Combined androgen blockade and treatment of localized prostate cancer: a real hope when approaching the year 2000

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Abstract
Summary and conclusions The present data show that an optimal use of the available diagnostic and therapeutic approaches can have a major impact on quality of life and survival in prostate cancer. The only way to have a major impact on prostate cancer death is clearly treatment of localized disease. Moreover, it has become clear that, in analogy with breast cancer where significant survival benefits were obtained only after 2-5 years of adjuvant Tamoxifen therapy, combined androgen blockade must be administered for much longer periods than done so far, most likely up to 5 years. Although PSA shows unique usefulness as an early sign of recurrence of cancer after any form of therapy, its high sensitivity to androgen deprivation needs caution. In fact, serum PSA decreases to undetectable levels much before generalized apoptosis or control of cancer proliferation is achieved. In other words, an undetectable serum PSA is not equivalent to cancer cell death. It should be remembered that the only form of endocrine therapy demonstrated to prolong life is the one where androgen blockade was administered continuously for years without interruption. Before being recommended, intermittent therapy needs to be proven in large randomized trials as being equivalent to continuous treatment on survival, the prime and essential objective of prostate cancer therapy. It is pertinent to remember that continuous androgen blockade is the only treatment shown to prolong life in both metastatic and localized disease. The important benefits of androgen blockade in localized prostate cancer are in agreement with the well known observation that, in patients with metastatic disease treated with CAB, progression occurs almost always in the bones and not in the prostate, thus clearly indicating that prostate cancer localized to the prostatic area is highly sensitive to androgen deprivation. All available means should be taken to prevent prostate cancer from migrating to the bones, where treatment becomes extremely difficult and cure or even long-term control of the disease is no longer possible. A major source of controversy concerning early diagnosis and treatment of prostate cancer is that, until recently, no prospective and randomized trial had shown statistically significant benefits of treatment of localized prostate cancer on survival (Kolata 1987). The absence of data from well designed clinical trials was erroneously interpreted as negative data. Most fortunately, two prospective randomized trials have recently demonstrated for the first time that not only quality of life but, most importantly, prolongation of life could be achieved in localized prostate cancer patients treated with androgen blockade. In the EORTC trial performed in stage T3 patients, survival at 5 years was increased from 62% in the group of patients who received radiation therapy alone to 79% (45% difference) in those who received androgen blockade using an LHRH agonist for 3 years and an antiandrogen for one month in association with rdiotherapy (Bolla et al. 1997). A similar observation has been made in RTOG trial 08351 in the subgroup of high Gleason score patients (Pilepich et al. 1997). No valid reason remains to doubt that treatment of clinically localized prostate cancer can prolong survival. In addition to the major impact on prostate cancer deaths, the economic savings on health care costs has been previously discussed (Labrie et al. 1993b,d, Littrup et al. 1994, Aus et al. 1995). The calculations performed leave little doubt that the strategy based upon efficient screening and treatment, namely androgen blockade, surgery, radiotherapy or brachy-therapy alone or in combination with androgen blockade should play a key role in the successful fight against prostate cancer while decreasing the costs for the health care system and society (Labrie 1994, Labrie et al. 1995b). Major progress has been made by many groups during the last decade in the field of early diagnosis and early treatment (surgery, radiotherapy, brachytherapy, and hormonotherapy) of prostate cancer while our understanding of the endocrinology of this disease has also made significant progress, including the most important demonstration that androgen blockade prolongs life in both localized and advanced prostate cancer. There is no doubt, however, that only a concerted effort of urology, endocrinology, radiation therapy, and many other specialties can set the stage for the most successful fight against this most devastating disease. The significant progress made, however, is a stimulus to move forward at an even more accelerated pace.

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