Radiation Used in Too Many Men With Indolent Prostate Cancer

Pam Harrison

February 23, 2015

Men with low-risk prostate cancer — regardless of clinical characteristics or tumor biology — are being overtreated, often with radiation therapy, a population-based assessment has shown.

The study was published online February 19 in JAMA Oncology.

"The study was not so much about how prostate cancer is treated here in the United States, but what's driving the decision-making process," said Karim Chamie, MD, from the David Geffen School of Medicine at the University of California, Los Angeles (UCLA).

"By far the biggest predictor of someone getting radiation therapy is not how old they are or how sick they are or whether their Gleason grade or PSA scores are high or low, or even how aggressive their cancer is," he told Medscape Medical News. "The biggest predictor of someone getting radiation therapy is a referral to a radiation oncologist. Once a patient is referred to a radiation oncologist, there is an extremely high chance that they are going to get radiation therapy."

In their study, Dr Chamie and his colleagues identified 37,621 men at least 65 years of age who were diagnosed with prostate cancer from 2004 to 2007 in the Surveillance, Epidemiology, and End Results (SEER)–Medicare database.

"The plurality of the cohort was 70 to 74 years of age, white, married, without any comorbid conditions," the researchers note.

In most men, tumors were stage T1, prostate-specific antigen (PSA) levels were 4.1 to 9.9 ng/mL, Gleason grade was 6 or lower, and disease was classified as intermediate risk using the D'Amico criteria.

The treatment options were radiation therapy (57.9%), radical prostatectomy (19.1%), androgen-deprivation therapy (10.8%), watchful waiting or active surveillance (9.6%), and cryotherapy (2.6%).

"The biggest drivers of whether someone goes to surgery or not are patient and demographic factors: age, comorbid conditions, the aggressiveness of their cancer, their PSA levels, clinical stage, and Gleason score," Dr Chamie said.

In fact, patient demographics and tumor characteristics influenced the decision to pursue radical prostatectomy in 40% of patients. In contrast, these factors influenced the decision to pursue watchful waiting or active surveillance in 12% of patients and the decision to pursue radiotherapy in only 3%.

Watchful waiting or active surveillance increased with advancing age. For men 70 to 74 years of age, the odds ratio (OR) was 1.82; for men 80 years and older, the OR was 5.12.

Consultation with a medical oncologist resulted in an 83% increase in watchful waiting or active surveillance (OR, 1.83). However, consultation with a radiation oncologist decreased the likelihood of this approach (OR, 0.19).

"A urologist looks at a patient and says, 'you are too ill, too frail, too sick, so I don't think you'd be a good candidate for surgery because I don't think I can operate on you safely'," Dr Chamie said.

"What happens is that urologists refer a patient to a radiation oncologist because they know that radiation therapy is safe and that the patient is not going to die from treatment. That's one take-home message," he explained.

The other take-home message is that even if a patient's life expectancy is limited and he is not likely to die from his cancer, "treatment with radiation therapy is often fraught with complications — bowel dysfunction, overactive bladder, incontinence, erectile dysfunction — and these things matter," Dr Chamie said.

But if a patient doesn't live 15 years after treatment, he will not reap the survival benefits from radiation, "and of the years he does live, he may be dealing with the complications of radiation therapy," he noted.

"I think the biggest reason the majority of patients with low-risk cancer are being overtreated is because urologists feel that they have to have their cancer treated, and if patients are too sick to have surgery, they refer patients to their colleagues who are going to give them radiation therapy," he said.

At UCLA, there is a robust active surveillance program, and most patients in the program have indolent prostate cancer.

"We've been putting them on this active surveillance program," Dr Chamie reported. "That's both what I think should be done and what the American Urological Association strongly advises."

Recent Patterns

More recent patterns of practice point to far greater acceptance of active surveillance than were observed in the 2004 to 2007 study period, said Charles Bennett, MD, PhD, from the South Carolina College of Pharmacy in Columbia, who is one of the authors of an accompanying commentary.

 
There has been a sea-change in the way people get treated today.
 

"There has been a sea-change in the way people get treated today, and physicians are much more comfortable with active surveillance than they were at the time of the study," he told Medscape Medical News. "In Michigan, for example, as many as 50% of patients with [local] prostate cancer are under active surveillance."

Dr Bennett also emphasized that active surveillance does not mean no treatment. Rather, "it often means moving treatment forward so that patients get some years without treatment, but it usually ends up that they get treatment eventually, and that treatment is likely radiation therapy," he said.

Another factor affecting treatment decisions in men with indolent prostate cancer is that it is not clear whose cancer is truly indolent and whose is not.

"We can probably tell you who has less than 10 years to live and who doesn't. Traditionally, the guidelines have been such that for the person with a life expectancy of 10 years or less, we have been very resistant to recommend a surgical procedure, which is potentially a difficult procedure and the side effects from it can be significant," Dr Bennett said.

"We've been less anxious to say that a person with a limited life expectancy would not be a good candidate for radiation therapy because the toxicity of radiation therapy, in many peoples' eyes, is only short-term toxicity and not nearly as large or long-lasting as those associated with surgery," he explained.

Dr Bennett acknowledged, however, that the current trend of urologists owning radiation centers has had some influence on treatment decisions because urologists can now refer patients to a radiation oncologist rather than recommend prostatectomy, as they traditionally mostly likely would have done.

This study was supported by the National Cancer Institute, the South Carolina Center of Economic Excellence Center for Medication Safety Initiative, and the Doris Levkoff Meddin Medication Safety Program. Dr Chamie and Dr Bennett have disclosed no relevant financial relationships.

JAMA Oncol. Published online February 19, 2015. Abstract, Commentary

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