Radical surgery versus radiotherapy for adenocarcinoma of the prostate.
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Biomedical subjects
Publications and source records attributed to D F Paulson.
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Spontaneous metastasis and extensive invasiveness were observed in athymic nude mice injected with human prostatic carcinoma cells of the PC-3 line or heterotransplants of nude mouse supported PC-3 tumor. In 3 experimental series, 60, 63 and 50 per cent of the nude mice receiving subcutaneous inoculations of PC-3 cells or tumor heterotransplants developed 1 or more lymphatic tumor metastases. Examination of metaphase-arrested cells recovered from the metastatic sites confirmed the tumor origin as human in each case. Cells recovered from 1 nude mouse supported subline, MPC-3-10, frequently exhibited double minute chromosomes in addition to the typical PC-3 chromosomal profile. These observations provide the foundation for a study of the relationship between prostate carcinoma cell characteristics and lymphatic metastasis in the nude mouse.
This study was undertaken to determine the disease control and survival advantage of either extended field megavoltage irradiation or delayed androgen ablation in a randomized clinical trial. Comparison of the 2 treatments, using either time-to-first evidence of treatment failure or survival, demonstrates an advantage to extended field radiation.
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The monoclonal antibody alpha Pro3 recognizes an antigen concentrated in human primary prostatic carcinoma tissue removed surgically. Although the antigen was detectable in extracts of human normal and malignant nonprostatic tissue, as well as in benign prostate tissue, quantitative absorption analysis revealed a substantially greater quantity of the antigen in malignant prostate tissue. The antigen recognized by alpha Pro3 in primary prostatic carcinoma has an apparent nonreduced molecular weight of 175,000 and an apparent subunit molecular weight of 54,000. This antigen, p54, appears to be present on the surface of cultured prostatic tumor cells of the PC-3 cell line, but its location in vivo has not been defined. Successful competition between alpha Pro3 and prostatic carcinoma patient serum immunoglobulin for a Mr 54,000 antigen (reduced molecular weight) present in prostatic carcinoma tissue extract suggests that p54 may play a significant role in the immunobiology of prostatic carcinoma. alpha Pro3 has potential as a sensitive probe for an antigen relevant to human tumor biology.
Fifty-nine female patients with a history of at least three episodes of urinary tract infection in the preceding year were enrolled in a two-center, double-blind study comparing cinoxacin and placebo as preventive therapy. Evaluation of efficacy was based on the results from 41 patients for whom complete data were available. In the cinoxacin-treated group, 18 of 20 patients remained asymptomatic during the study, compared with 11 of 21 patients in the placebo group. This difference between the two treatment groups was significant (P = 0.031). One patient in the cinoxacin group and eight patients in the placebo group developed an infection during the study. This difference was also significant (P = 0.045). Nine patients spontaneously reported adverse reactions, four in the cinoxacin group and five in the placebo group. In four instances, these were sufficiently severe for the treatment to be withdrawn from one patient who received cinoxacin and three patients who received placebo. The results of this study have shown that cinoxacin was significantly more effective than placebo in preventing urinary tract infection in patients with a history of frequent recurrent infections.
In 42 patients with metastatic adenocarcinoma of the prostate, histopathologic specimens of the original prostatic biopsy and lymphatic metastasis were classified using the grading system of tumor differentiation described by Gleason et al. The observed similarity between prostatic biopsy morphologic and the morphology in the corresponding lymphatic metastasis supports the concept that the histologic growth pattern of the primary tumor is reduplicated in the metastatic lesions. The observation that a more anaplastic pattern did not appear in the metastatic deposits implies that factors other than cellular loss of differentiation are responsible for the cells' ability to metastasize.
We have used an immunoaffinity system whereby immunoglobulin from patients with prostatic carcinoma was coupled to solid phase protein A; the immobilized IgG was subsequently exposed to radiolabeled antigen from autochthonous or allogeneic primary tumor extracts or to radiolabeled antigen from a nude mouse-supported prostatic carcinoma cell line. Material specifically bound by prostatic carcinoma patient immune IgG was quantitatively eluted from the immunoadsorbent and characterized with regard to molecular weight. Sequential adsorption analyses of patient sera with normal human tissue pools, normal prostatic tissue, prostatic carcinoma tissue, and tissue from other urogenital malignancies has allowed a definition of those antigenic specificities relevant in the immunobiology of prostatic carcinoma. The patient humoral response was observed to be directed primarily toward a complex array of antigens representing normal human tissue components; serorecognition of prostate tumor associated antigens was discernible from that of common tissue antigens only after rigorous adsorption analyses. Preliminary results indicate that the prostatic cancer patient humoral antibody response may be directed toward either altered histocompatibility complex antigens or toward antigens physically associated with histocompatibility complex antigens.
Patients with hormonally unresponsive prostatic adenocarcinoma were subjected to a five-drug chemotherapy program using bleomycin, 5-fluorouracil, methotrexate, vincristine, and prednisone. Analysis of survival curves indicated that deletion of an alkylating agent from this five-drug program reduced survival when patients with equal risk factors were compared. Bleomycin was poorly tolerated by this aged population.
The clinical course of 75 males subjected to radical prostatectomy after pelvic lymphadenectomy were compared with that of 29 males receiving radical without lymphadenectomy. The adverse survival impact of positive pelvic nodes and the impact of pelvic lymphadenectomy are discussed.
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We studied 20 transitional cell tumors of the bladder and 25 adenocarcinomas of the kidney in vitro to determine their chemotherapeutic sensitivity. The different sensitivity patterns among the individual tumors were demonstrated. Identical drug sensitivity patterns could be identified in the primary and metastatic sites, and in tumor tissue removed from the primary and metastatic deposits in the same patient. Human renal adenocarcinoma maintained in the athymic mouse demonstrated identical chemotherapeutic sensitivity patterns in vitro and in vivo. Our data would support that these in vitro chemotherapy studies may assist in the selection of agents to use in human tumor-bearing hosts.
Of 44 patients with clinically localized prostatic adenocarcinoma and regional lymphatic metastases proved by staging pelvic lymphadenectomy 11 were treated by radical prostatectomy, 20 received extended field radiation and 13 were assigned to delayed hormonal therapy. The median survival for the entire group was 39.5 months. None of the 3 treatments appeared superior in prolonging survival. Furthermore, no enhancement of disease control could be demonstrated in either treatment group. Patients with prostatic adenocarcinoma and positive nodes appear to have equivalent adverse biological potential and should be candidates for treatments designed to produce systemic effect.
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