HORMONE THERAPY & SALVAGE RT

My memory is already slipping and not on Lupron yet! I went back and found these cites.

Peter had previously given me this cite

http://www.ncbi.nlm.nih.gov/pubmed/26416057

And Allen had given me this cite

http://meetinglibrary.asco.org/content/147682-156

Now only missing the information on the two months on hormones, pre RT.

This could be only related to initial treatment??

Bobby Mac

Allen, Thank you

Yes, I certainly ask many questions at my appointments.

Bobby Mac

Good question. I think Allen meant that it is a theory that AD can radiosensitize PCa?
This study couldn't find evidence that AD sensitizes cells to radiation. Maybe there are other studies with other results?
Lack of prostate cancer radiosensitization by androgen deprivation. Conclusion: Although the findings indicate that AD does not act by sensitizing prostate cancer cells to RT, the additive cell death and growth inhibitory effects of AD + RT are clinically meaningful.

The rationale for combining RT with ADT is based on the fact that both treatments kill cancer cells or suppress cancer cell growth, and that the combination lead to synergistic effect.

George_

The exact mechanisms are unclear. What we know is that androgen deprivation makes cancer cells weaker and less capable of surviving an attack by radiation-induced changes in the tumor. And we know that androgen activation is necessary for mitosis, and cancer cells especially do a lot of that. For an analysis of the possible mechanisms, see the following recent review:
Mechanistic Insights into Molecular Targeting and Combined Modality Therapy for Aggressive, Localized Prostate Cancer


Gemlin-
You misinterpreted that test-tube study - "LNCaP prostate tumor cells supra-additive apoptosis does not translate into radiosensitization... " Apoptosis is a minor mechanism for death of cancer cells- that's one of the hallmarks of cancer.

-Allen

Update today from my RO -

I had previously emailed him asking about delaying sRT for 60 days until Lupron weakened cancer cells, allowing radiation to work better. He replied "Waiting 2 mo after starting hormone therapy is not necessary in my opinion; although, US trials are often structured that way."

Today he called me to schedule a MRI and CT so he can do his radiation planning. I again asked him about delaying treatment for 60 days while on Lupron because I felt it would weaken, possibly radio-sensitize, the castrate sensitive cancer cells. He agreed with the weakening and radio-sensitizing of the hormone sensitive cancer cells and to wait for the 60 days of Lupron.

Not exactly sure why he changed his mind?

So I have been on Casodex 50mg for about one week and will have Lupron injection on 8/17/16 with salvage radiation to follow about 10/17/16.

Bobby Mac

I had my salvage radiation done at UCSF and they were strong believers in starting the radiation 2 months Bobby - after starting the ADT, for reasons Tall Allen said. As to the duration of ADT, their is approach is to vary depending on the risk. In my case (intermediate) they advised 4 months (I went with six). In high risk cases they would go longer, I think up to two years.

They also said that for most people the side effects of ADT for a relatively short period of 4-6 months are not that bad and they usually fully-reverse after ADT is over. So the philosophy is "it may help, we're not sure, and it doesn't hurt, so why not?" But the side effects of 18-36 months of ADT are much greater so the calculus shifts in the direction of "if there isn't a strongly substantiated survival benefit don't do it." There seems to be pretty good evidence, not great, that longer ADT's have benefits in people with more aggressive cancers.

Seeing your stats, have you had a conversation with your docs about prostate-bed only radiation versus whole pelvic radiation?

I met with my Surgeon who did my RALP.

He agreed that I should do Lupron for 2-3 months before sRT and thought two years hormone therapy seemed appropriate.

My RO had previously mentioned three years Lupron, but he has not completed planning and I have not discussed with him.

3-T MRI next Friday and RO will compare that result with the images from the 68 Gallium PSMA PET/CT.

Bobby Mac

You are on it...congrats now for a positive end point...barn before the horse...lidat...counter intuitiveness rules...there are no aliens...human beings...saturate the multiverse...Isaac Asimov...foundation series...look up...your ancestors/descendants are with you...in time...out of time...same time...crazy as i wannna be...
You want me to be right...and...lo...I am...

Thanks George -

My 68 Ga PSMA results indicated the prostate bed was positive.

Abdomen/pelvis - Postsurgical changes of prostatectomy, with faint uptake in the region of the prostate bed.
A small lymph node along the left pelvic sidewall 8 x 7 mm with mild uptake with a maximum uptake of 5.2. Also, foci of PSMA uptake in the region of the bilateral distal ureters with small external iliac nodes. Activity cannot be differentiated from the ureters and nodes, and these could represent metastatic disease.

So wouldn't I require the whole pelvic area?

Bobby Mac

I will tell you what I would do. As usual, this does not follow the guidelines.

I would have a CyberKnife radiation done to the prostate bed plus the 8 x 7 mm met. The other mets are so small that they would count as micrometastases if you would not have a PSMA PET/CT done. They may grow but new, visible metastases will result from micrometastes already present.

Including the pre-radiation ADT time I would have a 12 months ADT to tackle all the micrometastases. Then change that to an intermittent ADT and if the PSA rises make another PSMA PET/CT to see whats up and decide again.

You will probably have side effects from the ADT only and need just a few days for radiation.

Here is Dr. Scholz on ADT after surgery:
Hormone Blockade for Prostate Cancer Patients Having Surgery

Ed Messing writes:
" It follows directly that local treatments would be expected to have some benefit in managing limited metastatic disease (N+, M0, however defined) and that the more thorough the local/regional “sterilization” is, the greater the chance for systemic therapies to have long-lasting benefit."
www.cancernetwork.com/prostate-cancer/n-m0-prostate-cancer-local-therapy-systemic-disease

George

TA
obviously Dr Dattoli disagrees with you regarding the amount of IGRT required to wipe out micromets in pelvic lymph nodes since he applies 75 grays in 50 sessions. His meticulous process avoids the small bowel.
Bob

If you would use CyberKnife you would not have to worry about toxicity to the small bowel.

A salvage radiation should be done while the PSA is below 0.5 ng/ml. Stephenson found it will not help much if the PSA is higher than that:
Predicting the Outcome of Salvage Radiation Therapy for Recurrent Prostate Cancer After Radical Prostatectomy

I think 50 Gy with IMRT will do not much harm to the visible metastases. Piet Ost recommends 100 Gy BED for radiating metastases with CyberKnife, which is about 30 Gy with SBRT.

George