Understated Risk of Radiation induced Malignancy?

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Somebody in academics should run NGS on the samples for this trial and I’m sure you could come up with a paper on it.

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

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.

A fair evaluation. I agree that a single uncontrolled study that appears to find an outlier risk of secondary malignancy is likely to be just that, an outlier, and I agree if we were truly seeing that high a rate it would be more apparent in clinical practice. I was being a bit facetious in talking about quoting that number to patients, though I often will give a range in citing complications say something like "studies have found a range of risk from X to Y with Z seeming to be the consensus," That being said, it is a prospective study that looked at secondary cancer as a prespecified outcome, not a retrospective database like SEER which will be more prone to error. I posted it mostly to prompt discussion about risk, for which I think a 0.5-2% absolute risk is more likely to be accurate.

As for the comparison to operative death, I think that is an appropriate analogue but the risks are far different. The operative mortality from a robotic prostatectomy approaches 0.1 to 0.01%. A 1-2% risk of a dramatically bad outcome (Second cancer) when talking about prostate cancer is a big deal. In prostate cancer that would be more analagous to an outcome of profound incontinence requiring surgery like an AUS, which in most modern series is a ~1%ish outcome, which is still a significantly much less bad outcome.

Now compare that to bladder, with a periop mortality of 1-5% and overall worse prognosis. 1-2% risk of secondary cancer from xrt doesn't sound so bad.
 
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.

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.
Indeed. But secondary malignancies are often defined as a severe adverse event in the protocol and would be reported by the sites.
 
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That being said, it is a prospective study that looked at secondary cancer as a prespecified outcome, not a retrospective database like SEER which will be more prone to error.
This is wrong in this case. We are looking at a relatively rare event. A small randomized trial is meaningless. In this trial they compare 8 vs 1 events? Both arms are getting XRT?

Think how standard error and deviation scale with sample size. They go as the inverse square of the sample size. When you have a small sample (~175 men/arm) and a rare event, the standard deviation may be huge relative to the true value. (Lets say true value of XRT induce malignancy is 0.5% at 10 years, SD may be comparable to or much larger than 0.5 and the likelihood of getting a value like 4% is not that small).

Now take a huge sample like the SEER analysis, errors come from other places (underreporting, confounders in populations (why I references post-op RT vs surgery, a much better comparison), but there is very little impact of randomness on the outcomes.

Think of the hypothesis they are creating here? That chemo reduces XRT induced malignancies significantly? By thinking that 8 vs 1 event is meaningful? This is exactly how to be wrong.
 
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OMG


1% increased risk over baseline?
 
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Excellent, updating my prostate note template to say:

"The risks and benefits of definitive treatment options were discussed, including radiation therapy and radical prostatectomy. Patient was extensively counseled about a recent Harvard study (E. Christopher Dee et al, 2021) which demonstrated radical prostatectomy carries a 6% risk of secondary malignancy."

Since this thread has established we can pick and choose how to apply secondary malignancy risks from studies, @DoctwoB has convinced me that XRT has a 4% chance of secondary malignancy, and @Chartreuse Wombat has convinced me that surgery has a 6% chance of secondary malignancy. Thanks guys!
 
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1% increased risk over baseline?
Just a community doc here, but I really think stating anywhere between 0.5 and 1 % over a time frame of 10-15 years is reasonable and concordant with the bulk of large population studies that we have. Competing risk of dying from other things seems to eat into absolute risk of being diagnosed with second malignancy after this time frame even in the 50 something year old cohorts of pts. Given the patients that we typically treat with XRT for prostate cancer (I rarely treat pts in their 50s), I am very comfortable with any of my partners quoting these numbers.

FWIW, I quote somewhat higher lifetime risk for H&N cancers in my 50 somethings but it doesn't matter. These patients almost uniformly should get treatment and there is no alternative equivalent strategy. Also, the benefit of treatment clearly outweighs the risk.

I would completely ignore a number of 8 patients in a cohort of 175. Small number phenomenon.
 
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OMG

SBRT came within a statistical hair of decreasing second malignancy risk versus surgery.
 
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SBRT came within a statistical hair of decreasing second malignancy risk versus surgery.
Final score: Rad Onc: 28 Urologist: 0

1627213785566.gif

Unfortunately, this was only an exhibition game because in the real world, the urologists will continue to spread fake news to their patients and control the narrative. In the meantime, the rad oncs will continue to multiply in the dark and figure out ways to become extinct as we run out of available resources to sustain in our environment.

The rad onc was once a smart, rare but thriving creature that had potential to change the world. A field once valued as highly competitive field and prestigious .

We will celebrate this victory and use it to remember the time of better days.

1627214719101.jpeg
 
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How are we supposed to believe that SBRT is more conformal/has a lower conferred risk than brachytherapy?
 
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How are we supposed to believe that SBRT is more conformal/has a lower conferred risk than brachytherapy?
Since a RP had higher incidences, maybe the physical disruption of the prostate caused by the implant and surgery stimulated the normal cells to become malignant. Let’s call it an invasive induced malignancy.

Of course I don’t believe this but apparently we can make **** up now.
 
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Since a RP had higher incidences, maybe the physical disruption of the prostate caused by the implant and surgery stimulated the normal cells to become malignant. Let’s call it an invasive induced malignancy.

Of course I don’t believe this but apparently we can make **** up now.
Love it. Quoting it in my future discussions with patients. Sbrt has less secondary cancers than surgery. Done deal
 
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Since a RP had higher incidences, maybe the physical disruption of the prostate caused by the implant and surgery stimulated the normal cells to become malignant. Let’s call it an invasive induced malignancy.

Of course I don’t believe this but apparently we can make **** up now.
I've heard air makes cancer spread. Would be interesting to know if RALP has higher/lower secondary malignancies than open RP.
 
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Of course RT has lower secondary malignancy risk in the adult (non-pediatric) population. It’s called radiation hormesis. It’s practically malpractice to offer prostatectomy to a patient with prostate cancer if the goal is to omit the therapeutic benefits of radiation hormesis!
 
Surprised this hasn't been posted yet. 2nd malignancy rate after long-term follow up of SPCG-7 (RT + ADT vs. ADT alone for LA-prostate cancer): Second Cancers in Patients With Locally Advanced Prostate Cancer Randomized to Lifelong Endocrine Treatment With or Without Radical Radiation Therapy: Long-Term Follow-up of the Scandinavian Prostate Cancer Group-7 Trial - PubMed

What it lacks in N compared to SEER studies, I think it more than makes up for in the purity of a RT vs. no RT RCT with excellent follow up (the Scandinavian countries have national health databases that basically capture every citizen's entire health history).

Median follow up was 12.2 years, absolute 2nd malignancy risk increase of 1.8% at 10 years (19% relative risk increase, p=NS). Strongest increase was in urinary bladder cancers (SS), but most were superficial. Second strongest was lung cancer
 
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Surprised this hasn't been posted yet. 2nd malignancy rate after long-term follow up of SPCG-7 (RT + ADT vs. ADT alone for LA-prostate cancer): Second Cancers in Patients With Locally Advanced Prostate Cancer Randomized to Lifelong Endocrine Treatment With or Without Radical Radiation Therapy: Long-Term Follow-up of the Scandinavian Prostate Cancer Group-7 Trial - PubMed

What it lacks in N compared to SEER studies, I think it more than makes up for in the purity of a RT vs. no RT RCT with excellent follow up (the Scandinavian countries have national health databases that basically capture every citizen's entire health history).

Median follow up was 12.2 years, absolute 2nd malignancy risk increase of 1.8% at 10 years (19% relative risk increase, p=NS). Strongest increase was in urinary bladder cancers (SS), but most were superficial. Second strongest was lung cancer
Breast bud radiation also utilized. Absolute risk of second malignancies insanely high in this cohort. (~30% at 10 years in the non-radiated arm).
 
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Surprised this hasn't been posted yet. 2nd malignancy rate after long-term follow up of SPCG-7 (RT + ADT vs. ADT alone for LA-prostate cancer): Second Cancers in Patients With Locally Advanced Prostate Cancer Randomized to Lifelong Endocrine Treatment With or Without Radical Radiation Therapy: Long-Term Follow-up of the Scandinavian Prostate Cancer Group-7 Trial - PubMed

What it lacks in N compared to SEER studies, I think it more than makes up for in the purity of a RT vs. no RT RCT with excellent follow up (the Scandinavian countries have national health databases that basically capture every citizen's entire health history).

Median follow up was 12.2 years, absolute 2nd malignancy risk increase of 1.8% at 10 years (19% relative risk increase, p=NS). Strongest increase was in urinary bladder cancers (SS), but most were superficial. Second strongest was lung cancer
Nice reference. Sadly, no one actually reads the Red Journal
 
How many times do you hear the hypothesis that living near a transformer causes cancer? I had forgotten that one, until a week or so ago.
Dude, get it right. It’s windmills. Patients don’t even know what a transformer is anymore.
How are we supposed to believe that SBRT is more conformal/has a lower conferred risk than brachytherapy?
That was my exact though when I read the abstract. There are dose differences so potentially that’s important but the fact they mentioned the conformality of SBRT explaining why rates were so low was laughable.
 
The fact that ANYONE is quoting this trial, where RT was used in both arms, to say rate of RT-induced cancers is X, is just bonkers.

Honestly, between this and the 'emulation of a clinical trial' paper that D' Amico was on, he is on a pretty ****ty run of garbage research that he is associated with. Maybe he has dementia setting in.
 
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The fact that ANYONE is quoting this trial, where RT was used in both arms, to say rate of RT-induced cancers is X, is just bonkers.

Honestly, between this and the 'emulation of a clinical trial' paper that D' Amico was on, he is on a pretty ****ty run of garbage research that he is associated with. Maybe he has dementia setting in.
I think he feels compelled to keep feeding the beast by giving medical students and residents papers to write. Some call it mentoring others consider it leading lambs to slaughter.
 
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