Correspondence

Conservative Management of Prostate Cancer

N Engl J Med 1994; 330:1830-1832June 23, 1994

Article

To the Editor:

Chodak et al. (Jan. 27 issue)1 conclude that conservative management is an appropriate choice for some patients with clinically localized prostate cancer -- that is, those with a life expectancy of 10 years or less. However, because they did not detect a statistically significant bias due to the overrepresentation of men with low-grade, low-stage tumors in their patient population, Chodak et al. imply that conservative management is appropriate for all patients with localized prostate cancer.

In their sample of patients, the risk ratios for mortality due to prostate cancer increased proportionately, albeit not always significantly, with tumor grade and tumor stage (as compared with grade 1 tumors, grade 2 tumors had a risk ratio of 1.64 [P = 0.075] and grade 3 tumors a risk ratio of 10.04 [P = 0.000]; as compared with stage T0a tumors, stage T0b tumors had a risk ratio of 1.38 [P = 0.53], stage T1 tumors a risk ratio of 1.77 [P = 0.297], and stage T2 tumors a risk ratio of 2.38 [P = 0.78]). Chodak et al. claim that the overrepresentation of men with low-grade cancer in the earliest stages did not bias the outcomes favorably. However, among men with grade 1 tumors, the estimate of 10-year disease-specific survival was 96 percent for focal disease, as compared with 85 percent for nonfocal disease (P = 0.11), and the estimate of 10-year metastasis-free survival was 92 percent for focal disease, as compared with 79 percent for nonfocal disease (P = 0.09). For patients with grade 2 tumors, 10-year disease-specific survival was 94 percent for focal disease, as compared with 87 percent for nonfocal disease (P = 0.32), and 10-year metastasis-free survival was 78 percent and 57 percent, respectively (P = 0.63). Because of the small number of patients with focal grade 2 tumors, the P values were higher.

This analysis does not establish that no bias exists. With the limited sample and the favorable survival experience in the groups being compared, it would be difficult to reach statistical significance. Given that the survival results are in the expected direction -- that is, the risk ratios are higher for high-grade, high-stage tumors -- there probably is a difference that did not reach statistical significance in the sample studied.

The results of Chodak et al. pertain to patients in low-risk categories, but they do not necessarily apply to younger patients at higher risk, who are underrepresented in this population. These details are critical if one is to avoid ill-advised treatment decisions based on inappropriate generalizations.

William J. Catalona, M.D.
Washington University, St. Louis, MO 63110

1 References

1. 1

   Chodak GW, Thisted RA, Gerber GS, et al. Results of conservative management of clinically localized prostate cancer. N Engl J Med 1994;330:242-248
   Full Text | Web of Science | Medline

To the Editor:

Chodak et al. conclude that conservative management is a reasonable option for some patients, especially those with grade 1 or 2 cancer and a life expectancy of 10 years or less. This study provides important new data about the progression of prostate cancer managed conservatively: within 10 years, 13 percent of men with grade 1 or 2 cancer died of their disease, and distant metastases developed in 19 percent of those with grade 1 and 42 percent of those with grade 2 cancer. Sixty-six percent of patients with grade 3 cancer died of their disease, and metastases developed in 74 percent.

In the decision-analysis model of the Dartmouth Prostate Outcomes Research Team (PORT), treatment of prostate cancer offered only marginal benefit over conservative management, increasing the quality-adjusted life expectancy of a 65-year-old man with grade 2 cancer by only 0.33 year1. In this model, the most important determinant of the benefit of treatment is the rate of metastasis among patients with conservatively managed disease. We repeated the PORT analysis, using the model they graciously provided but substituting the metastasis rates for each grade obtained by Chodak et al., which were 3.3 to 7.8 times higher (Table 1Table 1Rate of Metastasis and Benefit of Treatment in Two Decision-Model Analyses of Patients with Prostate Cancer.)2.

At the metastasis rates reported by Chodak et al., treatment adds 2.41 quality-adjusted years to the life of a 65-year-old man with grade 2 cancer and benefits all grades, regardless of quality-of-life adjustments for complications of therapy. In threshold analyses, the annualized rates of metastasis at which therapeutic intervention becomes beneficial are 0.69 percent, 0.79 percent, and 1.29 percent for grades 1, 2, and 3, respectively -- rates substantially lower than in the series of Chodak et al.

We applaud the efforts of Chodak et al. to document the risks associated with watchful waiting. Some prostate cancers grow slowly and present little risk to an elderly man or a man with serious coexisting conditions. In fact, conservative management is the most commonly recommended approach for prostate cancer in this country3. But this study should not be interpreted as showing that younger men with a life expectancy of more than 10 years, particularly those with grade 2 or 3 tumors, should delay therapy. Doing so could result in a missed opportunity for cure and could subject the patient to the risk of metastasis of a cancer that is seldom cured once it extends beyond the prostate.

Peter T. Scardino, M.D.
J. Robert Beck, M.D.
Baylor College of Medicine, Houston, TX 77030

Brian J. Miles, M.D.
Houston Veterans Affairs Medical Center, Houston, TX 77301

3 References

1. 1

   Fleming C, Wasson JH, Albertsen PC, Barry MJ, Wennberg JE. A decision analysis of alternative treatment strategies for clinically localized prostate cancer. JAMA 1993;269:2650-2658
   CrossRef | Web of Science | Medline

2. 2

   Beck JR, Kattan MW, Miles B. A critique of the decision analysis for clinically localized prostate cancer. Presented at the National Conference on Prostate Cancer, Washington, D.C., December 3-5, 1993. abstract.
   

3. 3

   Mettlin C, Jones GW, Murphy GP. Trends in prostate cancer care in the United States, 1974-1990: observations from the patient care evaluation studies of the American College of Surgeons Commission on Cancer. CA Cancer J Clin 1993;43:83-91
   CrossRef | Web of Science | Medline

Author/Editor Response

The authors reply:

To the Editor: The comments by Catalona point up some confusion in the interpretation of our article. He is correct that the risk ratio was higher than 1 for stages higher than T01, A1, T0a, or focal disease; therefore, with a larger cohort, statistically significant differences could be observed between the lowest stage and higher stages. Nevertheless, the outcomes we reported based on all three stages are still reliable for more extensive tumors, because they are not significantly altered even if the lowest-stage tumors are excluded. Ten-year disease-specific survival is 87 percent as compared with 85 percent for grade 1 cancers, and 87 percent as compared with 87 percent for grade 2 tumors, respectively, whether the low-stage tumors are included or excluded. Nor do the results for metastasis-free survival change. Thus, our statement that the inclusion of low-stage tumors did not favorably influence the results for grade 1 or 2 tumors is valid.

As for applying these results to younger men, we disagree that these men are underrepresented, because 15 percent of our patients (123 of 828) were under 61 years old, which is comparable to the proportion in other series. It is important to note that their risk ratio for cancer mortality was significantly lower than that of older men. Although we believe that surgery is likely to yield higher rates of metastasis-free survival for men with grade 1 and 2 tumors, the magnitude of these differences will remain uncertain until a similar analysis is completed for radiation therapy or surgery.

We agree with Scardino et al. that a reanalysis of the PORT study is worthwhile. In that model,1 however, estimates of gains in life expectancy depend critically on the presumed efficacy of treatment, the cancer-specific death rate, and competing causes of death. A 65-year-old man with grade 2 cancer potentially gains 0.1 to 0.9 quality-adjusted year of life when the PORT model is calibrated with our 10-year disease-specific mortality rate; for a 70-year-old man, the potential change ranges from -0.1 to +0.4 quality-adjusted year. A difference in quality-adjusted years of life as high as Scardino et al. calculate would require a cancer mortality rate of 29 percent at 10 years, or twice the value we reported.

We also agree that with watchful waiting in men of any age, an opportunity for cure may be missed. Nevertheless, this does not invalidate conservative management as a reasonable option, particularly for men with grade 1 or grade 2 disease. The value of this study is that physicians may now present patients with reliable estimates of the outcomes after conservative management. Ultimately, patients must compare this information with the results and complications likely with radiation and surgery and must then decide which treatment most closely fulfills their personal goals. Recommendations based on the physician's bias do not guarantee optimal care for the patient.

Gerald W. Chodak, M.D.
Ronald A. Thisted, Ph.D.
University of Chicago, Chicago, IL 60640

1 References

1. 1

   Fleming C, Wasson JH, Albertsen PC, Barry MJ, Wennberg JE. A decision analysis of alternative treatment strategies for clinically localized prostate cancer. JAMA 1993;269:2650-2658
   CrossRef | Web of Science | Medline

Citing Articles (2)

Citing Articles

1. 1

   Woolf, Steven H., . (1995) Screening for Prostate Cancer with Prostate-Specific Antigen — An Examination of the Evidence. New England Journal of Medicine 333:21, 1401-1405
   Full Text

2. 2

   William J. Catalona. (1995) Surgical management of prostate cancer. Contemporary results with anatomic radical prostatectomy. Cancer 75:S7, 1903-1908
   CrossRef