Dec 9, 1999. The best time to start hormonal therapy for prostate cancer is controversial. A group of researchers compared immediate and delayed treatment in a group of patients who, in course of radical surgical removal of the prostate, had been found to have minimal residual disease in lymph nodes.

The findings suggest that for patients with node-positive prostate cancer, starting hormonal therapy immediately after radical prostatectomy and pelvic lymphadenectomy significantly improves survival.

The investigators are experienced but the study is small. A controversy over the findings started in the New Journal of Medicine, where the study is published. Leading urologist Patrick Walsh M.D. and his Johns Hopkins colleague Mario A. Eisenberger, M.D. questioned the results in an editorial Early Androgen Deprivation for Prostate Cancer?

As they note, blocking testosterone triggers a cascade of biologic events in man and in prostate cancer cells. This cascade results in damage to the DNA of androgen-sensitive prostate-cancer cells. This treatment, known as androgen ablation, used to be kept for men with metastatic disease, but lately has been used increasingly before and sometimes after surgery or radiation aimed at curing the disease. It is is also becoming quite usual to offer it early on to men who in biopsy before or during surgery are found to have micrometastatic cancer in their lymph nodes.

The New Study and What It Suggests

The new study enrolled 98 men who underwent radical prostatectomy and pelvic lymphadenectomy and who were found to have nodal metastases were recruited to this study. Half were randomly assigned to receive immediate therapy to block testosterone, either by means of the drug Zoladex (goserelin) or bilateral orchiectomy. The others were simply watched over until such time as the prostate cancer progressed. All the patients were assessed once every three months during the first year and then every six months.

After a median of 7.1 years of follow-up, 7 of 47 men who received immediate antiandrogen treatment had died, as compared with 18 of 51 men in the observation group (P=0.02). The cause of death was prostate cancer in 3 men in the immediate-treatment group and in 16 men in the observation group (P

At the time of the last follow-up, 36 men in the immediate-treatment group (77 percent) and 9 men in the observation group (18 percent) were alive and had no evidence of recurrent disease, including undetectable serum prostate-specific antigen levels (P

In the observation group, the disease recurred in 42 men; 13 of the 36 who were treated had a complete response to local treatment or hormonal therapy (or both), 16 died of prostate cancer, and 1 died of another disease. The remaining men in this group were alive with progressive disease at the time of the last follow-up or had had a recent relapse.

Nothing aside from assignation to one or other treatment group (immediate therapy or observation) could be found to explain the outcome.

The researchers conclude that "Immediate antiandrogen therapy after radical prostatectomy and pelvic lymphadenectomy improves survival and reduces the risk of recurrence in patients with node-positive prostate cancer."

Walsh and Eisenberger say that "the study by Messing et al. is important because it touches on critical issues concerning the treatment of prostate cancer. The most important message of this study is that although it suggests an advantage for early androgen-deprivation therapy, that conclusion is not definitive. It should provide the impetus for a vigorous exploration of the role of endocrine and nonendocrine approaches to the adjuvant treatment of prostate cancer."

Read the article abstract and the editorial at the New England Journal of Medicine online:

The New England Journal of Medicine -- December 9, 1999 -- Vol. 341, No. 24 Immediate Hormonal Therapy Compared with Observation after Radical Prostatectomy and Pelvic Lymphadenectomy in Men with Node-Positive Prostate Cancer Edward M. Messing, Judith Manola, Michael Sarosdy, George Wilding, E. David Crawford, Donald Trump

Early Androgen Deprivation for Prostate Cancer? Mario A. Eisenberger, M.D. Patrick C. Walsh, M.D. Johns Hopkins Medical Institutions Baltimore, MD

Members of this team of researchers are affiliated with the University of Rochester Medical Center, Rochester, N.Y. (E.M.M.); the Dana-Farber Cancer Institute, Boston (J.M.); the University of Texas, San Antonio (M.S.); the University of Wisconsin Comprehensive Cancer Center, Madison (G.W.); the University of Colorado Health Science Center, Denver (E.D.C.); and the University of Pittsburgh Cancer Institute, Pittsburgh (D.T.).