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  • Very Low Risk of Secondary Cancer After Radiation for Prostate Cancer - Low Enough?

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    Old 02-12-2021, 12:31 PM   #1
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    Lightbulb Very Low Risk of Secondary Cancer After Radiation for Prostate Cancer - Low Enough?

    Many of us who are considering radiation as our main treatment are concerned about the long term possibility that the radiation might cause a cancer to grow in another place, especially in the rectum or bladder. Indeed, some of us have heard the urologists (surgeons) we consult mention that possibility as they urge us to choose surgery as our treatment, and it seems we are fairly likely to hear that if we are young, especially in our forties or fifties. So what is the real risk?

    This has come up in a recent post in the thread: “A question on nerve sparing for radical prostatectomy" by the author of the thread, music4ever, who is putting into words what many of us have wondered about:

    "Two arguments I’m hearing on this forum from some that I don’t necessarily agree with.

    1) “Radiation is more targeted now than it used to be”. That’s great - maybe everyone will be fine in 20-30 years after radiation. But maybe not. It still seems to me we should want to avoid radiation in general if possible since it can impact rectum and bladder. Like chemotherapy, radiation kills cancer and everything else it’s path. Again can be good or bad. Aren’t the people getting it now still the guinea pigs for the long term effects of “modern” radiation techniques? Or how many years of data do we have?"


    We can ease our minds on one point: radiation does NOT kill "everything else" in its path. That's probably a pretty common misconception, something I did not understand myself for years. The reality is that healthy, non-cancerous cells are injured by radiation, kind of stunned, but if the dosing isn't excessively high or piled on too soon, those cells recover. Competently done, radiation won’t be too high or too soon for almost all of the healthy cells it passes through. So if the prostate is being dosed, for instance, healthy cells in the urethra will be stunned, irritated, and that's the reason we experience urinary urgency during treatment, which disappears shortly after radiation treatments end and the healthy cells are no longer irritated and have not suffered lasting injury. Because of its location, up until recently it was likely that a small part of the rectum might get enough radiation to cause some lasting effects, though mild for the vast majority of us, but not cause cancer. In very recent years the gel known as SpaceOAR has become standard-of-care to put a little space between the rectum and prostate, and it has proven effective in eliminating or reducing the effects of radiation on the rectum. Cancer cells on the other hand are not able to recover and gradually succumb to multiple doses of radiation, something that is believed to be accelerated by ADT.

    There is some encouraging information about secondary cancer caused by radiation, but it is impossible at present to get a firm, precise estimate. The encouraging part is that the risk is quite small based on historical data for ten and twenty years of follow-up. On the other hand, patients treated back then, especially twenty years ago, were typically treated with doses substantially lower than those delivered today, and it is possible that the higher doses could cause more secondary cancers. And from a personal standpoint, I know a fellow patient who did develop bladder cancer after radiation and is convinced the bladder cancer resulted from the radiation. Arguably today's higher doses are much better aimed than the doses received by men ten and twenty years ago, and for my friend, and also are aided by other technologies such as SpaceOAR; more favorable urinary and rectal side effect results suggests long term results will be even better, but that is obviously not guaranteed. Some doctors think young age does increase risk of secondary cancers for patients getting radiation.

    Here are results from one very large study from 2018 (https://pubmed.ncbi.nlm.nih.gov/30249519/ , Urol Oncol. 2018 Nov;36(11):500.e11-500.e19.
    doi: 10.1016/j.urolonc.2018.06.007. Epub 2018 Sep 21, The impact of age at the time of radiotherapy for localized prostate cancer on the development of second primary malignancies, Ross E Krasnow 1 , Dayron Rodrνguez 2 , Ramzy T Nagle 3 , Matthew Mossanen 4 , Adam S Kibel 4 , Steven L Chang 4 ):

    The rates of secondary primary malignancies (SPM):


    Treatment………………........………. 10 Years…….. 20 Years

    Radiation………..............……………..2.7%... ........5.4%

    Radical Prostatectomy…… ……..….1.9%...........3.6%

    Radiation Minus RP Difference……0.8% ………...1.8%


    The researchers tallied bladder or rectal tumors in 579,608 patients with localized prostate cancer treated with either radical prostatectomy (48.2%) or radiation.(51.8%) between 1973 and 2013. The results showed that younger patients were more likely to have recurrences, at about one and a half times the rate for RP patients, versus the lowest likelihood for the oldest group of patients (>= 75 years old) at just a bit over the rate for RP patients, which is what we would expect as there is much less time for patients treated when they were older to develop other cancers. At 10 years, mortality due to the secondary cancer occurred in about a third of the patients treated with radiation (28.9%), meaning that 71.1% had not died due to their second cancer at that point, and again the younger group had a higher proportion of death at nearly double the rate for RP patients (ratio 1.88) while the oldest patients had a mortality rate from second cancers about a quarter above RP patients (ratio 1.27).

    So, getting back to the results indicated in the table but putting them into words, at first glance the rates of secondary cancers for patients getting prostate cancer radiation are just 2.7% and 5.4% at the ten and twenty year points after radiation - quite low, but not zero. Now some of these patients would have gotten secondary cancer even if they had not been treated with radiation. If we use the percentages of RP patients having secondary cancers to estimate the percents that would have occurred without radiation, for ten years we have 2.7% for radiation minus 1.9% for RP, or .8% at ten years that might be due to radiation. Similarly, at 20 years, we have 5.4% for radiation minus 3.6% for RP, or 1.8% that might be due to radiation. Even if we boost these figures by the 1.88 ratio for radiation versus RP tumors in the youngest group of patients, those younger than age 55, we get just 1.55% at 10 years and 3.38% at 20 years – still quite low, but not zero.

    Furthermore, some radiation experts have argued that RP patients are a select group that has a lower overall chance of secondary cancer than other people, which means that if we compared rates of bladder and rectal cancer in prostate cancer radiation patients to those cancers in the general male population of non-prostate cancer patients, the difference might well be zero or very close to it. (https://www.practiceupdate.com/journalscan/50662/1/3?elsca1=emc_enews_expert-insight&elsca2=email&elsca3=practiceupda te_uro&elsca4=urology&elsca5=newsletter& rid=MTg5OTM3MjYwMzAyS0&lid=10332481&ct=t (EMAIL_CAMPAIGN_11_2_2018_12_48)&goal=0_ bc8795358a-d8ca6570db-149104261&mc_cid=d8ca6570db&mc_eid=75d2c 3263d#collapse1 . Here are some key lines from this analysis, one of the authors of which is Dr. Mack Roach, one of the most prominent radiation oncologists specializing in prostate cancer in the world: “However, as shown elegantly by Eifler et al, the standard mortality ratio (SMR) for patients receiving RP as compared with the general population is significantly reduced for all known major causes of death, including other primary malignancies, such as colorectal/anal cancers (SMR=0.43) and bladder cancer (SMR=0.47).1 Thus, RP patients are highly selected for and at significantly lower risk of multiple other comorbidities, including secondary malignancies related to PcRT (ie, 0.47 relative risk of mortality from bladder cancer in RP patients compared with the general population).” Here is the link to the abstract of the Eifler paper that they mention: https://pubmed.ncbi.nlm.nih.gov/22819416/ . One of the pertinent lines is: “Of men who died of a nonprostate cancer cause 44.0% died of a secondary malignancy.” Getting back to that ratio of .43 for colorectal/anal cancer for RP patients, the meaning is that for 100 cases in the general population dying of colorectal/anal cancer, only 43 RP patients would die of colorectal/anal cancer, and for every 100 cases in the general population dying of bladder cancer, only 47 RP patients would die of bladder cancer. To sum up, a better comparison to our radiation patients above to check any causation of secondary cancer by radiation would use numbers for bladder and rectal cancer in people who were not prostate cancer patients instead of using RP patients, and the expected result would be an even smaller difference (possibly even a favorable, negative difference).

    To keep the risks for radiation and surgery in perspective, we need to be aware that there is also a very low risk of mortality from radical prostatectomy surgery. I’ve seen statistics from studies indicating that that risk from the surgery itself, tallied, within 30 days of surgery is about .5% (half a percent) – very low, but not zero, which is one of the reasons that active surveillance for low-risk prostate cancer is now standard. Also, because death due to surgery is near term while from a second cancer caused by radiation would be long term, more years of life would be lost due to surgical death than due to such a second cancer. All that said, I have heard from experts that surgical mortality risk is substantially lower with high-prostate surgery volume, very experienced, expert urologists. To keep all of this in perspective, we need to remember that we would not undergo radiation or surgery if it were not for the great risk to our well-being and survival from higher-risk forms of prostate cancer; the risks from the therapies themselves pale into insignificance compared to the far, far higher risks from the disease!

    However, we are using analysis to estimate reality here; these are not results of gold standard, long-term, large Phase III clinical trials, the best form of evidence. Unfortunately, especially due to changing technology, that kind of evidence is virtually impossible to obtain. In other words, analysis appears to be the best we can do.

    What about the fact that higher doses of radiation are used now instead of substantially lower doses behind much of the historical data? Would this cause an increase in bladder and rectal cancer in the future compared to history? The way I look at this is that far superior imaging and aiming of the radiation dosing, as well as the SpaceOAR technology, should mean that there will be lower risks of bladder and rectal cancer. We do not have twenty or thirty year data to prove this, but the data we do have, now exceeding ten years, shows that modern targeted radiation has reduced side effects compared to older, lower dosing but less well aimed radiation. This suggests that long term rectal and bladder effects will also be reduced. The data we now have is clearly NOT proof, but it is encouraging.

    We also need to keep the future in mind. I believe it is likely that there will be further advances that reduce risk of side effects and complications, including the very low risk of bladder and rectal secondary cancers caused by the radiation treatment. Also, based on progress in treating bladder and rectal cancer, it is likely, I believe, that improved treatments for any of those rectal and bladder cancers that do occur will further extend survival and cure rates.

    All this said, each of us still needs to make our own judgment about how the risk of secondary cancer caused by radiation might affect our own lives and influence our treatment decision. Part of our decision making involves reaching a level of comfort with each alternative. I hope what I have provided helps inform us and also stimulates discussion in this thread.

    So the bottom line is that there is pretty good evidence, but not proof, that the percentage of prostate cancer patients experiencing rectal and bladder cancers due to radiation is very small, that any that do occur tend to occur years after treatment, that those cancers are often treatable with good results, and that most patients will survive those cancers.

    ….Jim

    - - - - - - - - - - - - - - - - - - - - - - - -
    21 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 remarkably low and stable at <0.01; apparently cured (Current PSA as of 12/2/2020). (Current T 93 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. What I experienced is not a guarantee for all but shows what is possible.

    Last edited by IADT3since2000; 02-12-2021 at 12:41 PM. Reason: Typos

     
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    Old 02-12-2021, 06:16 PM   #2
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    Re: Very Low Risk of Secondary Cancer After Radiation for Prostate Cancer - Low Enoug

    Quote:
    Originally Posted by IADT3since2000 View Post
    Many of us who are considering radiation as our main treatment are concerned about the long term possibility that the radiation might cause a cancer to grow in another place, especially in the rectum or bladder. Indeed, some of us have heard the urologists (surgeons) we consult mention that possibility as they urge us to choose surgery as our treatment, and it seems we are fairly likely to hear that if we are young, especially in our forties or fifties. So what is the real risk?

    This has come up in a recent post in the thread: “A question on nerve sparing for radical prostatectomy" by the author of the thread, music4ever, who is putting into words what many of us have wondered about:

    "Two arguments I’m hearing on this forum from some that I don’t necessarily agree with.

    1) “Radiation is more targeted now than it used to be”. That’s great - maybe everyone will be fine in 20-30 years after radiation. But maybe not. It still seems to me we should want to avoid radiation in general if possible since it can impact rectum and bladder. Like chemotherapy, radiation kills cancer and everything else it’s path. Again can be good or bad. Aren’t the people getting it now still the guinea pigs for the long term effects of “modern” radiation techniques? Or how many years of data do we have?"


    We can ease our minds on one point: radiation does NOT kill "everything else" in its path. That's probably a pretty common misconception, something I did not understand myself for years. The reality is that healthy, non-cancerous cells are injured by radiation, kind of stunned, but if the dosing isn't excessively high or piled on too soon, those cells recover. Competently done, radiation won’t be too high or too soon for almost all of the healthy cells it passes through. So if the prostate is being dosed, for instance, healthy cells in the urethra will be stunned, irritated, and that's the reason we experience urinary urgency during treatment, which disappears shortly after radiation treatments end and the healthy cells are no longer irritated and have not suffered lasting injury. Because of its location, up until recently it was likely that a small part of the rectum might get enough radiation to cause some lasting effects, though mild for the vast majority of us, but not cause cancer. In very recent years the gel known as SpaceOAR has become standard-of-care to put a little space between the rectum and prostate, and it has proven effective in eliminating or reducing the effects of radiation on the rectum. Cancer cells on the other hand are not able to recover and gradually succumb to multiple doses of radiation, something that is believed to be accelerated by ADT.

    There is some encouraging information about secondary cancer caused by radiation, but it is impossible at present to get a firm, precise estimate. The encouraging part is that the risk is quite small based on historical data for ten and twenty years of follow-up. On the other hand, patients treated back then, especially twenty years ago, were typically treated with doses substantially lower than those delivered today, and it is possible that the higher doses could cause more secondary cancers. And from a personal standpoint, I know a fellow patient who did develop bladder cancer after radiation and is convinced the bladder cancer resulted from the radiation. Arguably today's higher doses are much better aimed than the doses received by men ten and twenty years ago, and for my friend, and also are aided by other technologies such as SpaceOAR; more favorable urinary and rectal side effect results suggests long term results will be even better, but that is obviously not guaranteed. Some doctors think young age does increase risk of secondary cancers for patients getting radiation.

    Here are results from one very large study from 2018 (https://pubmed.ncbi.nlm.nih.gov/30249519/ , Urol Oncol. 2018 Nov;36(11):500.e11-500.e19.
    doi: 10.1016/j.urolonc.2018.06.007. Epub 2018 Sep 21, The impact of age at the time of radiotherapy for localized prostate cancer on the development of second primary malignancies, Ross E Krasnow 1 , Dayron Rodrνguez 2 , Ramzy T Nagle 3 , Matthew Mossanen 4 , Adam S Kibel 4 , Steven L Chang 4 ):

    The rates of secondary primary malignancies (SPM):


    Treatment………………........………. 10 Years…….. 20 Years

    Radiation………..............……………..2.7%... ........5.4%

    Radical Prostatectomy…… ……..….1.9%...........3.6%

    Radiation Minus RP Difference……0.8% ………...1.8%


    The researchers tallied bladder or rectal tumors in 579,608 patients with localized prostate cancer treated with either radical prostatectomy (48.2%) or radiation.(51.8%) between 1973 and 2013. The results showed that younger patients were more likely to have recurrences, at about one and a half times the rate for RP patients, versus the lowest likelihood for the oldest group of patients (>= 75 years old) at just a bit over the rate for RP patients, which is what we would expect as there is much less time for patients treated when they were older to develop other cancers. At 10 years, mortality due to the secondary cancer occurred in about a third of the patients treated with radiation (28.9%), meaning that 71.1% had not died due to their second cancer at that point, and again the younger group had a higher proportion of death at nearly double the rate for RP patients (ratio 1.88) while the oldest patients had a mortality rate from second cancers about a quarter above RP patients (ratio 1.27).

    So, getting back to the results indicated in the table but putting them into words, at first glance the rates of secondary cancers for patients getting prostate cancer radiation are just 2.7% and 5.4% at the ten and twenty year points after radiation - quite low, but not zero. Now some of these patients would have gotten secondary cancer even if they had not been treated with radiation. If we use the percentages of RP patients having secondary cancers to estimate the percents that would have occurred without radiation, for ten years we have 2.7% for radiation minus 1.9% for RP, or .8% at ten years that might be due to radiation. Similarly, at 20 years, we have 5.4% for radiation minus 3.6% for RP, or 1.8% that might be due to radiation. Even if we boost these figures by the 1.88 ratio for radiation versus RP tumors in the youngest group of patients, those younger than age 55, we get just 1.55% at 10 years and 3.38% at 20 years – still quite low, but not zero.

    Furthermore, some radiation experts have argued that RP patients are a select group that has a lower overall chance of secondary cancer than other people, which means that if we compared rates of bladder and rectal cancer in prostate cancer radiation patients to those cancers in the general male population of non-prostate cancer patients, the difference might well be zero or very close to it. (https://www.practiceupdate.com/journalscan/50662/1/3?elsca1=emc_enews_expert-insight&elsca2=email&elsca3=practiceupda te_uro&elsca4=urology&elsca5=newsletter& rid=MTg5OTM3MjYwMzAyS0&lid=10332481&ct=t (EMAIL_CAMPAIGN_11_2_2018_12_48)&goal=0_ bc8795358a-d8ca6570db-149104261&mc_cid=d8ca6570db&mc_eid=75d2c 3263d#collapse1 . Here are some key lines from this analysis, one of the authors of which is Dr. Mack Roach, one of the most prominent radiation oncologists specializing in prostate cancer in the world: “However, as shown elegantly by Eifler et al, the standard mortality ratio (SMR) for patients receiving RP as compared with the general population is significantly reduced for all known major causes of death, including other primary malignancies, such as colorectal/anal cancers (SMR=0.43) and bladder cancer (SMR=0.47).1 Thus, RP patients are highly selected for and at significantly lower risk of multiple other comorbidities, including secondary malignancies related to PcRT (ie, 0.47 relative risk of mortality from bladder cancer in RP patients compared with the general population).” Here is the link to the abstract of the Eifler paper that they mention: https://pubmed.ncbi.nlm.nih.gov/22819416/ . One of the pertinent lines is: “Of men who died of a nonprostate cancer cause 44.0% died of a secondary malignancy.” Getting back to that ratio of .43 for colorectal/anal cancer for RP patients, the meaning is that for 100 cases in the general population dying of colorectal/anal cancer, only 43 RP patients would die of colorectal/anal cancer, and for every 100 cases in the general population dying of bladder cancer, only 47 RP patients would die of bladder cancer. To sum up, a better comparison to our radiation patients above to check any causation of secondary cancer by radiation would use numbers for bladder and rectal cancer in people who were not prostate cancer patients instead of using RP patients, and the expected result would be an even smaller difference (possibly even a favorable, negative difference).

    To keep the risks for radiation and surgery in perspective, we need to be aware that there is also a very low risk of mortality from radical prostatectomy surgery. I’ve seen statistics from studies indicating that that risk from the surgery itself, tallied, within 30 days of surgery is about .5% (half a percent) – very low, but not zero, which is one of the reasons that active surveillance for low-risk prostate cancer is now standard. Also, because death due to surgery is near term while from a second cancer caused by radiation would be long term, more years of life would be lost due to surgical death than due to such a second cancer. All that said, I have heard from experts that surgical mortality risk is substantially lower with high-prostate surgery volume, very experienced, expert urologists. To keep all of this in perspective, we need to remember that we would not undergo radiation or surgery if it were not for the great risk to our well-being and survival from higher-risk forms of prostate cancer; the risks from the therapies themselves pale into insignificance compared to the far, far higher risks from the disease!

    However, we are using analysis to estimate reality here; these are not results of gold standard, long-term, large Phase III clinical trials, the best form of evidence. Unfortunately, especially due to changing technology, that kind of evidence is virtually impossible to obtain. In other words, analysis appears to be the best we can do.

    What about the fact that higher doses of radiation are used now instead of substantially lower doses behind much of the historical data? Would this cause an increase in bladder and rectal cancer in the future compared to history? The way I look at this is that far superior imaging and aiming of the radiation dosing, as well as the SpaceOAR technology, should mean that there will be lower risks of bladder and rectal cancer. We do not have twenty or thirty year data to prove this, but the data we do have, now exceeding ten years, shows that modern targeted radiation has reduced side effects compared to older, lower dosing but less well aimed radiation. This suggests that long term rectal and bladder effects will also be reduced. The data we now have is clearly NOT proof, but it is encouraging.

    We also need to keep the future in mind. I believe it is likely that there will be further advances that reduce risk of side effects and complications, including the very low risk of bladder and rectal secondary cancers caused by the radiation treatment. Also, based on progress in treating bladder and rectal cancer, it is likely, I believe, that improved treatments for any of those rectal and bladder cancers that do occur will further extend survival and cure rates.

    All this said, each of us still needs to make our own judgment about how the risk of secondary cancer caused by radiation might affect our own lives and influence our treatment decision. Part of our decision making involves reaching a level of comfort with each alternative. I hope what I have provided helps inform us and also stimulates discussion in this thread.

    So the bottom line is that there is pretty good evidence, but not proof, that the percentage of prostate cancer patients experiencing rectal and bladder cancers due to radiation is very small, that any that do occur tend to occur years after treatment, that those cancers are often treatable with good results, and that most patients will survive those cancers.

    ….Jim

    - - - - - - - - - - - - - - - - - - - - - - - -
    21 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 remarkably low and stable at <0.01; apparently cured (Current PSA as of 12/2/2020). (Current T 93 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. What I experienced is not a guarantee for all but shows what is possible.
    Jim, I debate this “secondary cancers from radiation” almost everyday on other forums. I ask the surgery advocate who posted to provide a link to support his statement. Often they do, and often the article is recent. But, when I dig down through the footnotes, from one source to earlier sources, I find that the men were actually treated in the 1980’s. That is light years ago in terms of radiation technology and accuracy.

    As you know, the modern age of radiation is from about 2005. Any conclusions based on earlier treatments are simply not valid when considering treatment today.

     
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    Old 02-12-2021, 06:23 PM   #3
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    Re: Very Low Risk of Secondary Cancer After Radiation for Prostate Cancer - Low Enoug

    Thanks for your post. This was one of the issues I was trying to get my head around when deciding between surgery and radiation. As you said there aren't data 20 yrs out, and by the time we have them there will probably be better radiation treatments.

    At any rate thanks for the post and some actual numbers, I was thinking the numbers were in the ball park of what you posted but had no numbers to know for sure. Having just picked radiation treatment I'm okay with those numbers.

     
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    Old 02-12-2021, 06:56 PM   #4
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    Re: Very Low Risk of Secondary Cancer After Radiation for Prostate Cancer - Low Enoug

    There are recent studies also, you just have to look for them. This paper is from the International Journal of Radiation Oncology, Biology, Physics ASTRO

    Clinical and Treatment Characteristics of Secondary Bladder Malignancies following Low Dose Rate Brachytherapy for Prostate Cancer (2020)
    https://www.redjournal.org/article/S0360-3016(20)31863-0/fulltext

    "Purpose/Objective(s)
    Brachytherapy is an effective option for patients with localized prostate cancer. While secondary malignancies are a well-known late complication of radiation therapy, there are limited data on such malignancies arising from prior prostate brachytherapy. We sought to characterize the clinical course and prognosis of secondary bladder malignancies associated with prostate brachytherapy.

    Materials/Methods
    We queried our institutional database for patients with bladder cancer diagnosed (1/2005-4/2019) who had previously undergone low dose rate (LDR) prostate brachytherapy. Patients with both muscle invasive (T2+) and non-muscle invasive (Tis-T1) bladder tumors were included; patients who underwent treatment elsewhere or who were not evaluable due to lack of documentation were excluded. Clinical and disease-specific characteristics were manually abstracted from chart review. Survival outcomes were estimated using Kaplan-Meier estimates.

    Results
    We identified 27,462 patients with a history of prostate cancer, of whom 375 carried a combined diagnosis of bladder cancer with 51 meeting inclusion criteria. Median time from brachytherapy to bladder cancer diagnosis was 9.3 years (range 2.7-24 years); median follow-up duration was 35.5 months. At diagnosis, no patient had unresectable (T4b) or metastatic (M1) disease. Tumors occurred more frequently on the posterior (34%) and lateral (60%) than anterior (2%) bladder walls. 32 (63%) patients had non-muscle invasive (NMIBC) disease and were managed with TURBT with (n = 16, 31%) or without (n = 15, 29%) intravesical induction/maintenance. 19 (37%) patients had muscle invasive (MIBC) disease; of these 2 were managed with serial TURBT, 11 with cystectomy, 5 with systemic chemotherapy, and 1 with definitive chemoradiation therapy. The 5-year progression-free survival for NMIBC and MIBC were 44.7% (95% CI 23.1-64.3) and 48.1% (95% CI 25.7-69.9), respectively; 5-year survival for NMIBC and MIBC were 75.6% (95% CI 49.7-89.4) and 93.3% (95% CI 61.3-100), respectively. Of the 7 patient deaths recorded during follow-up, only 2 were due to bladder cancer.

    Conclusion
    Secondary bladder malignancies following prostate LDR brachytherapy commonly present at early stage and are well managed with definitive surgical options. Cystectomy was required in the minority of patients presenting with muscle invasive disease and no patient presented with incurable disease at diagnosis. Death from secondary bladder cancer was rare and occurred in only two patients in our cohort."

    [Emphasis mine]

    My own reasons for choosing surgery and avoiding RT (and ADT) for my primary treatment had much more to do with early and later RT toxicities than second primary tumors, although I was concerned with them if salvage prostate re-irradiation had been necessary/proposed.

    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 02-13-2021, 09:04 AM   #5
    music4ever
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    Re: Very Low Risk of Secondary Cancer After Radiation for Prostate Cancer - Low Enoug

    Thanks for the post Jim. I do think that the 10 year data is relevant - since that represents the more modern treatments. And I’m sure the radiation treatments given now are even more targeted and SpaceOAR is helping too - so the numbers should get even better, not worse. It does look encouraging.

    My only thing is the data you presented focused on secondary cancers only. My original concern was long term side effects like bleeding of bladder or rectum, ED, or leakage. My impression is RP patients take a bigger hit up-front and have more issues for the first year, and radiation patients have worse side effects years down the road. Again being young this would be a concern for me. Is there any data out there on long term side effects of modern radaition techniques (say the last 10 years)?

     
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    Old 02-13-2021, 10:18 AM   #6
    Terry G
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    Re: Very Low Risk of Secondary Cancer After Radiation for Prostate Cancer - Low Enoug

    Jim, Individually each of us is a data point of one and personal experience from either our success or failure leads to bias. It’s always better to make judgement on sound data. I’m sure your post will lead many to make a better informed treatment choice. Thanks.
    __________________
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    DOB 7/21/47; good health; age 69 @ Dx
    Treated 6/17 SBRT @ Cleveland Clinic by Dr. Tendulkar
    Reduced ejaculate only side effect; everything works
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    PSA’s post.SBRT 1.1, 1.1, .9, 1.8, 2.7, 1.0, 0.3, 0.6, 0.8

     
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    Old 02-14-2021, 05:34 AM   #7
    IADT3since2000
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    Re: Very Low Risk of Secondary Cancer After Radiation for Prostate Cancer - Low Enoug

    Quote:
    Originally Posted by music4ever View Post
    ... Is there any data out there on long term side effects of modern radaition techniques (say the last 10 years)?
    Yes there is. I'm working on a fresh thread about that, but here's a preview. It's based on an excellent article by a fellow patient, technically well qualified, at https://prostatecancerinfolink.net/2021/01/26/sbrt-for-high-risk-prostate-cancer-patients/ . Some of the patients used SpaceOAR, as I recall it, but I'll need to check. The data he lists is for 4 to 6 years. I believe there is a lot more recent data, but I'll have to take a look.

    Here is a table I will use later that captures key studies he mentions.

    Treatment……..Follow-up….bRFS……....BED…....ADT,….…Late GU toxicity
    …&…………………(years)…..(percent)..…(Gy)…...m edian….…..Grade >=3
    …Source #…………………………………………….………months….(percent)… Source #

    SBRT (1)……………..4…………...82%….…198-253……9………………..2.3%

    Surgery +SRT (2)..5……………78%…………154……….6………………..8.0% (3)

    HDR-BT (4)…………5……………91%.......227-252……6.3…………3.0%-16%

    LDR Brachy
    Boost (5)…………5…………….86%...........227…….12………… …….19.0%

    HDR Brachy
    Boost (6)………..6…………….88%............267…….12…… ……………2.5%

    IMRT (7)……………5…………….88%............174…….28…… ……………2.5%

    Notes about treatments above:

    BED is biological effective dose.

    bRFS is biochemical (meaning PSA) recurrence free disease, in other words, non-recurrence.

    SBRT: Basically, a short course of external beam radiation, 5 to ~20 sessions
    (An awkward acronym standing for Stereotactic Body Radio Therapy)

    Surgery +SRT: A radical prostatectomy plus salvage radiation later

    HDR-BT: High Dose Rate- Brachytherapy means temporary seeds, done over 1-2 days

    LDR Brachy Boost: Low Dose Radiation permanent seed implant after external beam radiation

    ….Jim

    - - - - - - - - - - - - - - - - - - - - - - - -
    21 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 remarkably low and stable at <0.01; apparently cured (Current PSA as of 12/2/2020). (Current T 93 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. What I experienced is not a guarantee for all but shows what is possible.

     
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    Old 02-14-2021, 08:03 AM   #8
    DjinTonic
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    Re: Very Low Risk of Secondary Cancer After Radiation for Prostate Cancer - Low Enoug

    Jim,

    Are do the stats for RP + SRT includes men like me, who had surgery for high-risk but did not have SRT? If so, how do you know that from the reference?

    Are the follow-up periods (median follow-up of 7.1 years for SBRT) comparable? And what happens to high-risk SBRT men from, say, 7 to 10 years?

    With newer therapies BCR-free stats are used as a stand-in for overall and PCa-free survival. Radiologists are usually the first to point out that BCR-free stats do not translate to better OS. This was true in the very recent important studies that seemed to conclude that for perhaps all but worst risk post-RP adverse features, early SRT was no worse than adjuvant therapy. (This may cut down on overtreatment.)

    Even for BCR, we don't have a lot of data yet for SBRT in high-risk. I would point out the Conclusion of the SBRT high-risk study cited as the source:

    "Conclusions
    These data support a favorable toxicity and efficacy profile for SBRT for HRPCa. Further prospective studies are needed to evaluate the optimal dose and target volume in the context of SBRT for HRPCa."

    Thanks,

    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 02-14-2021, 08:25 AM   #9
    ASAdvocate
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    Re: Very Low Risk of Secondary Cancer After Radiation for Prostate Cancer - Low Enoug

    An important factor to consider is that more and more RT is including ADT. It appears to me that ADT is being recommended for most RT above Gleason(3+4). That will make it difficult to make comparisons of true monotherapies. I am also seeing (on other forums) ADT being used more pre-RP.
    __________________
    In Active Surveillance program at Johns Hopkins since July 2009.

    Seven biopsies from 2009 to 2021. Three were were positive with 5% Gleason(3+3) found.

     
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    Old 02-14-2021, 04:51 PM   #10
    IADT3since2000
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    Re: Very Low Risk of Secondary Cancer After Radiation for Prostate Cancer - Low Enoug

    Hi Djintonic - I'm responding to your questio:
    Quote:
    Originally Posted by DjinTonic View Post
    Jim,

    Are do the stats for RP + SRT includes men like me, who had surgery for high-risk but did not have SRT? If so, how do you know that from the reference?

    Are the follow-up periods (median follow-up of 7.1 years for SBRT) comparable? And what happens to high-risk SBRT men from, say, 7 to 10 years?

    ...
    These men all had salvage therapy. Here are some key details from the study:

    Tendulkar RD, Agrawal S, Gao T et al. Contemporary Update of a Multi-Institutional Predictive Nomogram for Salvage Radiotherapy After Radical Prostatectomy . J Clin Oncol. 2016; DOI: 10.1200/JCO.2016.67.9647.

    https://ascopubs.org/doi/full/10.1200/JCO.2016.67.9647 (The article I mentioned has links for each of the studies cited.)

    Here's key text about the patients from the abstract: “node-negative patients with a detectable post-RP prostate-specific antigen (PSA) treated with SRT with or without concurrent androgen-deprivation therapy (ADT) were obtained from 10 academic institutions.”

    I haven't looked at the whole study yet, but at a quick glance it has some interesting details.

    I hope to give a more complete response soon.

    ….Jim

    - - - - - - - - - - - - - - - - - - - - - - - -
    21 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 remarkably low and stable at <0.01; apparently cured (Current PSA as of 12/2/2020). (Current T 93 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. What I experienced is not a guarantee for all but shows what is possible.

     
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    Old 02-14-2021, 07:08 PM   #11
    DjinTonic
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    Re: Very Low Risk of Secondary Cancer After Radiation for Prostate Cancer - Low Enoug

    Quote:
    Originally Posted by IADT3since2000 View Post
    Hi Djintonic - I'm responding to your questio:

    These men all had salvage therapy. Here are some key details from the study:

    Tendulkar RD, Agrawal S, Gao T et al. Contemporary Update of a Multi-Institutional Predictive Nomogram for Salvage Radiotherapy After Radical Prostatectomy . J Clin Oncol. 2016; DOI: 10.1200/JCO.2016.67.9647.

    https://ascopubs.org/doi/full/10.1200/JCO.2016.67.9647 (The article I mentioned has links for each of the studies cited.)

    Here's key text about the patients from the abstract: “node-negative patients with a detectable post-RP prostate-specific antigen (PSA) treated with SRT with or without concurrent androgen-deprivation therapy (ADT) were obtained from 10 academic institutions.”

    I haven't looked at the whole study yet, but at a quick glance it has some interesting details.

    I hope to give a more complete response soon.

    ….Jim
    My point is that in comparing BCR-Free survival stats for treatment modalities for high-risk men, one also has to include the high-risk men who had RP only. Some of us go on to experience BCR and get salvage therapy and some do not. Otherwise you are not comparing apples to apples and are not looking at the outcomes for the entire RP cohort.

    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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