- G9 PCa with recent biochemical recurrence after 2016 RP and adjuvant radiation and ADT therapy. Two years undetectable, then 0.4 in September and 0.8 in October.
- Met with Dr. Mario Eisenberger on 10/10/18 at Johns Hopkins. His recommendation was to check my PSA level in 3 months to determine PSADT (the 0.8 result was subsequent to that visit). He also did not recommend starting ADT until the PSA reaches 10.
- Met with local MO yesterday and we discussed doing an Axumin scan "soon" and the likelihood of starting treatment (possibly ADT & Zytiga) in January...well before hitting the arbitrary 10 that JH referenced. We also decided to send some tissue off to Foundation One for testing.
Questions:
- Is it worth doing the Axumin scan now or should I wait until my PSA rises and increases the odds of finding imagable mets?
- From the limited sample size my PSA has doubled in 6 weeks, which is obviously bad news. Can you get an accurate PSADT from just a few data points, and with relatively low values? If so, I'm more inclined to follow the local MO's recommendation to start treatment earlier than the JH recommendation.
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Most MOs look for one of 3 signs to begin lifelong ADT. Either (1) a detectable metastasis, (2) a rapid doubling time or (3) a high PSA (e.g., 10). It's true that you should have a third PSA reading to compute an accurate PSADT.
Thanks Allen. Any thoughts about the benefit to me of having an Axumin scan now while my PSA is relatively low (0.8)? It’s been approved by my insurance but as I understand it, it isn’t as sensitive at low PSA levels as the G68-PSMA scans. I’ve thought about having the Axumin scan now and if it doesn’t show anything perhaps pay for the G68-PSMA scan at UCLA. Would that be a sensible approach in your opinion?
You have to consider what difference it would make in your treatment decision. If you're going to go on ADT anyway based on your PSADT, why bother? It may only serve to create anxiety.
The MO thinking is that ADT & Zytiga is likely “early in the new year”. The scans I’m contemplating would be in advance of that. The hope would be that it discloses oligometastatic PCa that could lead to a different treatment decision. IF this is a reasonable hope then the question becomes which scan, Axumin or PSMA, gives the best chance of returning an actionable result (if there is one)? If the Axumin scan (ins paid) “works” then no need to spend the money for the more sensitive PSMA. If it doesn’t work then pay for the more sensitive scan. Is this a reasonable approach?
Tall Allen you’re definitely the wiz kid here but question. You say most MO’s wait but didn’t most of them wait to do Zytega and chemo until the studies showed that earlier had huge advantages in life extension? Doesn’t it seem to reason that early is better ? Why wait ?
In general, earlier is better. But there are exceptions. Chemo, for example, doesn't increase survival in men with few mets. My guess is there is an optimal timing for immunotherapy too (not too early and not too late). The reason to wait for lifelong ADT is for the freedom from symptoms of ADT. The TOAD RCT suggests that earlier is better, but we will be more certain if they do 8 years of f/u.
With a psa of 0.8 a psma pet/ct wil have more sensivity than an axumin scan. If you have metastases an adequate treatment could be started without waiting for a psa of 10 and bigger metastases. It may be possible to get a psma pet/ct at ucla or ucsf. They are not covered by insurance. I am in a similar situation and the plan is to get a psma pet when the psa is around 0.3.
Gleason 8. 2016 DaVinci removal and 3 months later 39 radiation sessions. Have had persistent PSA since removal. It doubled from beginning radiation and the time I finished. In at 0.042 out at 0.080. Doubling rate has been every 3 to 4 months to last PSA blood work last month. My only exception was a consistent low PSA. I am currently as of the 1st of October 1.7 . I am part of the trial at UCSF for GA68-PSMA and had this last month (October 12th). No scan (3)before has shown anything. The GA68 came back multiple lesions ,10+both lungs. Various sizes 9mm and smaller.
My MO already has me back to UCSF for second opinion next Monday. Lung only mets is very atypical . The doctor he wanted me to see was booked through December. He got this doctor to see me first thing Monday morning. My MO is worried that I can't wait until January of next year. He and I impressed with GA68-PSMA.
There is another scan trial you might want to look at. It is run by NIH, and there is no cost to the patient. You have to get yourself to Bethesda, Maryland, but they provide partial reimbursement for travel and lodging. Check out trial NCT03181867. They are recruiting now. It is also PSMA-based using the (18)F]DCFPyL radiotracer agent, I believe it is slightly newer than the Ga68 agent. One of the benefits of this trial is that it includes an MRI. That way you get the benefit of the PET scan and the MRI, giving the doctors information on both the location and the degree of activity in the tumors.
"Androgen deprivation therapy (ADT) is the first line of therapy for advanced prostate cancer [1]. However, the optimal timing to administer ADT is unknown in patients diagnosed with localized disease and treated with curative intention that later present a PSA-only relapse (no symptoms, no detectable metastasis)[2]. Specifically, there are no published randomized trials of immediate versus deferred ADT initiation in this subset of patients [3]. The American Society of Clinical Oncology guidelines state that “the Panel cannot make a strong recommendation for the early use of ADT”, and that “the critical issue is to determine whether there is benefit and how large it is for starting ADT while patients are asymptomatic” [4].
"Randomized controlled trials have shown that castration of asymptomatic patients not suitable for curative treatment resulted in longer time to disease progression [5,6] and lower prostate cancer mortality [4,7] as compared with castration at symptom onset. On the other hand, deferring ADT until overt progression (metastases or symptoms) may preserve quality of life [6,8,9] and cognitive function [10] for a longer period.
"An intermediate strategy for patients with PSA-only relapse would be to use PSA levels and clinical events to decide the timing of ADT initiation. The National Comprehensive Cancer Network considers asymptomatic patients with rising PSA level as a “therapeutic dilemma regarding the role of ADT” [11]. Given the strong association of PSA dynamics (i.e. PSA doubling time) with disease progression and prognosis [12–14], PSA evolution and clinical events-based initiation may provide the optimal balance between deferring ADT for patients who do not need it and starting ADT immediately in patients with an aggressive disease. Results from an ongoing phase III clinical trial that uses PSA and clinical events-based ADT initiation are not yet available [ClinicalTrials.gov identifier: NCT00110162]."
"Our study suggests little or no survival benefit of immediate ADT initiation compared with deferred ADT initiation (at clinical progression) among prostate cancer patients with PSA-only relapse. No survival comparisons between ADT initiation strategies guided by PSA and clinical events have been previously reported for patients with biochemical-only relapse. Therefore our study provides at least a first approximation to answer the “when to start ADT” question in these patients.
"Two randomized trials have compared immediate versus deferred ADT in other types of prostate cancer patients. The EORTC 30891 trial [6,27] compared deferred ADT at symptomatic progression versus immediate ADT (either orchiectomy or LHRH-agonist) in 985 patients not eligible for curative treatment. This trial found a 21% increased mortality (95% CI: 5% to 39%) and no differences in prostate cancer mortality (HR 1.05, 95% CI 0.83-1.33). About 26% of trial participants assigned to deferred initiation died without fulfilling criteria to start ADT, and only 55% of those who started ADT did so according to the protocol. The MRC PR03 trial [28] compared immediate versus deferred ADT initiation at clinical indication for treatment (criteria for “clinical indication” left to the treating physician) in 938 patients with locally advanced or asymptomatic metastatic prostate cancer. This trial found lower prostate cancer mortality, but not lower overall mortality, in the immediate treatment arm [7].
"An observational study compared early versus late ADT initiation in patients with PSA-only relapse using observational data from the Department of Defense Center for Prostate Disease Research Database [29]. This study did not find a lower metastasis-free survival (overall survival was not evaluated) for early ADT, but the study results are hard to interpret because the analysis (i) was based on “prevalent” users rather than “incident” users, which may result in selection bias [30], and (ii) adjusted for PSA using standard regression, which may introduce bias because PSA is a time-varying confounder. Standard regression may not appropriately adjust for time-varying confounders affected by treatment [31]. The magnitude and direction of these potential biases cannot be predicted and their results should be taken with caution. In contrast, our study uses incident users and adjusts for time-varying confounders using inverse probability weighing to emulate the NCT00110162 trial. This methodology has been previously used to appropriately adjust for confounding in several clinical applications [23,25,32]. Had we used a naïve approach such as standard outcome regression with time-varying variables, the adjustment for confounding would have been incomplete (all-cause mortality HR 1.16, 95% CI 0.73-1.83).
"Like any observational study, the validity of our estimates requires that all baseline and time-varying confounders are correctly measured. This requirement is especially important in our study because our estimates suggest that there is substantial confounding. The HR in the unadjusted analysis (2.12) went down considerably after adjusting for baseline confounders (1.51), probably because physicians tend to initiate ADT earlier in those patients with worse prognosis (e.g. higher Gleason grade). The HR moved even closer to the null (0.91) after adjusting for time-varying PSA, Karnofsky functional status, fatigue and bone pain. The effect of adjustment was even more evident when analyzing prostate-specific mortality. The downward movement of the HR with increasing levels of adjustment makes it conceivable that immediate ADT initiation might actually be beneficial, but that our adjustment for confounding was incomplete.
"In summary, our study provides evidence on the when to start ADT question. In the absence of randomized trial results, our findings suggest that starting ADT at PSA relapse does not have a major impact on overall survival compared with deferred ADT initiation at disease progression."
Thanks Patrick, those studies certainly seem to support the Johns Hopkins inclination to wait longer than most before beginning ADT. My local MO is of the opinion that a rapid PSADT trumps the benefit (freedom from side effects) of waiting. Hard to go against JH advice...but a current (though early) PSADT of 6 weeks is sobering.
I am in a similar situation as you right now. My oncologist wants me to get the Auxumin scan so he can have those results and then move forward with the proper treatment. My PSA has doubled every 6 weeks and is now 2.70. Our previous visit it was 1.34 and he wanted the best scan for the money and felt like we should wait for it to be a bit higher. I am all in favor because I also want to see the scan. Waiting for the PSA to hit 10 is risky and the scan does not need it to be that high to be effective according to what I have been told and what I have read. You make the call that works best for you.
Thanks Rick, we do indeed seem to be on the same rocky path. Has your MO expressed an opinion on how long you should wait (how high your PSA s/b) before having a scan? Also, have you considered the G68-PSMA scan? From what I’ve read, those are even more sensitive and therefore more likely to work at lower PSA levels. Of course those are not covered by insurance but trials apparently are available - though I know little about them at this point. I also see that UCLA offers the test for $2,650. The question in my mind is - is there a tangible advantage in getting scan results earlier? The answer helps inform the decision about when to do the Axumin scan...or to potentially get an even earlier result with the PSMA scan. The problem is, no one really knows that answer. Intuitively, earlier seems better than later so long as you wait long enough that the scan of choice “works”. But...how long is that? My MO wants to proceed now (at 0.8) with the Axumin. Sounds like your wanted to wait longer. As you said, ultimately we have to make the call that’s right for us.
He did feel like it would be better at 2 or 3 then when it was under. He was concerned that waiting too long would risk it going to the bones. Hopefully it is not already there. The old PET scans required you to be at 10 to be effective, but that is the beauty of this now. It is also covered by insurance, but still pricy out of pocket unless you are already there. I went to the Auxumin website and it helped me feel better informed as well.
I share in this same dilemma; RALP, G9, ECE and a detectable PSA (1.5) post surgery in 2014. Follow on ADT (9 Mo Lupron) and 35 sessions IMRT at 70 Gy but some confusing PSA values before commencing ADT (PSA dropped from 1.5 to 0.22 and then to <0.1 with no conventional treatment). PSA dropped to undetectable during the ADT and remained undetectable throughout radiation and after until PSA bounces detectable to undetectable in 2016. Recently, 7 straight PSA increases peaking at 0.846 Jan 2018 but dropping on the next two checks with no treatment to 0.7, then to 0.136? Last PSA Sep 2018 up again to 0.268.
I too have considered one of the advanced scans but have been discouraged by the accuracy of the results in the lower ranges of PSA. Also, the points raised by Tall Allen and pjoshea13 regarding the impact on treatment decisions and when to initiate. My current understanding is that resumption of ADT ( with positive scan) would be recommended as SOC at the very least. The underlying theory seems to be that the PCa is systemic at that point. Depending on the scan results as to location and on the agressiveness of the treating physician(s), additional second and third tiers of treatment (based on PSA kinetics and tumor location/number?) may be recommended.
Then there are the research results showing that (1) ADT typically becomes ineffective at 18-24 months, (2) 8 years from BCR to detectable Mets (3) QOL implications of ADT+ if Assymtomatic and in reasonable health (4) conflicting results on early vs late initiation of ADT and/or 2nd level therapies. No doubt I may have some selection bias going on in avoiding a resumption of ADT and/or ? for as long as possible. And then there are the complementary/alternative possibilities being discussed on this and other forums.
I should add that I feel blessed to be in this current predicament and in otherwise excellent health. I plan to continue to follow these and other sources of information while monitoring PSA, requesting consults, and trying to reach an informed decision on where to go from here.
Your present state will like be my husband's future in a few months. Our uro-onc has proposed that when the PSA is sufficiently high for good accuracy, the plan is to do a Ga 68 scan and radiate any mets found. The argument is that ablative radiotherapy will be more effective while he's hormone sensitive.
If your PSADT continues at this rate, your PSA will be over 12 in January. That is well within the range of even a bone scan/CT. The benefit of oligometastatic treatment is questionable, but letting the cancer proliferate with a doubling time this rapid is unquestionable.
At the current 6 week doubling rate and today’s 0.8 value, I calculate a PSA around 3.2 in late January. Am I missing something? Does the rate escalate over time?
My error. You wrote "0.4 in September, 0.8 in October... so it could be 1.6 in November, 3.2 in December, 6.4 in January, and 12.8 in February" The rate may or may not change over time. Whatever it is by January, it will be detectable by ANY PET scan if you allow it to continue at that rate.
Sorry for the confusion. To be precise the 0.4 was 9/11. Two weeks (9/25) later retested at 0.5. The monthly test will begin from there. 10/25 was 0.8...hence the current (early) PSADT of 6 weeks. At this rate it projects out to 3.2 by 1/25/19 I believe.
I am in a somewhat similar place, but it has been a few years to get here. The Axumin looks to be an excellent idea. I will look for results when using Axumin with PSA of 3. VS Watchful Waiting until PSA is higher.
I'm also gleason 9 with fast psadt. I had the axumin scan when psa reached 2.0 to ensure best results. It found a femur met which I treated with SBRT of 27 gy in three sessions. But I also went back on ADT3 and started xgeva. After stopping ADT3 after 13 months, my psa again started to rise, doubling in two months. So I had PSMA Ga 68 ct pet when psa was 1.9 which found focal radiotracer uptake in right scapula and left third rib. CT Scan did not correlate. So I restarted ADT3 to see if I'm castrate resistant and restarted xgeva. I'm planning SBRT to the two new mets. No radiotracer uptake was found in any area previously treated with radiation (pelvic lymph nodes, prostate bed and femur) nor in any other soft tissue. If psa does not decline I'll start second line ADT.
It's recently been proven that treatment of oligomets with radiation is effective in increasing survival.
Agreed...but sometimes you have to take chance in advance of that evidence. It seems like a reasonable chance to take if it doesn’t take away from, or delay standard therapy. With my current set of circumstances, my MO tells me that I’m looking at survival of 3-5 years with standard care. So... what have I got to lose?
I very much agree. I think it can be used in some cases where it is SAFE to do so. But safety is not guaranteed. In the study that Bob is referring to, 3 of about 67 men who received SBRT for oligometastases DIED as a direct result of their treatment: "one from a pulmonary abscess; one from subdural hemorrhage after surgery to repair a SABR-related perforated gastric ulcer, and one from radiation pneumonitis." in addition, 30% of SBRT treated men had grade 2+ adverse events. Sometimes the treatment is worse than the disease.
One man in my support group asked an RO for treatment of his 3 metastases. The RO would only treat 1 of the 3. He found another RO who agreed to treat them all. He has suffered from digestive problems since, and within a few months, more mets had become detectable.
Understood. Like most things in life it comes down to the cost benefit equation. If I was being told that my time horizon was 10-12 years then I’d have a different risk tolerance than I have with my current 3-5 span. I don’t want to take foolish risks but any option has to be viewed within the context of my PCa’s aggression level.
No. Metastases from, say, lung cancer, are very different from metastases from prostate cancer. Their whole natural history and prognosis is different.
The radiation oncology center that yreated me in 2000 reccommended scan after psa reaches exceeds 1.0. At that point sensitivity and soecificity reach acceptable levels they said. So thats what i did. My doubling time, however was about 6 months so did not have long to wait
The PET/CT Axumin scan is recommended for those that have biochemical recurrence. That's the 3 lab tests (minimum) to show the rise. It also can be used to calculate your PSADT, as mentioned by others here. According to Radiologists and MO I have spoken with and the Axumin website, the higher the PSA, the more accurate the scan but that's true of all PET scans. Their rule of thumb is PSA of 2 to get a 75% level of accuracy. Obviously,if you wait longer, the accuracy of the scan goes up but so too do your risks for losing the upper hand over any aggressive version of this disease.
I am scheduling getting one after a year past BR because I went back on Lupron after finding out, which lowers your PSA, making the scan less accurate. Ihave now been off Lupron for 6 months and have a doubling time of .8 months and a PSA of 2.14. My Gleason 9, biochemical recurrence, PSADT and reaching the minimum threshold of PSA of 2 is why I am getting the scan. Even if it shows no mets, I will have a snapshot of what's going in my body and have some information to guide treatment.... do I go back on Lupron, EBRT, both or some other treatment that targets my specific condition.
Same to you my friend. Have you considered any of the several G68-PSMA scan clinical trials? Since you’ve already reached the 2 threshold you mentioned for 75% accuracy it may not be worth the hassle. I’m just below 1 but doubling quickly so I’m investigating that angle as a way to scan early.
If you review my profile you’ll see that I had scans at Psa readings between 1.2 and 2.3 and then had ADT3 and focal radiation, as I’ve been oligometastatic with, in my case , 2 or less mets albeit fast Psa doubling time. I’m also gl9 and consider myself fortunate to have few mets upon recurrence. I hope you are as fortunate. Waiting til Psa reaches 10 seems strange to me since the latest ct pet scans are very accurate at 2.0. So why wait to get axumin or PSMA scans?
No way I’m waiting until my PSA reaches 10. The last reading in October was 0.8. Monday (11/26) is the next blood draw. I expect the PSA will be > 1. That’s the threshold I was targeting.
My local MO also convinced me to seek out one more opinion before scanning and starting treatment. So Thursday 11/29 I visit Dr. Matt Smith up at Mass. General in Boston. When setting up that appointment I asked if I should have the scan in advance of my visit - they indicated that it would be wise to talk with him first.
BTW, I did some investigation on the PSMA trials and was unsuccessful in getting into any, except the one at UCSF. That’s apparently one in which you pay (after submitting to insurance). I’m not sure what the likelihood is that insurance would pay for any of that so at this point the Axumin scan is Plan A unless I hear something to the contrary from Dr Smith this week.
I don't know if any of these trials allow men who already have had SRT, but you can call...
If you are recurrent after prostatectomy (which you are), you can have a Ga-68-PSMA PET scan done at UCLA for $2650, which is their cost. Call Johannes Czernin:
The PSMA scan at UCSF, which as I pointed out is cheaper, does not disqualify you if you had prior treatments including SRT, but I believe they required that you not be on ADT for a while . I had been off ADT for about 3 1/2 months ( that is my last 3 month shot was 6 1/2 months prior on March 31) when I had the PSMA scan in mid October.
Thanks Bob. I’m still working full time and too young for Medicare. A preliminary check indicates that my insurance won’t cover any of it - though there is an appeal process. If the Axumin does the trick then why fight city hall? I guess the answer is to get an earlier picture of what’s going on. If someone said definitely that it would make a difference doing a PSMA scan now vs. waiting to do the Axumin when my PSA hits 2, then I’d gladly take on the insurance fight and be prepared to pay out of pocket. But so far no one has made that statement - no doubt because it’s impossible to say. Monday’s blood test and Thursday’s doctor appointment will give me new input into the decision.
I honestly don't think a scan now will make a difference in your decision. I think the bigger question is whether you are more comfortable starting ADT now or waiting for some other indicator (bone scan/CT - detectable met, high PSA, or rapid PSADT). There is moderate evidence from the TOAD trial that there is an advantage to starting earlier, but the trial was small and only has 5-yr results so far, which is too early. I think Matt Smith is very good - let us know what he says.
Both the axumin scan and the PSMA scan are more sensitive at Psa of 2.0. If your Psa is rising so slowly that you’re afraid to wait until it reaches 2.0, you’re lucky and less likely to have worrisome cancer .
Since my psa doubled in two months “waiting” was not my problem!
Hi Bob - It’s unlikely to be much of a wait for me either; my current PSA is 1.1 and the PSADT is 1.7 months. After meeting with Dr. Matthew Smith in Boston yesterday I’ve decided to do the Axumin scan in early January. I post an update on how that consultation went once I get home - flying back to Florida now.
Twelve months ago I paid out of pocket $4,500 for Axumin PET scan in Birmingham with a PSADT of 2.7 months and a PSA which should have been around 2 to 2.5 based on PSA readings month before and after. The scan showed nothing but I appeared to have early excretion of the agent through the urinary tract system which affects about 10% of patients and can obscure uptake in the prostate bed area. A bad scan administration time pelvic window can also cause the urinary tract to light up. The PET center had done about 50 scans and I asked for a third scan read by a PET center in Atlanta and they said the scan results were inconclusive and recommended another Axumin scan to be performed. (Maybe because of early excretion or that I had had a kidney stone removed out of my ureter a week before the scan which was stupid because my ureter and kidney lit up on the scan??) I couldn't afford another scan but was able to qualify for a clinical trial where I was assigned to the Enzalutamide mono-therapy open label arm in May before which my PSA was around 8. I analyzed the lower resolution Axumin and CT scan results for hours and hours slice by slice think I found what could have been a been a sclerotic lesion in my lower vertebrae. I emailed the slice to the PET facility that did the scan and the radiologist did not change their report nor did they comment on it. My urologist said that what I found was very interesting and he wanted to hear their opinion but nothing ever came of it. He requested a more sensitive MRI bone tracer specific scan but Blue Cross Blue Shield of Alabama would not approve. The Axumin PET is not as useful in picking up bone metastasis .
I don't mean to go on and on here but am simply saying that when you have recurrence it is a rocky road navigating reimbursement and bumping around healthcare providers like a pinball machine with some flippers that don't work. I just hope I have enough energy at the end of the game to jostle the machine with my hips like I used to see the older boys due to at the arcade when I was a wee lad in the 1970s. Anyone have another quarter?
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First phone visit with academic hospital on my biochemical recurrence post robotic radical prostatectomy (University of Wisconsin - Madison)
Axumin PET Scans?
Axumin verses Bonescan
