Biochemical recurrence almost 5 years after RP - how urgent is further treatment?

Hello, first post but been lurking for a few weeks now.

I've joined this forum to do research for my husband as we navigate this journey, which doesn't seem to get easier! Sorry, this post is a bit lengthy.

History:
Dec 2011 - PSA 11.78. Lump discovered by DRE, biopsy done - Gleason Grade 4/5 and 4/5 = score of 8/10.  Age 62.

Jan-March 2012 - researched options including radiation, surgery and ADT. Consulted radiologist, 3 surgeons and medical oncologist. Different opinions as to staging.

March 2012 - enrolled in clinical trial for healthy men with aggressive PCa. He was in the arm of 6 months neoadjuvant hormone and chemotherapy (docetaxel every 3 weeks) followed by surgery - vs just surgery. 

Mar-Aug 2012 Continued in clinical trial on hormones and chemotherapy. Serious side effects from both treatments, but PSA dropped steadily from 10.0 (pre-treatment) to 1.06 pre-surgery.

Aug 2012 - left nerve sparing radical prostatectomy. Unable to grade tumor due to treatment effects. No evidence of extraprostatic tumor extension. Seminal vesicles negative for tumor. One periprostatic lymph node positive for metastatic prostatic carcinoma, with extranodal extension. Perineural invasion present.

PSA testing every 3 months on clinical trial. Not ultra sensitive tests, though.

Dec 2013 (15 months) - first detectable PSA at 0.05. Previously all at <0.04.
Jan 2015 (13 months) - doubling to 0.10
Dec 2016 (23 months) - doubling to 0.23
Mar 2017 - 0.22
May 2017 - 0.20 (retested prior to medical oncologist meeting).

Surgeon advised in March that this is now considered a biochemical recurrence. He recommends radiation therapy bracketed by 9 months ADT as best chance for a 'cure'. Referral to radiologist scheduled for late May. GP referral at our request to medical oncologist who supervised the clinical trial scheduled for mid-May.

We rejected radiation therapy initially as the possible long term side effects seemed to outweigh the possible benefits. What's the point of defeating prostate cancer but getting bowel or bladder cancer instead? Seems like radiating the prostate bed now is even more likely to cause other cancers as the prostate is no longer there to shield other organs.

So I have been researching ADT, which he has experience of, but only for 6 months. Not a great option but at least side effects are treatable and mostly reversible?

The big question- With these numbers is just active surveillance an option? 0.20 seems like a pretty low number for almost 5 years out of surgery, and the rate of increase isn't that fast. Hopeful that better treatments are becoming available in the next few years.

Any studies that have looked at this option?

He's an active healthy 68 year old and hopes to live well into his 90s.

Appreciate any insights from members, this board has already been very helpful.
Thanks! Susan

Hi Fairwind, my husband was Gleason 4+4=8, not 10. By the time of his RP, the chemo and hormones appear to have knocked the tumor down and made it difficult to determine its Gleason score. We do agree that blind radiation doesn't make a lot of sense now!

Post Edited (SusanHU) : 5/7/2017 5:38:30 PM (GMT-6)

Susan,
I can't say whether salvage radiation (SRT) is the best course for your husband now. It could well be, or maybe it would be better to go directly to ADT. That's a decision above my pay grade and why you need to consult with an RO and an MO before making a decision. But I hope I can allay your fears about side effects from SRT. The vast majority of people who have SRT come through it with minimal side effects and with little risk of other cancers caused by the SRT. There are exceptions--notably one of our members who was badly damaged by botched SRT--but that is the exception.

Based on everything I know in my 15 years dealing with this disease, active surveillance is not an option for your husband at this point. I wish I could say it were, but with a PSA of 0.2 after surgery and adjuvant ADT, he needs further treatment.

I had SRT with a PSA of 0.44 (way later than called for by today's standards). In the long-run (now 7 years later) it didn't cure my PCa, but it did buy me years of more-or-less normal life before needing to go on ADT which is where I'm headed soon. My only negative effects from SRT were urinary urgency beginning about half-way through the treatments, which resolved about a month after treatments ended; and some intermittent rectal bleeding which began about 8 months after SRT ended and returned to normal about 8-12 months after that.

I'm not worried about additional cancer potentially caused by the SRT, which I consider unlikely in my lifetime. On balance, the benefit of the past 7 years without need for starting ADT was a reasonable trade in exchange for the very small risk of the SRT inducing other cancers.

Please take my experience for what it is worth -- just one person's experience and opinion. But don't rule out SRT if your husband's doctors can present a reasonable case that it may still be curative or may delay start of ADT.

Jim

Hi, many thanks for comments. I'll try to reply to questions.

First, we are in Canada, in the Vancouver area. This probably limited his treatment options, on the other hand his treatments, including surgery, have cost us nothing thus far.

A bit more history:

The surgeon who did the biopsy disagreed with the RO as to staging (Stage 2 vs Stage 3b). Based on a DRE, the RO believed that the tumor had spread to the right seminal vesicles, which were not sampled during the needle biopsy. Accordingly, he was proposing 3D-CRT, not brachytherapy nor IGRT/IMRT, which is "only used if the cancer is just in the prostate, not if pelvic nodes are involved." The radiation would be preceded by hormone therapy for 4-6 months and followed by hormones for a year or more. My subsequent research led me to believe that IMRT was restricted in Canada due to cost, so it seemed that what he was proposing was not well targeted, and we had little confidence in that treatment.

The original surgeon was young and not very experienced. So we sought a second surgical opinion, and also an opinion with a medical oncologist. As luck would have it, the oncologist was recruiting for a North American clinical trial, and the carrot was that the surgery would be done by Dr. Martin Gleave at the Prostate Center (Vancouver General Hospital / University of British Columbia), who is one of the top prostate surgeons in North America, and certainly in Canada. So he enrolled in the trial, and as more luck would have it, was randomized to the arm that got the chemo and hormones before surgery.

Won't go through all the details of his 6 months in hell, followed by RP, but the final result was that there were no positive margins on the tumor, no evidence of spread to the seminal vesicles and just one periprostatic lymph node involved. So not perfect, but we thought they were much better results than if he had gone with either radiation and hormones or RP followed by hormones. And we interpreted the statement 'tumor shows variable treatment effect, precluding accurate Gleason grading' to mean that if anything, the Gleason score would be lower than G8, not higher. Possibly we were overly optimistic!

So here we are 5+ years later with a PSA score that has been slowly rising and seems to be bouncing around a bit, from 0.23 in December to 0.22 in March and 0.20 in May, all above that magic 0.20 number unfortunately.

Fairwind, if the PSA test can't be relied on because the cancer may have mutated and not producing PSA, and it may be years before it will show up on scans (we will find out this month what scans are available to us in Canada, but they will not likely be ultra-sensitive), then it seems to me that we're flying blind.

But I can't see where salvage radiation makes sense now, as you're right, we can't assume it's still in the prostate bed after 5 years. Also, I must say that Tall Allen's post on 'Why salvage radiation is bad' was influential to our thinking:

https://www.healingwell.com/community/default.aspx?f=35&m=3301835

That said, we will be seeing an RO later this month, so will take advice from him too.

I was a business consultant for 25 years, so I'm the researcher, as my husband just finds it too overwhelming and depressing, and research is not his skill set. He's relying on me to advise him on the pros and cons of various treatment options. Although he does want to live into his 90s, quality of life is also a big consideration! I've done a lot of reading (and YouTube viewing!), including it seems every book written on prostate cancer, though as I've no medical background it's been a challenge to sift through the jargon.

What I have concluded is:

A 'cure' is the carrot held out by the cancer industry to encourage men to subject themselves to treatments that may have serious QOL implications.

Because the disease is slow growing, current treatment options are based on older clinical trials. The one my husband was in will continue for another 10 years before concluding whether neo-adjuvant chemo and hormones before RP make a positive difference. If so, that treatment may be 'mainstream' a decade from now (or maybe not, depending on cost considerations).

He will have fewer treatment options in Canada than if he were in the USA covered by good medical insurance. We're seeing the medical oncologist on Wednesday, and we're hopeful he will know what 'state of the art' looks like for these hormone/chemical treatments, as the Prostate Center has a number of very well qualified researchers in this field.

Right now a clinical trial that combined various hormone therapies with immunotherapy would be greatly of interest!

Will keep you posted.
Thanks, Susan

Susan, I applaud your diligence and effective research. Right now no one can tell you where the cancer is as it is unlikely that any kind of scan will show anything at the low current PSA.

Traditionally, salvage radiation to the prostate bed and pelvic lymph nodes is the current step for you, but in many cases the cancer is elsewhere and the radiation wouldn't be effective. That is the dilemma. Certainly, ADT is warranted whether you choose SRT, as it is evident the cancer is on the march, somewhere. Until your husband is castrate resistant, no other treatments would yet be in order.

Have you investigated any other clinical trials that might bring in one of the immunotherapies? Have you discussed Provenge with the MO?

Finally, regarding secondary cancers from radiation. This simply is not a risk factor in determining whether to use SRT. Recent study showed that 3 in 290 men experienced such a secondary cancer over a 20 year period. This is slightly lower than risk you already took with dying from the surgery or complications from the surgery. Not only is this very low risk, but it is mostly based on older, less accurate radiation machinery than is used today. The machines that will be used for any radiation are much more accurate and less damaging to the benign tissues.

Susan,

I had robotic surgery, and two years later had IMRT/IGRT, I too had fears of secondary cancers. After ad nauseam research on the subject I found the risk are VERY low, while payoff are high for a cure. So I had 39 treatments for a total of 70.2 gray. You hear about horror stories of prostate radiotherapy, and I too feared side effects during and after the treatments. My RO told me not to worry (doesn't all doctors say this?), and not to change anything I was doing, including my diet.

Well, I can tell you my 2 months of radiotherapy was a non-event. I suffered ZERO effects during and up to the present, which is 1 1/2 years since completion of radiotherapy. In fact, during my exit exam with the RO (about a week after my completion of radiotherapy) I honestly asked him if they really had the linear accelerator turned on.

BTW, 3D-CRT is an older technology which does increase the potential of side effects. Current technologies include IGRT/IMRT, and VMAT, are more precise and capable of reducing radiation exposure to areas that don't need radiation.

Radiation to the pelvic bed can still be a curative approach for your husband. And ADT can have some serious side effects including coronary artery disease. Depending on your husband health and any other comorbidity factors, ADT might pose a far greater risks than radiotherapy.

With GS9, I would want to throw everything at it in hopes for a cure.

Hi Susan,

On immunotherapies-- the only one approved so far for prostate cancer is Provenge (I'm not sure if Canada offers it), but it is only approved for cancers that are metastatic and castration-resistant. Your husband is hopefully many years away from that situation, When new ones get approved (perhaps Keytruda and ProstVac), they will be for men in that situation first. There is a ProstVac trial at NIH for hormone-sensitive, recurrent PC, but it is a Phase 2 study not scheduled for completion until 2019. If that is successful, they will start recruitment for a larger Phase 3 study (which the FDA requires) with results about 5 years later. By that time, your husband may be metastatic and castration resistant, so it will be irrelevant.

SEs after SRT- yes, it's true that urinary SEs are worse after salvage than primary RT, but I hope you are not exaggerating how bad it is in your mind, and with this long a recovery period, it is much better and approach the primary RT SE rates:

Urinary and sexual healing improved by waiting to start salvage radiation

Secondary cancer risk - yes it is higher, but it is still minuscule. As you can see in the following "In another study by Abdel-Wahab et al. (2009), they found a higher rate – 3.7 RTSPCs per 1,000 - in patients receiving salvage radiation for a recurrence after primary prostatectomy. " And to address your question about 3D-CRT: "The 3DCRT, IMRT, and VMAT plans all had about the same relative risk of RTSPCs of the bladder, rectum and colon." This is a non-issue.

/pcnrv.blogspot.com/2016/08/radiotherapy-induced-second-primary.html

Susan said...
I'm also sure that SRT+ adjuvant ADT will be more effective than either alone, but I've not seen any studies about how much will be attributable to the SRT vs the ADT...

This does not cover its use with N1 PC, but it gives some idea:
/pcnrv.blogspot.com/2016/08/combining-androgen-deprivation-therapy.html

Susan said...
though we may wait to see if the PSA drops below 0.20 on the next test, since it has dropped from 0.23 in December to 0.20 now.

That is almost certainly ill-advised. As I said, 0.2 is already too high, and it makes no difference if it is lower, but can make quite a bit of difference (4 times the risk) if you wait and it goes higher. Again, the situation is even more dire with N1 disease.

/pcnrv.blogspot.com/2016/09/very-early-salvage-radiation-has-up-to.html

I do not think it a good idea to wait for salvage therapy in a man with known N1 PC. Honestly, the cancer may already be systemic and incurable, and I'm surprised that it was let go this long. Once cancer is in the lymph, it can flow anywhere.

Susan
Everyone here has been so nice and polite. Your husband's numbers are at the edge of having a chance at cure or durable remission. I would fire a business consultant that put my business in this much jeopardy. The risks that you are continuing to put forth simply are not validated.
Do I understand correctly, Your husband has node involment- why has he not already had salvage radiation? There should be a sense of urgency in getting things going with a RO not waiting and seeing a MO or waiting for a drop in the next psa. None of that will matter if you continue down your current path and miss your opportunity. My salvage radiation was a non-event and seems to be working. I am sure that your husband is grateful for all you are doing for him. As you already are aware, there are no guarantees on any of your options.

So sorry you all are still fighting the beast.

With a positive node and my Decipher genome test results, MD Anderson Urologist/RO automatically put me on a track for ADT and then SRT.

Hi Susan,

Your informed choice whatever it is, will be the right choice for you and your husband.

Saying that I can completely understand where most of the posts in this thread are coming from. It is to correct the impression you have from another thread and to restate that although there are some risks to radiation, the risks are very low and it is probably the last real curative option your husband has.

It is quite unusual on this site (in fact I cannot remember any recent instance) to advocate speed in getting treatment as many posters on this site often encourage people to slow down. The reason people are advocating speed is that they want the SRT to have the highest chance of being curative and they are aware that at higher PSAs that the chances are higher that it won't be curative.

It is possible that you are not after a cure or you believe that there are other options for a cure that are not understood by people here. It is good that you are speaking to other medical professionals, you will be able to be ask questions from them and come to your own conclusions.

Regards and good luck Susan,
An

A few suggestions to make your meeting more productive...

• Bring your questions in writing and leave space to write down the answers on the spot. (I'm not a fan of recording the conversation. Taking notes forces you to understand the gist or to understand that you don't understand. Listening o an hour long recording is difficult).

• Debrief with your husband immediately afterwards at a coffee shop while it's fresh in your mind. You may find that you heard different things.

• If you have any studies in peer-reviewed professional publications that you would like the doctor to comment on, email them in advance of the meeting with a short note saying "I'd like to discuss this with you tomorrow." Don't throw a bunch of papers at him and expect him to be familiar with it all.

• On the other hand, if he says something that doesn't sound right, there's nothing wrong with saying "That is new info to me and I'd like to learn more about it - is there a reference you can steer me to?"

• Afterwards, I like to send a brief thank you note, briefly summarizing what was discussed and what the next steps are.

Susan
Sorry that you need to be here but you've received great advice. I think my case is illustrative of a typical path of high risk PCa. My signature shows most of my journey . Back in 2013/14 it was accepted doctrine that once PSA post RP reached .2 twice in a row it was considered recurrence and time for SRT along with ADT. Since unlike hubby I had no malignant nodes , I had SRT to prostrate bed only. I quickly had recurrence and when PSA reached 1.2 I had an MRI which found node involvement. So I had IMRT at very high strength to all pelvic nodes along with ADT. Again I had recurrence after ceasing ADT and when PSA reached 2.3 I had a CT PET scan with axumin which found a met in my Right femur. All other areas are clear so the previous treatments worked in the areas treated. But high risk PCa moves faster than treatments. So I'm back on ADT and looking into SBRT to that met which is in a weight bearing bone.
My point here is that when hubby's PSA reached .2 he was at and some would say past the point where SRT with ADT to both the
prostate bed and all lymph nodes was and is warranted.
Further analysis seems unnecessary.
Keep us informed.
Bob

Unfortunately, there is no evidence that spot treating a recurrence in the prostate bed is of any use. Prostate cancer is multi-focal and it spreads multifocally. Just because some of the cancer is visible on a PET scan already tells you nothing about all the cancer that is not yet visible on that PET scan. You have to treat what you can't see as well as what you can see.

A PSA of 0.2 is at the dividing line over which the odds of it being incurable go up four-fold:

/pcnrv.blogspot.com/2016/09/very-early-salvage-radiation-has-up-to.html