It's been a couple of months. My dad, newly diagnosed with metastasized PC, has suffered many discomforts from Docetaxel and other medicines prescribed for treatment. Despite the blood clot in his neck, hives, extreme fatigue, neutropenia, bone pain, nausea....etc......his PSA came down from 1200 to 20. We are pleased with the results! Genetic testing determined that he did not have any Germline mutations, although many in his family are BRCA2 positive. However, testing on his biopsied lymph node revealed 25 SOMATIC GENE MUTATIONS! His doctor has not seen a tumor burden like this before! The doctor will be taking my dad's case report to an upcoming Genomic/Immunotherapy conference at CITY OF HOPE for further advice from other colleagues.
***Anyone else tested positive for somatic gene mutations?
Thanks for sharing this Linda this is very interesting. I am awaiting results from my somatic tests - blood was drawn last week and I have follow-up appointment on 22 Oct - so I can't answer your question yet, but I would be very interested to know what treatment your father gets.
Like your dad, my germline testing came back clear but given aggressive nature of my PCa, MO is expecting to see something in somatic tests - she has already enrolled me in PARP inhibitor trials but that of course will ultimately depend on test results.
Good luck with your next treatment and keep fighting!
We are just learning which meds are useful for somatic mutations. So far, there are only two meds in our armamentarium - carboplatin and the PARP inhibitors. Keytruda was FDA approved for a rare somatic mutation in prostate cancer - MSI-H or dMMR. There are clinical trials of medicines specifically targeted to some mutations. It is probably more useful for ruling out certain therapies than for ruling some in. One problem with genomic changes in tumors is that it's a moving target - as the cancer progresses, mutations increase exponentially.
Thanks TA, very interesting. A researcher I spoke to recently has thoughts that success of BAT my also depend on certain genetic mutations. We know that BAT is only successful on some men and hopefully current trials will get to bottom of this. Have you read anything about BAT and genetics?
There is a case report of an extraordinary response to BAT in a patient with BRCA 2 and ATM mutations. The authors concluded:
" The results for this patient, who is experiencing a durable complete response to BAT, support the hypothesis that patients harboring mutations in DNA repair pathway genes may be particularly sensitive to BAT. Further testing of BAT in patients with DNA repair deficits or testing of BAT in combination with agents targeting the DNA repair pathway is warranted."
It is hypothetical that there is a better response to BAT if there are mutations in the repair pathway. I hope they could test this hypothesis so they could better select patients for BAT.
I'm doing the PARP inhibitor Lynparza (olaparib) right now for my CDK12 mutation. After 2 months, my PSA is still in the high 700's, but appears to be stabilizing. Next in line are platimum-based chemo, then the checkpoint inhibitor Keytruda, which seems particularky successful in men with this particular mutation.
Please let us know what the doctor learns at the conference.
I have an OLD original PG tumour which was not operable, Gleason 9, and Psa only 6 at diagnosis with aggressive cells in 2009 at age 62.
I think my many bone mets strated way back before diagnosis as tumour grew from small in PG in maybe 2005 with Psa < 5, and Gleason 5 maybe, but without any treatment PG tumours can begin spreading early in the initial growth time.
I have had ADT since 2010, and by now I guess I might have countless mutations.
I think the ADT kept most mets to undetactable size until 2016 when I had first PsMa Ga68 PET/CT scan in May 2016. They found PG was sure active and dangerous to rectum and bladder and two upper lymphs were found with Psa at 5.6.
I began Cosadex added to Lucrin injects and had a month of IMRT to PG and to the two lymph nodes and that reduced Psa as can be seen in my Psa graph at
I got 6 months of low Psa measurements and I haver had 3 more PsMa scans which showed no increase in PG Pca and mu last PsMa scan last Wednesday which was 12 weeks after start of chemo showed no lymph node Pca and all thoracic organs free of detectable Pca, and my main concern is many bone mets.
Lord Noze what mutations I have, but the Docetaxel seems to have killed most soft tissue mets, Psa did go up to an alarming 45 from 12 at start of chemo, but Psa a week later was 36, and I have not updated that yet on draing at website, so maybe the Psa is slowly working away to reduce Pca, rather like a vicious but bright eyed little fox terrier might attack a big brawny Roteiler Cancer dog who is not too bright, and which develops multiple personalities ( mutations), and the little chemo terrier jumps between Rottie's legs and bights the legs, and Rottie's
dangling balls, and after awhile, Rottie has troubles so bad that most of him decides to select DEATH on his menu for life app.
The latest PsMa scan showed all my bone mets are PsMa avid, ie, they would be able to attract Lu177 if is is pumped in with its ligand leading it to gate crash the cancer parties going on inside my bones where they think they are safe.
My guess is that regardless of mutations, if the cancer mets all have PsMa avidity, then Lu177 will kill whatever is there and within range of the radiation distance travelled.
My CT scans show that since the previous CT scan as part of PsMa Ga Pet/CT scan in May, 2 months before start of chemo, Bone mest have increased in number and size. Psa increased with inital flare from 12 to 27 when chemo started, fell to 27, then up to 40, then slower rise to 45, then down to 36 in week, which indicates halving rate of about 3 weeks and it that trend continues, maybe Psa declines rapidly now, showing the Little Chemo Terrier deserves and extra dog biscuit as a reward.
There is a point where Psa tends to not show the real Pca cancer load by the time it finds its real home within the castles of the body, the bones. Radium 223 is not bad for bone mets because it goes wherever calcium transfer activity is occuring, but only for the time while it is active during its short half-life.
Just what the real nature is of bones where Ra has gone and killed Pca is not something I know, but maybe the holes where cancer lesions were become calcified messy stuff, rather like chalk, so without bone repair, and IMHO, the ealier a many gets Lu177 of Ra223, then he will retain enough bone health to do a good lifestyle providing he does not try to do a stupid thing like try to become a weightlifter and take part in competions between Old Bah Studs aka masters' athletics etc.
So if I stop mu bone mets growing, I should be able to continue cycling for many years. During 10 days leading up and including trip to hospital last thursday I managed 220km+ including a 60km cycle on last Sunday.
In other words, its best I don't fear the worst about the targeted systemic
theranostic RT, the side effects can't be much worse than a pile more chemo, and both togther and with my fitness I might score a much longer extension to my life without co-mobidity conditions weakening me so much I can't get the benefits of thr treatment. Its really only luck that by this time in my life and the progress of my Psa has reached a point at the time soon after Lu177 has become available in a nearby city in Sydney, only 300km away from where I live in Canberra, and I get to stay a day of two with my dear older sister who lives there.
The referral to Dr Lenzo went through last week and their office arranged a Skype conferance for next Sunday arvo, so the arrangements for Lu177 have been started, and meanwhile I had Chemo 5, and will have chemo 6 maybe before first Lu177, and of course Little Chemo Terrier will be acompanied by Auntie Lutetia and methinks when Rottie opens the door of his cells to let the new guest in he gets a terible shock, and asks " I hope ya didn't bring Unkel Radium" . Lutetia then attacks Rottie, but despite the fiercest female attack from Lutetia, and with little chemo chomping up bits and peices, Rottie can leave a slightly indigestable amount of DNA behind, and that can grow and with even more mutations, but all that takes time, and that time is your extension of life at the cost of a few $$$$$. I sort of know where I am headed, and I think I have a more postive predictable outcome from what is ahead. HOPE is what we need, not dismay, and I hope to be around for awhile. But if Lu177 was not with us, I'd be in awful position, experimenting with chemo, and probably never winning the time I'd want. It seems to me the Lu177 has been tested enough for me to have confidence I might be in the 80% of men who get Psa reduction > 50%, and probably on the higher side of mean life extension of 14 months with Lu177.
Ppl mentioned immune therapy, and there isn't yet anything fully approved except Provenge treatment which has bank account smashing costs, and extension to life of 4 months; BUT, some guys got 9 years, ie, they got it soon after it was invented and are alive and well because the white cells treated were able to live on when white cells multiplied over time, and thay remained effective and mutations must have not got in the way.
Marsden Hospital in UK is beavering away to make their own version of immune therapy, and 15% get huge good response despite bad levels of bone mets. Well, 15% is not good but it tended to be with guys with many mutations. Its just not available here in Oz, and may never be approved if the success rate remains low.
Side effects can be horrendous with IT because altered white cells might destroy some healthy cells.
I am lucky to live on a western country with modern caring medical system. Many of the finest human beings work within our hospitals, despite what negative minded press reports say.
I must now eat, Its day 1 after chemo, had 13km bike ride, and next 4 days I shall not feel like my usual self, but I aim to keep cycling on each day of the chemo cycle because I feel better, and Psa seems to be falling, and docs have never seen a guy who cycles during chemo cycles. I offered to cycle a few km for my oncologist, and he looked much better when I saw him yesterday......
Patrick. My brother had two PSMA Lu treatments in Sydney. His numerous bone mets all but disappeared, with only a small spot on a rib remaining. As an author of a couple of books on PCa, I was surprised that they didn't zap this remaining zone with SBRT or give him a third Lu injection (pricey!). His PSA had dropped to near zero. 18 mths later (Nov 18) his PSA was 9 and has now doubled. He is having another Lu injection next week and is again starting Enzalutamide.
It seems that if Psa goes real low after Lu177, and PsMa scans show very few "PsMa avid" lesions, there is Pca still present, but its at a lower amount and not enough to attract Lu177 after more Lu177. So having say 3 Lu177 shots can means the 3rd does not do much, so its money wasted.
But just what happens later when Psa rises is not always clear because
it could be mutated, and not respond to more lu177. Or the higher Psa is due to mets that were so small for first two Lu177 shots that they did not show up in PsMa scans and did not get much Lu177 but they might now be seen because they have grown bigger but the scans should show all this by being compared. SBRT is just more fancy EBRT and it has side effects that are always bad later.
I had Calypso IMRT at Epworth for 31Gy to PG and to 2 lymph nodes near oesophagus in 2016. This was salvation RT and I was first in Oz to be done where my primary treatment was EBRT and ADT, which did not work very well probably because the Pca has spread to hundreds of places before diagnosis of Gleason 9+9 in 2009 with Psa at only 6.0. ADT did most suppression of both Pca in PG and all the mets.
Cost of the EBRT at Epworth was $26,000 plus scans plus cost of living in Melbourne for 5 weeks. But Epworth paid accommodation at Ryder-Cheshire, and the 2 upper lymph nodes were about $5,000 in the total.
Medicare coughed up %12,000, so the lymph nodes alone may have been $8,000, with less time, but with Medicare maybe 1/2 the cost of a LU177 shot at $9,600 each, plus trip from Canberra to Sydney, and no medicare. All that any man can do is pay for what's available and hope for best.
Die early if you can't pay.
You say your brother has Psa doubling rate of about 3 weeks. That is terrifying.
I hope whatever he choses will work, but not having delays of treatment would be important, and often the way a cancer "wins" is where the treatment seems to work initially, but cancer grows so fast between treatments that treatments cannot be repeated more often and then have less effect...... and there is no time to have cancer DNA analyzed for best possible chemo. I face a similar outcome where I end up having to admit there is no point having any more treatment.
But your brother seemed to get 18mths respite, and mean time is 14mths for Lu177. I know I am certain about uncertainties now.
Patrick Turner.
Thanks for sharing your story. Wishing you much success
Linda, Genomic sequencing determined I had a HBM of 253 nu, qualified me for several clinical trials and checkpoint inhibitor Blockade immunotherapy PDL1 Keytruda..I'm 6 yrs into treatment 50 infusions and I'm in Complete Durable Clinical Remission NED.
Hello Hotrod65I’ve been following your story both here and on the internet. It’s outstanding! My dad has just had his second infusion of Keytruda. Do you remember how long it took to see positive results such as PSA decrease? His PSA rose after the first infusion. I was wondering if the medication is cumulative and needs more time to work. We are hoping for good results based on genetic MSH3 mutation, and somatic MSH2, POLD1 mutations.
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