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  • Lack of Evidence That Surgery Is As Good As Radiation for Higher-Risk PC Patients

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    Old 03-04-2020, 01:54 PM   #1
    IADT3since2000
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    Lack of Evidence That Surgery Is As Good As Radiation for Higher-Risk PC Patients

    Based on what I consider sound evidence, I believe that modern radiation (including appropriate imaging and ADT in support) is superior to surgery for most intermediate-risk and high-risk prostate cancer patients. Based on a lot of personal research into published medical research studies at the time, that belief was behind my own choice of radiation plus ADT in my attempt at a cure in 2013 for my initially high-risk case (diagnosed in December 1999 and treated with intermittent ADT (Androgen Deprivation Therapy) until that point). Surgery was once the gold standard, clearly superior to radiation, and that's why I initially chose surgery; but after rejection by the surgeons on the grounds that my case was too risky, within months I learned that radiation at the time offered me a slim chance of success. Some surgeons claim that surgery is still the gold standard, or at least as good as radiation. But technology advances, and many of us are convinced that advances in radiation have now far outrun advances in surgery. This thread will help put that to the test.

    I do recognize that surgery does cure a substantial proportion of patients, many even without a subsequent round of adjuvant of salvage radiation (plus ADT), but I am convinced there is a substantial advantage for modern radiation in odds of success against recurrence, and patients considering treatment options need to be aware of these odds. I do not believe that there is overall equality between radiation and surgery; I have seen data in support of equality claims, and on analysis, it does not stand up. However, I do also believe surgery is superior for some patients, such as those with chronic prostatitis, with extremely large prostates that cannot be sufficiently reduced, with certain pre-existing conditions, at times with prior radiation to the general area for other conditions, and for patients for whom there are no sufficiently convenient quality radiation options.

    Patient preference is also important, and some patients have a strong preference for surgery or for radiation despite their circumstances and research evidence. Fortunately, many of us will do well with either. But I am initiating this thread to see if we can find any sound studies that favor surgery, or even indicate equality with radiation. For board readers who want to see studies that favor radiation, the work of the Prostate Cancer Results Study Group has a good list in the references section to its published journal article at http://www.prostatecancertreatmentcenter.com/prostate-cancer/study-group/. (The study group's website is at: http://www.prostatecancertreatmentcenter.com/prostate-cancer/study-group/ .)

    I hope to update this first post by listing candidate studies suggested by our board participants and follow-up with reference to posts that evaluate these studies. I have done one evaluation and will post it to start off. It is extra long as it illustrates the critical flaws found in many studies, and I hope other reviews will be short.

    So here goes.

    Post #...Study Title................................... ........................................ ...................................Evaluating Post #s

    Other
    thread........ “Survival Significance of Patients With Low Prostate-Specific Antigen and .............................#s 2, 3
    .................. High-Grade Prostate Cancer After Radical Prostatectomy, External Beam Radiotherapy,
    ...................or External Beam Radiotherapy With Brachytherapy” [2019


    Jim

    - - - - - - - - - - - - - - - - - - - - - - - -
    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 remarkably low at <0.01; apparently cured.. Supportive diet/nutrition, exercise, supportive medications during this journey, as well as switches in antiandrogen, 5-ARI, and bone drugs.

    Last edited by IADT3since2000; 03-04-2020 at 02:42 PM. Reason: Adding to list; sentences re my initial surgery choice

     
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    Old 03-04-2020, 01:59 PM   #2
    IADT3since2000
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    Re: Lack of Evidence That Surgery Is As Good As Radiation for Higher-Risk PC Patients

    1. Highly Skeptical of Chinese Study Conclusion of an Advantage for Surgery Over Radiation For High Gleason/Lower PSA Men: Study Appears Seriously Flawed and Unsupportable to Me, also Contrary to Reliable Research


    (Part 1 of 2 - Post is in two parts due to length restrictions.)

    2. Some of us just want a person exuding authority to take control of our case and tell us what to do. Others of us are searching for evidence to inform our therapy decisions so that we can work in partnership with our doctors, even changing doctors when that seems wise. The following Chinese study was raised in a previous thread as possible evidence that surgery is superior for patients with higher-risk prostate cancer. I reviewed the complete paper, and found the study to be inconsistent with the preponderance of credible evidence I have seen and reviewed, indeed upon which I based my choice of radiation for a once life-threatening case. The short version of this post: the research design artificially disadvantages radiation in several ways, yielding an apples-to-grapefruit type comparison, and the unweighted data still, despite several artificial research design disadvantages, show an advantage for radiation. The following detailed review spotlights typical critical flaws found in this and many other studies where surgery appears to have better results than radiation for higher-risk prostate cancer (with low-risk prostate cancer arguably a draw, but with active surveillance the best choice for most).

    I am numbering main paragraphs to foster understanding and discussion.

    3. Fortunately, I have an unusually strong background in statistics and experimental design (see post #42, https://www.healthboards.com/boards/cancer-prostate/1048766-club-membership-cards-mailed.html), and that has enabled me to find credibility in the work of the Prostate Cancer Results Study Group (see link later), which essentially demonstrates, with abundant but arguably not yet conclusive evidence, that radiation plus ADT appears to be a substantially better choice for most patients with higher-risk prostate cancer. Therefore, I spent some time analyzing this Chinese study, including trying to communicate with the Chinese research team and succeeding in communicating with one of the doctors who did a pre-publication peer review of the study. This post is my analysis, and the title is my conclusion for those who just want the bottom line.

    4. Which Study: This is the study mentioned in several posts that was initially mentioned in post #1 of this thread at 02-07-2020, 12:15 PM by Djin Tonic (https://www.healthboards.com/boards/cancer-prostate/1048828-advantage-rp-over-rt-subgroups-high-grade-pca.html). The link to the study, entitled “Survival Significance of Patients With Low Prostate-Specific Antigen and High-Grade Prostate Cancer After Radical Prostatectomy, External Beam Radiotherapy, or External Beam Radiotherapy With Brachytherapy” [2019, Full Text] is https://www.frontiersin.org/articles/10.3389/fonc.2019.00638/full. I gave some preliminary comments on the study in post #29, 02-13-2020, 03:00 PM, but at that time I lacked confirmation of several important points, which I now have.

    5. Why Focusing on This Study Can Help Us Understand Typical Flaws in Studies that Favor Surgery Over Radiation for High Risk Prostate Cancer Patients, Undermining Their Conclusions: This study contains several of the common critical flaws in studies favoring surgery, flaws that often produce an “apples-to-grapefruit” comparison that is misleading and not useful rather than a useful “apples-to-apples” comparison. For those who don’t like fruit analogies, let’s try racing – the 100 yard dash: the study is like giving the gold medal to a racer who gets to start a second ahead of time against an opponent who has to start a second later and carry a 20 pound extra weight, with the finish based on the chest passing 100 yards for the first runner versus the back heel passing for the second. A lot of studies have these critical design flaws. Understanding these critical flaws can help patients sort the wheat from the chaff in other studies.

    6. Some of the typical flaws, occurring in this study in my opinion are: failure to adequately account for differences in average ages and other current serious health conditions (“comorbidity”) in men in surgery groups versus radiation groups; failure to adjust for the benefit of adjuvant or salvage radiation in men in surgery groups; failure to treat Gleason scoring equally in the surgery and radiation groups; and failure to treat staging information equally in the surgery and radiation groups. Such flaws can and fairly often do completely undermine the validity and conclusions of published medical research studies, in my opinion as a now savvy layman (but no enrolled medical education). Awareness of such flaws helped me sort through competing claims of research studies when I was choosing whether to take a curative shot with surgery or radiation, which I resolved strongly in favor of radiation (2013) for my high-risk case. The criteria used by the Prostate Cancer Results Study Group in selecting studies deemed credible as evidence go a long way toward minimizing these flaws, and are stated at the group’s website, http://www.prostatecancertreatmentcenter.com/prostate-cancer/study-group/ .

    7. The Prostate Cancer Results Study Group (PCRSG) results, which group non-recurrence results from many qualifying studies for different treatments and show them graphically based on risk group and length of follow-up, helped me. The PCRSG used several techniques to avoid or minimize the flaws evident in this study. Here is a link to their work, based on a 2012 journal publication: http://www.prostatecancertreatmentcenter.com/prostate-cancer/study-group/ Generally, with research on low-risk patients being of limited value since the advent of active surveillance as an option, their results for intermediate-risk and high-risk patients show superior results for radiation, often with androgen deprivation therapy (ADT). It is also clear that surgery is successful for fairly substantial percentages of men with higher-risk prostate cancer, just not typically nearly as successful as radiation. The Study Group’s graphs for “higher risk” men show surgical success rates of up to around 60%, long-term, in some studies, though substantially lower in other studies, with the bulk of radiation studies showing substantially superior results. Different types of radiation and combinations, as well as other therapies, are displayed using symbols of different shape and color. Patients who really want to get into the grass roots can go to the references for the study, a list that shows each study that was a data point in the results graphs. One shortcoming of the study is that it was based on data going into the 2012 paper. That meant that many of the radiation patients in the long-term results were not treated with advanced imaging guidance, and may not have been treated with at least 18 months of ADT, which is now known to be important for achieving best results for high-risk men (with a short course best for intermediate risk men). Also, the minimum EBRT radiation dose for inclusion in the PCRSG study was 72 Gy, which is now known to be inferior to a dose of 78-81 Gy. In short, results for patients being treated in more recent years should be even better.

    8. My Review and a Supportive Confirmation: I have now had time to review the study carefully and get some semi-confirming information regarding its data on Gleason scoring and staging. Two of the Chinese researchers listed as corresponding authors have not responded to my inquiries, stated in my post #32 of 02-20-2020, 03:50 PM, but one of the reviewers did respond that my first two assumptions, in those inquiries, appeared to be correct, adding that SEER data did cover radiation but with uncertainty about the timing. The following is based on assuming that the Gleason scoring was based on the higher of the original biopsy OR the post-prostatectomy specimen, which is almost but not quite stated in the paper, and that staging data were also based on the higher of pre-RP clinical data or post-RP pathology and other data, whichever were higher, which is not stated in the paper but which appears to be the case based on data in the paper and the peer reviewer’s statement that that appeared to be the case. As noted earlier, I have had no enrolled medical education, but I had an extraordinarily strong statistical and experimental design background in academic study, more than 225 classroom hours, plus strong life experience in analysis. In contrast, my impression is that most pre-med and MD students, other than those with additional research-credential study, likely have only one course in elementary statistics under their belts when they start practicing, equivalent to about 45 classroom hours. I have been following prostate cancer research for more than 20 years, since my diagnosis.

    9. The Study’s Conclusion, and My Impression: The study concluded that: - “RP patients with low PSA levels and high GS [Gleason scores] had better OS [Overall Survival] compared to either EBRT [External Beam Radiation] or EBRT+BT [Brachytherapy], while RP and EBRT+BT resulted in significantly lower PCSM [Prostate Cancer Specific Mortality], compared to EBRT.” – appears seriously misleading to me as the study was an apples-to-grapefruit comparison. While the second line of the conclusion is more in line with what I would expect – “Moreover, EBRT+BT and RP were associated with similar survival of patients with age of > 70 years old, or PSA levels of ≤ 2.5 ng/ml.” -, even there elimination of the flaws, were it possible, would show superiority of radiation, in my opinion.

    10. Key Flaw in the Study: Unequal Gleason Scoring The study used the higher of two possible Gleason scores for each patient in the study: “GS provided by the SEER program represents the highest GS found during a surgical or non-surgical biopsy.” This means that the higher Gleason score from either the clinical, pre-RP biopsy or the pathology biopsy of the removed prostate was used. As we patients are well aware, radiation patients do not have the latter biopsy. Therefore, in determining which patients were “high-grade” in this study, we KNOW that the radiation patients were all high grade based on their original clinical biopsy, but it is likely that a portion of the surgery patients had Gleason score 7 or even Gleason score 6 or lower clinical biopsy results that were only later upgraded. Given that the surgery patients had PSAs of 10 or lower, and that at least (see below) two thirds of them had stage T1 or T2 cancer per Table 1 in the study, that would have made them “Intermediate-risk” or “low-risk” patients based on the initial biopsy. It is known that pools of patients considered low- and intermediate-risk have considerably better outcomes of patients considered high-risk, so this establishes that you have a group (actually two groups) of high-risk radiation patients (EBRT alone, and EBRT plus seeds), competing for survival against a mixed group of low-risk, intermediate-risk and high-risk surgery patients. So even though the RP group was determined to be high-risk, , many based on the post-surgical pathology, that RP group was bound to be a more favorable group of high-risk patients, such as less extensive spread within the prostate, and likely fewer high-risk individual tumors in each patient’s prostate, than in the two radiation groups. As we know, biopsies sample only a small proportion of a patient’s prostate, whereas a post-surgery biopsy is comprehensive.

    11. Key Flaw in the Study: Unequal Staging Data Similarly, it appears that the T1, T2, T3, T4 staging information from each patient was based only on the initial, clinical biopsy and other (DRE, etc.) staging data for the radiation patients but was based on the higher of that data or post-surgery data (such as positive margins, extracapsular extension, positive seminal vesicles, etc.) data for the surgery patients. The reviewer concurred with me that this was probably the case, but evidence in the study also suggests it is the case. Consider the proportions of men with each stage in Table 1 of the study:

    Table A. Percentages of patients in the Chinese study with each stage of prostate cancer

    Stage……………………….RP…………………EBRT……………EBRT+BT

    T1…………………………. 0.5% …………… 54.5% ............. 60.6%

    T2……………………….. 62.5% …………… 39.2% ............. 33.7%

    T3……………………….. 34.7% …………….. 5.5% ............... 5.5%

    T4…………………………. 2.4% …………….. 0.8% ............... 0.2%

    Totals…………….…. 100.1% …………. 100.0% ………….. 100.0%

    12. The line for Stage T1 patients is our first clue. As all of these patients had a PSA score of less than or equal to (<=) 10, indeed with the average for each group being around 6, it is likely that many would have been first alerted by a rising and/or elevated PSA score and a normal DRE (Digital Rectal Exam). Indeed, that is what we see for the two groups of radiation patients, where more than half had negative DREs as evidenced by the designation of stage as T1, meaning no nodule (and nothing visible by imaging if done). Surprisingly, the RP group had almost no patients staged as T1; this suggests that post-surgery results upgraded the initial staging, and that probably accounts for the proportionately much higher percentages for stages T2 and T3 for RP patients than for either group of radiation patients.

    13. Moreover, in the US it has been unusual to treat prostate cancer patients with radical prostatectomy if the disease had already escaped the capsule, as is indicated by T3 staging. Yet, as we see in the chart, just over a third of the RP patients were stage 3. This too suggests it is likely that RP patients were upstaged as a result of post-prostatectomy findings.

    14. The significance of this is that RP patients in the study are considered to be at much higher risk, based on staging, than their radiation counterparts, though this is probably false as it is based on a second cut at the staging apple provided by post-surgery observations. In other words, if pathologists had somehow done biopsies on prostates removed from all the radiation patients, they probably would have upstaged them to about the proportions seen for the RP patients, or, as the RT patients were older, somewhat higher in average staging; of course in reality, that cannot be done. However, when making treatment decisions, many of these RP patients and their doctors likely thought they were low- or intermediate-risk patients based on staging alone: likely low-risk, clinical pre-prostatectomy stage of T1 or T2 based on the analysis here, low or intermediate risk Gleason prior to upgrading after surgery as discussed above, and a PSA not exceeding 10 as a requirement for inclusion in the study). So again, this suggests that the truly and originally high-risk radiation groups are being compared to what would have been, based on pre-operative evidence, an RP group with a mix of low-, intermediate- and high-risk patients. That kind of situation pretty much guarantees artificially better results for the RP group. It’s an apples to grapefruit comparison from the get go.

    15. Key Flaw in the Study: Overall Survival Results - Unequal Starting (At Treatment) Average Ages in Each Group, with Aggravating Elderly Factor Confounds Claimed Superiority of RP for Overall Survival

    Not only were the radiation patients on average significantly older than the RP group, but a substantial proportion of them were entering the age range where many men near the end of their life spans, which, though I don’t feel that elderly at 76, a lot of people would call elderly. For elderly men, who are losing friends and peers to death as I am, upcoming life span is typically not long, a matter of a handful of years, especially for those of us with major challenges to our health; in contrast, men in their 60s (the RP group average) have many years of life before them, and typically have fewer threats to their health. This obviously is going to affect the “OS” (Overall Survival) result of a study by itself, regardless of disease or treatment. Again, this means the comparison in this study is apples-to-grapefruit and not apples-to-apples.

    Table B. Here are the age differences:



    Age/Life expect. …….RP…………………EBRT……………EBRT+BT

    Average (median)……64 ………………. 71................. 68

    Avg. birth year …… 1956 …………… 1949 ……………..1952

    Avg. added years* … 19 …………………. 14 …………….. 17 (Keep in mind, this is US population wide,
    ……………………………………………………………………………………..n ot just patients with a major disease like PC.
    ………………………………………………………………………………………Insurer s are not fond of issuing
    ………………………………………………………………………………………li fe insurance policies to us.)

    Avg. total years
    At death: ………………….. 84 …………………. 86 ……………… 85

    * Additional years of expected life for the average male who has attained the median age of one of the groups in the study, that is 64, 71, or 68; source: https://www.ssa.gov/OACT/population/longevity.html

    Continued in Part 2

    Last edited by IADT3since2000; 03-04-2020 at 02:15 PM. Reason: Graphic editing

     
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    Old 03-04-2020, 02:01 PM   #3
    IADT3since2000
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    Re: Lack of Evidence That Surgery Is As Good As Radiation for Higher-Risk PC Patients

    Part 2 of 2 re Chinese Study discussed in Post #2

    16. Now let’s take a look at what the average ages would be for men in each group in the study at the start, after 3 years, after 5 years, and after 10 years.

    Table C. Average Ages of Men in Each Group Projected at Treatment to 3, 5 and 10 Years Since Treatment

    Age/Life expect. …….RP…………………EBRT……………EBRT+BT

    Average (median)……64 ………………. 71................. 68

    + Three Years ………… 67………………… 74 ……………….. 71

    + Five Years …………… 69 ………….……. 76 ……………….. 73

    + Ten Years …………... 74 ……………….. 81 ………………… 78

    Avg. total years
    At death: ………………….. 84 …………………. 86 ……………… 85

    17. What this shows is that the EBRT group is not only 7 years older than the RP group (and 3 years older than the EBRT+BT group), but it is already, at treatment, in the age range where we tend to lose peers to death, in sharp contrast to the RP group, where death of peers is rather unusual. By five years since treatment the EBRT group is definitely in the “elderly” range, while the RP group is not. In other words, the odds of death from other causes than prostate cancer are substantially higher for the EBRT group when it hits the five year mark, and especially when it hits the 10 year mark. The final line of the table shows that the EBRT group, at 10 years from treatment, would be just 5 years from expected death for the average more-or-less healthy US man, not one with a major disease like prostate cancer. It makes sense that overall survival at the 10 year point would fall off sharply for the EBRT group from age alone, aside from any treatment effect. To a lesser extent, because the EBRT+BT group is younger, this also applies to the EBRT+BT group. The part of Table 2 in the study for Overall Survival Using Kaplan Meier Analysis is consistent with this analysis, as follows:

    Table D. Percentage Overall Survival of Men in Each Group Projected at Treatment to 3, 5 and 10 Years Since Treatment

    Treatment group. ….RP…………………EBRT……………EBRT+BT

    + Three Years ….. 98.3%……………… 94.0% …………….. 96.8%

    + Five Years ..…… 96.2% ……….……. 86.3% …………….. 92.5%

    + Ten Years ……... 73.5% …………….. 54.7% ……………… 66.5%

    18. Table 2 also contains a weighted adjustment section where age is one of the factors taken into account, though the method is not clear. As expected from the analysis above, the 10 year survival for the EBRT group imrpoves by nearly 4 years while that for the RP group drops by 6 years, with a drop of 5 years for the EBRT+BT group.
    19. My conclusion is that the overall survival data are not helpful because of the artificial aspects discussed above, chiefly the fact that those men in the EBRT group are, on average, approaching the natural limit on their life spans.

    20. Other Flaws in the Study

    1. It is likely that radiation received by EBRT and EBRT+BT patients was substantially inferior to what would be used today, leading to inferior results for the radiation groups. We do not know the quality of radiation used, and this is critical because old style radiation was definitely inferior in controlling cancer and avoiding a high level of side effects. We do know that the earliest radiation patients were treated not earlier than 2004, the earliest year for inclusion in the study. At that time many US patients were being treated with EBRT doses of 70 Gy or lower, and we now know that a dose range of 78-81 Gy is substantially superior for most patients. Moreover, advanced imaging to aid radiation targeting, which improved effectiveness and reduced side effects, was not widely accepted until at least 2007, well after the start of the study. This applied to brachytherapy as well as to EBRT. Finally, it was not known in the early 2000s that a course of ADT of at least 18 months substantially boosted radiation effectiveness for high-risk patients; unfortunately, the study provides no data on ADT use to support radiation.
    2. Adjuvant and salvage radiation data are not provided for the RP group.. It is a sound assumption that many of the RP patients would have had adjuvant or salvage radiation for their high-risk cases, but the study provides no data on this. In other words, success for the RP group is no doubt improved by radiation, but we do not know by how much.
    3. Similarly, use of ADT by RP patients after surgery is not provided, and this too would have improved results for the RP group.


    21. Assessment of the Value of this Study

    1. Understanding the effectiveness of RP versus radiation: The study does not help due to the critical and other flaws discussed above.
    2. Understanding prognosis for high-risk patients considering surgery:
    The study does not help because high-risk characteristics, such as Gleason and stage, are apparently based on post-surgery findings rather than initial biopsy findings.
    3. Understanding prognosis for surgery patients based on post-surgery findings (Gleason, stage): the study provides some useful information, especially for younger men like those in the study, with an average age of about 64.

    22. I am adding (3/11/2020) some text in blue from my post #29 02-13-2020, 12:00 PM, on DjinTonic's early thread (https://www.healthboards.com/boards/cancer-prostate/1048828-advantage-rp-over-rt-subgroups-high-grade-pca-2.html).

    However, some of the facts in the study support the opposite conclusion than the one in the study, which favored surgery; these facts support an apparent superiority of radiation for such high-Gleason score/PSA <=10 patients, and there are serious questions about the approach taken by the urologist authors in trying to support a conclusion that surgery is the better approach. I hope to have a lot more to say about that when I complete my look at the study.

    For instance, consider the proportions of patients who were alive in their early to mid-70s, specifically at ages 73 for the RP group, 75 for the EBRT group, and 72 for the EBRT+Brachytherapy groups. Remember that these were all patients in the SEER database that covers about 28% of the US population, therefore including all from the US SEER areas, who had a Gleason score of 8-10, a PSA of up to 10, and no detectable nodal or distant metastases (N0, M0), between 2004 and 2015.

    ...........................Survival at.............Overall
    Treatment ..........Average Age:.......... Survival


    RP............................73........ ........74% (73.5%)


    EBRT........................75.......... ......86% (86.3%)


    EBRT+Brachy............72............... .93% (92.5%)


    This table is from Table 2 in the report, with selection to focus on outcomes at nearly equivalent ages. Now there is a twist here, and the authors could cry foul, but it is still a factual and meaningful view of the data, though ignoring one key fact, which I will put below my signature to allow a little suspense and an opportunity for Board participants to try to figure this out as in a "Who Done It". The table shows a clear pattern of superior survival of radiation patients versus RP patients at approximately equivalent ages.


    Now here is data taken straight from Table 2 of the study about Prostate Cancer Specific Mortality (PCSM), and I’m going to use the figures for 3 and 5 years from diagnosis but not for 10 years, because the confidence intervals in the 10 year column are so wide, indicating low-confidence as to the true value of this projection and that the data in the study must be all over the map, not in a clear, fairly tight pattern:


    Prostate Cancer Specific Mortality (PCSM – Dying Due to Prostate Cancer, rounded and exact, the lower the percentage the better)


    ...............................PCSM at................PCSM at
    Treatment................3 Years:..................5 Years


    RP.........................6% (6%)#............16% (16%)*


    EBRT.....................2% (1.9%)#...........5% (5.3%)#


    EBRT+Brachy.........1% (1%)#..............3% (2.6%)#


    #For each of these values the confidence interval is fairly tight, indicating that the true value of the projection is very likely very near the indicated value.


    * For RP, the confidence interval at 5 years is wide, from a true value ranging from 12% to 22%, with 16% projected as the most likely, indicating that data points are widely spread. The CI interval means that the true value could be as low as 12% mortality or as high as 22%.



    It appears that at both the 3 and 5 year points, both forms of radiation have sharply lower death rates, which is counter to the study’s conclusion that RP patients do better. More on that, more reasons why it is probably an unsound conclusion, to follow, time permitting.


    (At ten years, RP shows the lowest mortality, but the confidence intervals for RP, EBRT, and EBRT plus brachytherapy are all very wide, indicating little reliability in the projected averages due to data points being very widely spread from each other. Various factors come into play, such as the increasing age of patients, which causes more deaths from other causes and a decreased ability to see what ages would have been like if death came from prostate cancer; increasing age typically means a substantial decrease in the number of data points upon which to base a projection for death specifically from prostate cancer.)


    My other posts on Djin's earlier thread (https://www.healthboards.com/boards/cancer-prostate/1048828-advantage-rp-over-rt-subgroups-high-grade-pca-2.html), some of which detailed additional problems, were:

    #13 02-08-2020, 05:09 PM Not Impressed with the Tilki 2019 study: Surgery vs Radiotherapy in the Management of Biopsy Gleason Score 9-10 Prostate Cancer and the Risk of Mortality

    #25 02-10-2020, 01:30 PM A Bit More on the Tilki Study, and What "Immediately Following" Means for Adjuvant Radiation Following Surgery

    #27 02-10-2020, 02:24 PMWhack-a-Mole Deja vu All Over Again - (I suspect)

    #29 02-13-2020, 12:00 PM Midway Point in Analysis of Chinese Study of US Patients with Gleason 8-10 and PSA of Up To 10 - Radiation Looking Better


    Jim

    - - - - - - - - - - - - - - - - - - - - - - - -
    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 remarkably low at <0.01; apparently cured.. Supportive diet/nutrition, exercise, supportive medications during this journey, as well as switches in antiandrogen, 5-ARI, and bone drugs.

    Last edited by IADT3since2000; 03-11-2020 at 09:33 AM. Reason: Graphic effects. Added blue text from earlier thread, refs - green -to earlier posts

     
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    Old 03-04-2020, 04:12 PM   #4
    Gerard1954
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    Re: Lack of Evidence That Surgery Is As Good As Radiation for Higher-Risk PC Patients

    Good stuff. Thank you for that information and knowledgeable opinion.

    I think with the leaps and bounds in radiation technology in recent years, for a lot of people your view is correct.

    This is especially so when the clinical indicators suggest a probability -- or even strong possibility -- that the disease is no longer organ-confined.

    Yet, there are three circumstances where surgery is strongly indicated, in my view: A) when the prostate is abnormally large; B) when the testing data suggests a likelihood that the disease has not spread beyond the prostate; and C) when the patient has access to an experienced and top-quality surgeon.

    Generally speaking, some combination of those three argues for surgery.

    In my case, I struggled with the decision even on the way to the hospital, second-guessing myself the whole way. But as it happened, radiation would have been a mistake for me for various reasons: my prostate was even larger than indicated by the MRI and my cancer even higher grade than indicated by the biopsy.

    Keep in mind also that more often than not, radiation comes paired with ADT -- which is a whole different set of issues, none of them pleasant.

    At the end of the day, it can be a crapshoot. There are things you know and things you don't know. So you make the choice based on what you know (or think you know) -- and hope it's the right one.
    __________________
    YOB: 1954
    PSA 4.4 -- Mar 2016; 5.9 Jan 2017; 7.7 Mar 2017
    3T MRI of prostate -- April 2017; prostate found to be enlarged (79cc) with two potentially cancerous lesions, one PIRADS-3 and one PIRADS-4
    Fusion biopsy -- August 2017; 14 cores taken, with two measured at Gleason 4+3, corresponding to the MRI PIRADS-4 target location
    RALP at Johns Hopkins -- February 2018
    Pathology report upgrades G4+3 tumor to 4+5. One additional cancerous nodule found, G3+4; organ-confined; margins clear, SV clear, LN clear
    Continence: One pad for two months, then dry; ED: Resolved with Cialis
    PSA less than 0.1: May 2018; Aug 2018; Dec 2018; Apr 2019; Aug 2019; Mar 2020

     
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    Old 03-05-2020, 01:55 PM   #5
    IADT3since2000
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    Re: Lack of Evidence That Surgery Is As Good As Radiation for Higher-Risk PC Patients

    Thanks Gerard for sharing your experience, which so well illustrates the puzzling circumstances confronting those of us with higher-risk prostate cancer. And welcome to the Board! I have a few thoughts in response to the general issues raised, but I donít mean to imply that your choice was not a good one; it strikes me that you chose an attractive and reasonable option.

    You are thinking that radiation is more appropriate where evidence suggests the cancer is no longer confined to the prostate:
    Quote:
    I think with the leaps and bounds in radiation technology in recent years, for a lot of people your view is correct.


    This is especially so when the clinical indicators suggest a probability -- or even strong possibility -- that the disease is no longer organ-confined.
    What I am seeing in the preponderance of research studies is that modern radiation is also an excellent choice, for most patients, when evidence suggests the cancer is confined. This was not the case back when I was diagnosed; surgery was clearly superior back then. Now, if the prostate is not too large (after reduction) for brachytherapy radiation, radiation does as good a job of wiping out cancer in the prostate as surgery. External beam radiation can handle even larger prostates, though extreme size does lower odds of success. If you know of a study you believe contradicts these claims, this is the place to bring it forward for discussion.[/QUOTE]

    You also identify some circumstances where you believe surgery is the best choice:
    Quote:
    Yet, there are three circumstances where surgery is strongly indicated, in my view: A) when the prostate is abnormally large; B) when the testing data suggests a likelihood that the disease has not spread beyond the prostate; and C) when the patient has access to an experienced and top-quality surgeon.

    Generally speaking, some combination of those three argues for surgery.
    My impression of medical research is that elements B) and C) in that combination are very important in making a patient eligible for surgery with good odds of success, but I am not aware of research that that combination makes radiation a less worthy choice. If a top quality surgeon is available and the radiation options are not good, that would certainly weight the scale toward surgery. But these days a short course of radiation is often an option, and most of us could afford to take a couple of weeks away from home for such treatment at a center with a good reputation.

    Consideration A), an abnormally large prostate, can be a show-stopper for radiation if it is too large. However, prostate size can be reduced by medication (usually Proscar/finasteride or Avodart/dutasteride) by about a third, which enables many patients to get the size down to around 60 cc, donít recall exactly what the maximum is but this is close, which is a limit for brachytherapy (seeds). External beam can handle somewhat larger prostates. In your case, 79cc X .67 = .53, which is definitely within the limit for brachytherapy, removing this as an obstacle. Did your medical team discuss size reduction with you?

    Consideration B) Ė whether the cancer is truly confined - is where radiation really shines with higher-risk cases, because the medical team typically does not have certain knowledge of containment, though imaging can provide strong evidence, and radiation can reach out beyond the prostate and wipe out cancer in those areas of possible but uncertain spread whereas surgery is limited to a sampling of lymph node that are sometimes extracted. That said, the Johns Hopkins folks are really good at all of this and have ready access to outstanding mpMRI imaging, so you enjoyed advantages that the average patient treated in many other places would not have.




    You feel that post-surgery findings indicated that radiation would have been a mistake, but that may not be the case. You wrote:
    Quote:
    . But as it happened, radiation would have been a mistake for me for various reasons: my prostate was even larger than indicated by the MRI and my cancer even higher grade than indicated by the biopsy.
    It looks like the evidence leans this way, but it is not clear cut; you probably would have done well with radiation, though that enlarged prostate, combined with your PSA doubling time, put you fairly close to the edge for feasible radiation, at least with seeds, while keeping surgery as an option, as I understand it as a layman. As noted above, your prostate would have had to have been quite a bit larger to be beyond the scope of radiation treatment. If my recollection is right that 60 cc is the limit for seeds, then your prostate could have been up to about 90 cc and still with a good shot at being reduced enough to fit under the limit. Doctors and patients would know ahead of time if the drugs had done a sufficiently good job. If the prostate were still too big after the reduction attempt, then surgery, or external beam radiation, would be the way to go. On the other hand, time is involved here, as is ADT, and itís subtle. The drugs would likely hold back the increase in cancer a bit, but not completely, and they would need months to work. Your PSA doubling time might be as short as 5 months, based on the last two values (and assuming all of the increase was due to cancer and not infection). That would not allow much time before your PSA would be above 10, which is not where surgeons like PSA to be when they operate. ADT would almost certainly set the cancer back, but many surgeons donít like to operate after a patient has had ADT (some do). On the other hand, external beam radiation can handle larger prostates, though my impression is that extreme size can be an issue there too.

    As far as the grade goes, that is not a problem at all for radiation. Again, for all of these issues, if you believe you know of research to the contrary, please spot light it for us.


    This brings us to ADT. You wrote:
    Quote:
    Keep in mind also that more often than not, radiation comes paired with ADT -- which is a whole different set of issues, none of them pleasant.
    ADT definitely is part of the discussion for higher-risk patients considering radiation, and thanks again for bringing your experience and thoughts to this thread. In 2017 (and now) radiation doctors would have wanted you on a short course (4-6 months) of ADT to support radiation. Did your medical team ever discuss a short course of ADT and countermeasures to its side effects with you? Did you consult with a radiation oncologist on this or other issues? The good news about ADT is that virtually all patients on a short course will recover from its side effects fairly quickly (and a bit longer from a long course). Also, a truth often neglected by doctors, based on what Iíve heard from fellow patients over the years, is that the side effects of ADT can be avoided or reduced in impact by using countermeasures.


    I like your conclusion.
    Quote:
    At the end of the day, it can be a crapshoot. There are things you know and things you don't know. So you make the choice based on what you know (or think you know) -- and hope it's the right one.
    This reminds me of my initial choice of surgery, which would have been a really poor bet for my then high-risk case. Fortunately, the medical folks at Johns Hopkins urology swiftly rejected me as a surgery candidate. In the moment I was crushed, but it turned out for the best. Hopefully this Board serves to help patients think through their options and make their outcome less of a crapshoot.

    Good luck, and I hope you will keep responding here and to other threads on the board.

    Jim

    - - - - - - - - - - - - - - - - - - - - - - - -
    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 remarkably low at <0.01; apparently cured.. Supportive diet/nutrition, exercise, supportive medications during this journey, as well as switches in antiandrogen, 5-ARI, and bone drugs.

     
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    Old 03-05-2020, 07:23 PM   #6
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    Re: Lack of Evidence That Surgery Is As Good As Radiation for Higher-Risk PC Patients

    My impression is that monotherapies are being used less and less for higher risk cases. It was easy to compare surgery against a radiation treatment when each was used as the sole intervention. Now, treatment plans involving multiple intervention modalities are being proposed for many risk cases, and even some high intermediate risk.

    MaxRP (RP+RT+ADT) is growing in usage; and, MAXRT (EBRT+BBT+ADT) is already a common combo. I'm even seeing articles about ADT before RP, to shrink the prostate and allow a cleaner operation. Such planned combination treatments make comparisons difficult, let alone causing MaxSideEffects (:
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    Seven biopsies from 2009 to 2021. Three were were positive with 5% Gleason(3+3) found.

     
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    Old 03-05-2020, 07:55 PM   #7
    DjinTonic
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    Re: Lack of Evidence That Surgery Is As Good As Radiation for Higher-Risk PC Patients

    With regard to surgery, we should distinguish cases (1) known to be metastatic at diagnosis (where surgery can be used with cytoreductive intent), (2) cases that are G9-10 or strongly suspected to not be prostate confined (locally aggressive and likely headed for MAXRP), and (3) the majority of cases, where RP is the sole treatment until/unless a decision for adjuvant or salvage treatment is made after RP. Neoadjuvant, e.g. ADT before surgery, can be used for some cases of (1) or experimentally in studies for other cohorts.

    Given the spate of recent studies on the association of even short-term ADT with cognitive impairment, I have doubts about a future for ADT before surgery for cases thought to be prostate-confined (see the recent review I posted recently) -- in addition to it making a definitive Gleason score very difficult or impossible.

    Djin
    __________________
    69 yr at Dx, BPH x 20 yr, 9 (!) neg. Bx, PCA3-
    7-05-13 TURP for BPH (90→30 g) path neg. for PCa, then 6-mo. checks
    6-06-17 Nodule on R + PSA rise on finasteride: 3.6→4.3
    6-28-17 Bx #10: 2/14 cores: G10 (5+5) 50% RB, G9 (4+5) 3% RLM
    Nodule negative for PCa. Bone scan, CTs, X-rays: neg.
    8-7-17 Open RP, negative frozen sections, Duke Regional Hosp.
    SM EPE BNI LVI SVI LNI(5L, 11R): negative, PNI+, nerves spared
    pT2c pN0 pMX, G9 (4+5) 5% of prostate (4.5x5x4 cm, 64 g)
    Dry; ED OK with sildenafil
    Decipher 0.37 (Low Risk), uPSA: 0.010 (3 mo.)...0.020 (3 yr. 7 mo.)

     
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    Old 03-05-2020, 08:08 PM   #8
    Gerard1954
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    Re: Lack of Evidence That Surgery Is As Good As Radiation for Higher-Risk PC Patients

    Jim, thanks for your informative response.

    Right, though my expertise and knowledge on the topic does not measure up to yours or some others here, based on the research I've done and some BCR studies I've seen, it seems clear that the major advances in radiation technology in recent years, HDR variants and otherwise, make that treatment option attractive and viable in a lot of cases for a lot of reasons -- to include organ-confined disease. And when the indicators suggest a likelihood or even strong possibility of locally advanced cancer, radiation seems the obvious choice.

    To answer your questions, I sat down with a couple radiation docs, one of them at Hopkins, in the lead-up to my surgery and got somewhat different input from them. Both recommended six months of HT, with the Hopkins guy favoring the administration of it in three 2-month doses. Also, Hopkins didn't want to do brachy whereas the other doc thought it an option if the prostate could be sufficiently reduced in size. Neither doc put HDR on the table.

    The thing is, though, both docs were proceeding on what turned out to be inaccurate data. My prostate was found to be 96CC at surgery rather than the 79 indicated by the MRI. And what the biopsy measured as a 4+3 Gleason lesion was upgraded to 4+5 by post-surgery pathology. This is in part why I think the radiation option might not have been the best for me -- plus I didn't want to deal with the effects of HT.

    As it is, two years later, and I've lucked out (so far). Hopkins takes an interestingly casual approach to the post-surgery surveillance regime. They use the standard test as opposed to the ultrasensitive, and after my latest number remained <0.1, told me I don't have to do another one for a whole year! Hey, who am I to argue with one of the premier urology departments in the world!

    Again, thanks for the thoughtful input. By the way, my first attempt to post this got hosed up, so hopefully some version of this will not appear in the thread twice.
    __________________
    YOB: 1954
    PSA 4.4 -- Mar 2016; 5.9 Jan 2017; 7.7 Mar 2017
    3T MRI of prostate -- April 2017; prostate found to be enlarged (79cc) with two potentially cancerous lesions, one PIRADS-3 and one PIRADS-4
    Fusion biopsy -- August 2017; 14 cores taken, with two measured at Gleason 4+3, corresponding to the MRI PIRADS-4 target location
    RALP at Johns Hopkins -- February 2018
    Pathology report upgrades G4+3 tumor to 4+5. One additional cancerous nodule found, G3+4; organ-confined; margins clear, SV clear, LN clear
    Continence: One pad for two months, then dry; ED: Resolved with Cialis
    PSA less than 0.1: May 2018; Aug 2018; Dec 2018; Apr 2019; Aug 2019; Mar 2020

     
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    Old 03-05-2020, 08:23 PM   #9
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    Re: Lack of Evidence That Surgery Is As Good As Radiation for Higher-Risk PC Patients

    Quote:
    Originally Posted by DjinTonic View Post
    With regard to surgery, we should distinguish cases (1) known to be metastatic at diagnosis (where surgery can be used with cytoreductive intent), (2) cases that are G9-10 or strongly suspected to not be prostate confined (locally aggressive and likely headed for MAXRP), and (3) the majority of cases, where RP is be the sole treatment until/unless a decision for adjuvant or salvage treatment is made after RP. Neoadjuvant, e.g. ADT before surgery, can be used for some cases of (1) or experimentally in studies for other cohorts.

    Given the spate of recent studies on the association of even short-term ADT with cognitive impairment, I have doubts about a future for ADT before surgery for cases thought to be prostate-confined (see the recent review I posted recently) -- in addition to it tmking a definitive Gleason score very difficult or impossible.

    Djin
    Djin, in addition to the recent articles tying ADT to dementia, I have been participating in groups on the largest social media site, where there are many first-time posters.

    The stories of their experiences in ďLupron HellĒ are very discouraging. Their accounts of the physical and mental suffering are depressing, to put it mildly. Many give up ADT before the course of treatment. It may save and/or extend OS, but the loss of QOL makes it a desperate choice.

     
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    Old 03-06-2020, 04:56 AM   #10
    Insanus
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    Re: Lack of Evidence That Surgery Is As Good As Radiation for Higher-Risk PC Patients

    There are two definitive (goal to cure) trials on going for stage 4 prostate cancer.
    Both involve hormones, then surgery, then radiation.

    There is another definitive trail for curing recurring prostate cancer post surgery using no radiation and just hormone deprivation.

    Is there a trial on going to use just radiation and hormone therapy to cure stage 4 PCa?

     
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    Old 03-06-2020, 05:33 AM   #11
    IADT3since2000
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    Re: Lack of Evidence That Surgery Is As Good As Radiation for Higher-Risk PC Patients

    Gerard, you're welcome, and thanks for answering my questions. While some of us have been at this a long time, folks like you have experience in making decisions and experiencing treatment and post-treatment in the current era, and learning about that helps us all.

    I'm really curious about how the MRI missed the size so badly:
    Quote:
    Originally Posted by Gerard1954 View Post
    
    The thing is, though, both docs were proceeding on what turned out to be inaccurate data. My prostate was found to be 96CC at surgery rather than the 79 indicated by the MRI.
    MRI, which I am assuming was multiparametric MRI (mpMRI), should have given a highly accurate estimate. Did anyone ever explain the discrepancy?

    Quote:
    Hopkins takes an interestingly casual approach to the post-surgery surveillance regime. They use the standard test as opposed to the ultrasensitive, and after my latest number remained <0.1, told me I don't have to do another one for a whole year! Hey, who am I to argue with one of the premier urology departments in the world!
    I don't understand why they are not using an ultrasensitive test, and why they are not monitoring PSA at least every 6 months, especially for an aggressive case like yours. To me, that just makes no sense. I wish we could have someone from Johns Hopkins explain their policy. However, I just checked the guidelines from the National Comprehensive Cancer Network (NCCN), a highly respected guideline group, and those guidelines do not specify ultrasensitive monitoring for post RP patients and do recommend testing every 6 to 12 months.

    Quote:
    Again, thanks for the thoughtful input. By the way, my first attempt to post this got hosed up, so hopefully some version of this will not appear in the thread twice.
    The Board software is tricky. I've learned to save my work before trying to post. There is also a way to get back to your work, usually, when the Board tells you you are not logged in when you try to post after you have logged in.

    Jim

     
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    Old 03-06-2020, 06:30 AM   #12
    DjinTonic
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    Re: Lack of Evidence That Surgery Is As Good As Radiation for Higher-Risk PC Patients

    Gerald, if I were you, I'd be measuring my PSA every 3 months preferably with Labcorp's 3-decimal test, but certainly with a test that returns at least 2 decimal places. With a post-op PSA history of all <0.1, you really don't know what your trend has been and whether you are in fact stable.

    How Accurately Can Prostate Gland Imaging Measure the Prostate Gland Volume? Results of a Systematic Review (2019)

    https://www.hindawi.com/journals/pc/2019/6932572/

    Quote:
    Abstract
    Aim. The measurement of the volume of the prostate gland can have an influence on many clinical decisions. Various imaging methods have been used to measure it. Our aim was to conduct the first systematic review of their accuracy. Methods. The literature describing the accuracy of imaging methods for measuring the prostate gland volume was systematically reviewed. Articles were included if they compared volume measurements obtained by medical imaging with a reference volume measurement obtained after removal of the gland by radical prostatectomy. Correlation and concordance statistics were summarised. Results. 28 articles describing 7768 patients were identified. The imaging methods were ultrasound, computed tomography, and magnetic resonance imaging (US, CT, and MRI). Wide variations were noted but most articles about US and CT provided correlation coefficients that lay between 0.70 and 0.90, while those describing MRI seemed slightly more accurate at 0.80-0.96. When concordance was reported, it was similar; over- and underestimation of the prostate were variably reported. Most studies showed evidence of at least moderate bias and the quality of the studies was highly variable. Discussion. The reported correlations were moderate to high in strength indicating that imaging is sufficiently accurate when quantitative measurements of prostate gland volume are required. MRI was slightly more accurate than the other methods.
    From the Full Text:

    Quote:
    5. Conclusions
    Our study suggests that the use of imaging to measure the PGV is still a topic of significant interest and that no previous systematic reviews have been undertaken. The correlation of the PGV measured by imaging with the reference methods was in the range of a distribution from 0.70 to 0.96, which is accurate enough for some of the purposes that require quantitative PGV measurements. MRI was slightly more accurate than the other methods.
    Djin
    __________________
    69 yr at Dx, BPH x 20 yr, 9 (!) neg. Bx, PCA3-
    7-05-13 TURP for BPH (90→30 g) path neg. for PCa, then 6-mo. checks
    6-06-17 Nodule on R + PSA rise on finasteride: 3.6→4.3
    6-28-17 Bx #10: 2/14 cores: G10 (5+5) 50% RB, G9 (4+5) 3% RLM
    Nodule negative for PCa. Bone scan, CTs, X-rays: neg.
    8-7-17 Open RP, negative frozen sections, Duke Regional Hosp.
    SM EPE BNI LVI SVI LNI(5L, 11R): negative, PNI+, nerves spared
    pT2c pN0 pMX, G9 (4+5) 5% of prostate (4.5x5x4 cm, 64 g)
    Dry; ED OK with sildenafil
    Decipher 0.37 (Low Risk), uPSA: 0.010 (3 mo.)...0.020 (3 yr. 7 mo.)

     
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    Old 03-06-2020, 07:45 AM   #13
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    Re: Lack of Evidence That Surgery Is As Good As Radiation for Higher-Risk PC Patients

    Quote:
    Originally Posted by Insanus View Post
    There are two definitive (goal to cure) trials on going for stage 4 prostate cancer.
    Both involve hormones, then surgery, then radiation.

    There is another definitive trail for curing recurring prostate cancer post surgery using no radiation and just hormone deprivation.

    Is there a trial on going to use just radiation and hormone therapy to cure stage 4 PCa?
    The NCCN guidelines list "EBRT with hormonal therapy" as the first recommendation for Stage T3a-T4 prostate cancer.

    So, it's way past trial stage, and has been used for years.
    __________________
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    Old 03-06-2020, 08:52 AM   #14
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    Re: Lack of Evidence That Surgery Is As Good As Radiation for Higher-Risk PC Patients

    I can appreciate the idea that radiation is better at achieving a cure than surgery in prostate cancer.

    However, a large number of men also have enlarged prostates that surgery can deal with directly as well. I guess that Proscar or ADT treatments can reduce prostatic size, but that takes time. Do these scrips work in shrinking a man's prostate who prostate has already been nuked?

     
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    Old 03-06-2020, 10:03 AM   #15
    Gerard1954
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    Re: Lack of Evidence That Surgery Is As Good As Radiation for Higher-Risk PC Patients

    Thanks for the follow-up, Jim.

    Re prostate size, I don't know, the MRI, which by the way was not done by Hopkins (nor was the biopsy), said 79CC.

    The post-op pathology report indicated a prostate "measuring 5.0 cm transversely, 4.8 cm from apex to base and 4.0 cm from anterior to posterior," which, by my math, comes to 96CC -- unless I'm not understanding something correctly.

    In addition, the surgeon told my wife afterward that the operation was extra long in duration because of the size of the prostate. (At times like that, you're glad your surgeon is very good at what he does.)

    At any rate, I don't know the reason for the discrepancy in measurements, assuming I'm calculating the post-op number accurately.

    Regarding the choice of assays and testing intervals, right, I'd actually seen that NCCN guideline suggesting 6-12 months, which is consistent, though on the longer end, of the guidance I just received from Hopkins.

    You know, I may go ahead and request six months. Or maybe not. I'll have to think about it.

    As an aside, I came across a study just last week, fairly recent, indicating no meaningful difference in overall survival rates between a cohort of men tested every three months and one tested on a once-annual basis. I wish I had thought to bookmark it, but maybe I'll try to track it down.

    Alright on the burning issue of standard versus ultrasensitive tests, thank you (and Djin) for your thoughts on that. It's interesting and perhaps instructive that a prestigious institution like Hopkins does not mandate the ultrasensitive test. On the contrary. And Hopkins is not the only leading cancer center to use the standard variant in post-op surveillance. There are one or two more (at least), though honestly, I don't remember which offhand. I've seen mention of them in this connection on message boards.

    The thing is, there are so many variables in the equation: how significant the statistical advantage to detecting possible BCR at extremely low PSA levels, especially when many cancer authorities still hold 0.1, 0.2, or even 0.4 as the trigger level for post-op intervention; the percentage of instances of BCR going on to metastatic cancer; the risk category of the cancer; the presence of indicators in post-op pathology suggesting locally advanced cancer or a higher likelihood thereof; the age of the patient; the all-important psychological factors of risk tolerance and health priorities, both physical and emotional; and more.

    My understanding is that Hopkins doesn't mandate the ultrasensitive test because it does not think the clinical advantages outweigh the anxiety of patients over tiny fluctuations in the measurement, not to mention the possible overtreatment temptations on the part of both docs and patients.

    That said, my first provider, a good and experienced doc in a very large urological practice, who ordered the MRI and did the biopsy, definitely uses the ultrasensitive test post-operatively.

    Moreover, I realize there is a solid (though not, in my view, conclusive) medical argument for it and that many guys opt for it. I totally respect their reasons for doing so. I'd be the last one to ever try and talk somebody, regardless of circumstances, out of it. In fact, I'd be more inclined to advise people to listen to guys like you and Djin.

    Still, based on my own personal equation, I'm comfortable going the other direction -- with the standard assay. I suppose a day could come when I regret that, but two years out, it hasn't arrived yet. Hopefully it never will.

    Meanwhile, again, thanks to you and Djin for your thoughts on all this.
    __________________
    YOB: 1954
    PSA 4.4 -- Mar 2016; 5.9 Jan 2017; 7.7 Mar 2017
    3T MRI of prostate -- April 2017; prostate found to be enlarged (79cc) with two potentially cancerous lesions, one PIRADS-3 and one PIRADS-4
    Fusion biopsy -- August 2017; 14 cores taken, with two measured at Gleason 4+3, corresponding to the MRI PIRADS-4 target location
    RALP at Johns Hopkins -- February 2018
    Pathology report upgrades G4+3 tumor to 4+5. One additional cancerous nodule found, G3+4; organ-confined; margins clear, SV clear, LN clear
    Continence: One pad for two months, then dry; ED: Resolved with Cialis
    PSA less than 0.1: May 2018; Aug 2018; Dec 2018; Apr 2019; Aug 2019; Mar 2020

     
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