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    Old 08-03-2022, 01:48 AM   #1
    Prostatefree
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    Promising therapy for BCR post RP

    "The subjects were randomly assigned in roughly equal numbers to one of three groups. The men in group 1 got PBRT by itself, while men in group 2 got PBRT combined with four to six months of androgen deprivation therapy, or ADT. (Also known as hormonal therapy, ADT blocks testosterone, a hormone, or androgen, that fuels growing prostate tumors.) The men in group 3 got PBRT, ADT, and also radiation to the pelvic lymph nodes, where prostate cancer typically goes first if it begins to spread. The investigators wanted to know which of these three strategies is most effective at keeping disease progression at bay."

    Those getting the most intensive therapy had better outcomes in lowering BCR PSA with pelvic bed radiation plus ADT plus radiation to the pelvic lymph nodes.

    The study did not determine if it increased survivability.

    Google: blog/promising-therapy-if-psa-rises-after-prostate-cancer-surgery-202208012792

     
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    Old 08-03-2022, 04:29 AM   #2
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    Re: Promising therapy for BCR post RP

    Thanks for the info. Hopefully trials like these will give doctors more effective techniques for completing the cure.

     
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    Old 08-05-2022, 05:17 PM   #3
    IADT3since2000
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    Re: Promising therapy for BCR post RP

    An abstract of the published report is available free online at https://pubmed.ncbi.nlm.nih.gov/35569466/ with these key citation details:
    Lancet. 2022 May 14;399(10338):1886-1901.
    doi: 10.1016/S0140-6736(21)01790-6.
    The addition of androgen deprivation therapy and pelvic lymph node treatment to prostate bed salvage radiotherapy (NRG Oncology/RTOG 0534 SPPORT): an international, multicentre, randomised phase 3 trial
    Alan Pollack 1 , Theodore G Karrison ... Howard M. Sandler .

    This trial of salvage prostate bed radiotherapy (abbreviated "PBRT" in this paper) has some impressive results at the five-year follow-up point.

    Group 3 is essentially the curative attempt that I had, but skipping the surgery.

     
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    Old 08-07-2022, 09:20 AM   #4
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    Lightbulb Re: Promising therapy for BCR post RP

    The bottom line for recurring patients: for a substantial proportion of patients short-term combination ADT coupled with pelvic lymph node radiation makes a big difference in success in avoiding further recurrence, compared to radiation without ADT just to the prostate bed.

    It is possible - I think likely - that modern imaging, perhaps with genetic or other tests, not available during the timeframe of treatments for this trial, will be a major help in steering patients to just prostate bed radiation or to the addition of combination ADT and lymph node area radiation.

    Impressive type of clinical trial: This was a randomized, Phase 3, large (1,716 patients completing the trial, an extremely high percentage of the 1,792 patients staring the trial), long-term (started enrollment in 2008, with a median follow-up among survivors of 8.2 years), multicenter-international (283 centers in the US, Canada and Israel), sponsored by the Radiation Therapy Oncology Group (RTOG), and funded by the US National Cancer Institute under the National Institutes of Health, with a number of leading physician/researchers and numerous leading centers that treat prostate cancer included in the authors list - all impressive features. In addition to details available in the published report - link provided in the previous post, further details are available at the clinicaltrials.gov site sponsored by the US government, specifically at https://clinicaltrials.gov/ct2/show/NCT00567580?term=RTOG+0534&draw=2&rank=1 .

    There were three trial arms, including from 564 to 578 patients for each arm who completed the study. The idea was to see if there would be improvement of results if short term (4 to 6 months) androgen deprivation therapy (ADT, aka hormonal therapy) - Group 2 - was added to the baseline therapy of radiation just to the prostate bed - Group 1 (where the prostate used to be prior to prostatectomy) and if adding both short term ADT plus radiation to the pelvic lymph nodes made an additional improvement - Group 3.

    Prognosis background for patients recurring after prostatectomy: This is the leadoff sentence in the abstract: "In men with a detectable prostate-specific antigen (PSA) level after prostatectomy for prostate cancer, salvage prostate bed radiotherapy (PBRT) results in about 70% of patients being free of progression at 5 years." (I suspect "detectable PSA" effectively refers to recurring patients who have a PSA of .2 or higher.) Now the figure of 70% freedom from further recurrence after salvage radiation to the prostate bed, using methods available when the study was started, is pretty good, but it still leaves nearly a third of patients whose cancer is progressing despite salvage radiation, and that is scary and discouraging.

    Key patient details at enrollment/assignment to trial arms: Basically this was a pretty favorable group of recurring patients, with the recurrence picked up fairly early, though a post-op Gleason score of up to 9 was acceptable. PSA was key, as usual, but these patients were not picked up with ultrasensitive PSA results below .1, and it is now known that early radiation is usually more effective. Patients were eligible for the trial if their PSA was between .1 and 2.0 ng/mL. Also, they had to have no evidence of lymph node cancer or metastasis (N0/Nx) with previous lymphadenectomy not ruling them out if no cancer was found. They also had to have T2 or T3 cancer based on post-op pathology and a Gleason score of 9 or lower, plus a good performance status, meaning they were able to function normally. The abstract spells this out with more detail.

    There were 564 patients who completed therapy in the arm including only radiation to the prostate bed, 578 completing therapy in the prostate-bed radiation plus ADT arm, and 574 completing therapy in the arm that got the works - radiation to the bed, ADT, and radiation to the pelvic lymph nodes.

    One notable difference from primary radiation therapy is that high-risk patients usually are treated with 18 to 24 months of ADT when they get their radiation that includes the pelvic bed. There likely were some high-risk patients in this study, but the proportions are not evident from the abstract.*** (See below.) Another notable feature, based on details from the description at clinicaltrials.gov, is use of combination ADT, specifically the typical Lupron-type drug (LHRH-agonist) plus an antiandrogen; based on the start date of the study, the antiandrogen was almost certainly Casodex/bicalutamide. (My own ADT in support of my course of TomoTherapy radiation included Lupron, flutamide (because it looked like Casodex was no longer effective) and Avodart/dutasteride for 18 months, based on expert advice.) My impression is that many patients getting primary or salvage radiation and ADT get just one ADT drug, typically an LHRH-agonist or antagonist, rather than the combination, and I think its noteworthy that the leading doctors and institutions in this study chose to go with a combo ADT approach.

    These days - now 14 years after the start of this study, the favored antiandrogen might be one of the next generation drugs - darolutamide, enzalutamide, or apalutamide. It's possible that abiraterone acetate (Zytiga) might be used instead of one of the LHRH affecting drugs, and, because of its superiority to the older drugs, a combination might be considered unhelpful. I'm confident these questions are being researched.

    Impressive results at this point, with more than 8 years of average follow-up:

    Group 1 - comparison group that got the traditional radiation only to the prostate bed: 70.9% freedom from recurrence, matching what was expected.

    Group 2 - prostate bed radiation plus short-term combination ADT: 81.3% freedom from recurrence. This improvement is not at all surprising. It is in line with convincing research that radiation does better, except for low-risk men, when supported by ADT.

    Group 3 - prostate bed radiation plus short-term combination ADT, plus radiation to the pelvic lymph nodes: 87.4% freedom from recurrence!

    So what do we conclude:

    It's obvious that adding even short-term combo ADT makes a big difference as results boosted the freedom from recurrence rate by about 10%, which is one third of the way toward 100% freedom from recurrence.

    It's also clear that patients who also got radiation to the pelvic lymph node area got another big boost in success, moving another third of the remaining distance from perfection, 6.1%, compared to the 18.7% left to travel above the results from Group 2.

    There will be further results published in the future as follow-up is continuing.

    The side-effect price of the added therapy was modest, except for the short-term ("acute") effects, where Group 2 experienced substantially more impact than Group 1, and Group 3 was substantially above Group 2. But long-term differences were minimal. As the abstract describes it, "However, late toxicity (>3 months after radiotherapy) did not differ significantly between the groups, apart from more late grade 2 or worse blood or bone marrow events in group 3 versus group 2 (one-sided p=0·0060) attributable to the addition of PLNRT in this group." I too have those "blood or marrow events", but they are not a significant health issue. Now all three groups were getting radiation in addition to an initial prostatectomy, and it's likely they were experiencing a substantially higher burden of side effects than if they had gone straight to radiation plus ADT and including radiation to the pelvic lymph node area, without surgery.

    One encouraging point is that excellent results are possible even when radiation is delayed by patients who first elect surgery and then experience additional delay until their recurrence is recognized. While this obviously allows time for metastases outside the prostate to grow, mutate and spread, it is clear from this study that the Group 3 approach is able to help a very impressive percentage of patients with such risk avoid an additional recurrence after salvage therapy!

    As for survival results, it's way too early. As is well known, this kind of patient should experience group survival rates at 15 years from prostatectomy above 95% based on what I've read and understood as a layman.

    Bravo to the researchers! And thanks to Prostatefree for initiating this thread!

    *** Added after posting in the "One notable difference" paragraph: I will be adding more regarding the choice of the length of ADT. Watch this space.

    ….Jim

    - - - - - - - - - - - - - - - - - - - - - - - --
    22 years as a survivor. Doing well. Diagnosis Dec 1999 PSA 113.6 (first ever), age 56
    Gleason 4+3=7 (J. Epstein, JHU), all cores +, most 100%; "rock hard" prostate with ECE - stage 3, PNI, PSADT determined later 3-4 months; technetium bone scan and CT scan negative; prognosis 5 years.
    Later ProstaScint scan negative except for one suspicious small area in an unlikely location. ADT Lupron as first therapy, in Dec 1999, then + Casodex in March 2000, then + Proscar and Fosamax in Sep 2000. Rejected for surgery January 2000; offered radiation but told success odds were low; switched to ADT only vice radiation in May 2000, betting on holding the fort for improved technology; PSA gradual decline to <0.01 May 2002. Commenced intermittent ADT3 (IADT3) with first vacation from Lupron & Casodex. Negative advanced scans in 2011 (NaF18 PET/CT for bone) and 2012 (Feraheme USPIO for nodes and soft tissue). With improved technology, tried TomoTherapy RT, 39 sessions, in early 2013, plus ADT 3 in support for 18 months (fourth round of IADT3), ended April 2014. Continuing with Avodart as anti-recurrence shield. Current PSA, for some reason based on a less sensitive test on 7/20/2021 was <0.05, still apparently cured in my ninth year since radiation (PSA as of 12/2/2020 was <0.01). (T 93 as of 12/2/2020.) Supportive diet/nutrition, exercise, supportive medications during this journey, as well as switches in antiandrogen, 5-ARI, and bone drugs. Barely noticeable side effects from radiation; continuing low T, likely do to long use of ADT, but good energy and adequate strength. I have a lot of School of Hard Knocks knowledge, and have followed research, which has made me an empowered and savvy patient, but I have had no enrolled medical education. I have also had 225 undergraduate classroom hours just in statistics and experimental design, plus more in graduate school, which dwarfs what most doctors have, and that has made my “hard knocks” experience more meaningful. What I experienced is not a guarantee for all but shows what is possible.

    Last edited by IADT3since2000; 08-07-2022 at 11:49 AM. Reason: Added *** note and corrected typo: "i6" to "6". Added re side effects.

     
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    Old 08-08-2022, 07:14 AM   #5
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    Re: Promising therapy for BCR post RP

    I really don’t find anything in this study as being news. There have been other studies indicating the same results. The real measure of success should have been 5 years after a T recovery of >300.

     
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    Old 08-08-2022, 11:23 AM   #6
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    Re: Promising therapy for BCR post RP

    A Breakthrough Advance Kind of Study, Just Ho Humm Routine, Something in Between?

    Hi Insanus. You posted:

    Quote:
    Originally Posted by Insanus View Post
    I really don’t find anything in this study as being news. There have been other studies indicating the same results. The real measure of success should have been 5 years after a T recovery of >300.
    It's important to all of us on the Board to separate the wheat from the chaff. The "wheat" in this case would be a study that changes standard practice and deserves the attention of recurring patients considering strategy and their physicians. The "chaff" in this case would be a study that is well within the bounds of standard practice, supporting approaches that are already routine parts of standard practice and do not deserve our extra attention - automatic pilot type stuff. My impression is that you are suggesting this study is chaff. I too found aspects of this study familiar, but it also struck me that it was different and significant enough that it would advance the state of practice.

    Your skepticism motivated me to check the authoritative, widely-used guidelines for prostate cancer published by the authoritative group National Comprehensive Cancer Network, Version 4.2022 — May 10, 2022, which is a few days prior to the publication of this study on May 14 in the Lancet, a highly respected medical journal. (This is something all of us can do after registering. We don't need to be health providers or have any medical education or credentials at all.) I looked under the topic "RADICAL PROSTATECTOMY PSA PERSISTENCE/RECURRENCE" found on page PROS-10 of the "Evidence Blocks" version of the guidelines (for physicians version vs. patients version, which we patients can do too, though the patients version may be easier to understand).

    As expected, the guideline shows that advanced imaging of bone and soft tissue, as well as PSA doubling time (PSADT) and the Decipher test, and even a prostate bed biopsy depending on the circumstances, now play up-front roles in determining strategy. Such imaging was simply not available when this study was launched, nor was the Decipher test. The flow-diagram of choices has two arms, with the upper arm - Studies negative for distant metastases or imaging not performed - being comparable to patients in this study, though any imaging at the time of the study (enrollment starting in 2008) would have been much less effective. There are three approaches recommended:

    - EBRT (External Beam Radiation Therapy)

    - EBRT plus Androgen Deprivation Therapy (ADT)

    - Observation (basically waiting for symptoms to appear, which, in my view, may be wise if the patient has a short life-expectancy)

    Note the contrast to the findings of this study, which show a quite substantial advantage if ADT is added. To me, that is, by itself, "practice changing", and warrants further spelling out of the current "EBRT +/- ADT" guideline strategy.

    Note also the referenced section covering "Principles of Radiation Therapy", which is on page PROS-F, 2 of 6 of the current guidelines, under the subtopic "Low-Volume Metastatic Disease," "It remains uncertain whether treatment of regional nodes in addition to the primary improves outcomes; nodal treatment should be performed in the context of a clinical trial." Now patients in this study were at lower known risk than those with "Low-Volume Metastatic Disease," and yet radiating the pelvic lymph nodes was not known to be beneficial even for those with known but low-volume metastatic disease, so presumably it would be of even more uncertain value for the men in this study. But the study, a powerful clinical trial such as alluded to in the sentence from the guideline, shows a very clear benefit to treatment of regional lymph nodes. How can that not be practice changing, as the study showed a very substantial boost from radiating those nodes in conjunction with ADT? I will be surprised if the guidelines do not change soon in these respects with a reference included to this study.

    My bottom line: this study is high quality wheat and not chaff.

    That said, I tend to look at the prostate cancer world from the viewpoint of a patient who once faced life-threatening prostate cancer with a short prognosis. Other perspectives, perhaps yours, can spot different details that matter. If you know of studies that contribute the same message with equivalent force and credibility, please give us references.

    ….Jim

    - - - - - - - - - - - - - - - - - - - - - - - --
    22 years as a survivor. Doing well. Diagnosis Dec 1999 PSA 113.6 (first ever), age 56
    Gleason 4+3=7 (J. Epstein, JHU), all cores +, most 100%; "rock hard" prostate with ECE - stage 3, PNI, PSADT determined later 3-4 months; technetium bone scan and CT scan negative; prognosis 5 years.
    Later ProstaScint scan negative except for one suspicious small area in an unlikely location. ADT Lupron as first therapy, in Dec 1999, then + Casodex in March 2000, then + Proscar and Fosamax in Sep 2000. Rejected for surgery January 2000; offered radiation but told success odds were low; switched to ADT only vice radiation in May 2000, betting on holding the fort for improved technology; PSA gradual decline to <0.01 May 2002. Commenced intermittent ADT3 (IADT3) with first vacation from Lupron & Casodex. Negative advanced scans in 2011 (NaF18 PET/CT for bone) and 2012 (Feraheme USPIO for nodes and soft tissue). With improved technology, tried TomoTherapy RT, 39 sessions, in early 2013, plus ADT 3 in support for 18 months (fourth round of IADT3), ended April 2014. Continuing with Avodart as anti-recurrence shield. Current PSA, for some reason based on a less sensitive test on 7/20/2021 was <0.05, still apparently cured in my ninth year since radiation (PSA as of 12/2/2020 was <0.01). (T 93 as of 12/2/2020.) Supportive diet/nutrition, exercise, supportive medications during this journey, as well as switches in antiandrogen, 5-ARI, and bone drugs. Barely noticeable side effects from radiation; continuing low T, likely do to long use of ADT, but good energy and adequate strength. I have a lot of School of Hard Knocks knowledge, and have followed research, which has made me an empowered and savvy patient, but I have had no enrolled medical education. I have also had 225 undergraduate classroom hours just in statistics and experimental design, plus more in graduate school, which dwarfs what most doctors have, and that has made my “hard knocks” experience more meaningful. What I experienced is not a guarantee for all but shows what is possible.

     
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    Old 08-10-2022, 11:47 AM   #7
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    Re: Promising therapy for BCR post RP

    I am just saying there are older studies that support the findings of the one you posted. While any change treatment? That’s to be seen.

     
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    Old 08-10-2022, 11:58 AM   #8
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    Re: Promising therapy for BCR post RP

    I am just saying there are older studies that support the findings of the one you posted.

     
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    Old 08-10-2022, 03:26 PM   #9
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    Re: Promising therapy for BCR post RP

    And my main point is that none of those earlier studies was "practice changing" as compared to this study. For instance, a short-term follow-up Phase 2 study, especially if not randomized, is unlikely to change practice; rather, it would be a spur to follow-on Phase 3 studies like this one that are likely to change practice if they have favorable results, as this study does.

    Jim

     
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    Old 08-13-2022, 09:21 AM   #10
    Insanus
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    Re: Promising therapy for BCR post RP

    The key we are all seeking is an increase in cancer specific survival. A 60 month study cannot provide that data. Yes, there was an increase in BR survival, that could be expected from ADT treatment. The problem is ADT has a specific effective period in each patient. If that value is 24, using 6 early may not equal > cancer specific survival 10 years later.

    I am living the treatment as listed in the study and I can tell you that until >7 years one should not make any assumptions.

     
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