Need thoughts on whether my physician is on the right track recommending only 6 months of ADT (Lupron). I'm early 60s and very fit. Just completed salvage radiation to PB and PLN and 6-month Lupron shot. Radiation therapy began 6 months following RALP. Happy to get off ADT (usual side effects, but not terrible), but some risk factors have me questioning the decision not to continue ADT in some form. Most notable in my mind: (1) PSA test 6 weeks out from RALP (Sept 3, 2021) was unmeasurable, but at 3 months PSA was climbing and by 4-5 months from RALP PSA was 0.4 ng/ml, doubling time was 0.1 years; slope log (PSA) 4.7; velocity 1.2 ng/mL/yr (from MSKCC calculators); (2) Decipher score 0.99; (3) surgical path: 80-85% Pattern 4; cribriform architecture w/ductal component; intraductal carcinoma; perineural invasion; extra prostatic extension (focal); negative margins. The ADT decision seems focused heavily on Gleason score (downgraded at post-surgery to 7 (4+3) from biopsy score of 9 (4+5) (details in bio), negative Pylarify imaging, and lack of node involvement. I understand we can let ADT work its way out of my system and watch PSA levels, but my PSA has always been low (never exceeded 3.5 ng/ml notwithstanding bilateral tumor of significant volume and biopsy G9 score), somewhat undermining my confidence in PSA as an early warning indicator of growth or spread. Thanks for any thoughts you can provide!
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CHICAGO — It may be time to revisit clinical guidelines for a subset of patients with prostate cancer, say researchers.
Current guidelines recommend all men be offered hormone therapy when receiving salvage radiotherapy (SRT) following prostate cancer surgery and subsequent biochemical recurrence.
But a new, secondary analysis of a major clinical trial in this setting now indicates that one treatment plan may not fit all.
"Our data demonstrate that men with lower PSAs are more harmed then helped by long-term hormone therapy," said lead author Daniel Spratt, MD, an associate professor of radiation oncology and chair of the Genitourinary Clinical Research program at the University of Michigan Rogel Cancer Center, Ann Arbor.
Initial findings from this major trial — NRG Oncology/RTOG 9601 — found that adding 2 years of anti-androgen therapy to postoperative radiation therapy in patients with recurrent disease increased overall long term survival. The results of that study led to the recommendation that this population should be treated with both radiation and long-term hormone therapy after surgery.
However, the new subset analysis of these data shows that men with low PSA levels after prostate surgery gained no overall survival benefit from long-term hormone therapy and, in fact, it greatly increased their risk of dying from other causes.
Patients with PSA levels less than or equal to 0.6 ng/mL were twice as likely to die from causes other than cancer when hormone therapy was added to their treatment regimen, and the greatest mortality risk was among those with the lowest PSA levels (0.2-0.3 ng/mL).
There are some brand new data (it hasn't yet been published) out on this subject. Here's what we knew before the new data, which explains why only 6 months of ADT was recommended:
But the new (last week!) data from the RADICALS-HD trial show that long-term (24 months) adjuvant ADT can significantly increase metastasis-free survival compared to 6 months or no ADT. The difference is particularly important for high-risk cases like yours:
My comment was related to the RADICALS HD trial, which as many before that, was not pre-sRT PSA stratified. It was not meant for the PSA of the OP. Finally, the results of said trial are already obsolete as the metastases FS was decided by pre-PSMA imaging. We now very well know that a percentage of those previously thought of as non-metastatic are indeed metastatic when imaged with PSMA PET/CT. This percentage rises with PSA at imaging, thing that explains the prognostic value of the pre-sRT PSA. By today's imaging capabilities only patients with a clean PSMA scan should be eligible in trials bearing MFS endpoints.
There is no doubt that the MFS benefit of long-term ADT would have been better with PSMA screening. That makes the findings more important, not obsolete.
I would get a second opinion from a reputable GUMO, but if your side effects are not severe I would be inclined towards a longer course too.
Important that your doctor knows you are handling the Lupron well. Many docs are becoming sensitive to its reputation and reacting to that, prescribing shorter courses. The data will always improve but it can take a long time.
Personally, I consider ‘dying from causes other than cancer’ to be extremely likely and highly underrated. Most of us will be taken out by heart disease, Lupron only hastens it. We should exercise hard and regularly to prevent that, but instead too many of us conceptualize it and worry about cancer instead.
It’s good news on the downgraded Gleason to 4+3 from RARP. And your choice to have SRT to both the prostate bed and PLN fields is the right one, especially with no activity outside the pelvis on PSMA PET.
As for duration of adjuvant ADT with SRT, the clinical trials in metastatic disease clearly favored two years or up to 30 months. However, the trial patients were mostly more advanced. And ADT is certainly not innocuous and accrues harm to the body. I faced this same dilemma when I had SRT to pelvic nodes as I was also Gleason 4+3, non metastatic on PSMA, and had a similarly low PSA around 0.4 at time of treatment.
That last is a key point. A subgroup analysis in one of the large trials found that 6 months ADT was equivalent to longer in those with low PSA at the start. Given that, I opted for just six months as my 2 ROs suggested. It is a difficult decision and perhaps there is more information from trials on this that has come out since 2019. You might as well see how it goes for the six months and how well you tolerate ADT and are able to maintain muscle and strength on it. Then you can choose whether to continue based upon that. But I do not believe it is necessarily wrong for you to discontinue ADT after six months, especially if it is causing sarcopenia, etc. Good luck. Paul
Mr. Ethanol (for medicinal purposes I presume 🤣), in that ESMO interview I note that the 2 years ADT vs none improved 10 year “event free survival “ from 72% to 78%. Significant statistically (.03) but not a huge numerical difference. Did not see Hazard Ratio confidence intervals on the slide. So I still stand that it is your personal choice with no slam-dunk answer for everyone. Just one opinion and I am biased in that my body really does not do well on ADT.
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