Investigating Proton therapy for salvage treatment following RARP

[ragnar2020]

I had RARP nine months ago, and I'm investigating salvage treatment now. I am G9/10 with pT3a NO EPE but with PCa in the margins. My bone scan was negative. Prior to RARP my PSA had reached 4.9 after doubling from the previous year. I'd be very interested in hearing from others who have used proton therapy (PT) for their salvage treatment of the prostate bed and the pelvic lymph nodes following surgery but prior to a determination of BCR.

[fluffyfur]

We were told by two well respected RO's that it is experimental and not recommended.

[ragnar2020 in reply to fluffyfur]

Hi fluffyfur,

Thanks. I'm curious about the RO's responses. Where were they located, and did they have access to PT for their patients if the ROs chose to use it? Since PCa treatment is big business, I like to know if a medical recommendation might be forthcoming because of financial incentives of the docs involved or alternatively if a doc's lack of training in a specific treatment or the ability to offer a particular treatment might influence their opinion of that treatment. There are twenty-six PT centers located in the US, and several are attached to major cancer treatment facilities. I've read a half dozen journal articles comparing PT with other forms of RT, and it appears to me that PT is no longer considered to be futuristic. But the PT machines are limited, and the treatment cost is higher than other forms of RT. Stand alone Rt regional clinics are not going to have a proton machine. This is why I'd like to hear from PCa patients who have had the PT, where they had the PT and how they navigated the financial landscape of insurer payments.

[fluffyfur in reply to ragnar2020]

MD Anderson, Houston and UCLA. MD Anderson has a huge proton therapy center. I don't think enough clinical trials have been conducted with large sample sizes thus they still see it as experimental. Especially in the adjuvant/salvage. Personally for my husband the unknown risks were too scary and he opted to go with VMAT.

[Tall_Allen]

An important trial found that waiting until PSA reached 0.1 or 3 consecutive increases provided the same results as immediate SRT. No need to jump the gun.

prostatecancer.news/2019/09...

[ragnar2020 in reply to Tall_Allen]

Hello Tall_Allen,

I enjoy reading your posts, have learned a lot, and I thank you for your time and the work you do maintaining your blog. You help a lot of people sort through this maze of PCa info.

I have a copy of that trial, and it offers some comfort. But, for myself with high risk disease, G9/10 but nothing yet in the SD nor in the twelve nodes that were removed during surgery and undetectable PSA presently, it appears that I still might have just localize PCa that spilled into the prostate bed marginal tissue and is not systemic disease yet.

I’d like to avoid future potentially damaging RT and ADT SEs following what I suspect will be eventual BCR if at all possible. This is why I’m considering PT salvage treatments if I can qualify for it.

Thanks for taking the time to read

my post and reply. I appreciate it.

Jeff

[Tall_Allen in reply to ragnar2020]

You should understand that, as far as we know so far, proton and X-ray have the same toxicity. Here's what we have on modern proton machines for primary therapy:

prostatecancer.news/2016/08...

And here's what I've seen for 2-year follow-up with salvage proton:

tandfonline.com/doi/full/10...

We don't have any long-term results for proton salvage, but I expect it will also be comparable to X-ray salvage RT. Remember, the Bragg peak is only a theoretical model, and different effects come into play with clinical use in humans. Do they treat the pelvic LN area with protons? They used to treat just the prostate bed with protons and the wider area with X-rays (as in the study above)- I don't know if that's changed.

There is a trial at UCLA for salvage SBRT, but I worry about toxicity because the soft tissue there moves around a lot. They have a new Viewray MRI-guided linac that may mitigate my concerns if it can target soft tissue landmarks, but it is also just theoretical for now.

prostatecancer.news/2018/01...

[Tall_Allen in reply to Tall_Allen]

This retrospective study had 4-year f/u and detected no difference in the toxicity of salvage radiation between protons and X-rays:

acsjournals.onlinelibrary.w...

[ragnar2020 in reply to Tall_Allen]

Hello Tall_Allen,

Thanks for the follow-up and links. It is all helpful info. I have not

met with the PT team at UF in Jacksonville yet, but your question about how they will treat the pelvic lymph nodes is on my list when we do meet. The Covid issues have complicated personal in person communication. I haven’t gotten a pdf of the 9/19 ACS article yet, but a doc friend with access is working on providing it to me. I’m sure I’ll have more questions to ask them.

Because of both CAD and the RARP removal of the NVB, ED is not an issue for me with salvage treatment. I’m a seventy-three year old guy trying to maintain QOL as my primary goal.

Thanks again,

Jeff

[Hidden in reply to ragnar2020]

One additional question Jeff for your PT team regarding the gantry's 3D positional capabilities. Some engineering background first: Cyber knife was made possible when they "miniaturized" the photon source to the point that it could be carried autonomously by a robotic arm of the type used in automotive assembly lines. These robots, I don't recall exactly, but may have 12 degrees of freedom in positioning. This is by no way possible with protons where the origination and beam forming stages occupy a small factory's space and their peak electrical demand is a fraction of a MW. A bit better are the IMRT machines who's "head" can rotate within a circle's ark. In some literature that I have come across protons were shot from two low angle, quasi diametrically opposite directions. I think (?) that the latest make proton machines can mimic the IMRT's spatial movement capability and as such, apart from relaying solely to the Bragg effect for controlling spillage, they can profit from the modulation of the angle of incidence . I do not think they can modulate the intensity as well that IMRTs also do. Hope to have been clear.

[ragnar2020]

Hi Fluffyfur,

Interesting. That answers a couple

of questions and eliminates the financial self-interest issue from the doc’s recommendation. There are so many radiation centers in the country relative to the number of to PT centers it is not surprising that comparisons of the results comparing IMRT with PT are minimal.

There is a nationwide clinical study now occurring that is comparing the two treatment options for salvage treatment, and that trial will continue until 2050. But it is going to be a long time before anyone reading this message board will see comparison conclusions based upon a large sampling.

Even though PT treatments began in 2002 at MGH and now the treatments have been used for eighteen years, they are still considered “new” for much of the extremely conservative PCa SOC world. The fact that PT obtained FDA approval and Medicare coverage were two huge milestones that the 26 PT centers have overcome.

I believe that docs who specialize in PT at the PT centers undergo additional training after they have been trained as RT docs. I haven’t asked about this training issue yet, but it makes me wonder about referrals of patients from a RO to a PT center for PT treatments. Referral motivation to other providers for competing treatments is always a touchy subject. It forces us to dig into the journal articles to try and find unbiased analysis.

I hope your husband’s VMAT went well.

Thanks for your reply,

Jeff

[fluffyfur in reply to ragnar2020]

Jeff he just started and had similar positive margin(s) as you did. However his Gleason was a 7. His RO at MDA is not doing nodes or ADT but I realize your GS makes your situation different. I guess I'm questioning why you want Proton over IMRT? Side effects? Or are the BCR statistics better? It's always good to look into all options but I do agree with Alan below, that your doctor is so important. We can find the best treatment on the planet but if the treatment is being given by a jerk then it may not be worth it. Keep us posted.

[Hidden]

I have a self-derived explanation for the reasons patients may be dissuaded regarding salvage PT after RALP. The latest generations of such machines are capable of very tight focusing of their beams. In marketing jargon this registers under the "pencil beam" term. Pencil beam is very useful when precisely hitting specific volumes, like the prostate gland. It works on the same principal like cyberknife with the advantage of a more controlled energy discharge in the longitudinal sense. In salvage irradiation the target (prostate bed / whole pelvis) is considerably wider, so the advantage gets lost. I am aware of Heidelberg offering a combo package for initial treatment. Proton to the prostate plus IMRT to the surrounding areas. The "experimental" BS is a very old trick of the drs when they don't want to divulge their tricks of the trade. Proton irradiation to the head was first practiced in Sweden during the 60s, but if one asks they will fly the "experimental" red flag.

[ragnar2020 in reply to Hidden]

Dear Justfor,

Thank you for taking the time to

reply. I have been wondering about

the mechanics of the PT beam when treating the prostate bed area

and the pelvic lymph nodes, and had heard that the salvage treatment might involve a combination of IMRT and protons. It is on my list to discuss with the docs when we meet.

Everyone is marketing their treatments and keeping the smoke and mirrors in place because they need to pay for their expensive equipment and keep the lights on at the facilities.

Thanks for taking the time to share your POV.

Jeff

[AlanMeyer]

Two years ago I had the opportunity to talk to two different professors of radiation oncology. I asked them about proton beam vs. x-ray treatment. Both of them said the same thing - there is no difference in treatment effectiveness. Whether protons or x-ray photons are used, the effect on the cancer is based entirely on the dosage. Equal doses of the two modalities, targeted to the same spots, will have the same effect on the cancer. The only potential difference is in the side effects. When I asked them about side effects neither one would commit to saying that protons were better. Of course each understood the theory behind the Bragg Peak but, IIRC, couldn't say whether, in practice, it made a practical difference. They thought that a lot of the important areas of side effects were not far away but right in the target zone of the radiation. The urethra runs right through the prostate. Important nerves and blood vessels run right across it. The rectum and the bladder neck are pretty close to it. They wanted to see more trial data before drawing conclusions about side effects.

I'm not an expert in any of this and my opinion shouldn't count for much but, for whatever it's worth, here it is: Where there is no clear advantage to one treatment technique over another, I'm inclined to choose the best doctor and staff. You want someone who is knowledgeable, careful, and deeply committed to his patients. How you determine all that is partly by recommendations, by searching the Internet, by looking at affiliations, and by gauging the doctor's performance in the office with you. Does he take your questions seriously? Does he answer candidly without BS - making unrealistic claims? Does he allocate sufficient time to you for your appointments? Does he give you honest and realistic projections of your chances of success and of side effects?

I mentioned the doctor's staff as well as the doctor because, at least in my experience, the staff is heavily involved in the treatment. The doc creates a treatment plan but much of the actual treatment may be administered by radiologists and technicians. I like it when the staff also seems caring and committed.

Best of luck in your treatment.

Alan

[ragnar2020 in reply to AlanMeyer]

Hello Allen,

From my investigations, I believe everything that you’ve presented.

I used your selection guidelines when I chose my care team at MGH when I shad the RARP surgery. I rejected another prominent institution nearby because I did not feel that their surgeon was trustworthy. He had lied to me during a diagnostic procedure when he blamed his mistake on his staff. It was his error not the folks who worked for him. I walked away from him and began explorations elsewhere.

I’ll keep your guidance in mind as I proceed with this investigation phase or my salvage therapy and make decisions with the best

information that I can obtain. Thanks for taking the time to respond.

Jeff

[patandemma in reply to ragnar2020]

I think you are very smart to realize there may be financial biases in recommending one form of RT over another. You should get an RT consult at an institution that offers both..

I chose PT to treat my prostate and thoracic spine bone mets thus avoiding unnecessary collateral damgae to my lungs,heart,esophagus,and sternum from from conventional RT.

My RT also PROPHYLACTICALY treated lymph nodes along my iliac vessels.This was four and a half years ago

[wilcoxsaw]

Ragnar,

Proton beam therapy, in use since 1990 by Loma Linda University Medical Center and now 30 plus proton centers in the US and other centers internationally, has treated 30,000 + men with prostate cancer. It is neither experimental nor investigational. Much research is available through many proton centers, the National Association for Proton Therapy, Brotherhood of the Balloon, and other sources. There are currently two clinical trials underway comparing proton to photon treatment, one being led by Dr Mendenhall in Florida and a second at Massachusetts General. Neither has published data yet, neither trial is completed. There are however a number of studies that have been published that one can find regarding the long term use of protons.

Because of the physics of the proton, the Bragg peak, the amount of radiation deposited on healthy tissue is less than with photon radiation in it's various forms. There are those that will argue that point, but the physics are undeniable, the proton is a particle not a beam and the dose to healthy tissue is less because the proton can be stopped at the target volume.

Salvage therapy using protons only is available, and is being done by proton centers that use scanning beam technology. Dr. Rossi, at California proton Center in San Diego, among others using that technology has the ability to use protons only for salvage therapy. Mass Gen does not use proton treatment for salvage therapy in their proton center per a patient that was treated there recently. As tall Allen mentioned, some centers use a combination of protons and photons such as Loma Linda because they use passive scatter technology which limits the size of the target volume that can be treated using their proton equipment.

I had 15 proton treatments on 2 identified nodes using scanning beam, one near my spine, the other attached to the bowel. Because of the ability of the protons to minimize radiation to adjacent critical structures even though passing through or across those structures such as other areas of the bowel, acetabulum, and previous radiation field I had no long term side effects or radiation damage from that treatment.

If you meet with a radiation oncologist specializing in scanning beam proton technology, that MD could determine whether or not you might be a candidate for this treatment, and what imaging and psa levels would be necessary to best identify areas needing treatment.

Hope this helps

Scott

[testr]

I had a failed RP, with rising psa, so I had to do something.

I won't get into a discussion about proton's pros & cons.

I respect those who disagree with me.

Everyone is different. U have to decide for yourself.

I consider ALL radiation to be "bad" and to be avoided

if it is at all possible to do so.

My deciding factor was secondary cancer %.

I have a screen capture of a study somewhere showing

12% for non-proton and 6% for proton.

(This makes sense if u think about no exit dose for proton.)

I investigated 8 centers & 10 doctors for proton.

(3 different drs at U Penn.)

All of the doctors were good, it's just that

the "best for me" in my opinion from my investigation is Dr. Rossi.

He had the most experience by far compared to the other doctors.

but I chose him because his treatment plan was the best by far for me.

He also was willing to give me the highest total dose.

(I recommend to always double check your total dosage yourself

by doing the calculations yourself using 2 different online calculators.)

He was at California Protons. (If he was at a different location,

I would have gone to that location.)

My criteria was simple: try to get the best, so that I had no regrets,

no matter what. I had 3 mo of Firmagon while getting the proton.

My treatment ended at the end of March 2018.

I haven't been testing my psa since feb 2020 (due to covid).

It was <0.006 then, but I don't know what it is now.

If you are a military veteran you might be able to stay

at Fisher House during your treatment. I don't know

what the medicare coverage is now but in 2018 it was 80% covered.

AARP Plan F paid for the other 20%.

Radiation + Firmagon made me extremely tired,

but that's normal, from what I hear.

Would I do it again? Yes.

And I say that not knowing my future outcome.

All u can do is the best u can do.

What ever you decide, I wish you the best.

[ragnar2020 in reply to testr]

Hello testr,

Thanks so much for taking the time to

post your experiences and recommendations. IMO, this website is one of the best uses of the web. How else would I ever get information from someone like yourself?

I’m in investigation mode trying to learn as much as I can so I can make some logically informed choices. This far, I believe that ART makes sense for long term survival and QOL. Now, I need to determine when and with whom to get PT ART done.

I value your input and advice a lot. Thanks again.

Jeff

[petercraig2]

Hello Ragnar,

From what I see your PSA is undetectable and scans are clean so it would seem you are all good.

However if it should chance to rear it's head with a rising PSA I suggest a PSMA Ga-68 PET/CT scan to identify any site of prostate cancer anywhere in the body. I was slightly different with a rising PSA after surgery but scans were completely clean so I went to hospital in Berlin for Ga-68 PET/CT scan it showed cancer in lymph nodes of lower abdomen and they recommended surgery or Cyberknife.

When I returned to Canada the radiation oncologist insisted that full prostate bed radiation was the only safe therapy and regrettably I submitted to the pressure sales.

In retrospect I would have found a cancer therapy centre that could do SBRT comparable to Cyberknife with higher radiation dosage once a week and targeted at specific cancer sites. From everything I have read it is more effective, longer lasting for low to medium risk cancer and much less disruptive to colon and bladder.

Prior to 35 days of radiation I had already started using Estrogen transdermal patches and PSA was dropping rapidly and still on patches with PSA now <.008 and steady.

For now I am technically in full remission and learned to live with Man boobs, small price to pay.

Best of luck

Peter

[ragnar2020 in reply to petercraig2]

Hi Peter,

Thanks for your reply and description of your treatments. I’ve determined my care plan for now. I investigated proton beam therapy for eventual ART when and if the PSA begins to rise. PBT is what I plan to use.

The GU and GI toxicity from PBT compared to ART using IMRT are less. You will hear discussions that claim there is no blind study proof, but those arguments are financially bias to protect older technologies and entrenched ROs. There are probably 4000 radiology treatment facilities in the US and there are 39 proton beam centers. The medical business community is not going to close down 4000 RT centers without a lot of opposition just because newer PBT procedures have less toxic outcomes. We’d like to think it would happen that way, but it will not.

I’ll need to pay out of pocket for the best PSMA PET scan available unless thé US Medicare system has approved it for use when my PSA begins to rise.

I plan to use estrogen gel for ADT when the need arises. Unfortunately, it looks like my future PCa care is going to be largely self-managed, but I’m fine with that program since the docs at the major centers for care are restricted in the choices of care that they can recommend and oversee by the SOC guidelines of their institutions and by their insurers. It is today’s capitalistic reality in the US.

Jeff

[Hidden in reply to petercraig2]

That is the major hurdle regarding a PSMA PET CT. You have to find someone who can dig the information out of it, instead of putting it aside and do what he/she would had done without it.

[ragnar2020 in reply to Hidden]

Hi Justfor,

As I understand the technology, until

a met is large enough to be detected

[ragnar2020 in reply to ragnar2020]

Hi Justfor,

It is my understanding that until one has a met that is large enough to be detected by the specific PSMA PET imaging technology, no PSMA PET scan will find the met. The RO at a PBT center cannot target thé met with a proton beam if they can’t see it. When I’ve spoken with an RT at UFHPTI and CPC, they both encouraged me when the time comes for me to be treated by them, I should have a PSMA PET scan to identify any distant mets prior to ART or salvage treatment. The ROs explained to me that they have used PBT to treat distant mets after detection of them by PSMA PET scans.

Does this answer address your comment? Hope so.

Jeff

[Hidden in reply to ragnar2020]

It does, but in a reverse fashion than the one you thought of. It strengthens my comment instead of weakening it. See, they spoke of distant mets as if they would do their routine job to the prostate bed and it's neighbourhood, regardless of any findings therein or about. Personalized treatment, as in dose painting, still seems very distant.

[ragnar2020 in reply to Hidden]

Hi Justfor,

When I asked the RO at the PBT centers why and when I should begin ART their answer was based upon statistics. Since in my case there were PCa cells located in the prostate bed as determined by the post surgical pathology report and because when BCR has occurred as indicated by a rising PSA, it has been statistically determined that the growing PCa cells are most likely located first in the prostate bed.

The ROs at the PBT centers believe it is logically to radiate the prostate bed and try to nuke the PCa cells that were left behind in the bed and are now probably growing. Those PCa cells are probably shedding PSA and causing the PSA biomarker to rise. However, those cells are probably too small to be seen by PSMA PET imaging. Thus the concept is too nuke the whole prostate bed area but spare the surrounding tissue. This can be done best with PBT. This is how I understand the concept. They suggest that I get a PSMA PET scan prior to PBT of the prostate bed to see if the scan turns up any distant mets before nuking the prostate bed only. If mets were to occur, then those distant mets would be treated too.

This is how I believe it will work.

Jeff