Commentary (Chodak): Locoregional Therapies for Early-Stage Prostate Cancer

The article by Stock provides a comparison of outcomes following radiation therapy and radical prostatectomy in men with clinically localized prostate cancer. The reliability of this comparison is complicated by the lack of randomized trials and the obvious selection biases inherent in uncontrolled studies. Ultimately, however, the value of either therapy depends critically on the difference between radiation or surgery and watchful waiting--an issue that is not addressed in this article.

Watchful waiting involves giving no local therapy; the patient receives treatment only if symptoms develop. The high prevalence of the disease and the increasing likelihood that men will die of causes other than prostate cancer as they age means that some men who undergo treatment may not have required it, which biases treatment outcomes to a more favorable result. Although uncontrolled studies of watchful waiting have all been subjected to valid criticisms, recent data provide useful information on outcomes with this management approach.

Recent Data on Watchful Waiting

One study is a pooled analysis of six studies on watchful waiting performed between 1985 and 1992 [1]. All the original case data were reviewed and combined after it was demonstrated that pooling the data would not yield biased results. The study found that the most important predictor of cancer-specific and metastasis-free survival was tumor grade, with stage relatively unimportant. At 10 years after diagnosis, cancer-specific survival rates for well-differentiated, moderately differentiated, and poorly differentiated cancers were 87%, 87%, and 34%, respectively, and metastasis-free survival rates were 82%, 58%, and 26%, respectively.

Importantly, the exclusion of stage A1 tumors did not significantly affect the results; in other words, the results were not favorably biased by the number of patients with stage A1 disease included in the analysis. Also, although the average patient age was older then that in many radical prostatectomy series, men who were under age 61 at diagnosis and were managed with watchful waiting had significantly better results than older men with well-graded or moderately graded tumors. Lastly, all-cause survival in patients from two of the four countries was similar to expected survival for the age-matched general population of those nations.

Another recent study reviewed all the pathology data from men in Connecticut who were diagnosed with a T1 or T2 tumor and followed for over 10 years. This study found 10- and 15-year cancer-specific survival rates of 91% and 91%, respectively, for patients with low-grade cancer (Gleason score, 2 to 4), 76% and 72% rates for Gleason grade 5 to 7 cancers, and 53% and 46% rates for Gleason grade 8 to 10 cancers [2]. These results indicate that the reduction in cancer mortality at 10 years resulting from surgery is approximately 0% to 5% for men with low-grade tumors, 10% to 15% for those with intermediate-grade cancer, and 20% to 25% for those with high-grade lesions.

Although biochemical disease-free survival rates show that many more men have persistent disease and are therefore not cured by prostatectomy or radiation therapy, local treatment still appears to offer varying gains in 10-year survival depending on the patient's age and tumor grade. Since these comparisons are possible only up to 10 years, however, the relative value of treatment in men with a longer life expectancy is more uncertain. Clearly, 50-year-old men with well-differentiated cancer may derive benefit from treatment, but this will occur infrequently before 10 to 15 years.

Morbidity Trade-offs

A critical aspect when assessing the relative gains afforded by treatment are the trade-offs from morbidity, which is usually more disturbing when assessed by patients than when assessed by physicians. Using a decision model to estimate the difference in quality-adjusted life expectancy for watchful waiting, radical prostatectomy, and radiation therapy, Fleming et al reported that substantial differences are probable only for 65-year-old men and men with poorly differentiated cancer, with diminishing benefits for older men or those with well-differentiated cancer [3]. Recently, this analysis has been criticized [4], but important technical flaws in the critique can explain most of this difference. More importantly, if the complication rates reported by patients rather than physicians are used, the gains in quality-adjusted life expectancy with treatment diminish further.

Thus, the value of radiation and surgery must be compared with the outcomes from watchful waiting in order to assess whether significant gains do, in fact, occur.

References:

1. Chodak GW, Thisted RA, Gerber GS, et al: Results of conservative management of clinically localized prostate cancer. N Engl J Med 330:242-248, 1994.

2. Kolon TF, Albertson PC: Conservative management of clinically localized prostate cancer: Fifteen year survival analysis stratified by age and histological grade at diagnosis. J Urol 150:229A, 1993.

3. Fleming C, Wasson JH, Albertson PC, et al: A decision analysis of alternative treatment strategies for clinically localized prostate cancer. JAMA 269:2650-2658, 1993.

4. Beck JR, Kattan MW, Miles BJ: Critique of decision analysis for clinically localized prostate cancer. J Urol 152:1894-1899, 1994.