Alexander M. Castellino, PhD
December 11, 2014
National guidelines from associations such as the National Comprehensive Cancer Network (NCCN) and the American Urological Association recommend that men with a life expectancy of less than 10 years who have prostate cancer not be aggressively treated with radiation or surgery.
Despite these recommendations, the Urologic Diseases in America Project demonstrated that these men often receive aggressive treatment. In fact, more than half the men 66 years and older with a limited life expectancy are aggressively treated. The findings were published in the December 1 issue of Cancer.
Age at diagnosis and comorbidities are used to estimate life expectancy, but the estimate is poorly integrated into treatment decision making, said senior researcher Timothy J. Daskivich, MD, from the University of California, Los Angeles.
“Aggressive treatment of men with limited life expectancy for low- and intermediate-grade prostate cancer is, at best, a poor gamble and, at worst, harmful,” he told Medscape Medical News.
In an accompanying editorial, Matthew R. Danzig, BS, and James M. McKiernan, MD, from the Department of Urology at the Herbert Irving Cancer Center, Columbia University, in New York City, note that “the authors demonstrate that the likelihood of receiving aggressive treatment declines with increasing age and CCI [Charlson Comorbidity Index], but not to the extent that it proportionally matches the diminishing life expectancy.”
Dr Daskivich and colleagues must be credited for bringing this problem to the attention of the community, said David F. Penson, MD, MPH, Hamilton and Howd Chair in Urologic Oncology and director of the Center for Surgical Quality and Outcomes Research at Vanderbilt University in Nashville, Tennessee, who was not involved in the study.
Although these are data for patients treated from 1991 to 2007, the problem is real and the analysis is robust, he told Medscape Medical News. However, he added, we have reason to hope.
The Urologic Diseases in America Project
For their population-based study, the researchers identified 96,032 men 66 years and older diagnosed with early-stage prostate cancer from 1991 to 2007 from the Surveillance, Epidemiology and End Results (SEER) database.
Men were divided into four age groups: 66 to 69 years, 70 to 74 years, 75 to 79 years, and 80 years and older.
The CCI, which assesses inpatient and outpatient claims, was used to the determine the burden of comorbid disease at diagnosis. Men were assigned a CCI score of 0, 1, 2, or 3 and higher, with a lower score indicating fewer comorbidities.
Treatments were identified with ICD-9 codes, MedPAR Common Procedural Terminology codes, the National Claims History database, and Outpatient files from the Medicare dataset.
Aggressive treatment was defined as radical prostatectomy, radiation therapy, or brachytherapy in the first year after a diagnosis of early-stage prostate cancer. Nonaggressive treatment was defined as watchful waiting, active surveillance, or androgen-deprivation therapy (ADT).
When the 10-year cumulative incidence of mortality from causes other than prostate cancer reached 50%, life expectancy was considered to be less than 10 years.
In their editorial, Danzig and Dr McKiernan note that this calculation is a “novel element of the study,” because life expectancy is based on actual outcomes of the sample population.
Men 66 to 69 years of age with a CCI score of 2 or higher were considered to have a life expectancy of less than 10 years, as were men 70 to 74 years with a CCI score of 1 or higher, and men older than 75 years (regardless of comorbidities).
Aggressive Treatment Despite Age and Comorbidities
Older men with more comorbidities are less likely to receive surgery because of the elevated likelihood of perioperative morbidity and mortality, the researchers note. And some patients are being diverted from surgery to radiation therapy when the true best practice in many cases might be conservative management, they point out.
Table. Treatment of Men With a Limited Life Expectancy
| Age Group, Years | Aggressive Treatment, % | Radiation, % | Surgery, % |
| 66 to 69 | 68 | 50 | 30 |
| 70 to 74 | 69 | 53 | 25 |
| 75 to 79 | 57 | 63 | 13 |
| 80 and older | 24 | 69 | 9 |
“Although radiation therapy does not carry the perioperative risk of surgery, caution must be taken to avoid conceiving it as a benign alternative,” the editorialists write.
Even in men receiving no aggressive treatment, the researchers report that ADT was used as a primary option in 27% to 44% of men. This approach is both dangerous and unnecessary, especially for men with multiple comorbid conditions, they explain.
Why Are Men With a Limited Life Expectancy Treated Aggressively?
When asked why men with a limited life expectancy are being treated aggressively, Dr Daskivich explained that “the guidelines on assessment of life expectancy in men with prostate cancer are vague.”
The NCCN suggests using life tables and adjusting life expectancy up or down by 50%, depending whether a man is in the highest or lowest quartile of health, but they do not explain how to determine who is in these quartiles. Therefore, physicians are left to make an educated guess, and patients understandably overestimate their longevity, Dr Daskivich told Medscape Medical News
Dr Penson noted that even clinicians are a bit “rosy” when it comes to estimating life expectancy. “Even when we see sick patients, we hope for the best,” he said.
Danzig and Dr McKiernan agree. Clinicians are known to be poor estimators of life expectancy, although several tools are available to urologists to facilitate this task in men with prostate cancer, they write.
They commend the researchers on their calculation of actual other-cause mortality. “In addition to highlighting the overtreatment that may be occurring in low- and intermediate-risk patients, the study by Daskivich et al offers a valuable calculation of actual other-cause mortality rates among a large, population-based sample of men with localized prostate cancer stratified according to age and CCI,” they note.
It is possible that, given the broad time range used in the study, the high rates of aggressive treatment in men with limited life expectancies were overestimated. The trend toward more conservative management for men with low-grade disease is recent, the editorialists note. However, even after correction for year of surgery, the likelihood of aggressive treatment did not diminish.
The lack of information on the clinical decision-making process is a limitation of the study, according to Danzig and Dr McKiernan. There are several reasons aggressive treatment might have been undertaken, including an overvaluing of the benefit of treatment, a failure on the part of the clinician to have an appropriate discussion with the patient, and a patient choosing aggressive treatment, the editorialists report.
Even being on active surveillance is not a neutral state, according to Danzig and Dr McKiernan. It can be accompanied by high levels of anxiety, stress, and quality-of-life deterioration in patients poorly suited to ambiguity. Such patients should be provided appropriate emotional and social support.
But clinical practice is changing, said Dr Penson. The understanding of prostate cancer has evolved considerably from the 1990s, and clinicians are becoming more comfortable with just observing low-risk patients, he explained.
Clinicians also now have better data and a better understanding of what comprises low-risk disease, he pointed out.
We are already starting to do better, he told Medscape Medical News. He cited several studies that show an increase in active surveillance.
A recent study from the Michigan Urological Surgery Improvement Collaborative showed that 49% of patients with low-risk prostate cancer received active surveillance (Eur Urol. 2015;67:44-50).
In addition, the population-based CAESAR study is seeing a decrease in aggressive intervention in low-risk disease and an increase in active surveillance, Dr Penson said.
“Treating patients with low-risk disease aggressively is a perfect storm of societal belief, physician training, and lack of understanding of the disease,” he told Medscape Medical News.
Our understanding of prostate cancer has changed, and physicians are becoming more comfortable with observing low-risk patients, he added.
Dr Daskivich, Mr Danzig, Dr McKiernan, and Dr Penson have disclosed no relevant financial relationships.