Salvage Radiation Therapy with or without ADT added?

@animate
You are very welcome : ).

It is really so hard to make decision - for the longest time ADT was always involved in sRT. But, now that they conducted studies looking into different cohorts of patients it seems that it is not always necessary.

My husband has very high Decipher and is gleason 9 with cribriform and IDC so he has to have ADT for 6 months, no matter what his PSA is.

Talk to your RO and also perhaps seek a second opinion - or maybe just be on a safe side and take Orgovyx for 6 mos . ? I know that I would, but I am "zero risk" person in general lol.

Wishing you super successful sRT with zero side effects 🍀 !

@animate I understand your fears concerning cardiac issues with ADT; but if you have no uncontrolled co-morbidities (treatable with meds) or history of stroke or ischemic heart disease, it should not be a problem.
I would check with a cardiologist for sure before deciding…Best,
Phil

@animate With Lupron you are stuck once they stick the needle in you regardless of the side effects. A 3-month shot of Lupron will suppress testosterone for 6 months or more. You need to count the recovery time since the side effects are primarily due to lack of testosterone, not the drug. It is unlikely your doctor is counting the recovery time. Being young there is only a slight chance you will not fully recover (chances go up the longer on ADT and older you are). Use it or lose it applies with ADT. My testes decreased by about 40% in 6 months on Orgovyx. Recovered about 80% of testosterone in 7 weeks. Had some recovery of testes. I did not have hot flashes, etc. but that is reported by over 50% even with Orgovyx. ADT does improve the effectiveness of radiation, but it might be overkill in your case. With positive margins and a clean PSMA PET, it is probably in the pelvic region.

@animate That’s good that you previously had a PSMA PET scan that showed something; that means that you (probably) aren’t one of the ~15% that are PSMA-negative. (It’s “probably” because even within one person, some prostate cancers can be PSMA-positive, and some not.)

Yes, the results of a PSMA PET scan can impact how treatment is managed.

As for ADT helping or hurting you, isn’t that the way it is with every aspect of prostate cancer diagnosis and treatment? Everything seems to hurt and/or help. But, prostate cancer is a bad-ass disease, and you have to hit it appropriately the first time - not too soft or it’ll come back; not to hard or you risk serious side-effects (that might even be worse than the cancer itself). Finding that “Goldilocks zone” is the goal. For me, ADT fit into that “Goldilocks zone.

My proton radiation treatments (April-May 2021) were my primary treatments. Prior to that, I was on active surveillance for about 9 years. So, I had plenty of time to look into all treatments and pick the one that fit my priorities the best.

There really wasn’t much to recover from the treatments. My wife later told me that if she hadn’t known I was undergoing radiation treatments, she wouldn’t have realized it from any change in me. And the short amount of time that I was gone each day for treatment were no different than any other time when I simply left to go shopping or to the gym.

I had minimal side-effects from the ADT due to the low testosterone - just mild “warm” flashes, significant muscle atrophy (w/about a 30% loss of strength), and my libido went to zero (but, never had ED). When testosterone returned, all those side-effects subsided.

I agree with @brianjarvis on the encouragement to exercise. There is strong evidence that the types of exercise program exercise oncologists, especially Rob Newton, have been advocating for years can counter the side effects of ADT, as well as provide as significant an additional survival benefit as other first line treatments such as chemo, or ADT.

@brianjarvis
Brian - you said that you lost about 30% of strength. Does that mean that you lost muscle even with regular exercise ?
Were you able to rebuild your muscle and strength ?

@surftohealth88 Yes. I’ve spent 2-3 days/week in the gym for as long as I can remember so, I know my strength levels.

But, without testosterone - due to the ADT - muscle mass, and the strength that comes with them, is impossible to maintain. (My testosterone level dropped at one point to 3.0 ng/dL, but typically remained in the high teens to low twenties.)

The key is to begin resistance-training exercises well before starting ADT, maintain throughout, and continue beyond,

Interestingly, having had just two Eligard injections - one in April 2021, the 2nd (& final) in July 2021 - I recall telling my wife (in late January 2022), that I thought the Eligard was wearing off because I was beginning to lift heavier weights at the gym. Since I wasn’t due for another “official” bloodwork for another couple of months, I self-ordered another PSA & testosterone test, and those came back as 0.13 & 403.0, respectively, showing everything was going exactly as expected - that is, PSA staying low and testosterone slowly increasing as the Eligard was leaving my system. The muscles and strength all slowly returned.

May be pertinent...
https://www.urotoday.com/conference-highlights/apccc-2026/168595-apccc-2026-in-which-patients-is-metastases-directed-therapy-without-systemic-therapy-sufficient.html

Prostate Cancer News, Reviews & Views
Sunday, August 28, 2016

Combining Androgen Deprivation Therapy (ADT) and Salvage Radiation Therapy (SRT) improves outcomes

For the first time, a randomized clinical trial (GETUG-AFU 16) proves that adding a short course of ADT to SRT improves the progression-free survival over SRT alone. This confirms the implications of several earlier studies, and is not especially surprising. Many radiation oncologists already integrate ADT into their SRT treatments of selected patients.

Carrie et al. (updated 5/2019) conducted a multi-institutional study in France on 743 patients with the following characteristics:
· Randomized for SRT between 2006 and 2010
· All had undetectable PSA post-prostatectomy
· PSA≥0.2 ng/ml and < 2 ng/ml at study entry
· Stage pT2 (54%) or pT3 (46%)
· Positive margins (51%)
· Seminal Vesicle Involvement (SVI) (13%)
· No positive lymph nodes or signs of progressive disease
· PSA doubling time> 6 months (74%)
· Gleason 7-10 (76%)
· Median age – 67 years
Low Risk = Gleason 7, negative margins, PSADT>8 months and no SVI
High Risk= all others
The treatment consisted of:
· External beam RT: 66 Gy to prostate bed ± pelvic lymph node radiation
· 369 patients received 6 months of goserelin, 374 received no hormone therapy

After a median of 112 months of follow up, the results were:

10-year progression-free survival was 46% lower without ADT (HR=0.54)
HR=0.47 among low risk patients
HR=0.56 among high-risk patients

10-year metastasis-free survival was 75% with ADT, 69% without ADT (HR=0.73)
Acute toxicities: 89% with ADT, 79% without ADT
· No difference in Grade 3 acute toxicities
· No difference in late toxicities

Based on this, the authors conclude, “RT+HT could be considered as the standard in this situation.” The authors are of course privy to data we have not yet seen. It behooves us to further explore this rich source of information, to the extent that the sample size permits, to help determine which patients are most likely to benefit from the combined modality. There may be some with, say, low Gleason score, Stage pT2, small positive margins, and low, slowly rising PSA levels who do not need ADT, or may even be safely watched. Others, with evidence of systemic micrometastases may benefit from even more extensive ADT (see below).

Timing of the initiation of SRT is an issue in this study. SRT was delayed until there was a confirmed indication of biochemical recurrence (PSA≥0.2 ng/ml). However, three randomized clinical trials published after this study started have confirmed the benefit in biochemical control of beginning radiation much sooner in PSA progression. It is unclear whether ADT would have been as beneficial or necessary at all had therapy begun when PSA reached 0.03 ng/ml on an ultrasensitive test.

Several randomized clinical trials have demonstrated a benefit to adding ADT to RT for first-line treatment of advanced prostate cancer. There have been several retrospective analyses that hinted that ADT could enhance the effectiveness of SRT as well. Cortés-González et al. in Sweden reported a 4-year biochemical no evidence of disease of 63% among men treated with 3 months of hormone therapy before SRT. Choo et al. in Toronto reported a 7-year freedom from relapse rate of 79% among men treated with 2 years of ADT after SRT. Pai et al. in Vancouver reported 5-year biochemical disease-free survival of 80% if they had adjuvant radiation with ADT pre-treatment, but 67% without the pre-treatment; and 62% if they had salvage radiation with ADT pre-treatment, but only 27% without the pre-treatment.

An earlier randomized clinical trial (RTOG 9601) proved that 2 years of anti-androgen therapy with bicalutamide improved the 7-yr freedom from progression to 57% compared to 40% for SRT alone. Incidence of metastases was also significantly reduced, and toxicity was about the same, except for an increase in gynecomastia and liver toxicity. Howard Sandler added this comment:
"So, in my view, 9601 endorses ADT or bicalutamide for men with elevated PSAs after surgery, but most rad oncs have a PSA threshold: if the PSA is low, then RT alone, if the PSA is high, RT+ADT. There is variation in this threshold. My own personal threshold is 0.5 ng/mL."

Further evidence for the systemic effect of ADT came from a retrospective study by Soto et al. at the University of Michigan. They reported that concurrent ADT was beneficial only among those who had been originally diagnosed as high risk (the group most likely to evince micrometastases).

Among the factors yet to be learned are the optimum duration and timing of the added ADT. In a retrospective study, Jackson et al. at the University of Michigan reported 5-year incidence of distant metastases was 6% if they received more than 12 months of additional ADT after SRT, but 23% if they received less than 12 months of additional ADT. In fact, every month of ADT was associated with a 10% reduction in biochemical failure, distant metastases, and mortality.

(Update 3/21/2019) Fossati et al. identified 3 risk factors that determined optimal duration of adjuvant ADT with salvage RT:
Stage ≥ pT3b
Gleason score ≥ 8
PSA≥ 0.5 ng/ml

Men with 2 or 3 risk factors benefited from up to 3 years of adjuvant ADT; men with 1 of the 3 benefited from up to 12 months of ADT; men with no risk factors did not benefit from adjuvant ADT.

12 years ago when my PSA hit .2, 3.5 years After a prostatectomy, They gave me a six month Lupron shot and two months later I had eight weeks of salvage radiation. That was just considered standard of care back then.

The American Society of clinical oncology has this to say about it

From Ascopubs about what PSA to do salvage radiation.
≤0.2 ng/mL:
Starting at this level maximizes disease control and long-term survival. Patients treated at PSA < 0.2 ng/mL achieve higher rates of undetectable post-SRT PSA (56-70%) and improved 5-year progression-free survival (62.7-75%).
Delaying SRT beyond PSA ≥0.25 ng/mL increases mortality risk by ~50%.

0.2–0.5 ng/mL:
Still effective, particularly for patients with low-risk features (e.g., Gleason ≤7, slow PSA doubling time). The Journal of Clinical Oncology recommends SRT before PSA exceeds 0.25 ng/mL to preserve curative potential.

0.5–1.0 ng/mL:
Salvage radiation remains beneficial but may require combining with androgen deprivation therapy (ADT) for higher-risk cases.

This article discusses the above;
https://ascopost.com/news/march-2023/psa-level-at-time-of-salvage-radiation-therapy-after-radical-prostatectomy-and-risk-of-all-cause-mortality/
Some recent studies have shown that giving ADT at the same time as salvage radiation, or right after it is completed, actually may be more effective than giving it before radiation.