A PUBLICATION OF THE PATRICK C. WALSH PROSTATE CANCER RESEARCH FUND

Radical Prostatectomy vs. Radiation: How to Compare the Results? 

Here is one of those situations that prompts annoying phrases like “comparing apples and oranges.” There are plenty of answers, but making sense of them is a different proposition altogether. The question seems pretty simple: How can you compare the results of radiation therapy and radical prostatectomy for curing cancer? How can a man trying to make a decision about treatment — or a man who has already had either treatment, and is looking for reassurance that his cancer is gone or going away — know what to look for?


Frankly, it’s a lot easier with radical prostatectomy. In the span of a few hours, the prostate is out, gone from his life forever. His PSA should be undetectable, at a level below 0.2 ng/ml., within a few weeks or months, depending on how high it was before the operation (the half-life of PSA in the blood stream is two to three days). That level is the point at which surgeons define “biochemical failure.” If that level changes — and even more specifically, when it starts to change, and by how much — there are loads of data, most of it collected and studied meticulously from thousands of patients over the last two and a half decades right here at Hopkins. It is infinitely helpful that a surgeon takes out the diseased prostate, and then a pathologist can pick it up, turn it over, put pieces of it under the microscope, and just generally study the heck out of it. A urologist can tell you, based on your surgical margins and the Gleason score of the prostate specimen, the probability that you will have an undetectable PSA in 10 years. There is even a formula for estimating whether a man is at high risk of an early PSA recurrence, based on factors including whether cancer was found in his lymph nodes, at the edges of the surgical margin, or in the seminal vesicles. This doesn’t mean that PSA will return, but scientists at Hopkins have studied enough men to get a pretty good idea. If the PSA goes up after surgery, doctors also can tell, based on the time it takes for the PSA level to double, which men are most likely to benefit from radiation therapy, and which men should seek more aggressive treatment.

But radiation is different, for several reasons. For one thing, the treatment is ever-more sophisticated. With each impressive technological breakthrough, the long-term results start from scratch; this is nobody’s fault — it’s just the inevitable price of developing better therapy. So there really aren’t long-term results for any of the new forms of radiation therapy for prostate cancer, because it is constantly being refined. We know, easily, that the treatments available now are much better than they were even a decade ago. This is very good news, but it makes it tough if you’re looking for a long-term result.

The other problem is the nature of radiation itself. Because of the way radiation kills cancer cells, it is simply impossible for doctors to come up with a PSA cutoff, as they can after surgery. This is because radiation oncologists design their therapy to kill prostate cancer, not to kill normal prostate tissue. The entire prostate is not destroyed; some tissue remains behind, and continues to make small amounts of PSA.


Radiation oncologists, then, have a real challenge when it comes to interpreting a man’s PSA scores after treatment. There is “good” PSA, still being made by the remaining normal tissue. And sometimes there is “bad” PSA, if a few renegade cancer cells somehow managed to survive the treatment. There is currently no way to tell if this PSA is something to worry about. Instead, the thing to do after radiation therapy is to watch what PSA does over time.

There are plenty of answers, but making sense of them is a different proposition altogether.

The basic idea is that if the PSA is coming from benign tissue, it should remain stable; if it is coming from cancerous tissue, the PSA will rise.

But first, it falls. When it reaches its lowest point, this number is called the PSA nadir; it’s different for every man. Because radiation’s effect is so gradual, it may take several years for a man’s PSA level to hit rock bottom. However, some men reach this point within a few months. Yet another difficulty is that if a man has had hormonal therapy before or during radiation, this can artificially lower the PSA level, and when the effect of the hormones goes away, the PSA can rise — because the man’s testosterone levels are coming back up, not because of cancer. There is no prostate cancer crystal ball to tell how a man is doing after radiationtherapy, but many radiation oncologists use a definition called “nadir + 2.” This says that if a man’s PSA has risen 2 ng/ml higher than its nadir, his cancer has not been cured. A drawback to this approach is that it may delay a man’s knowledge that treatment has failed to cure cancer.

Back to the original question: How to compare radiation and surgery for prostate cancer? In a recent study, Matthew E. Nielsen, M.D., and colleagues Danil Makarov, Elizabeth Humphreys, Leslie Mangold, Alan W. Partin, and Patrick C. Walsh, examined the effect of the nadir + 2 definition on the interpretation of failure after surgery in 2,570 men who underwent radical prostatectomy from 1985 to 2004. Their work was published in the journal, Urology. First, they looked at the surgical definition of treatment failure — a PSA higher than 0.2 ng/ml. Of these men, 88.6 percent had an undetectable PSA at five years after surgery; 81.2 percent at 10 years, and 78.1 percent were cancer-free after 15 years. Men with a PSA higher than 0.2ng/ml may have had a nearly undetectable PSA, and no symptoms of cancer, but according to the surgical definition, their cancer was not considered cured. Using the nadir + 2 definition, they found, overestimated the rate of cure: In these same men, 94.6 would be considered cured at five years, 89.4 percent at 10 years, and 84.3 percent at 15 years would considered cancer-free — even though they clearly had a rising PSA.


“Because patients in this series who experienced a detectable PSA level took more than five years to progress to a PSA level of 2 or greater,” notes Walsh, “the five-year biochemical control rates with the definition of 0.2 ng/ml or more following surgery should be compared with the 10-year biochemical control rates for radiation therapy using the nadir + 2 definition. Until we come up with something better, this is the best way to compare the two forms of treatment.”

 

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