• Progression-free survival (PFS) was 11.9 mo. for metastasis-directed therapy (MDT) vs. 5.9 mos. for observation. (HR=0.44)
• Radiographic progression-free survival (rPFS) was not significantly different
• Time to castration resistance was not significantly different
• Overall survival was not significantly different
• PFS increased by about 5-6 months regardless of whether there were high-risk mutations (BRCA, ATM, RB1, TP53).
• rPFS did not significantly increase for either risk group.
What may mislead patients is the endpoint used in this analysis.
Progression-free survival (PFS) =a PSA rise or radiographic progression or new symptoms or initiation of ADT or death.
In 52.5 months, there was very low mortality, asymptomatic local control is good. Initiation of ADT is always based on PSA rise or radiographic progression. So with no difference in radiographic progression (rPFS), the difference between PFS and rPFS is just PSA. Therefore, the extended follow-up found that MDT only treated PSA without any real impact on survival or progression of the cancer. Future trials will determine if there is any real benefit.
How did they define MDT in these trials? Were all treated with ADT? Now that PSMA PET studies are available the studies need to be repeated as the accuracy of older radiologic techniques may have assigned subjects inappropriately to the oligometastatic category. Did they do a subanalysis based onthe selection of initial treatment?
1-3 mets defined oligometastatic in both trials. In the ORIOLE trial, conventional (bone scan/CT or MRI) imaging was used. However, they also checked it with PSMA PET and found that there was only a PFS advantage only when all metastases found with both conventional imaging were also found with PSMA. Choline PET was used in the STOMP trial.
None were treated with ADT.
Initial treatment was predominantly RP , and some had salvage RT.
There are several limitations to this report. First, the genomic analysis did not have an a priori end point and was based on small sample size. Thus, prospective validation is needed. Second, differing imaging modalities were used (conventional in ORIOLE and choline in STOMP) and with the introduction of PSMA, how we define omCSPC might change in the future. Nevertheless, these data provide a framework to investigate such questions in the future.
In conclusion, long-term outcomes of STOMP and ORIOLE demonstrate sustained benefit to MDT over observation in omCSPC. Genomic alterations appear to have prognostic value in this patient population, suggesting that biomarkers should be evaluated in future studies to optimize patient selection.
My point (as I wrote) is that these two Phase 2 trials, even when extended and combined to increase statistical reliability, failed to provide any indication that MDT delays metastatic progression or increases survival.
I'm not certain that I understand the premise of this study.
That is you have a metastatic tumor and you treat it with presumably radiation, you have a better outcome than if you do nothing?
And this might vary based on yet to be determined biomarkers?
"In conclusion, long-term outcomes of STOMP and ORIOLE demonstrate sustained benefit to MDT over observation in omCSPC. Genomic alterations appear to have prognostic value in this patient population, suggesting that biomarkers should be evaluated in future studies to optimize patient selection."
In the discussion section at the bottom there was this tidbit
“There are several limitations to this report. …..2) differing imaging modalities were used (conventional in ORIOLE and choline in STOMP) and with the introduction of PSMA, how we define omCSPC might change in the future.”
With psma scans now becoming more common, being able to pick things up months or even years sooner, the debate will likely continue.
It cuts both ways. 3 mets on a conventional scan would likely mean more than 3 on a psma scan, but 3 mets on a psma scan you are now seeing things that were not previously seen.
Not for nothing but zapping those bastards offers hope. Even if its a small chance of a durable remission, its still a chance.
Having hope helps
Keeping you away from hormone therapy also has quality of life benefits.
I can also say that my MO has indicated that we will definitely be playing whack a mole until i get mets that cannot be safely zapped.
The last paragraph of the report concluded
“In conclusion, long-term outcomes of STOMP and ORIOLE demonstrate sustained benefit to MDT over observation in omCSPC.”
If you are only interested in treating PSA, it is positive. Most men are interested in preventing new metastases and extending survival. This analysis did not show that MDT did either.
I'm not saying that it doesn't help, I'm just saying there is no evidence yet to support that.
Thx for your comments TA. However this is very frustrating for us laymen. You imply no real benefit for MDT. However the study authors say :
“The primary end point was progression-free survival (PFS) calculated using the Kaplan-Meier method.”
And then they say;
“Long-term outcomes from the only two randomized trials in omCSPC suggest a sustained clinical benefit to MDT over observation. “
The two conclusions from the same studies seem on opposite planets. Do you think they are interpreting their own results incorrectly because they are erroneously correlating lower PSA with a “clinical benefit”? Why would they be so blind to what you seem to believe is obvious?
Read my comments. I posted this explanation because I knew many patients (and doctors) would misinterpret the study. If you have questions about my explanation, I would be glad to respond. Confirmation bias can blind anyone.
So you think the Mets they zap go away and reduce the PSA they were producing…. but nothing occurs to slow the advance of the infinite micro mets that will keep growing and kill you in the same amount of time, whether you zapped a few early mets or not?
I don't know. And neither does anyone else, which is very much the point. Until we know more. what is the harm of zapping a few early metastases where it is safe?
The breast cancer randomized trial (NRG BR-002) of SBRT (+ standard of care (SOC)) to oligometastatic breast cancer failed to slow progression or increase survival over SOC alone. There were 125 patients (65 SBRT+SOC, 60 SOC). An expanded trial was canceled due to futility.
But maybe MDT does something for prostate cancer? We shall see. Meanwhile, I think it is a mistake to forgo ADT just because metastases have been zapped and PSA is lower.
Retrospectively, DeBleser reported on over 500 patients treated with 6 months of ADT + SBRT to all oligorecurrent metastases (detected with C-11 Choline PET scans). They found no benefit if there were any distant metastases at all. There are similar prospective randomized trials in place. You can read about the study here:
I think the interpretation of these studies and their application is complicated both by the advent of PSMA as well as the heterogenous nature of subject group. Studies like support moving beyond the "findings" and the importance of skilled clinicians who can determine the applicability of a published study to your individual situation. This is best handed at an NCCN Center of Excellence by a GU oncology specialist.
Tran did use PSMA PET in ORIOLE to confirm what he found on conventional imaging. He found that there was no benefit even in PFS if there were any untreated metastases.
Sadly, there are some clinicians, even at NCCN hospitals who misunderstand this, because the endpoint used is misleading.
Does this mean that radiating my extended lymph node chain beyond the two adjacent to my prostate that showed uptake, does not offer any better long term survival?
No. N1 (pelvic lymph node metastases) is different from M1 (distant metastases) . N1 treatment may be curative if the entire pelvic lymph node area is treated:
I have mets in 2 lymph nodes. I wonder if the mets in local pelvic lymph can spread easily since I am mitigating with bicalutimide monotherapy. (150mg /day) - PSA went from 12 to .25 in weeks with this and very few side effects...
Should there be a rush to do radiotherapy to the pelvis...?
Onco will not answer this question reasonably and seems the drive is just to push more treatment.
There's nothing in your profile, so I'm guessing that you've had a prostatectomy, If they are in pelvic lymph nodes (stage N1), you can still be cured with whole pelvic salvage radiation and 2-3 years of hormone therapy. You should talk to a radiation oncologist.
You shouldn't radiate your lymph nodes beyond pelvis.
The best would be not to radiate your lymph nodes at all if you know that the extended lymph node chain is infected with cancer.
You should have only global therapy and no local therapy except later local therapy for paliation. (Xofigo extends life but can be deployed only when you develop bone pain).
Newly diagnosed patients should use global therapy (for the case like yours.):
ADT and early chemotherapy and Provenge then Enzalutamide
when Enzalutamide fails liquid biopsy at PSA above 5 or even better 10.
Then depending on the actionable mutations you could have Olaparib or Keytruda etc.
Until now I personally had 4 PSMA PET scans every 2 weeks, starting day zero (the same time as I started ADT) then after week 8 I had early chemotherapy 6 cycles of Docetaxel. ADT is for life for me.
I am not a doctor but I would do like this. Contact your MO for your specific case.
Here is a recent review with a more positive view on met-directed radiotherapy. From the International Journal of Radiation Oncology, Biology, Physics, July 22, 2022.doi.org/10.1016/j.ijrobp.20...
"The role of radiotherapy in systemic prostate cancer has historically been limited and palliative in
nature, but recent studies demonstrate the value of radiotherapy–especially metastasis-directed SABR–
in patients with limited metastases. This effect is noted in both hormone-sensitive and hormone-
resistant prostate cancer, with significant improvements in biochemical and radiologic progression-free
survival noted in both settings. Based on this review of the existing literature on radiotherapy in
oligometastatic prostate cancer, we recommend that SABR for metastatic sites be considered, especially
for patients with three or fewer metastases for whom significant local tumor control and progression-free survival have been demonstrated."
We have to be very careful not to mix apples and oranges.
What is good for you may not be helpful for others.
I fully understand that they are talking about oligometastatic prostate cancer up to 3 mets.
Unfortunately I have at least 15 bone mets and I am not sure what else.
I was explicitly told by my MO to do only global therapies. I asked him why he said that I should do Xofigo last and he replied to me that Xofigo is a local therapy.
We understand that Xofigo extends life and I also understand that bone pain paliation will be very important. I said to someone that yes Xofigo is very expensive and administration is complex but when you are in pain you would do everything and pay all your money.
Therefore I don't underestimate the value of local therapies but you can't expect to extend life in my situation with local therapies.
If you are low volume than you could maybe hope for the best with local therapies. Your life expectancy is probably longer than mine.
You can get it when your PSA is only 0.5 but there is no guarantee that they would find anything in my situation (i still have a prostate). Therefore it is better for me to wait until PSA 1 or even better 2 with the PSMA PET scan as if they don't find anything I would need to repeat it. The radiation sums up.
I am interested if the cancer did spread to my brain and to see if I am a candidate for spinal cord compression?
I can't give you any advice on this, it's beyond my capacity. But it seems you know what you are doing. I can only wish you the very best of luck on your journey.
The authors write: "In conclusion, long-term outcomes of STOMP and ORIOLE
demonstrate sustained benefit to MDT over observation in omCSPC" (oligometastatic castration-sensitive prostate cancer). The primary outcome measure was defined as "ADT free survival" for STOMP and "Progression at 6 Months" (mostly PSA progression) for ORIOLE. These trials were not designed to provide different results, e.g. overall survival.
I think you should combine ADT with MDT as it is done with salvage radiation. However, the trials wanted to be able to report results quickly. This would not be possible, if they tested the combination of ADT and MDT.
PSA is not always a good indicator of progression as seen by these results. PSA response is often used as an early indication, makes sense but should be taken with a grain of salt.
No, based on what? There is still no proof of benefit, so if safe, why not? There is some proof that it enables men who are on iADT to have longer vacations, but there is no proof that iADT is as good as continuous ADT in the first place. It is definitely a bad idea to forgo ADT entirely when PSA is reduced by MDT.
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Apalutamide for Metastatic Castration-Sensitive Prostate Cancer
Time to PSA Nadir is related to progression-free-survival
