL was I have no urinary issues from the radiation… most of the prostate was just cancer.

Currently, off of Abiraterone due to liver agitation and I’m moving to Nubeqa.

So, I’ve had the RAPL, Radiation and ongoing ADT + Nubeqa/Abi

Currently, PSA is undetected.

I’m about 1.5yrs into this scenario.

Whether or not my choice to have the RAPL is efficacious… we will see. It’s what was done with the information available at the time… it progressed rather rapidly and felt since the surgery was queued, I did not want to lose the momentum and followed through.

Nerve involvement was present and the week before surgery erections were problematic (not impossible).

Interesting note, I still have a libido through all this and followed up with Sexual Therapy via Dr Mullhall at MSK.

Check my profile for treatment details.

Best of luck to you.

IK

[lovepockets in reply to IKNY]

Gleason 10, stage 4 with many bone mets. Too many to radiate. Immediately started on Darolutamide and relugolix. Docs said it wouldn't do any good to remove the prostate at this stage. Then had 6 rounds of Docetaxel which I tolerated fairly well BUT would highly recommend icing hands and feet during the chemo treatments. This helps with neuropathy.

PSA was non detectable for around 18 months. Then it went from .1 to .24, had a psma scan and it showed one small tumor at the base of my prostate towards my rectum. I just finished 28 sessions of radiation and will be seeing the doctor next week after PSA test. Bottom line is my doctors said it was too late to remove the prostate so why go through the surgery and side effects.

[Cold77 in reply to lovepockets]

lovepockets: the icing sounds like a good tip. How much does a person need to bring?

[Cold77 in reply to lovepockets]

Also, I appreciate the answer about what the docs told you: "too late to remove the prostate so why go through the surgery and side effects."

[Cold77 in reply to IKNY]

Thanks IK. Very helpful to hear about your experience. My prostate, also, is mostly cancer.

[RoseDoc]

Once the tumor has spread, a prostatectomy is not indicated. Usually radiation is the treatment for a case such as this along with ADT. Triplet therapy is usually administered simultaneously followed by 2+ years of ADT.

[Cold77 in reply to RoseDoc]

Thank you RoseDoc.

Part of me wanted to know "why" removing the thing doesn't help, in terms of the mechanisms involved. But most of me just wants to beat back what's ailing me.

My (overly-simplified!) mental model was that this cancer is like an invasive weed in the yard. The prostate is where the weed got in and established itself and "debulking" was like digging up the big patch of weed growth.

In this analogy, the metastases represent where "seeds" from the big patch have landed and germinated and will now grow into their own "seed-producing" patches. RP/radiation of the prostate seemed like ridding the yard of the "seed source" and chemo is like applying Round-Up.

But I suppose this mental-model is missing much of what's really happening, and much of what's really happening occurs in a black box, where outcomes of treatments are what we have and what matter most.

[RoseDoc in reply to Cold77]

Once the tumor has spread, most would not recommend a prostatectomy.

I would suggest you go to a major center such as UCSF, Mayo, MD Anderson or Memorial Sloan Kettering and follow their recommendations. Generally, radiation of the prostate and triplet therapy would be the course of treatment.

I wish you luck. It is a long and, at times, convoluted journey. Find good docs and stick with them.

[Cold77 in reply to RoseDoc]

Thank you for your advice.

[Derf4223 in reply to Cold77]

Strongly recommend you read up on trials like Latitude and Charted and so on. Make notes and take those into meetings with MO's and RO's. PCA is a defect in one's own cells, a defect that has many genetic variants and which often becomes resistant to treatments. It spreads via micro metastases and can latently hide in our bodies. Get a DNA test for bad cancer genes (a list which grows all the time.) Even get a tumor's genes tested. At the same time, exercise copiously including resistance, and lose weight because that will be virtually impossible (rather the opposite) once ADT commences.

[CAMPSOUPS in reply to Derf4223]

and the PEACE trial too

[Cold77 in reply to CAMPSOUPS]

Thanks. This one seemed to address the question: "Efficacy and safety of prostate radiotherapy in de novo metastatic castration-sensitive prostate cancer (PEACE-1): a multicentre, open-label, randomised, phase 3 study with a 2 × 2 factorial design"

[Cold77 in reply to Derf4223]

Thank you for the suggestions. "It spreads via micro metastases and can latently hide in our bodies" seems like a good model of what's going on.