Management of primary stage D prostatic cancer

Androgen withdrawal rarely if ever results in a cure of prostatic carcinoma. Thus, if the object of therapy is to cure rather than palliate, it is necessary for us to alter our strategem so as to trick the prostatic cancer cells into dying while sparing the host. Data has been presented that suggest that tumor cell heterogeneity and the preexistence of populations of cells resistant to androgen withdrawal are responsible for the failure of hormonal therapy. Additionally, the use of androgen withdrawal as a single mode of therapy may actually induce a more rapid emergence of cells resistant to chemotherapeutic intervention by increasing the genetic instability of the tumor population. Assuming that a tumor is composed of a heterogeneous population of cells and the institution of unimodal therapy will exert a destabilizing influence on the tumor, the logical therapy for disseminated disease would be multimodal therapy. Animal models suggest that the most effective therapy for disseminated disease would be a combination of androgen withdrawal and cytotoxic chemotherapy instituted as early as possible when the number of cells capable of division, stem cells, is at minimum. Whether or not early, sequential withdrawal, repletion, withdrawal of hormones to synchronize the tumor cell cycle and increase the growth fraction of the tumor will have any beneficial effects remains to be determined. This form of androgen priming should be safer than in patients with hormonally refractive disease since LHRH initially stimulates testosterone production without any significant irreversible sequelae. Although the above therapeutic logarithms may prove to have no therapeutic advantage over androgen withdrawal alone, it certainly seems a good starting point for a change in our therapeutic concepts. Only by adopting new approaches based upon what we know about tumor biology can we hope to impact on the current dismal prognosis.