Surgery or ? for treatment of recurrent castrate-resistant Pca

Bill

I am glad for your return to this forum. You got a difficult case but your willingness in accepting your fate, no matter the way you may use to kill the bandit, is great news. Your post shows your spirit high and positive. This is a good start for a salvage treatment.

You know that we are no “experts” in PCa affairs but a team of curious so that our opinions are from laymen answering on experiences obtained along our years of survivorship and some researches we come across.

From your descriptions I cannot see a reason to classify your case as hormone refractory or radiation resistant (which term I think it incorrect). You did not share details on the levels and times of the PSA tests to give you a better opinion, but the serum does not decrease that fast. The drugs used in the hormonal protocol also may have not driven you to castrate levels (T lower than 20 ng/dL). Many facts could be behind the reason of your results. Circulating T takes time to “clean up”.

The increase of PSA after radiation is also common in guys with the prostate in place. Localized inflammation is thought to be behind the reason of a surge in PSA. There is a phenomenon called bounce PSA that patients experience after radiotherapy with similar characteristics to those you describe. The PSA results become erratic going up and down for a period that can last 2 to 3 years after the therapy, reaching a nadir much later. Your need for catheterize to void is prove that inflammation is present. Neither ADT nor RT would improve the symptom that fast. Hyperplasia needs to be handled with due drugs.

The negative scans are good news. That is evidence that the cancer may be totally localized which aspect could be render surgery to debulk the whole gland a success. In any case, after RT the surgery may lead to nasty side effects of incontinence as you already found out. By the way, a surgeon cannot distinguish normal from tumor tissue just with the open eye. When dissecting the “flesh” they try taking the most of it to be sure that they catch the whole cancerous tissue.

My suggestion is that you give more time to ascertain of recurrence and that you continue with the adjuvant ADT protocol. You need to get a second opinion about the problem in voiding. A cystoscopy should be done to look for any restriction from the side of the bladder. The second-line hormonal drugs are more “refined” and address intratumoral aspects, and you would not lose anything in taken them if such timing comes in need in the future.

You should have the testosterone tested. Low T and high PSA is the rule to classify you as HT refractorty.

Your previous story is here;
http://csn.cancer.org/node/258414

Best regards and luck in your journey.

VGama 

Bill

I am sorry for the comments on your status. I did not know the details and just wanted to pass you some hits that could be of help in your decisions. You are consulting a good team of physicians and they know well what the best is for you. Dr. Susan Slovin, a medical oncologist and researcher at the MSKCC, gave me precious suggestions when I recurred after surgery (2001) during a nasty “foggy” period of my journey.

I disagree with your concern for posting all the information regarding your case. The worse for cancer patients is not knowing about real facts. I correspond to other PCa forums too, but I like the CSN because it is free of “restrictions”. We can share more openly the details and aspects evolving our problem. It is good to read plain stories of the many survivors, even the nasty ones. It makes us to be more respectful to one another and become closer in the common matter.
Many of you, physicians, for whatever reason it may be, think that we patients are better if kept in the “dark”, so you tend not to be so descriptive or disclose the “baddy” of the story. However, in this forum we go against that principle and discuss openly the feelings even when complaining about our doctor’s appointments and views. Surely you are welcome with or without the concerns.

You got a very difficult cancer to treat. The initial diagnosis with Gleason 9 and voluminous tumour (14 positive cores) plus positive DRE (suggesting extraprostatic invasion) made you to choose RT+ADT. I think you did well. Your fight is still going on and you need to get to a decision with the intent in holding any progression.
Your exchanged posts with Casey (http://csn.cancer.org/node/258414#comment-1368807) on the multimodal therapy approach are a good start to look at for your continuing treatment. I do not suggest surgery yet because of the loss in quality of life and because of the timing so close to RT (8 months). You can do it at a later date as the action would be debulking the gland, which in the presence of ECE does not assure complete cure but longer survival. With that in view, surgery can be done any time, though, keeping in mind that in a later date would allow the cancer to spread further (if nothing is done in-between). The recent negative image exams may consider your case localized yet.

When a case becomes hormone refractory while a guy is having a traditional ADT protocol, it is so considered because the cancer starts using drugs like Casodex (antiandrogens) to satisfy its own food demand. These drugs got similar bio structures as the real stuff and they are available plenty (one is taking it) to feed on. Stopping Casodex one may experience the so called AAWR (withdrawing response). Hormone refractory in such a case should be termed antiandrogen refractory not ADA refractory.
Continuing with a LHRH agonist seems proper because it avoids the circulating testosterone. But it does not stop the cancer from availing androgens from other sources. That is when one must be looking for alternatives.

The first thing should be trying to arrest the PSA down to remission levels. Dr. Myers uses a cocktail with leukine. You could do some researches on the second-line HT drugs used by famous oncologists. Ketoconazole or Zytiga with prednisone avoids the manufacturing of androgens at all levels in the body, including adrenal ones. The cancer itself for survival (Darwin natural selection principle) will produce and refine androgens at low levels but very potent (kind of DHT). Avodart and still better Xtandi work to avoid such refinement of androgens.

The multimodal principle is that cancer must be attacked from several fronts so that it has no chance to recuperate. In fact it goes against the sequentials used up to date in many oncology centres, the NCCN guidelines and the FDA. Cocktails seem to be the way for getting most out of a multimodal therapy in advanced difficult cases. These must be continuously supervised because of possible drugs interaction.

I know of a guy Gs9 that chose “the mother of all treatments”. He started with surgery plus chemo and continued with RT plus ADT, all in a series. He is doing OK with a PSA of less than 0.05. I think that you do not need the help of this “mother” but you should try getting the opinion of an oncologist of the grade of Scholz, Myers or Leibowitz. Your insurance may not cover the cost of the consultation; in any case you can follow the treatment at your local oncologist.

Prostate cancer cells may become more aggressive after been radiated. No one knows what will occur after RT because these affected cells maybe at the timing of mitosis or at the beginning of its life cycle. One may expect different occurrences depending on the timing when the DNA is damaged. The ones that cannot divide because of “bad copy” and die are the ones that may represent the success of the RT. The ones that “managed” to divide with its DNA intact may be the ones you name radio resistant. Chemo may work alike radiation destroying the DNA of cells causing the impossibility of dividing. The scale of a chemo therapy is worse because it affects the whole body (many side effects) while radiation is directional affecting the ones in its target.
I think of RT being instantaneous in its destruction (ionizing) of DNA. The results may take over one year to be seen. It all depends of the time cells take to duplicate in greater number with or without proper genetic materials, for one acertain conclusions.

Looking into your latest PSA histology, I wonder if the result in January 0.34 is in fact the nadir in treatment terms. Your RT ended two month earlier in October, so that there was no down trend verified. The increase could be expected (as we discussed before) due to bounce. When in RT environment one should think that the ADT is not “acting” alone. To expect a lower PSA due to ADT administration is controversial. Inflammation commonly leads to erratic levels independently of the effects of the hormonal manipulations. I see your latest result of 6.43 meaningful in the overall analyses because the biopsy made your PSA going up even in the presence of the ADT effects.
Can you share the PSA and T levels before RT? I guess they were low too, due to ADT (mono therapy period).

I know you are concerned with the increase and I am sorry if I cannot help you. All what I can give are lay opinions. I hope you find a decrease in PSA in three months time, after allowing the biopsy-inflammation to heal. I would suggest you to get by that time another image exam with C11-choline. This may rule out metastases in the lymph nodes (local) or at far places.
I also recommend you to get now a dexa scan and ecg, to monitor any trouble that ADT may cause in the future. Bisphosphonates are typically used in ADT protocols. Care for any deficiency in Vitamin D and be cautious for any anemia condition. These are common aspects in matters with cancer.
Losing of 40 Kg in 10 months is big. You need to care for diets recommended to PCa patients in treatment. Here is a link;
http://cancer.ucsf.edu/_docs/crc/nutrition_prostate.pdf

Best wishes for improvements.

VGama 

How about a trip to Portugal to enjoy the “real” Mediterranean diet and our wines. Let’s meet at the airport.

Mounty said:

your comments and those by VG

 

VG and Mrs. PJD,

Thanks very much again for your comments and insightful questions – I’m happy to hear from both of you again. Twice in the last day I’ve worked for an hour or so on a response that addresses your questions and comments in detail and then saw my text disappear with an errant mouse click. I’m going to try again (with wordprocessing software this time). I apologize for the length.

A month after the onset of ADT, PSA had declined to 26 (from 34) and a month later (at the onset of RT), it was 13. Usually PSA declines by 80% or more within the first 30 days after ADT commences. After RT PSA went from 6 to 1 in three sequential readings in October, November and December before it finally bottomed out at 0.34 in January. (VG, radiation treatment ended in August rather than October, so the interval to nadir was four months, not two.) Combined with the steady increase since then and the absence of erratic fluctuations at any point, I think this means the 0.34 reading in January really was a post radiation nadir. I'm guessing that the absence of erratic fluctuations in PSA as it steadily decreased and then increased again over a period of months argues against post-radiation bounce or some other sporadic factor, like inflammation (although I agree with you VG that inflammation may be contributing).

With regard to questions about a genetic component to the disease, a month ago my wife and I met with a genetics counselor to discuss my extensive family cancer history (early onset Pca diagnosis (Gleason 6, age 41) for a younger brother (a radical RP 11 years ago solved his problem), Pca diagnosis at age 70 in our Dad, who may have had an aggressive tumor but died six years later of other problems; early onset uterine cancer diagnosis in a younger sister (sometime in her 30s; she’s now in her early fifties and is healthy), early onset breast cancer diagnosis in our Mom, who died of breast cancer; and numerous cases of early onset disease in siblings of my parents (all five of my mother’s siblings died of cancer).  This history certainly points to a heritable genetic component.  A screen ordered by the genetics counselor of my DNA for germline mutations in 30 genes that predispose to cancer is underway.  It’s possible this screen may identify a common denominator between the prostate tumor and the two benign tumors.

 VG – note that Casodex was withdrawn about a month ago – we expect (or hope anyway) to see a decline in PSA and slower progression via the mechanism you describe, but won’t know for several weeks until the effects of the recent biopsy and a recent UTI are resolved.  Mrs. PJD – regarding your question about second opinions on the pathology of the primary and imaging studies – I think with this question you’re confusing me with someone else who obtained a second opinion from Epstein at JH regarding their primary. The cores harvested from my prostate last year were read by three sets of pathologists, including those at my institution and pathologists at MSKCC, but not Johns Hopkins. All concurred on the diagnosis of prostatic adenocarcinoma. The biopsy of the leg tumor was not definitive, but pathology of the tumor after it was resected by surgeons at MSK clearly indicated a benign tumor, which is consistent with the earlier diagnosis based on imaging studies by sarcoma doctors where I work.  The cores from the re-biopsy of the prostate in July or of the rib tumor have not been read by a second set of pathologists. Last year’s MRI of the pelvic region indicated SV involvement, but not lymph nodes. This year’s MRI  shortly before the re-biopsy failed to detect lymph node involvement this year as well.

 Recent discussions with clinicians of treatment possibilities going forward (in addition to Casodex withdrawal) have focused on four options: 1. salvage radical prostatectomy; 2. debulking surgery; 3. second-line ADT, including abiraterone and/or enzalutamide, and 4. immunotherapy (Provenge). Both the latter two options would be good ones except that they’re not approved for nonmetastatic disease, and I’m not yet metastatic (thank God! – but it’s ironic that if I had not had the rib yanked out and biopsied, the positive bone scans that detected the rib lesion probably would have been sufficient to convince my insurance company that I was metastatic, and therefore eligible for any of these expensive options. (Most of the clinicians assumed the lesion was metastatic and one even argued I should not bother to have the rib resected because he was certain this was the case – I don’t think anyone was seriously considering  the possibility of a third unrelated tumor). Although I’m extremely happy to be nonmetastatic, this puts us in kind of a tough spot – unlike many other patients who are castrate-resistant, but not metastatic, I’m dealing with an extremely aggressive tumor that’s throwing out PSA at a rapid rate usually seen only in aggressive systemic disease, and more often in much older men. This is creating a sense of urgency about the situation, which I think is what’s driving the argument for many of the clinicians for the surgery options, despite the risks (the vote at the conference was 9 for surgery and 3 against, not the 6 vs. 3 I indicated to VG earlier).

 At the moment I’m disinclined to go with either of the surgery options that have been proposed (salvage RP or debulking), but I haven’t ruled them out – although I’ve also told our friend Tp23 (from last year’s thread) that if I eventually choose surgery, he should whack me on the head with a 2 X 4 until I come to my senses. I’m willing to risk the permanent complications that would likely result if I thought the chance I would be rid of disease was reasonably high, but it’s not. The worst outcome would be permanent bowel and urinary incontinence due to the surgery followed by the onset of aggressive metastatic disease six months later.

 To be honest, I posted to this forum again partly because I’m suffering from fatigue associated with the seemingly endless process of looking for answers to tough questions (Mrs. PJD, you may recall that you lectured me on this topic last year, and it was a very valuable lesson). I was hoping that someone reading my posts would come to the rescue and tell me, “OK, this is what you need to do” and why and then I can just do it, no more questions asked.  This is not the way this stuff sometimes works, of course, especially not with complicated cases like mine. I did, however, momentarily lose sight of the appropriate questions, and this is where both of you have  been enormously helpful once again with your recent posts. It did not occur to me, for example, that the prostate tumor could be evolving into something more aggressive than an adenocarcinoma, or that the read on the rib biopsy might be wrong - and so a second opinion on the re-biopsy cores and the rib slides is warranted. This is a key point, and I’m making arrangements for additional independent reads. It also didn’t occur to me (and I don’t know why other than fatigue!) that if we’re dealing with a prostate tumor that’s evolved into something other than an adenocarcinoma, the source of the rapidly rising PSA could be soft tissue mets, which we haven’t looked for.   I was thinking that the F-18 (NaCl) bone scan (which was in fact a PET/CT scan) was sufficient.  Both of you suggested a C-11 scan, which I had been dismissing as unnecessary but now I realize this was a mistake.  It also did not occur to me that measuring DHT might be informative – I’ll bring this up with the clinicians.  I know very little about HDR Brachytherapy, which has not been discussed (or ruled out) by the clinicians – I’m now looking into it.

VG – you are absolutely correct that it was a mistake to hold back in my previous post on details of my case for the reason I stated. I agree that this forum works so well because of the free exchange of information.  In fact, I’m hoping that this thread will be helpful to others with advanced cases like mine – as we discussed last year, VG, too often those with advanced cases at diagnosis don’t post to this forum, and I feel badly that I stopped posting for more than a year. For others in the same boat but are more recently diagnosed, some of the terminology VG and Mrs. PJD and I are using may not yet be familiar to you.  I’m happy to answer any questions you might have.

Thanks again VG and Mrs. PJD – this has been a big help. Let me know if you have any additional suggestions or questions.  I’ll post on progress in the future.

 P.S. I think you are correct, Mrs. PJD, that the clinician’s comment that “throwing new drugs” at the problem would not have much of an effect would be unprofessional, but only in other contexts  (an office visit between patient and clinician, for example). But in this case, I think it was OK. It was made at a clinical conference that involved a spirited debate about my case that reflected the clinicians’ frustrations as well as mine. It was directed at other clinicians more than it was at me. VG, the best medicine might be a trip to Portugal, which I’m planning to make when I can.  I will keep you posted on this as well!

 

Mounty said:

High Risk PCa

In fact I did not understand the subtlety of your earlier question of what Dr. Jon Epstein’s at Johns Hopkins take was on the earlier prostate tumor biopsy, which as I indicated earlier, was analyzed by three sets of pathologists, including those at my institution and at MSKCC, but not pathologists at JH. It’s difficult to parse the information content of subtle comments like yours made in a forum that I expect to involve straightforward information. Perhaps Dr. Epstein is “the best”, as you suggest, but I rely on far more information than the suggestions of anonymous contributors to forums like this one when making decisions about which experts are best to assess the clinical data relevant to my case, and I think this process should be respected.  Social networking cancer forums like this one are, in fact, useful, but in my case they certainly haven’t been a substitute for medical websites and other resources that contain more rigorously evaluated information, which is especially easy for me to access as a scientist. One reason I haven’t posted at this forum for more than a year is because of the amount of time I’ve spent tracking down information elsewhere. In any case, your earlier posts identified some useful approaches that I had not considered – this one, not so much. I’m not sure exactly what I said that deserved this response.

 

Not sure what upset you as nothing I wrote was meant to do so. Sorry you took it that way and out of context. I could say the same thing--that I’m not sure exactly what I said that deserved your unkind response, subtle or not. 

Bill

You are in the good track. You got the puzzle pieces and now you need to set them into the right places.

I read above in one of your posts that you will make a decision, starting with an investigation on your present “real” status. What kind of cancer cells do I have and to which extent is the cancer localized. This is important to know before you continue with any aggressive radical treatment, with intent at cure.

With your latest information regarding the time of HT and RT and tests, I would think that you have an earlier recurrence, but ………… ???????????? …………………… there could be some doubts in the judgement of the biochemical failure. There are no statistics for levels of PSA in combo treatments (RT+HT) but a much lower level and faster should be expected to occur after neoadjuvant HT plus RT. If RT has been alone in the setting, the “fast drop” of PSA after RT would be related to RT failure (decreases less than 12 months are linked with earlier recurrences). This could be judged that the cancer is not just localized. How to find its hidden place should take prime attention.

Interestingly, if the cancer is found at fewer places (your above comment) you still got a good weapon to kill the bandit. Spot RT is possible at some places as far as its newer location does not fall within the field of previous isodose planning. At the same area, RT is not recommended for a period of 5 years (norms of tissue radiation absorption limits). The danger would be fistulas. Another salvage treatment to consider after radiation treatments is cryotherapy to freeze the prostate gland to kill any remaining cancer cells. Salvage surgery is always controversial. A renowned professor and expert in medical oncology and urologic cance says this;

Some highly skilled surgeons can perform a salvage prostatectomy, but the larger consideration is whether it is worth doing at all. One could make a strong argument that in most cases, rising PSA after radiation therapy indicates systemic disease, and any type of local therapy — even salvage prostatectomy — is not going to solve the larger problem of cancer cells that have metastasized elsewhere. For those cells, you need hormone therapy

In any case, if the continuing therapy is that for the destruction of the DNA (your family cancer genetics), chemo may be useful at this stage. I would suggest you to do some researches (common to you as a scientist, right?) into the matter while waiting for the above discussed tests and exams. Look for the latest chemo compounds (eg; Jevtana, etc), and find out about the useful typical additions to HT protocols such as; leukine for reinforcement of the immune, revlimid, emcyt, thalidomide and angiostatin for avoiding formation of new blood vessels, samarium, and strontium to reinforce bone avoiding those cysts that can turn PCa, etc.
Drugs that complement CAD protocols could include; Proscar (5-ARI), Celebrex (anti-inflammatory), Calcitriol (vit D). You may also add Climera patches to counter the side effects from hypogonadism.

Another though is the use of estrogens in your case with female related cancer family. DES is something in use around the world but not so frenzy in the USA. You could use patches on/off periods and control the period with levels of PSA.

Independently of what you are going to take, I would suggest you to add more tests to your periodical PSA+T, for means of monitoring and control. These biomarkers are secreted by cancers similar to your conditions. These are; PAP (prostatic acid phosphatase), CEA (carcinoembryonic antigen), NSE (neuron specific enolase) and CGA (chromogranin A).

I am giving you a good set of home work. This is easy for you to solve because of your close medical “family”. I am sorry if some members of this forum are straight forward with opinions that may hurt the feelings. We all want just to help. You are passing a bad chapter in your life, but it will improve. I would recommend you to continue this thread posting at the end not in between to get a better narration and understanding of our discussions.

Best wishes and luck in the decisions ahead.

VGama   

Come on. The Autumn may be the best timing for visiting Tras-os-Montes e Alto Douro and enjoy the local produces. Regain of Peace of Mind is assured.