I'm looking for some wisdom from my learned brothers.
The Urologist who diagnosed me (April 19th) told me that my PC was advanced and I had 'positive margins' which I understand to mean that there is evidence the cancer in my prostate was evident at the very end of at least some of my biopsy cores (10 of 12 cores had cancer present). He said that I could not have surgery because the cancer has almost certainly grown outside of the prostate and therefore surgery was not an option. He sent me for a bone scan which confirmed I have metastasis in many places in my skeleton, with 2 or 3 'significant spots' in my femur and spine.
I consulted a second Urologist for a second opinion and he asked for a PSMA/Pet scan and an MRI and after viewing the results, he said that me cancer was extensive, but he considered that I was a candidate for surgery. He said he had done 1,500 radical prostatectomies and although my case was 'tricky' he was prepared to 'have a go'. He said there are risks of complications, but he believed that he could operate. He also said that most other surgeons would not attempt the procedure (he was a bit cocky, but I don't think that's a bad thing - you want a surgeon who is sure of his abilities).
When I asked him if there was a survival benefit he said 'For sure'. He said that the prostate is the 'cancer factory' and 'de-bulking' the tumor is definitely a good thing.
I have tried to do some research on the subject and I have not found much to support or discredit what he has told me. Much of what I have found is contradictory. One study I found confirmed there is a survival benefit, but the authors admitted the study probably suffered from 'selection bias' as the candidates chosen, probably had a better survival profile than the ones who were not selected for surgery.
I am just wondering if anyone has had to make a decision like the one I have to make and/or whether anyone has any insights into the benefit (or otherwise) of surgery, where one has metastatic prostate cancer, with advanced local PC also.
If I don't go for surgery I have one of the forms of radiation as an option. I can't say why exactly, but I am leaning towards not having the surgery, with all of the resultant complications, but I am open minded.
Thanks in advance.
Paul.
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There has been a change in thinking about surgery with advanced cancer that may of spread past the postate to the pelvic lymph nodes. There is recent studies that have shown positive 10 year survival rates with surgery vs radiation as the first line of treatment. Often surgery can find cancer in the lymph nodes that are not picked up by CT scans. The pathology report gives the doctors better understanding of the cancer. It also leaves open having radiation/hormonal/chemo as secondary treatments. If you have radiation first, you can not have surgery. Surgery does come with some side effects, but they are getting better treating them.
I am 58 and I had a Gleason score of 8, with a CT scan showing it may of spread to at least one lymph node. After considering my options, had Da Vinci surgery April 18, 2016. Pathology report: rare ductal cancer, T3N1, with 1 of 14 lymph nodes removed being full of cancer. Having the surgery gave my doctors a better understanding of the nature of my rare form of prostate cancer which will help them treat it. They would not of had this information if I had radiation first. I am 6 weeks post surgery and my PSA is <0.1. I will start hormonal treatment later this week and radiation once I have better control of my bladder, which is getting better.
When I had surgery 12 years ago, my urologist warned me that if there was lymph node involvement, I would be sewn back up with prostate intact. This, in fact, happened to his other patient of the day, who had "far less serious disease", supposedly.
That was the norm back then, but over the years I have read of the value of debulking via surgery.
Celebrity surgeons concerned about their statistics might pass on men with high Gleasons or PSAs, but there seems to be value for high-risk cases.
I searched PubMed for <prostatectomy[title] "high risk"[title] >:
"The objective of our study is to report the outcome of upfront RP in our patients with high-risk prostate cancer (Stage ≥ cT2c, a pre-operative serum prostate specific antigen >20 ng/ml or a biopsy Gleason score [GS] 8-10)."
"RP provides accurate pathologic staging of patients with high risk prostate cancer, allows better stratification of patients for further adjuvant therapy and either as an initial approach or part of a multimodal regimen, can provide durable local control and provides excellent CSS {cancer specific survival}."
First of all, we need more info---what is your PSA? and what is your Gleason score? These are very important to determine the aggressiveness of the cancer.
And time is of the essence---you need to get treatment as soon as possible; waiting only gives the cancer more time to grow and spread.
I suggest that you look at my own profile---it's too long to type again here.
Learning that you have advanced cancer is devastating at first, but we get past it and move on with our therapies.
Nowadays, the standard treatment, if surgery isn't viable, they'll put a patient on hormone therapy---Firmagon or Lupron (Firmagon is better at first--Lupron produces a testosterone flare when first administered) and bicalutamide, with Avodart fot the "triple blockade." And nowadays, chemo is given also, at the start of the hormone treatments, which most studies indicate increases longevity---hitting the cancer hard and aggressively.
And there are other treatments, but you don't have much time to choose---delay allows more cancer cells to grow and spread. The sooner you get into whatever treatment you and your doctor decide on, the better the results.
Surgery wasn't possible in my case, as the prostate had invaded the bladder and was up against the rectum/colon wall---and was also partially blocking both ureters and bladder outlet. Surgery would have meant removing the bladder and a colostomy, so the hormone therapy shrank the prostate, as well as the extensive lymph gland involvement, and also stabilized the bone metastases to spine and sacrum.
You've begun a difficult journey, and it's not easy, but we can live with prostate cancer, and you're not alone. I'm very surprised that your doctor didn't discuss the hormone therapy with you, and it is another option. Some guys respond very well to the hormone therapy, for ten or twenty years.
Thanks CERICWIN , I didn't add all the info, but my Urologist did discuss ADT and I am currently on a Zolodex with Androcur to control 'flare'. My PSA was 8.5 in Sep 2015 and 15.0 on April 10, 2016 - the day of my biopsy. My biopsy was 12 cores, Gleason 8 in most, but Gleason 10 in 2 cores.
When I was diagnosed nine years ago, there was a very high risk the disease had escaped the prostate, but my scans all appeared clean. I went ahead with surgery. Unfortunately, it turned out my margins were positive. Lymph nodes were negative. I was into hormones and radiation within a few months. If you proceed with surgery, you will not be preempting other treatments. It seems to me that radiation might be the better approach, but it's really up to you and your doctors. Are you seeing docs who specialize in PCa? I think that's the key to your decision--a specialist, not just a urologist/surgeon.
Thanks YostConner . I am seeing a Urologist and a medical Oncologist, who I believe are specialists in PC. I live in Perth, so I believe I am seeing the best available in our location.
I strongly agree with YostConner's recommendation that you should see an oncologist, one who specializes in prostate cancer if possible, and ASAP!! Especially considering that you have bone metastases. Regarding the question of whether protastectomies are beneficial to Stage 4 M1b prostate cancer patients, I was told by MD Anderson that about half their oncologists and urologists believe that prostatectomies for Stage 4 M1b patients are beneficial and about half feel that they are not beneficial. Concerning this, a clinical trial is underway right now at MD Anderson to help answer this very question -- in the clinical trial a patient will receive either Lupron therapy only or a protestectomy + Lupron therapy based on a bernoulli randomization.
I didn't actually address the question: "Surgery or Radiation?"
One of the dirty little secrets of PCa treatment is that the treatment a patient opts for often depends on whether the patient first sees a urologist or an oncologist. I discovered this big time before my surgery.
I was already scheduled for RP when I received a call from the father of an acquaintance. I was living in Virginia, about 40 minutes north of Charlottesville. The caller (who I had never met) asked how I could possibly elect surgery before speaking with Dr Myers, when I was so close?
The caller was a retired doctor who had only just completed radiation in Florida, as recommended by Myers. He went on a bit about the "country club" setting, as though it was a vacation. But, after 90 minutes of being urged to see Myers, I agreed. I called the office & Dr Myers answered. He said that my case was much like his own & he would fit me in at the end on the next day.
I had an appointment with my urologist the next day, & I told him about Myers. Up until then, he hadn't steered me away from radiation, but he said "If he says you should have radiation, get a third opinion - & make sure it's from a urologist!"
"So I'm in Myers' office filling out a lengthy questionaire that seems as much to do with my state of mind than my cancer, & I suddenly realize that I hadn't been asked for insurance details. Stupid of me, but I had never gone to a doctor who didn't accept insurance. I wasn't about to write a check for $1,500.
The two ladies at the desk apologized for not warning me & telling me what the fee was. They seemed very concerned that I was scheduled for surgery that week. I was urged to get a second opinion, & to get it from an oncologist. "Urologists are too eager to cut!"
Now, someone newly diagnosed with PCa should not suddenly find that the experts are at war. Where is the AMA in this?
Anyway, cutting to the chase, while oncologists might claim that urologists are not competent to treat cancer, we have studies that compare survival odds by treatment method. Oncologists say that RP is no longer the gold standard, but RP gives significant 10-year survival advantage.
Before electing surgery 12 years ago, I found an online tool where one entered age, Gleason, stage etc. It returned probability of surviving 10 years. I was shocked to find that, if I were healthy, my probability of surviving 10 years would be a percentage in the low 90's. With RP, the number went down about two points. Doing nothing sent the number down to the high 80's - with radiation adding a mere couple of points. With a 4+% advantage, I was naturally drawn to surgery.
There is a problem when seeking opinions from patients. Even when treatment proved to be ineffective, a patient will be inclined to argue that it was the correct choice. LOL.
I was 56 at RP, so there was no treatment age bias. I had no comorbidities. Statistics get a bit more complicated above age 70. If urologists have a bias towards surgery, it disappears with the age of the patient.
Morbidity issues are serious, regardless of treatment. As Dr. Freedland has said, they are an "expected consequence" of treatment - not a potential "side-effect".
One thing that concerned me about radiation was the increased risk of colon cancer. This appears only after 5 years. Cancer patients have an increased risk of a second cancer type anyway. The numbers are actually not that daunting. Dr Myers - the big fan of radiation - has nonetheless described radiation as "the treatment that keeps on giving." I don't know how significant radiation exposure might be 15-20 years out. Obviously, surgery is clean, from that perspective.
Thanks for the extra info Patrick, very interesting. I have watched a few youtube videos of Dr Meyers and he seems to be at the leading edge in terms of survival of his patients. It's pretty rare to find an Oncologist who also has advanced PC.
Thanks Joe. I haven't yet spoken to a Radiation Oncologist, just a Medical Oncologist and 2 Urologists. My Dad used to say, "Don't ask a barber if you need a haircut". Who would you suggest for the third opinion?
yesterday there was a posting on Health Unlocked by a gentlemen by the name Charles ( Chuck ) Maack. he is a 24 year survivor of P/C and has devoted his life to staying on top of the latest research. i would suggest consulting him. in his posting he provides info. on how to contact him
Ask your Urologist one question. Doc, if you were in my shoes, what would you do? His answer most likely will be to find a Medical Oncologist who specializes in advanced prostate cancer preferable one who is a researcher in academia if he is totally honest with you. Academia and Research where the newest treatments are developed to tackle Stage 4 metastatic prostate cancer.
PS. That is what I did twelve years ago and I haven't looked back....
Thanks Hidden , the medical Oncologist I'm seeing fits your description. By the time I see her next on June 14th, she will have been to some major conference in the US (Chicago I think). I still need to decide how to deal with the primary cancer source.
Please speak with a radiation oncologist who will explain the radiation approach the doctor would recommend for you. Urologist's do not discuss radiation therapy well.
Radiation is capable of debulking the cancer in your prostate as effectively as surgery. It sounds like the surgery being offered would be followed up by radiation fairly quickly. Both surgery and radiation have unattractive side effects. Having both seems to double up on the side effects.
With metatastic PC you are likely to need ADP/ HRT. A medical oncologist usually guides you through this. That's at least three types of doctors you should probably use, more with nutrition advice and alternative treatments considered. Their advice is often conflicting and always self-serving. They like what they do. Just make the decisions you feel are best and execute them well.
Dr. Charles Myers as a medical oncologist, pharmacologist, nutritionist, and metastatic PC patient himself is a good person to guide you along the path. He charges a fee but does not make money from the treatments he recommends.
You have a lot of good years left and a lot of options. Wishing you the best.
The beauty of having this support group is you get perspectives from many different sides based on actual experiences. One can't attach a value to that. It's comforting to be surrounded with brothers here after you find out about your condition. I wished I had this when I started my journey. In the end, it's up to us to make that decision and it seems you may not have time to wait. But you did the right thing in researching and coming to this group.
Surgery vs. radiation? All surgeries are not equal and so with radiations. The problem with PCa is there is not a comprehensive study which type of treatment would be best for a specific type of PCa. As we know, there are many types of PCa and it would be a great tool if biopsy results can tell us which direction to take, because frankly current scan technology can't tell whether our PCa is local or not. In your case, you do know.
Since you have a systemic disease, you will end up with having treatments for systemic disease, no matter what your primary treatment is. The end all question for you, I believe, is what is the quality of life acceptable to you while you battle this disease with treatments from beginning to end that would have some side effects.
Once it's out of the prostate, onc assumes it can be anywhere even if it's just a single cell. No one, I believe, can positively say that one's PCa is local or advanced. For the fortunate ones, PCa may become undetectable or no longer an issue for the rest of their lives. For you and the rest of us, we go through our journey with PCa. So the question of quality of life is paramount. And it's the hardest to answer, because we don't know how we're going to respond to treatments and the side effects of them. The good thing to know is there are a number of treatments now available to prolong our lives.
I now have an undetectable PSA for 9 months. My onc is treating this as a chronic disease and will continue my treatment so long I'm able to manage the side effects. It could have been different to someone who suffered from side effects than I did. Stopping my treatment due to side effects could mean the progression of PCa.
I went with an onc when I found out I had advanced PCa. This is my specific experience. I felt I found a doc ( an hour drive away) who had the expertise (he's both a uro and an onc). After some discussion, I made the decision to entrust my care to him. And so far so good, I pray to the Lord.
Depending on where you live, there maybe a doc that can help you end the debate in yourself. If it's any comfort, you're not alone. I hope we have armed you sufficiently to come up with your questions.
Just like with gourd above, I went with a doc tied to academia and research. And I hope I can say the same thing years down the road, I never look back. It's always early on, as you'll find, you'll have doubts on the decisions you made. Just remember, we make the best stab to battle this and that what makes your decision the best one specific to yours.
Thanks yope4 , very wise words indeed. I've never heard of any Australian doctors who are both Urologist and Oncologist, so I think you are lucky to have found your specialist. I understand that my disease is systemic and I will need treatment which covers my whole body, but I guess I am wondering if the surgery option proposed by my Urologist, improves my chances over Radiation, but I take your point that it's not that simple. As a 49 year old, I also see this as a chronic condition that I may have to live with for the rest of my life, but I have two young daughters and I will do anything to make sure they don't grow up without a Dad. Cheers Paul.
Paul, it was the most difficult decision I ever made in my life. It took me 2 months to decide my mode of primary treatment. At the time, I didn't know I already had mPCa. All of my scans were negative of PCa outside the prostate. In a way, my decision was a lot simpler since my main consideration was which one would have the least side effects I can live with, confident that either one would take care of the local site. In my case, I chose proton radiation. It was painless and I live one hour away from Hampton Rds. where such facility existed.
Micro mPCa can't be detected by todays technology. And the PSA from the micro mPCA is masked by the PSA coming from the prostate. Post radiation, my PSA rapidly declined, then bottomed out. After some bouncing around it started to rise. (an abdomen MRI with endorectal coil showed no recurrence in my prostate). Either choice of primary treatment would not have eliminated my mPCa. This is what we all face and it's why either treatment has "failure".
In your case, you'll have mPCA no matter what your choice is. Again, I have to say all surgeries or all radiations are not equal. Had I known, John Hopkins was the most respected and the most experience on RP, it would have been my choice even if I'm 3 hours away from JH. And among all radiation treatments, I knew that proton was the most precise and targeted with the least damaged to surrounding tissues... it was the choice for me other than surgery.
I can only relate my specific case to you and hopefully, you can draw your conclusions from there. My suggestion is if it's possible, form a team of uros and oncs and have them discuss together your best prospect and present it to you. Having young children would make a world of difference to their recommendation.
It's possible that doctors would consider the management of your treatments after primary treatment the more important and critical to your care. As Bob said above, either surgery or radiation can de-bulk your PCa.
Hi yope4 , thanks very much for your detailed response and apologies for taking so long to respond, I've been overseas and had little internet access during that time. I have heard that Proton Beam Radiation is a good option, but it's not available to Australians to my knowledge, I believe you have to go to South Korea and the costs are huge. Thanks again for your comments.
The cow is out of the barn; Treat the metastasis with radiation on each location when it begins to hurt. There are other treatment plans but this is working for my ribs, vert. hip, and brain. We have decided to treat pain only with meds and radiation. Good luck and God bless. You are welcome to call me anytime and I will be glad to share my experiences.
Thanks Bob, I appreciate your comments and your offer. I live in Australia, but with Google phone etc, it's not an issue calling the US anymore, so I may take you up on your offer one of these days.
I was diagnosed with a Gleason score of 8. PSA from agent orange is a very aggressive cancer. I opted for surgery because surgery is not possible after radiation. I had no signs of cancer in my lymph or bone scans, but after 3 months, my PSA was 0.07 which meant there was still some cancer cells lurking in the margins. Also, the tumor had broken through the prostate. They gave me 26 treatments of external radiation with a hormone shot. I am glad I opted for surgery first. Even though I go to the VA, the doctor's are from Duke Medical center. Seems the VA in Durham and Duke have a close relationship.
In my experience, this is an evolving subject. My diagnosis back in November2015 was similar to yours and I was told that the "standard of care" when cancer was suspected in the lymph system used to be just hormones. Now, they treat it more aggressively if the patient is otherwise healthy and willing. I chose to go the full gamut, received a ADT shot right away, then had an open prostatectomy about 4 weeks after that. My recovery wasn't too bad. I did lose the nerve packets so I do not have normal sexual function now but being alive is more important to me than that. I recovered my continence almost right away fortunately so that is a necessary step for radiation treatments. i am now on Lupron (ADT) and will start radiation July 5. In my view, despite the risk of side effects, I want to do as much as possible to reduce the chance of the cancer coming back. So in addition, I'm eating more healthy and trying to walk for a hour 5 days a week. I am adding a medical oncologist to my treatment team next week. I know that some people feel that their urologist doesn't know anything about cancer treatments, but in my experience that is not true. I don't know that there is a "right" answer to you question, but if you are like me and want to be aggressive, I am happy that i had the surgery. That seemed to keep all my options open. By the way, my urologist ordered something called a Decipher test. You might want to ask about it. We had it done post-surgery but before deciding whether to pursue radiation. The results suggested that radiation is a wise next step for me as I'm still high risk for recurrence. Check it out.
Thanks Chuck, I will look into the Decipher test, thanks for the tip. My Urologist suggested I see a Medical Oncologist and get an ADT therapy in combination with Chemo (Docataxel) as this improves survival and also is likely to shrink the primary tumor prior to surgery. He suggested I have the surgery about 3 months after the chemo.
Hi Paul, Please let us know what your Gleason score is and what the cancer percent was in the core samples. That aside, I have a few thoughts that come from personal experience. I opted for Da Vinci RP at the end of 2014. My Gleason was 9, 4/5 of 12 cores positive, all on left side of prostate, +/- 10% positive for cancer in core samples. Pre-surgery there was signs of perineural invasion on left side, and involvement of left seminal vesical... this was based on pre-surgery CT scan, bone scan, and coil MRI. I opted to do nerve sparing on right side, since no cancer involvement shown in pre-surgery scans. Surgery results after pathology: 1mm positive margin on left side; both seminal vesicals had invasion with focal positive margins on right vesical, 1 of 7 positive lymph nodes. Gleason reduced to 8... the only good news. Two months post surgery, PSA at < .02. Just getting reasonable continence back at month 4 when started radiation therapy, 32 sessions. Also went on Lupron for 6 months concurrently. On the starting day for treatment, PSA had climbed to 0.27. Within a few weeks of ending therapy, I had major incontinence until I got a male sling implant at the end of 2015. Problem solved on that front, from the day after surgery,100% continent ever since!
So, here's what I gleaned from my travails. They saw no positive lymph nodes pre-surgery, and no right side seminal vesical invasion... yet there was. Both were eliminated as by surgery as future means of cancer spread. The positive margins was just bad luck, or judgement error in how far to swing wide for margins around prostate, or unavoidable. I can't look back, but for you, if you go RP, ask for them to swing as far out on margins as possible, even though you have mets to bone. Also, if you have mets, then it would appear you have at least one positive lymph node from which they came. Why not eliminate it or others up front? Also, they will have the prostate cancer samples from pathology to do genetic testing on down the road if needed, the vanguard of cutting edge aggressive prostate cancer therapy. If you have bone mets, unfortunately, you'll probably have to have hormone deprivation. That will end the ability to have an erection while on it. That is one of the main concerns for not having surgery. So the hormone deprivation somewhat negates that argument against surgery. The chance of incontinence is low, but even in my case, where there was removal of the nerve bundle and seminal vesicals, and radiation therapy, and substantial incontinence at a year post op, that problem was fully resolved. Finally, go to a great comprehensive cancer research center.
Thanks Hadley, for your detailed response. I just reviewed my biopsy pathologists report and I'm not sure I know how to answer your specific questions. I did have 11 of 12 cores with cancer present, mostly Gleason 8, but one was a 10. Perth, does not have a specialist cancer centre, but my Oncologist is involved in Academia and does get involved in research trials. I appreciate your comments about your own experience.
A Gleason score of 8 is an aggressive form, and 10 the most aggressive; you need to get into treatment quickly. My own beginning PSA was 744, Gleason 8, 12 out of 12 biopsy samples showing about 95% malignant, with an aggressive form which had already escaped. Scans showed "innumerable" pelvic lymph gland metastases and mets to spine and sacrum. As the prostate had grown so large, it was invading the bladder, partially blocking both ureters and bladder outlet, as well as pushing into the rectum/colon wall. Delay in treatment could have caused complete ureter blockage and kidney damage or worse. The prostate had become very painful, and I couldn't even sit straight on it.
My uro got me into treatment, hormone treatment, just in the nick of time, and the prostate and lymph glands shrank, and bone mets were stabilized. You can see the details on my profile.
Recently, my prostate had a growth spurt, and I had to have twenty radiation treatments to shrink it again---my radiation oncologist characterized it as being, "about the size of an apple," and demonstrating with his hands a medium-size apple. It had become excruciatingly painful again, even moreso than the bone mets.
Slice it dice it nuke it, I've always been a start a the beginning and work towards the end type of guy. In the end you are the one who has live with what ever path you chose, originally my urologist wanted me to do the seed route, said if i we're his dad that's what he would recommend. I said no cut it out and we'll go from there, post opp psa was 0.60 G8 with ece and seminal vesicles , negative margins, pre surgery biopsy showed only two of twelve cores positive. Did the RT and 24 months ADT. I am 18 months post ADT psa 0.01 testosterone 490 fingers crossed it continues. I wish you well, .
I had surgery in 2009, followed by ADT + IMRT very quickly when it turned out (surprise to my surgeon) that PSA post-surgery never went below 1.
Two things mentioned by others that I would reinforce:
Side effects from surgery + RT to prostate bed/pelvic nodes can be expected to be significantly more than from just one of these treatment modes
Not all RT is the same. When exploring this option, I would consider the combo of radioactive seeds implanted in prostate (to achieve max tumor kill in this area) plus EBRT to address areas beyond prostate warranting RT. I know of one patient who researched this topic extensively & elected that approach. In your case, also doing ADT (that you're already on plus chemo (dovetail) seems prudent.
Paul, there's great insight here from many folks. I'm brand new to this community. Just want to offer one other idea. Could you get a biopsy of one of your 'significant spots' either through needle or liquid (liquid = blood biopsy to capture circulating tumor dna) and have that genetically profiled? Can you find a doc in Oz that will do that for you before forcing you through the trial and error of today's standard of care? Everybody's cancer is unique. Here in the states, if your Oncologist pushes insurance hard on molecular profiling (repeatedly) sometimes the payer will throw in towel and cover the costs. Otherwise bone biopsy out of pocket is ~$5k and genetic testing (CLIA certified lab tests focusing on gene panels at big cancer centers = ~$3k, commercial providers like Foundation Medicine probably ~$5-6k). This is why i think it's important: nearly all men with metastatic disease become resistant to ADT, failing first gen (Lupron/Eligard) and ultimately developing resistance to second gen (abiraterone / enzalutimide). But why is it that some guys get multiple years out of these ADTs and some guys get just months or are resistant from day one? I think the answer is in your tumor DNA. Regardless of surgery or radiation, your doc is going to want to start you on ADT because of your bone mets and maybe chemo like docetaxel. Genomic sequencing and the right docs to assess the results may help you pick the right path to take from the get go. Without getting overly scientific, google AR pathway mutations like AR-V7, NCOR1, FOXA1, or PI3K pathway mutations (PIK3CA, PIK3CB, PTEN) or DNA repair pathway (BRCA1, BRCA2) to get a better picture. I have aggressive PCa, spread to bone quickly and I didn't even bother with second gen ADTs after I found my cancer was hyperactive along the PI3K pathway. I've been progression free for 14 months after getting on a Pi3k inhibitor trial.
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