A Meta-Analysis of Non-Metastasized Prostate Cancer Studies — Appears to Indicate that Higher Dose Radiation Therapy Does Not Improve Survival — and a Comment about Arguably Lazy Medical Establishment Thinking

© 2016 Peter Free

 

29 March 2016

 

 

This is a cross post — from my scientifically oriented BrainiYak column

 

I justify it here due to:

 

(a) its importance to men suffering from localized prostate cancer

and

(b) its fit with my ongoing critique of non-scientific, excessively profit-oriented medicine.

 

 

Citation — to study

 

Nicholas G. Zaorsky, Scott W. Keith, Talha Shaikh, Paul L. Nguyen, Eric M. Horwitz, Adam P. Dicker, and Robert B. Den, Impact of Radiation Therapy Dose Escalation on Prostate Cancer Outcomes and Toxicities, American Journal of Clinical Oncology, DOI: 10.1097/COC.0000000000000285 (published ahead of print, 24 March 2016)

 

 

Citation — to press release

 

Thomas Jefferson University, For prostate cancer, more radiation may not improve survival, EurekAlert! (29 March 2016)

 

 

When you’re looking at the wrong thing, you unsurprisingly get mistaken results

 

From the press release:

 

 

Dr. [Robert] Den . . . and colleagues analyzed data from 12 randomized controlled trials of external beam radiation treatment for men with non-metastatic prostate cancer, which included a total of 6884 patients.

 

By pooling data from multiple clinical trials, the researchers were able to see trends that would not have been apparent in the individual studies.

 

Rather than use the typical proxy for patient improvement, the prostate cancer antigen (PSA) test, the researchers looked at long term outcomes such as the development of metastatic cancer and death from cancer.

 

They found that while PSA levels decreased as patients received higher doses of radiation, the overall survival and incidence of metastases, among other measures, did not improve.

 

"It's important to check our assumptions," says Adam Dicker. . . . "This study suggests that our reliance on the PSA test as a proxy for patient outcomes may not as useful as many researchers thought, which has broad implications for the design of future clinical trials and the interpretation of current and previous studies."

 

Dr. Den's study also demonstrated that increasing dose was not associated with worse treatment toxicity, suggesting that current practices are safe. "These data suggest that other therapies may be needed with radiation to increase survival," says Dr. Den.

 

© 2016 Thomas Jefferson University, For prostate cancer, more radiation may not improve survival, EurekAlert! (29 March 2016) (extracts)

 

 

Here is the science-ese

 

From the abstract — notice the lazy, unnecessary, and irritating use of acronyms — my translations of these are contained within brackets:

 

 

Freedom from biochemical failure (FFBF) [— meaning freedom from elevated PSA levels, see pertinent study here —] is a common primary outcome of randomized-controlled trials of prostate cancer (PCa).

 

We aimed to determine how increasing the PCa [prostate cancer] biologically equivalent dose (BED) of external radiation therapy (RT) is correlated with FFBF and overall patient outcomes: overall survival (OS), distant metastasis (DM), and cancer-specific mortality (CSM); as well as genitourinary (GU), and gastrointestinal toxicities.

 

We performed a meta-analysis of 6884 PCa [prostate cancer] patients from 12 randomized-controlled trials of external beam RT [radiation therapy]. Mixed effects regression models were used to estimate weighted linear relationships between BED [biologically equivalent doses] and observed percentages of 5- and 10-year outcomes.

 

For toxicities, a subset analysis of using 3-dimensional conformal RT (3D-CRT) versus intensity-modulated RT (IMRT) was performed.

 

Increasing BED [biologically equivalent dose] correlated with improved FFBF [freedom from biochemical failure]:

 

10-year absolute improvement of 9.6% and 7.2% for low-risk and intermediate-risk patients, respectively . . . but not with improvement of OS [overall survival], DM [distant metastasis], or CSM [cancer-specific mortality] at either time point.

 

BED [biologically equivalent dose] escalation was not correlated with increased acute toxicities; it was correlated with increased late gastrointestinal toxicities in patients treated with 3D-CRT [3-dimensional conformal radiation therapy] . . . . IMRT [intensity-modulated radiation therapy] patients had significantly fewer late toxicities, despite being treated at higher BED [biological equivalent doses].

 

RT BED [radiation therapy biologically equivalent dose] escalation has resulted in significantly improved PCa FFBF [prostate cancer freedom of biochemical failure] at up to 10 years; but not with improvement in OS [overall survival], DM [distant metastasis], or CSM [cancer specific mortality].

 

Thus, FFBF [freedom from biochemical failure, meaning freedom from elevated PSA levels] is a poor surrogate of overall patient outcomes for trials of RT [radiation therapy].

 

Late toxicities were less frequent with IMRT [intensity-modulated radiation therapy] than with 3D-CRT [3-dimensional conformal radiation therapy], even at higher BED [biologically equivalent doses].

 

© 2016 Nicholas G. Zaorsky, Scott W. Keith, Talha Shaikh, Paul L. Nguyen, Eric M. Horwitz, Adam P. Dicker, and Robert B. Den, Impact of Radiation Therapy Dose Escalation on Prostate Cancer Outcomes and Toxicities, American Journal of Clinical Oncology, DOI: 10.1097/COC.0000000000000285 (published ahead of print, 24 March 2016) (paragraphs split, my translations contained within brackets)

 

 

The moral? — This mistake (in both proxy and anticipated clinical outcome) is typical of the medical field

 

Here, “medicine” was too “lazy” to look at actual survival rates. It substituted proxy PSA levels as a measure of radiation-based therapeutic success and then (equally typically) concealed what it was doing by bestowing an idiotically unindicative name — “freedom from biochemical failure” — to further divorce us from recognizing that a proxy was being used.

 

Instead of initially setting up our research to look at what really matters — real survival and real outcomes — we frequently shortcut the research process, so as to save money and time and keep doing whatever it is that we so profitably do. (See here, for example.)

 

Typically compounding the effects of this almost intentional research ignorance, we further cover our erroneous clinical tracks by saying — based on equally errant examinations of the existing evidence — that what we mistakenly do (or did) is not really bad for you.

 

Notice here, Dr. Den’s reported reassurance that providing unnecessary and unhelpful radiation is nevertheless “safe”. Evidently overlooking the fact that it is almost certainly more expensive and probably has some unmentioned — apparently non-fatal, but probably long term and unpleasant — side effects.

 

We see that Medical Establishment thinking is frequently not our friend. Profits, not rationality, drive way too much clinical practice and research methodology. This patient unfriendliness is additionally camouflaged behind a wall of often silly, almost always opaque, jargon that serves to make the Establishment sound more intelligent than it is.

 

I am not attacking medical practitioners. They are just as trapped in our frequently evidence-distorted system as their patients are.