Questions, post SRT - what next?

[ken12491]

Hello, fellow members:

Me:

age 67 now

dx - 1/17/17 - G9 - SVI at age 65 ( regional )

RP 2/27/2017

post RP PSA - .81

started ADT lupron on 5/2/17 at MSK PSA went to Nadir 28 days later

T - Levels down to low 20s

T - Levels now 12/17/18 are 421, they were 503 prior to the start of ADT on 5/2/17

stayed at nadir from 5/30/17 till post SRT point on 1/17/18 - PSA went to .19 on 1/17/18

Dr will repeat PSA soon.

Questions/advice

Is BCR after SRT .2 or greater?

How many BCRs does a Dr. use to start treatment again? I heard it depends, could be 2 or 3.

Would that treatment mean - back on ADT?

Is it worthwhile to go back on ADT at such a low level - less the 1.0? My urologist said he would treat at 1.0

My PCP even questioned chasing down the .81 after RP --- however, it made sense to me to treat it, so I did.

A fellow member in this community cited this to me --- net, one could wait till PSA hits 2 to begin ADT if one was asymptomatic? He cited this study:

ncbi.nlm.nih.gov/pmc/articl...

Does anyone have additional ' prediction tools/nanograms that fits my situation? I am really big and hold a lot a faith in them, the bigger, the better - does anyone have opinions on them?

I have two, one from the Clevland Clinic and another one from SMK.

Interesting one from MSK, says, if I plug in my #s, and did absolutely nothing to have treated the PC - only 18% would have died from it - at 15 yrs 23% would have been stuck down form PC. The tool takes into consideration other factors that you might have, that could bring you down, but just 18 and 23 percent from PC...

Here's the link...

webcore.mskcc.org/survey/su...

No proposed treatment has yet been discussed with me and this situation is a moving target, but there are times where I feel the QOF vs treatment that brings you down to have no QOL, may not be for me. To worry from test to test and flip out over a slight increase in PSA just may not be worth it --- but again -- I have to wait and see what if anything is waiting for me. I recall meeting a guy at MSK having RT, after 10 yrs, PSA showed up?

Please try that MSK prediction tool - am I missing something here. When I bought these tools up to my RO, he showed no interest at all.

Comments, ideas would be much appreciated.

thanks, Ken

[GP24]

With a Gleason 9, SVI, regional and a post-RP PSA of .81 you have an aggressive cancer. In the study you cited it says: ".... starting ADT immediately in patients with an aggressive disease."

You could have intermittent ADT, but you should continue with ADT.

I do not like nomograms since they are often based on statistics that are quite old and new treatments became available since then.

[ken12491 in reply to GP24]

GP24 - u have given some good input and I have learned from u b4.... I too know the nomograms might be outdated, but even if outdated --- they show somewhat of a positive outcome --- just wonder how reliable they are..The one I showed in my post was an interesting one--- it was for guys that had NO treatment, so it really doesn't contain ' outdated ' info... Thanks, Ken.

[Tall_Allen]

"Is BCR after SRT .2 or greater?" You didn't give details of your SRT, but I assume they did it right -high dose to prostate bed (72 Gy), pelvic LNs treated (about 50 Gy) up to common iliac LNs, and at least 6 months of adjuvant ADT.

At this point, you can defer ADT as in that retrospective study you cited or you can go for ADT, as in the TOAD prospective randomized clinical trial:

thelancet.com/journals/lano...

Sure signs that it is time to start ADT are (1) detection of metastases (2) Rapid PSADT or (3) high PSA. As you can see in the TOAD trial, QOL was the same. ADT was usually iADT in that trial.

You are using the wrong nomogram. That one shows life expectancy for UNTREATED men.

[ken12491 in reply to Tall_Allen]

Thanks, TA --- no, I was ,meaning to point out that the tool showed ' untreated men ' had a fairly good chance w/o doing anything ---- and I'm thinking since all I had done, my odds would be a bit better --- that was the logic - do u see that, or am I missing something? Let's say, the Dr. gives me all that input, and I say, no --- he then says, looks here, the tool gives u some idea of what u could expect.

You say ' "Is BCR after SRT .2 or greater?" --- what do u mean with the question mark?

Since I was at MSK, I should hope they did it right --- all I know is that the Dr. said; very high doses ' of radiation to the bed ( 15 ) and the 1st 25 went to the surrounding areas. and completely covered the LN area, despite having a scan done 1 day prior to RT that showed no enlarged LNs

[garyi in reply to ken12491]

I believe Allen is asking if your suspected BCR, after your SRT, is 0.2 or more.

[ken12491 in reply to garyi]

hi - it was .19 - that's less then .2

[Tall_Allen in reply to ken12491]

You put in the question mark - I was just quoting you.

[ken12491 in reply to Tall_Allen]

thanks - I was just confirming that a BCR was .2 and above... you are now saying less than .2 is not - i m .19 - too close for comfort.

I remember at one point the dr said to me, that he wanted me at 300 t levels and non-detectable PSAs - to me the inferred medication forever - he never came right other and said that but the implication is there in my opinion.

Is it possible that I will now have a new acceptable nadir? and since my T Levels went from 29 to 421, the .19 might be accepted as the new bench mark?

if it continues to go up what, in your opinion - when did/would YOU start on ADT again? In the end, the Dr and I will decide but you know more than others that have responded to my posts?

This besides having this horrible disease is the worst part - when to act .... .21 or ..26, those #s - you have to wonder, w/o real evidence from a scan, it's so difficult for me and so many others to act. If the QOL didn t factor in, I would stay on them at any level.

I hope you respond to my reply about the MSK prediction tool...

Thank you again for your support/ education.

[Tall_Allen in reply to ken12491]

0.19 is the same as 0.2.

Although it is still too early to convincingly proclaim a benefit to early ADT from the TOAD randomized clinical trial (the only one), it does suggest that early eradication of cancer cells with iADT, reducing the cancer load, has a bigger effect than the selective pressure exerted by ADT. In fact, castration resistance set in EARLIER among those who delayed ADT. Here's what the lead author (Dr. Duchesne) wrote about it:

"The results delivered by this trial have been both unexpected and thought-provoking. Despite the fact that the trial recruitment was prolonged and fell well short of its target, the results are clinically and statistically in favour of immediate intervention when survival and disease progression end points are considered, with hazard ratios around the 0.5 mark. The key clinical point is that we can now advise men what likely lies ahead of them, who is at greater risk if delaying treatment, and what delays they might achieve if that is their choice."

"The results also add further weight to the hypothesis that treating small volume or occult disease is more effective than treating overt disease. This trial was predominantly for patients who had failed curative treatments, but who had only microscopic disease at randomization. This concept obviously underpins the use of adjuvant therapy, but here we are treating only those known to have disease, rather than the whole population most of whom would not benefit from adjuvant therapy. PSA as an early harbinger of relapse is useful indeed."

"Where the unexpected results are concerned, we have the following: firstly that the effects on overall survival are not just from a reduction in prostate cancer deaths but also from deaths from other causes. Other trials have also shown this, which suggests a real finding, the causes of which remain unclear. Secondly, the effects on global health-related quality of life, at least over the first two years, showed no major difference between immediate and delayed therapy, meaning that men may choose to start relatively early with major detriment. This may relate to the use of intermittent schedules for two thirds of both arms, which did not appear to have an impact on disease control (data not shown in the publication), despite the lack of firm evidence supporting its use. An exploratory unplanned analysis in fact suggested that the highest survival rate was seen in men treated with immediate intermittent therapy."

"One of the most thought-provoking findings was that the development of the castration-resistant phase occurred significantly earlier in the men who started treatment after a delay, a counter-intuitive finding. This may again be linked to treating low volume disease before it grows resistant clones."

As for QOL, here's what they found:

thelancet.com/journals/lano...

I have no idea what I would do in your place because I'm not, and everyone is different in what is most important to them.

I don't know what comments you want about the nomogram. Do you hope to live more than 15 years? The nomogram was constructed for the benefit of older men with comorbidities who were diagnosed with PCa but never treated.

[Shooter1]

Didn't have to worry about getting back to PSA1 after robotic asst. rp. Pre-surgery PSA53, 6 week check up PSA 64 and climbing fast. Gleason 9/10 on what was removed. Clear bone scan and ct scan pre surgery. That's what you can call aggressive. 2 1/2 mo later scans showed in lymph nodes (new ones) and 3 bone mets.

2yrs into this on Xtandi and PSA at 0.132. No ADT for life acct, ochiectomy.

[pjoshea13]

The issue of when to start ADT after BCR following primary treatment is complicated [IMO] by the fact that ADT is effective for a limited period of time.

For me, the case for delay would be to delay ADT morbidity & also delay CRPC. One could always use Casodex during the delay period. The PSA doubling time would be a key factor in any decision, of course.

From the CaPSURE study [1]:

"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."

From another recent paper [2]:

"We found no association of salvage androgen deprivation therapy with all-cause or cause specific mortality in most men with biochemical recurrence after primary radical prostatectomy or radiotherapy for clinically localized prostate cancer. Men with quickly progressed disease may derive a clinical benefit from salvage androgen deprivation therapy."

-Patrick

[1] ncbi.nlm.nih.gov/pmc/articl...

[2] jurology.com/article/S0022-...

[Break60]

I’m surprised that your T went from low 20s to 421 from 5/17 to 1/18 yet PSA went from .81 post RO to .19 post SRT. Looks like the SRT caused the decline. How long were you on Lupron?

The classic definition of BCR is two successive PSA readings of .2. Obviously .19 =.2 so you’re there with another reading of .2.

What I did with BCR after SRT is wait til PSA reached between 1 and 2 to get an MRI which found two mets in lymph nodes then I hit ALL pelvic lymph nodes with IMRT . I’ve done the same since using ct pet ( see my profile) and used sbrt to zap bone mets but went back on ADT as well. Zapping oligomets along with systemic therapy is controversial but it’s been my strategy. Gleason 9 needs aggressive tx! I’ve employed intermittent ADT which for me has resulted in ADT lasting so far for 4 1/2 years but I also have been on metformin, celecoxib, Crestor, estradiol and cabergoline. Snuffy Meyers recommendations. “ Whatever works”. Nomograms are SOC which I have not complied with.

Good luck.

Bob

[ken12491 in reply to Break60]

Hi - I was on Lupron, 1st shot May 2017, last one, Feb 2018.... I didn't t expect the t levels would go up so fast -

[Break60]

Ken 12491

If you had gotten a regular (non ultra sensitive) PSA test you would have gotten a result of 0.2 which as I said is .19 rounded to one decimal place. Even .24 would read as .2. You’re making way too much over one hundredth of a point as the basis for restarting treatment. Assuming you got 3 month Lupron shots you were “ done” in May 2018 but residual remains in your system for up to a year. ADT works remarkably well for you, but it would seem that since you’ve had RT to prostate and pelvic lymph nodes you need a pet ct scan if Psa starts to double rapidly.

Bob

[Hidden]

I may sound cold though I do not mean to be, but with a 9, your decision to stop Luoron/Eligard is well ...... T recovered nicely with out suppression, btw. No one will criticize your choice of QOL over cancer treatment...... Good luck in fighting this bastard.

GD

[j-o-h-n]

Ken, who is your MO at MSKcc? In NYC (Kimmel center)?

Good Luck, Good Health and Good Humor.

j-o-h-n Wednesday 01/02/2019 6:58 PM EST

[Hawk56]

So, most common definition for BCR is two successive increases in PSA after surgery where the initial PSA was undetectable. In my case, surgery in Mar 14, PSA undetectable until Sep 15 when it was .2, then in Dec .3, at that time my urologist said "your cancer has returned...!"

Great...at that that time the standard of care was SRT, 39 IMRT, 70.2Gya. There were some emerging studies that said combining some time of ADT, 6-18 months and possibly including the pelvic lymph nodes.

At the same time, Mayo was collecting evidence that the standard treatment field for pelvic lymph node radiation was often not enough as it missed pelvic lymph nodes that were being identified in C11 Choline scans. That would have true with me as after SRT failed, the C11 Choline scan at Mayo showed activity outside of the standard treatment area for pelvic lymph node radiation treatment.

My radiologist talked me out of adding six months of ADT, saying there was not "long term data..." As the SRT was an epic failure, it was clear to me that listening to my radiologist was a mistake, had I combined the ADT with the SRT, well, I might (no, would) have had a different outcome. Two lessons learned from that experience, I consult with my medical team but I decide on the degree of treatment and 2nd, who cares about long term, let's talk about the treatment working for five years and then deal with the next five years as new treatments and imaging come onto play. Not going with a treatment because there is not long term data (10-15 years) may mean passing up an opportunity.

Some thoughts, can you do imaging, either one of the FDA approved ones which are C11 Choline or Aximum, or a clinical trial such as the PMSA...knowing where the PCa is is invaluable in the treatment decision. My radiologist was able to build a better treatment plan with boosts and wider margins to the four pelvic lymph nodes.

You have to weigh quality versus quantity of life in your treatment decision. Many factors go into that, your age, general medical, mental and physical health...I weight quantity with a reasonable QOL, so opted for combined therapies, in my case 19 months of ADT, six cycles of taxotere and 25 more radiation treatments.

That was my decision, overwhelm my PCA in a period where I felt it was vulnerable to a combined regimen. Finished my treatment in May, October PSA was still undetectable, T up to 171. Rather than linear and sequential treatment, each generally destined to fail, I believed that bringing those treatments forward in the disease and combining them would give me the best chance of an elusive cure, if not that, a long progression free survival period and increased overall survival.

As to the nonograms, well, they are population based medicine and often based on historical treatments so ok, but didn't figure into my treatment decisions.

Good luck with your decision. There's lots of guys who can and will relate their experiences and research to aid in your data collection to inform your decision.

Kevin