Cryoablation Treatment of High Risk Patients

Doug,

I'm confused by your signature. You were diagnosed in 2008 with GS9 and PSA of 30, but there is no mention of RP - I assume you did not have an RP or RT then - is that right? And the T3b was diagnosed by some kind of imaging - right? I'm guessing that you decided at that time that your disease was incurable, which is a reasonable assumption with those adverse findings, but you did decide to manage it with hormone therapy for years.

Then in 3/2014, you had focal cryoablation (the term "salvage" denotes a second kind of treatment, but this was your first treatment other than hormones). And this was done with the expectation that this would do... what? - slow down the cancer by taking out the larger tumors? And now - what is it you hope to accomplish with another round of ablative therapy?

I'm trying to understand your expectations - then and now.

If you expect a cure by getting rid of the two larger tumors, that is highly unlikely. The cancer by now is almost certainly micrometastatic and systemic. You shoot it down in one place, it will grow in another. And the more ablation (of any kind) you have done, the higher the probability for adverse side effects.

If you expect to slow down the progression of the cancer, I don't think that focal ablation is your best bet. Some try for cytoreduction via RP or whole pelvic RT in the hopes of slowing it down after its metastasized. It's an unproven therapy, but some early results are interesting.

I know there are some high risk patients (I think about 100 in the whole US) in the cryo registry who have been treated with partial gland cryoablation. I have not seen any reports on FLA in high risk patients, and there are no clinical trials even contemplated for it that I'm aware of. In fact, I haven't seen any reports of any kind of focal ablation in high risk patients. There have been reports on whole gland ablation, but those are god-awful.

I hope I understood your situation correctly, please correct any misunderstanding.

- Allen

Doug,

Thanks for the clarification. The part about the IMRT was missing. I think I understand now.

Beyond FLA, there are a few options you may want to look into:

Don Fuller in San Diego has been running a clinical trial of SBRT for local radio-recurrent PC. His results so far have been very good.

High-dose-rate stereotactic body radiation therapy for postradiation therapy locally recurrent prostatic carcinoma

I know UCSF has some experience using HDR brachy for local radio-recurrences. You might want to contact Joe Hsu there. Mitchell Kamrava at UCLA may have done some too.

Feasibility of high-dose-rate brachytherapy salvage for local prostate cancer recurrence after radiotherapy: The University of California–San Francisco experience

Also at UCSF, they've successfully used LDR brachy for this purpose. Katsuto Shinohara would be their expert. You might call Steven Frank's office at MD Anderson to see if he does it, as it's closer.

Salvage permanent perineal radioactive-seed implantation for treating recurrence of localized prostate adenocarcinoma after external beam radiotherapy

You will have to check with your insurance to see if they are covered. I would think that salvage radiation might be covered, but insurance companies are unpredictable.

- Allen

Boon1, Thanks for sharing that. So they treated 9 high risk patients, and 8 of them had no biochemical recurrence, which is very good.

I'm unclear about their "high risk" classification: there were 5 patients with Gleason scores ≥8, 1 patient with Stage >2 (he was T4), and 1 patient with PSA>20. Even if there was no overlap in those high risk features (i.e., the patient with T4 had low Gleason score and PSA), there is at least one unaccounted for. (possibly there were some with multiple intermediate risk features that they classified as "high risk"). On a sample of only 9 patients, a few missing ones can make a big difference. Also, we don't know how many of those were among those who were retreated, and what the cumulative toxicity is for that.

So my feeling is that focal cryoablation as an initial treatment for high risk patients remains highly experimental. The cancer control and the urinary, rectal, and sexual SEs of treatment are no better than whole gland HDR brachytherapy which has a better established track record - so what is the advantage? Also, I don't know how many men with high-risk PC would meet the qualifications of only one or two positive cores, and those cores would have to be away from critical structures (rectum, bladder neck, neurovascular bundles, urethral sphincter).

- Allen

FRom what I've seen in other sources, as well as what has been discussed in here, cryo still seems to be very much a niche treatment. It has promise, it seems, but limited use. As TA asks, what is the advantage?

20 years or so ago, when it was first developed, it was seen as the ultimate response to open radical RP, as a 'minimally invasive' treatment with just as good cancer control. It seems that it (whole gland cryo) was a flash in the pan, quickly replaced by brachy. Now it's coming back in a new form. Maybe it has promise, or maybe it won't prove out. More data is needed.

Disclaimer: my dad was treated with whole-gland cryo at Cleveland Clinic in the early 90's. He had 10 good years after treatment, and then the PC came roaring back as mets first on his bladder and ureters, then in his lumbar spine, which is what killed him.

Boon1-

Just to be clear, I didn't say they were being treated for recurrent PC. What I questioned was how many of those 9 patients had to be retreated. In the paper you cited, 10 of the 70 total patients were retreated. I was wondering if the retreatment rate was higher among the 9 high risk patients, and what their SEs were after retreatment. He does say that "However, 11 of 54 patients (20%) were ultimately rendered impotent by additional treatment." Other than potency and continence, the study does not report any other urinary or rectal SEs (but that does not mean they did not occur). He does mention that sparing of both neurovascular bundles was a rare occurrence (only 4 of 70 had both spared).

Boon1 said...
I would also say that the cancer control and SE results he -- and co-authors Bostwick and others -- reported are far superior to the results for other treatments, including whole gland HDR brachytherapy. I was stunned by the numbers.

You may want to read the following study:
High-Dose-Rate Interstitial Brachytherapy as Monotherapy for Clinically Localized Prostate Cancer: Treatment Evolution and Mature Results

After 5 years of f/u, biochemical control was 93% among the high risk patients (compared to 89% for focal cryo), late grade 3 urinary toxicity was 3.5%, and late grade 3 rectal toxicity was 1.6%. Two patients (out of 718) developed grade 4 incontinence. Among previously potent men, only 11 percent lost potency sufficient for intercourse. So 89% of previously potent patients retained potency after HDR brachy, compared to 74% after focal cryo. So this study, on a 10 times larger sample, found that there was better cancer control, better potency retention, and probably similar urinary and rectal SEs with HDR brachy.

- Allen

What you missed is the full text, which I have seen. You can take my word for it, or you can purchase it. There were 146 men in their high-risk group (vs 9 in the cryo study you referenced).

I frankly think PCTRF misses a lot. Whether it's accidental or because they have an agenda, I cannot say. I do not think it's a reliable source.

- Allen

That's a very odd thing to say. It was published in 2012 - just 2 years before the study you cited. It takes time to accrue patients and let the data mature to the point where one can report long-term results. In fact, it has been replicated by Yoshioka, but that was also reported "way back" in 2012.

If you need very recent data and you are therefore willing to look at shorter follow-up, I'd point you to a study of intermediate and high risk SBRT-treated patients published by Cleveland Clinic last week. There were only 24 patients (I haven't read the full text yet, so I don't know how they split). With 2 years median f/u, they report 96% biochemical relapse-free survival (bRFS) and no acute or long-term grade 3 urinary or rectal toxicity.

Of course, the "gold standard" for high risk patients is EBRT with a brachy boost. In 2014, Bolderas et al reported on 347 high risk patients who were treated with EBRT with a HDR brachy boost. The 5-yr biochemical recurrence-free survival was 91%, and the late-term grade 3 urinary and rectal toxicity was only 0.8% and 1.6%, respectively. In 2013, Chen et al. at Case Western Reserve reported 94% 4-yr bRFS.

- Allen

Allen, the study was indeed published in 2012. As I mentioned, I had skimmed the study (in my haste to get to a 4th of July event), and I had focused on data collection dates, not data publication dates.

Anyway, your latest post is very useful. In it, you focus (understandably) on urinary and rectal SE's. From both studies you've cited, did you get any sense about the treatment's success in avoiding ED? Dr. Onik's published results included a 94% success rate in "maintaining potency" after first treatment; including retreatments, 74%. That's impressive.

Thanks again for your helpful posts. I have also thought about treatment at the Dattoli Center, which, as you undoubtedly know, features brachytherapy as a core element of its treatment. Boon

Good point about not kidnapping Doug's thread. (Sorry, Doug!)

And, Allen, thanks for your useful thoughts in your posts.

Will start up new thread as needed!

Best to all, Boon

Take another look. The results I showed you - the 93% - were among the 146 high risk patients. Results were of course even better among the lower risk patients.

Al, it is you who needs to take another look, and to be more careful when you quote studies to prove a treatment point, especially when you're not a doctor.

The 146 "high risk" patients included only 13 with Gleason scores of 8, 9, or 10. That fact is quite germane to the vast majority of us on this site who are considering various treatment options.

And my (uncontested) point still stands that, out of the 718 patients in that study, only 13 had Gleason scores of 8, 9, or 10. The great majority of patients, 551, had Gleason scores of just 6. Given the large number of 6's and the tiny number of 8-10's, the study you cited is hardly a persuasive study for the treatment examined. B

Post Edited (Boon1) : 7/10/2016 8:36:32 AM (GMT-6)