Understated Risk of Radiation induced Malignancy?

[DoctwoB]

Dropping this hear to poke the bear/stir up some discussion

https://ascopubs.org/doi/full/10.1200/JCO.21.00596

RCT of adding docetaxel to RT+ADT for unfavorable intermediate risk disease. No difference in OS with adding docetaxel. But more concerning is the fact that they found a 4.6% incidence of radiation induced cancer (rectal or bladder) at 10 years of follow up. That I find highly concerning, I had quoted my patients likely a 1% risk.

Sample size isn't huge, so luck could play a role. Also uncontrolled, meaning no general population arm, which presumably would have a certain incidence of rectal or bladder cancer over 10 years (though not 4.6%). If true, or near true, however, that is very alarming. If prostatectomy had a 5% risk of rectal injury (a less severe outcome then a second malignancy) we would not be doing prostatectomies.

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[RadOncDoc21]

Dropping this hear to poke the bear/stir up some discussion

https://ascopubs.org/doi/full/10.1200/JCO.21.00596

RCT of adding docetaxel to RT+ADT for unfavorable intermediate risk disease. No difference in OS with adding docetaxel. But more concerning is the fact that they found a 4.6% incidence of radiation induced cancer (rectal or bladder) at 10 years of follow up. That I find highly concerning, I had quoted my patients likely a 1% risk.

Sample size isn't huge, so luck could play a role. Also uncontrolled, meaning no general population arm, which presumably would have a certain incidence of rectal or bladder cancer over 10 years (though not 4.6%). If true, or near true, however, that is very alarming. If prostatectomy had a 5% risk of rectal injury (a less severe outcome then a second malignancy) we would not be doing prostatectomies.

If both arms received radiation, how can they equate one arm had higher “RT-induced malignancies.”

Maybe the chemo helped “control” the new “primary malignancies.”

Now if one arm had RT and the other didn’t, then there may be something to tease out but come on D’Amico!

 

[StIGMA]

From the paper, "the observation of reduced RT-induced cancer incidence with docetaxel use has not been previously reported." They could have also stated "reduced cancer incidence with docetaxel" just as well. It's rationale that killing pre-malignant cells could reduce malignant risk, especially in a short/mid-term basis. This is how topical 5FU is used for premalignant skin conditions for example. The additive absolute risk of malignancy due to RT can be quoted as 1% or less-- this paper does not speak to this.

 

[RADONC4285]

Dropping this hear to poke the bear/stir up some discussion

https://ascopubs.org/doi/full/10.1200/JCO.21.00596

RCT of adding docetaxel to RT+ADT for unfavorable intermediate risk disease. No difference in OS with adding docetaxel. But more concerning is the fact that they found a 4.6% incidence of radiation induced cancer (rectal or bladder) at 10 years of follow up. That I find highly concerning, I had quoted my patients likely a 1% risk.

Sample size isn't huge, so luck could play a role. Also uncontrolled, meaning no general population arm, which presumably would have a certain incidence of rectal or bladder cancer over 10 years (though not 4.6%). If true, or near true, however, that is very alarming. If prostatectomy had a 5% risk of rectal injury (a less severe outcome then a second malignancy) we would not be doing prostatectomies.

This is a completely random result imo . How on earth would chemo reduce RT related malignancy? RT induced malignancy happens years after RT, so don't see how it would be impacted by chemotherapy

 

[DoctwoB]

From the paper, "the observation of reduced RT-induced cancer incidence with docetaxel use has not been previously reported." They could have also stated "reduced cancer incidence with docetaxel" just as well. It's rationale that killing pre-malignant cells could reduce malignant risk, especially in a short/mid-term basis. This is how topical 5FU is used for premalignant skin conditions for example.

That is interesting physiologically, but giving chemotherapy to prevent a cancer sounds like breaking someone's leg to prevent falls.

 

[StIGMA]

That is interesting physiologically, but giving chemotherapy to prevent a cancer sounds like breaking someone's leg to prevent falls.

They are giving it for the prostate cancer.

 

[Chartreuse Wombat]

Small, underpowered study n=350. Assumed HR of 0.48 on OS for docetaxel. To be fair RTOG 0521 assumed HR of 0.49 but the sample size was 600 patients (nearly double)

In small studies like this weird things can happen. I don't believe the risk of second malignancy is that high. No other large prospective study has shown anywhere near that level of risk.

Small studies are prone to bizarre outcomes like the randomized trial of daily image-guidance versus weekly image-guidance that showed worse OS in daily IGRT group despite better bRFS, clinical BRFS and lower toxicity in the daily group.

Daily Versus Weekly Prostate Cancer Image Guided Radiation Therapy: Phase 3 Multicenter Randomized Trial - PubMed

Compared with weekly control, daily IGRT control in prostate cancer significantly improves biochemical progression-free and clinical progression-free interval, and rectal toxicity.

pubmed.ncbi.nlm.nih.gov

 

[Chartreuse Wombat]

Just for fun I looked at the rate of second cancers of any type leading to mortality on RTOG 0521

Oy!

Chemotherapy reduces the risk of dying of a second primary!!!

I don't believe this is true but another example of how small numbers can trick us

 

[Radonky]

First, I have problems with calling it RT induced cancer. Both cohorts recieved RT, so how can you claim it was RT induced? My assumption is that it is statistical noise, and in an otherwise negative trial, needed some "masala" (spice for the non biryani folks) to have an intriguing abstract for JCO.

 

[RadOncDoc21]

Unfortunately, docs (looking at you urologist!) will take this “data” and use it to sway patients away from meeting the rad onc.

 

[ramsesthenice]

Dropping this hear to poke the bear/stir up some discussion

https://ascopubs.org/doi/full/10.1200/JCO.21.00596

RCT of adding docetaxel to RT+ADT for unfavorable intermediate risk disease. No difference in OS with adding docetaxel. But more concerning is the fact that they found a 4.6% incidence of radiation induced cancer (rectal or bladder) at 10 years of follow up. That I find highly concerning, I had quoted my patients likely a 1% risk.

Sample size isn't huge, so luck could play a role. Also uncontrolled, meaning no general population arm, which presumably would have a certain incidence of rectal or bladder cancer over 10 years (though not 4.6%). If true, or near true, however, that is very alarming. If prostatectomy had a 5% risk of rectal injury (a less severe outcome then a second malignancy) we would not be doing prostatectomies.

One thing you can tell your patients for sure, that I tell all of my patients getting pelvic radiation, is that they can't smoke. We know that smoking greatly increases the risk of developing a secondary lung cancer in patients receiving thoracic (including breast) radiation. Just as there is a strong synergistic enhancement between asbestos and smoking. No reason to believe it isn't true for the bladder as well and there is some decent data to support it (though it is understudied if you ask me).

Like others said above, its simply not rational to expect that 6 cycles of drug would have a marked effect on premalignant cells destined to become secondary cancers. Most of them shouldn't even be premalignant when they are getting DTXL. That is why there is typically a 10-15 year lag in diagnosis.

 

[deleted1111261]

Dropping this hear to poke the bear/stir up some discussion

https://ascopubs.org/doi/full/10.1200/JCO.21.00596

RCT of adding docetaxel to RT+ADT for unfavorable intermediate risk disease. No difference in OS with adding docetaxel. But more concerning is the fact that they found a 4.6% incidence of radiation induced cancer (rectal or bladder) at 10 years of follow up. That I find highly concerning, I had quoted my patients likely a 1% risk.

Sample size isn't huge, so luck could play a role. Also uncontrolled, meaning no general population arm, which presumably would have a certain incidence of rectal or bladder cancer over 10 years (though not 4.6%). If true, or near true, however, that is very alarming. If prostatectomy had a 5% risk of rectal injury (a less severe outcome then a second malignancy) we would not be doing prostatectomies.

Totally poking the bear!

There is no no-RT arm. Old people with cancer can still get cancer.

Protect trial didn’t show any additional non prostate cancer deaths in RT arm and it’s a way bigger trial.

This is a nuisance finding. Clickbait!

 

[CaesarRO]

There's a nice discussion on Twitter



ProtecT had much higher numbers and reported second malignancy with all 3 low risk options, even just watching them!

 

[SubserviantToABR]

Should've received carbon ions: Risk of subsequent primary cancers after carbon ion radiotherapy, photon radiotherapy, or surgery for localised prostate cancer: a propensity score-weighted, retrospective, cohort study

 

[elementaryschooleconomics]

This is a completely random result imo . How on earth would chemo reduce RT related malignancy? RT induced malignancy happens years after RT, so don't see how it would be impacted by chemotherapy

Studies like this always make me think of:

Testing multiple statistical hypotheses resulted in spurious associations: a study of astrological signs and health

To illustrate how multiple hypotheses testing can produce associations with no clinical plausibility.We conducted a study of all 10,674,945 residents …

www.sciencedirect.com

 

[DoctwoB]

Small, underpowered study n=350. Assumed HR of 0.48 on OS for docetaxel. To be fair RTOG 0521 assumed HR of 0.49 but the sample size was 600 patients (nearly double)

In small studies like this weird things can happen. I don't believe the risk of second malignancy is that high. No other large prospective study has shown anywhere near that level of risk.

Small studies are prone to bizarre outcomes like the randomized trial of daily image-guidance versus weekly image-guidance that showed worse OS in daily IGRT group despite better bRFS, clinical BRFS and lower toxicity in the daily group.

Daily Versus Weekly Prostate Cancer Image Guided Radiation Therapy: Phase 3 Multicenter Randomized Trial - PubMed

Compared with weekly control, daily IGRT control in prostate cancer significantly improves biochemical progression-free and clinical progression-free interval, and rectal toxicity.

pubmed.ncbi.nlm.nih.gov

Ha, didn't see that part. Anyone expecting anything in localized prostate cancer (including the actual primary treatment) to have a 50% overall survival benefit at 10 years is deluding themselves. A magic pill that instantly cured prostate cancer without any side effects wouldn't have a 50% OS benefit.

 

[DoctwoB]

Should've received carbon ions: Risk of subsequent primary cancers after carbon ion radiotherapy, photon radiotherapy, or surgery for localised prostate cancer: a propensity score-weighted, retrospective, cohort study

In all seriousness there does seem to be a signal to the noise, but the noise is very noisy. A quick lit review for shows relative risks of pelvic malignancy from 10-90% higher after prostate XRT. Getting to absolute risk numbers is a challenge and only reported in some studies, or would require deeper dives into data then im intersted in performing. Obviously there are confounders, most notably that xrt patients are older and more likely to smoke then surgical patients (one of the studies showed RP patient have a lower second cancer risk then gen population, which makes sense, because as we know RP prevents heart disease and cancer). Some of the studies control for this reasonably well, some don't. Most of these studies are in the 5-10 year follow up range, which is obviously inadequate for assessing secondary cancer risk.

How will I counsel my patients? In talking about the risk of secondary cancers from xrt, I've quoted a risk of about 1% based on a few studies I had seen. Based on what I've seen now, I'll more likely quote anywhere from 0-4% depending on the study you look at.

 

[deleted1111261]

In all seriousness there does seem to be a signal to the noise, but the noise is very noisy. A quick lit review for shows relative risks of pelvic malignancy from 10-90% higher after prostate XRT. Getting to absolute risk numbers is a challenge and only reported in some studies, or would require deeper dives into data then im intersted in performing. Obviously there are confounders, most notably that xrt patients are older and more likely to smoke then surgical patients (one of the studies showed RP patient have a lower second cancer risk then gen population, which makes sense, because as we know RP prevents heart disease and cancer). Some of the studies control for this reasonably well, some don't. Most of these studies are in the 5-10 year follow up range, which is obviously inadequate for assessing secondary cancer risk.

How will I counsel my patients? In talking about the risk of secondary cancers from xrt, I've quoted a risk of about 1% based on a few studies I had seen. Based on what I've seen now, I'll more likely quote anywhere from 0-4% depending on the study you look at.

How do you say 4.6% from that study that doesn’t have a no RT arm? It’s very odd to pick that up as a reference point for 2nd malignancy.

 

[BobbyHeenan]

Protect data (tweet below) suggests no major difference. Sure, XRT can definitely cause second cancers….but using a trial without a “no XRT” arm for comparison as a bench mark is nuts.

Number one factor for a second cancer - age. These dudes get old and get other cancers. Teasing out how much is from xrt is very very hard. To me protect trial seems as good as any comparison we have bc every patient has one baseline cancer. Better than a “population” based comparison.

….not to mention any theoretical no-second-malignancies-from-surgery advantage is thrown out the window when the patient needs post op xrt.

 

[Chartreuse Wombat]

Relative risk and absolute risk are bad estimates without a no RT arm/group. The best paper I know of is from long ago.

Increased risk of rectal cancer after prostate radiation: a population-based study - PubMed

We noted a significant increase in development of rectal cancer after radiation for prostate cancer. Radiation had no effect on development of cancer in the remainder of the colon, indicating that the effect is specific to directly irradiated tissue.

pubmed.ncbi.nlm.nih.gov

The RR was 1.7 looking at second cancers in patients treated with RP and XRT compared to RP alone.

The 70% increased risk was all over the urology trade publications "radiation bad".

To me the best metric to inform patients is the number needed to harm (NNH) (i.e. the number of men that need to be treated with XRT that will result in one additional bladder or rectal cancer) NNH=1/ARR

Using this paper the NNH is approximately 150-200 estimating the 15 year risk from the Figure below. Notice the y-axis. Baseline risk of rectal cancer in RP no XRT group is less than 1% at 15 years

 

[elementaryschooleconomics]

How will I counsel my patients? In talking about the risk of secondary cancers from xrt, I've quoted a risk of about 1% based on a few studies I had seen. Based on what I've seen now, I'll more likely quote anywhere from 0-4% depending on the study you look at.

How do you say 4.6% from that study that doesn’t have a no RT arm? It’s very odd to pick that up as a reference point for 2nd malignancy.

Yeah, that would be like me, in discussing surgery vs XRT, telling patients (based on this, Table 14) that they could have "up to a 60% risk of incontinence with surgery".

Do I really think that number is accurate? No. But does the literature back me up? Sure. But that's the problem with 30,000+ papers being published per year: you can find data to say anything. Most importantly, that 60% number came from a study just looking at incontinence after RP...not after RP vs XRT.

In a paper comparing radiation to radiation...how can you draw conclusions about secondary malignancy risk comparing surgery to radiation?

 

[deleted1111261]

You hate to make it about specialties, but you just don’t see this kind of analysis from RO side. @DoctwoB - you seem generally reasonable. How do you make this assessment with no RP or AS arm, and ignore PROTECT results ?

 

[theradiator]

Yeah, that would be like me, in discussing surgery vs XRT, telling patients (based on this, Table 14) that they could have "up to a 60% risk of incontinence with surgery".

Do I really think that number is accurate? No. But does the literature back me up? Sure. But that's the problem with 30,000+ papers being published per year: you can find data to say anything. Most importantly, that 60% number came from a study just looking at incontinence after RP...not after RP vs XRT.

In a paper comparing radiation to radiation...how can you draw conclusions about secondary malignancy risk comparing surgery to radiation?

Isn’t the underlying problem corruption of elite institutions and brands? After all, if any one of us tried to publish this data with these rubbish conclusions, I’m quite confident that it would be summarily rejected, likely with a scathing critique from D’Amico himself.

 

[ROforbetterorworse]

I'm going to start saying 100% risk of incontinence from now on

 

[DoctwoB]

Relative risk and absolute risk are bad estimates without a no RT arm/group. The best paper I know of is from long ago.

Increased risk of rectal cancer after prostate radiation: a population-based study - PubMed

We noted a significant increase in development of rectal cancer after radiation for prostate cancer. Radiation had no effect on development of cancer in the remainder of the colon, indicating that the effect is specific to directly irradiated tissue.

pubmed.ncbi.nlm.nih.gov

The RR was 1.7 looking at second cancers in patients treated with RP and XRT compared to RP alone.

The 70% increased risk was all over the urology trade publications "radiation bad".

To me the best metric to inform patients is the number needed to harm (NNH) (i.e. the number of men that need to be treated with XRT that will result in one additional bladder or rectal cancer) NNH=1/ARR

Using this paper the NNH is approximately 150-200 estimating the 15 year risk from the Figure below. Notice the y-axis. Baseline risk of rectal cancer in RP no XRT group is less than 1% at 15 years

View attachment 340873

That’s a good analysis in removing the surgical selection bias issue. But that does conform with some other data in that you could probably double or triple that number if you include bladder or anal cancer, which puts you somewhere in that 1-3% range, even with 15 year follow up. And that is with lower dose salvage xrt compared to primary xrt. If you radiate a 55 year old who lives for 35 more years does the risk increase linearly? Plateau? Increase exponentially?

 

[DoctwoB]

I'm going to start saying 100% risk of incontinence from now on

Lest you think I’m one sided, I do tell my patients that (or close to it). The spiel includes that almost all men will have some degree of leakage after cath removal (though my personal 1 week pad free rate is 50%).

In all honesty the hand waving away of this concern, which while far from validated is VERY concerning, is a bit un patient centered. I spend a lot of time with my friggin vasectomy patients warning them that their 1-2% risk of post vasectomy pain can be life altering, and we’re talking about friggin rectal and bladder cancer.

 

[TheWallnerus]

That is interesting physiologically, but giving chemotherapy to prevent a cancer sounds like breaking someone's leg to prevent falls.

Well my friend it depends on what you call “chemotherapy”

The Final Verdict on Finasteride | SWOG

SWOG Cancer Research Network, an international cancer clinical trials group funded by the National Cancer Institute (NCI), part of the National Institutes of Health, opened the PCPT for enrollment 25 years ago. The PCPT enrolled 18,882 men from 1993 to 1997, making it one of the largest prostate...

www.swog.org

 

[DoctwoB]

You hate to make it about specialties, but you just don’t see this kind of analysis from RO side. @DoctwoB - you seem generally reasonable. How do you make this assessment with no RP or AS arm, and ignore PROTECT results ?

I don’t ignore protect results. They are reassuring about the safety of xrt (though they only report death from second cancers, not incidence IIRC), and the 10 year follow up is an issue. But I interpret the result in light of the body of evidence. If we took protect (or PIVOT or PLCO) as gospel then none of us would actively treat prostate cancer at all would we.

 

[DoctwoB]

Well my friend it depends on what you call “chemotherapy”

The Final Verdict on Finasteride | SWOG

SWOG Cancer Research Network, an international cancer clinical trials group funded by the National Cancer Institute (NCI), part of the National Institutes of Health, opened the PCPT for enrollment 25 years ago. The PCPT enrolled 18,882 men from 1993 to 1997, making it one of the largest prostate...

www.swog.org

Ugh. That trial/concept refuses to die. At least we will help their LUTS while preventing cancers that don’t need to be prevented.

 

[thecarbonionangle]

im not surprised urology continues to have such low ability to critically analize data.

 

[DoctwoB]

How do you say 4.6% from that study that doesn’t have a no RT arm? It’s very odd to pick that up as a reference point for 2nd malignancy.

Hey I’m just a dumb surgeon/non cancer specialist reading a high end peer reviewed cancer journal 😂.

yes this this not the ideal trial design you would use to answer this question. But that doesn’t make a rate of almost 5% of in field cancer not exist.

 

[communitydoc13]

Totally bogus. Radiation induced malignancy happens but rarely and with latency. I didn't even read the study but I'm guessing these men are pushing 70 on average (as is typical of prostate studies) with a baseline risk of pelvic malignancy close to this.

Second solid cancers after radiotherapy for breast cancer in SEER cancer registries

Radiotherapy for breast cancer reduces disease recurrence and breast cancer mortality. However, it has also been associated with increased second cancer risks in exposed sites.We evaluated long-term second cancer risks among 182 057 5-year survivors ...

www.ncbi.nlm.nih.gov

Best data I've ever seen for 2nd malignancy comes from massive post mastectomy database study from the era where post mastectomy RT was dealers choice. (This was over 180K women in study). By the time you parse the data down to a one liner, the absolute risk of 2nd malignancy in these women (50+ year olds and prob significant fraction of smokers in this era) was about 8% at 13 years in both arms with an absolute increase of about 0.4% in the RT arm.

Or in their own words"

"Overall, 5–6% of second solid cancers in irradiated women were estimated to be attributable to radiotherapy exposure. Among all breast cancer survivors, this figure was 3%. Our findings suggest that most second solid cancers after treatment for breast cancer are related to other risk factors such as lifestyle or genetic factors. When women and their physicians make treatment decisions, the risk of radiotherapy-related cancer needs to be placed in perspective and balanced with the known tumour control and mortality benefits achieved from treatment."

Hard to believe a much bigger relative contribution in 70 year old prostate patients.

 

[TheWallnerus]

Lest you think I’m one sided, I do tell my patients that (or close to it). The spiel includes that almost all men will have some degree of leakage after cath removal (though my personal 1 week pad free rate is 50%).

In all honesty the hand waving away of this concern, which while far from validated is VERY concerning, is a bit un patient centered. I spend a lot of time with my friggin vasectomy patients warning them that their 1-2% risk of post vasectomy pain can be life altering, and we’re talking about friggin rectal and bladder cancer.

I don’t think rad oncs should hand wave it. You are right about that. There are many nuances to the second malignancy tale though. In young women with Hodgkin dz who would ordinarily have ~10 percent lifetime risk of breast cancer, when there is spillover RT to their breasts the second malignancy risk can be tripled to 30%. A particularly truculent med onc calls this a rad onc Pyrrhic victory. However the same fields and doses will give a 60yo woman <1% measurable increased risk. Most rad oncs feel much the same way about the older men with CaP we irradiate, namely that second malignancy risks are uncommon. However all the more reasons to be judicious about irradiating very low risk disease or men younger than 50. Rad oncs irradiate many body sites in men and women across many ages though; we would all feel 0-4% second malignancy risk to be not inaccurate but too imprecise.

 

[TheWallnerus]

Ugh. That trial/concept refuses to die. At least we will help their LUTS while preventing cancers that don’t need to be prevented.

Redirect Notice

www.google.com

 

[elementaryschooleconomics]

In all honesty the hand waving away of this concern, which while far from validated is VERY concerning, is a bit un patient centered. I spend a lot of time with my friggin vasectomy patients warning them that their 1-2% risk of post vasectomy pain can be life altering, and we’re talking about friggin rectal and bladder cancer.

I think part of this is you (likely) haven't seen the "behind the scenes" discussions about this on our end for not just prostate patients but for all patients?

I obviously can't speak for all Radiation Oncologists, but in my experience, the risk of secondary malignancy is discussed with virtually all patients at the time of consult (or thereabouts). This becomes particularly emphasized with younger patients, and for me, personally, has been quite difficult with patients/parents and considering risk/benefit ratios (i.e. when a teenager has a disfiguring recurrent keloid on the ear). On the planning end, I know many of us try to make sure our plans are minimizing dose spillage into normal structures not only for common radiation adverse effects but also increasing the risk of secondary malignancy.

Answering the question "how much does therapeutic radiation increase the risk of developing radiation-induced malignancy" has, I would venture to guess, not been answered to anyone's satisfaction, whether from the bench or in the clinic. I was literally pulling papers on this a few hours before this Tweet because I was talking about this with my physicists as we were reviewing a plan, and all of us were left unsatisfied.

I'm SURE there are Evangelical Radiation Oncologists out there who tell patients that there is no risk. They are wrong, and (I assume) they are few and far between. However, this single study is another single data point in the literature bath that is radiation-induced malignancy, and will not change the way I practice medicine in any way.

 

[medgator]

im not surprised urology continues to have such low ability to critically analize data.

If only they got paid to interpret data correctly..... Worked for overusing lupron in the 90s!!

 

[communitydoc13]

Second primary cancer risk of radiation therapy after radical prostatectomy for prostate cancer: an analysis of SEER data - PubMed

Radiation after radical surgery increased late primary pelvic SPC. No increases were seen in secondary pelvic or extrapelvic SPCs.

pubmed.ncbi.nlm.nih.gov

Remarkably similar ratios to the above linked breast paper in the most appropriate comparison (post-prostatectomy XRT vs. surgery alone, (reduces many confounders)).

Again, ~5% of 2nd malignancies appear to be radiation induced in these populations.

 

[ROforbetterorworse]

Lest you think I’m one sided, I do tell my patients that (or close to it). The spiel includes that almost all men will have some degree of leakage after cath removal (though my personal 1 week pad free rate is 50%).

In all honesty the hand waving away of this concern, which while far from validated is VERY concerning, is a bit un patient centered. I spend a lot of time with my friggin vasectomy patients warning them that their 1-2% risk of post vasectomy pain can be life altering, and we’re talking about friggin rectal and bladder cancer.

No vasectomy for me until March Madness discount

March Madness brings increase in number of vasectomies

David Fleming follows the trend of men scheduling their procedures during tourney time for a guilt-free way to catch every second of the games.

www.espn.com

 

[madchemist89]

There is an article that is a printed version of a speech given by a radiation oncologist (maybe red journal? forgot author as well). He compares the risk of secondary malignancy from RT to be similar to operative mortality. That has really stuck with me. Wish I remembered the article.

 

[Palex80]

We ran 5 (?) randomized trials on adjuvant RT for prostate cancer following prostatectomy.

Perhaps one should gather all that data as a metaanalysis and make up two groups: adjuvant RT + salvage RT vs. no-RT and then see what comes up?

There should be a few thousand patient datasets there.

 

[TheWallnerus]

We ran 5 (?) randomized trials on adjuvant RT for prostate cancer following prostatectomy.

Perhaps one should gather all that data as a metaanalysis and make up two groups: adjuvant RT + salvage RT vs. no-RT and then see what comes up?

There should be a few thousand patient datasets there.

Good thought. I hadn't thought about it before. I checked the Bolla and the SWOG; couldn't find a mention of second primary cancers.

yes this this not the ideal trial design you would use to answer this question. But that doesn’t make a rate of almost 5% of in field cancer not exist.

Here are some random wide-net, probably biased, retrospective abstracts with giant N-values. Again, "Almost 5%" is kind of imprecise but not exactly horribly, shootably-offensive wrong.

Please send patients for RT. We call urologists "The Patient Givers" or alternatively "Those Who Doth Refer." We promise we are honest about the risks. Happy Friday.

Second primary cancer risk of radiation therapy after radical prostatectomy for prostate cancer: an analysis of SEER data

Second Primary Cancer After Radiotherapy for Prostate Cancer—A SEER Analysis of Brachytherapy Versus External Beam Radiotherapy

Radiation Therapy for Prostate Cancer Increases Subsequent Risk of Bladder and Rectal Cancer: A Population Based Cohort Study

Analysis of second malignancies after modern radiotherapy versus prostatectomy for localized prostate cancer

Does radiotherapy increase the risk of colorectal cancer among prostate cancer patients? A large population-based study

Estimation of secondary cancer risk after radiotherapy in high-risk prostate cancer patients with pelvic irradiation

High prevalence of secondary bladder cancer in men on radiotherapy for prostate cancer: evidence from a meta-analysis

 

[Mandelin Rain]

All I know is, Anthony D'Amico should be ashamed of himself.

 

[communitydoc13]

Amazon product

If I had any impact on resident education, I would require this book and actually have a quiz. No discrete calculations. Just intuitive conversations about expectation values, rare events, wrong application of p-values, etc. Gives anyone who gets it a good intuitive feel for when a statistic is meaningful or not.

 

[ramsesthenice]

I can’t remember who first said you know a good compromise when no one is happy. I think the academic compromise is probably closer to the truth here.

let’s start with 4%. That is 1/25 patients. And also an unmistakable number that could not be physically overlooked without actively trying. It is also an extreme outlier from a single arm of a small study in which another arm with RT didn’t see anything like this. DoctwoB, I think you are generally a very reasonable voice who I appreciate best my a part of our community which is why I am confused you seem to feel like you need to discuss a controversial outlier with your patients. They have a hard enough time understanding the basics. I don’t think you are under any obligation to discuss nuanced data from post hoc analyses that don’t match up with higher quality data or your own clinical experience.

Now to my friends, I doubt 1% is quite high enough. We know that as time ticks by data from follow up degrades in quality and we are almost certainly under reporting. It also depends on what you consider a secondary cancer. Are you including Tis bladder tumors? Or just invasive tumors. I also did a little math exercise for myself. I treat pretty much all of the secondary cancers managed with RT for our state post prostate RT (any pelvic really, but only talking prostate here). I treated 4 last year. I noodled our urologists and colorectal surgeons and roughly counting 80% were managed surgically. Entering the number of patients diagnosed in our state database from 10 years ago and a reasonable estimate of the number of radiated patients at that time, I get something close to 2%. Of course, the RT patients are more likely to smoke and eat high meat diets which also increase their risk of bladders and rectal tumors so it’s a little hard to guess how much of that 2% is excess from radiation.

 

[BobbyHeenan]

Amazon product

If I had any impact on resident education, I would require this book and actually have a quiz. No discrete calculations. Just intuitive conversations about expectation values, rare events, wrong application of p-values, etc. Gives anyone who gets it a good intuitive feel for when a statistic is meaningful or not.

Agree.

I would also add Nassim Talebs Incerto series as well.

 

[TheWallnerus]

I can’t remember who first said you know a good compromise when no one is happy. I think the academic compromise is probably closer to the truth here.

let’s start with 4%. That is 1/25 patients. And also an unmistakable number that could not be physically overlooked without actively trying. It is also an extreme outlier from a single arm of a small study in which another arm with RT didn’t see anything like this. DoctwoB, I think you are generally a very reasonable voice who I appreciate best my a part of our community which is why I am confused you seem to feel like you need to discuss a controversial outlier with your patients. They have a hard enough time understanding the basics. I don’t think you are under any obligation to discuss nuanced data from post hoc analyses that don’t match up with higher quality data or your own clinical experience.

Now to my friends, I doubt 1% is quite high enough. We know that as time ticks by data from follow up degrades in quality and we are almost certainly under reporting. It also depends on what you consider a secondary cancer. Are you including Tis bladder tumors? Or just invasive tumors. I also did a little math exercise for myself. I treat pretty much all of the secondary cancers managed with RT for our state post prostate RT (any pelvic really, but only talking prostate here). I treated 4 last year. I noodled our urologists and colorectal surgeons and roughly counting 80% were managed surgically. Entering the number of patients diagnosed in our state database from 10 years ago and a reasonable estimate of the number of radiated patients at that time, I get something close to 2%. Of course, the RT patients are more likely to smoke and eat high meat diets which also increase their risk of bladders and rectal tumors so it’s a little hard to guess how much of that 2% is excess from radiation.

Started strong. Horse started bucking a little there at the end!

 

[ramsesthenice]

Started strong. Horse started bucking a little there at the end!

No one goes to a rodeo to watch critters calmly walk in circles.

 

[elementaryschooleconomics]

No one goes to a rodeo to watch critters calmly walk in circles.

Sometimes I wonder, "why do I spend so much time on SDN"?

It's for threads like this, that's why!

 

[Lamount]

Does radiation cause secondary cancers

I can’t remember who first said you know a good compromise when no one is happy. I think the academic compromise is probably closer to the truth here.

let’s start with 4%. That is 1/25 patients. And also an unmistakable number that could not be physically overlooked without actively trying. It is also an extreme outlier from a single arm of a small study in which another arm with RT didn’t see anything like this. DoctwoB, I think you are generally a very reasonable voice who I appreciate best my a part of our community which is why I am confused you seem to feel like you need to discuss a controversial outlier with your patients. They have a hard enough time understanding the basics. I don’t think you are under any obligation to discuss nuanced data from post hoc analyses that don’t match up with higher quality data or your own clinical experience.

Now to my friends, I doubt 1% is quite high enough. We know that as time ticks by data from follow up degrades in quality and we are almost certainly under reporting. It also depends on what you consider a secondary cancer. Are you including Tis bladder tumors? Or just invasive tumors. I also did a little math exercise for myself. I treat pretty much all of the secondary cancers managed with RT for our state post prostate RT (any pelvic really, but only talking prostate here). I treated 4 last year. I noodled our urologists and colorectal surgeons and roughly counting 80% were managed surgically. Entering the number of patients diagnosed in our state database from 10 years ago and a reasonable estimate of the number of radiated patients at that time, I get something close to 2%. Of course, the RT patients are more likely to smoke and eat high meat diets which also increase their risk of bladders and rectal tumors so it’s a little hard to guess how much of that 2% is excess from radiation.

Another important consideration is that a high number of prostate cancer patients have germline mutations which likely both predisposes them to cancers, and makes them more likely to get radiation induced cancers (~5% with BRCA2 and 1.74% with mismatch repair mutations)

 

[RadOncDoc21]

Does radiation cause secondary cancers

Another important consideration is that a high number of prostate cancer patients have germline mutations which likely both predisposes them to cancers, and makes them more likely to get radiation induced cancers (~5% with BRCA2 and 1.74% with mismatch repair mutations)

Urologists: