Adjuvant immunotherapy for prostatic cancer

Treatment of adenocarcinoma of the prostate, other than when the lesion is localized within the gland, permitting total extirpation, is controversial. In the advanced stages of disease, treatment is minimally effective and more often than not, at best palliative, with often accompanying and further debilitating side effects. The implication from this dilemma is that new or presently successfully employed therapeutic modalities utilized for the treatment of other malignancies must be developed or applied for the treatment of prostatic cancer. Based on accumulating evidence of nonspecific and specific factors of tumour-host responsiveness suggestive of the participation of immunobiological phenomena and supporting clinical observations in patients with prostatic cancer, one avenue of approach has been the implementation of adjuvant immunotherapy. In spite of this evidence, approaches of immunotherapy in the prostatic cancer patient, as reviewed herein, have, until recently, been sorely neglected and few reports exist. Nevertheless, the rationale for the basis of prospective considerations of adjuvant immunotherapy presented have been derived to some extent, from these previous approaches, as well as from rapidly accumulating knowledge gained from recent studies of animal models of prostatic cancer. Knowledge that immunotherapy may be antagonistic rather than tumouricidal, resulting in enhancement of tumour, has emphasized that the principal problem lies not merely in augmenting, or in inducing the patient to manifest, an immune response to tumour but in directing that response toward that which will be tumouricidal. Here, the adjunctive use of immune modulators to augment the desirable and suppress the undesirable effects of immunotherapy may have application. Equally so, anesthesia, stress and trauma associated with conventional therapies for prostatic cancer, and the therapies per se, used alone or before immunotherapy for the necessary reduction of tumour burden, are to varying degrees immunosuppressive, and of real concerns in postoperative management. Therefore, to realistically consider a patient as a candidate for immunotherapy, the tumour-host relationship must be, similarly to the traditional staging and grading of tumour, quantitated prior to, during and following therapy. 'Immunostaging', a trial method of assessing a patient's immune status, may fulfill this role. 'Immunostaging' is based on evaluation of a broad spectrum of nonspecific and specific parameters of immunologic responsiveness, the sum total of which reflects an aspect of the patient's immunocompetence. Once this immunologic evaluation has been completed, the patient's immunocompetence may be 'immunostaged'. Knowledge of the patient's 'immunostage', together with that of the stage and grade of tumour, may then provide a better indication as to whether conservative or aggressive therapy should be used, as well as an indication of whether the therapy selected should be altered or, once initiated combined with other modalities. Admittedly, our present knowledge of prostatic carcinogenesis and of tumour-host responsiveness are far from complete. Nonetheless, profiling the patient's status through assessment of the stage and grade of tumour, and 'immunostage', together with the use of immunotherapy earlier in the course of disease, i.e., in patients with locally invasive tumours, where tumour burden has been reduced and where the patient's immunocompetence and thus, ability to respond is less impaired than in the patient with metastatic disease, more effective treatment of the primary tumour and of systemic disease may become a reality.