Superficial bladder cancer: comments on evaluation and management.
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Biomedical subjects
Publications and source records attributed to M S Soloway.
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Although the high incidence of subsequent tumors is well established there is accumulating evidence that few cases of low grade, low stage transitional cell carcinomas will progress in stage. Since the purpose of intensive endoscopic monitoring following initial tumor resection is to detect potentially lethal new tumors as soon as possible, we reviewed retrospectively the course of 36 patients with an initial grade I, stage O (Ta) transitional cell carcinoma to determine whether cytology was capable of achieving this goal. Of these patients 10 (28 per cent) had a subsequent tumor of a higher grade or stage. Cytology performed at or before recurrence was positive in 8 patients (80 per cent) and 2 (20 per cent) had grade II, noninvasive transitional cell carcinoma with negative cytology. Subsequent tumors in these 2 patients have been grade I. All 36 patients are alive. Given the patient inconvenience, expense and risk of infection of cystoscopy compared to cytology, this retrospective review suggests that when an experienced cytopathologist is available patients with grade I, noninvasive transitional cell carcinoma may be monitored primarily by urinary cytology with less frequent endoscopy. A prospective study must be performed to confirm this approach.
Twenty-seven patients with invasive bladder carcinoma (clinical stages T2 to T4) who were not candidates for cystectomy were treated by transurethral resection, cis-diamminedichloroplatinum (cisplatin) and full dose radiotherapy according to protocol 8 of the National Bladder Cancer Collaborative Group A. Nausea and vomiting occurred in 74 per cent of the patients but were mild in 41 per cent. Maximum followup was 27 months and during that time 3 significant toxic reactions occurred: renal failure, systemic sepsis and a transient partial small bowel obstruction. Of 17 evaluable patients complete responses of the primary bladder cancer to the treatment were achieved in 11 of 13 with stages cT2 and cT3 cancer and in 2 of 4 with stage cT4 disease. The members of National Bladder Cancer Collaborative Group A have found transurethral resection, cisplatin and full dose external beam radiotherapy practical clinically. Longer followup will be necessary to determine if the observed high initial complete response rate of the tumor indicates real lasting benefit for these patients.
Chemical carcinogenesis is currently regarded as a complicated series of events requiring initiation and promotion in specific sequences. Carcinogens are thought to be chemicals which can induce both initiation and promotion so that few if any additional host or environmental factors are required in the production of neoplasms. Most experimental studies to date have investigated bladder cancer using these highly active agents and the role of other substances in urothelial neoplasia has not been emphasized. We have examined the role of a variety of solutions, including water and saline, in pilot studies of urothelial carcinogenesis using the ALZA mini-pump for continuous infusion. Bladder tumors indistinguishable morphologically from papillary transitional cell carcinomas were induced. Although experimental induction of bladder cancer with powerful carcinogens may completely overwhelm host defenses and result in more and higher grade neoplasms, similar tumors may occur after exposure to substances not generally considered to be carcinogenic. This process, which probably requires cofactors and host-chemical interaction, may be more representative of environmental carcinogenesis than systems using powerful carcinogens and should be further investigated.
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At least 80 per cent of prostatic tumors exhibit some degree of hormone responsiveness. The preferred method of hormonal alteration has yet to be determined because new agents are currently undergoing clinical trials. The compounds tested have included cyproterone acetate, a progestational agent; flutamide, an antiandrogen that blocks the DHT-receptor complex in the tumor cell; and aminoglutethimide, which inhibits adrenal steroid production and, therefore, might further lower the level of circulating androgen following bilateral orchiectomy. The introduction of potent, synthetic analogues of gonadotropin-releasing hormone (GnRH) has provided another method of reducing the level of circulating androgen. A recent report on the efficacy of one of these analogues--leuprolide--in men with newly diagnosed metastatic prostatic cancer has revealed an initial response rate of 76 per cent (4% complete remissions, 32% partial remissions, and 40% stable) using National Prostatic Cancer Project criteria.
Before deciding to begin intravesical prophylaxis, the physician must categorize the patient with respect to the stage of the tumor and the multiplicity of lesions. This may require mucosal biopsies in order to determine whether the patient had unifocal or multifocal disease. Thiotepa, mitomycin C, and doxorubicin hydrochloride are discussed specifically and compared.
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A prospective multi-institutional randomized trial compared the use of cisplatin (DDP) alone to the combination of DDP and cyclophosphamide in patients with advanced urothelial cancer. Patients were stratified according to measurable or evaluable tumor and performance status. The dose of DDP was 70 mg/m2 and the initial dose of cyclophosphamide was 750 mg/m2. There were ten objective responders (20%), including five complete responders, among the 50 evaluable patients who received DDP alone, and seven responders (11.9%), three complete, among the 59 receiving the combination therapy. Approximately one third of the patients in each treatment arm were stable at the nine-week evaluation. There was no statistical significance between the response rates in the two treatment arms.
A tumor colony assay (TCA) was evaluated for its ability to predict anticancer drug responses in an N-[4-(5-nitro-2-furyl)-2-thiazolyl]-formamide (FANFT)-induced murine bladder tumor (MBT) model. Ten anticancer drugs were evaluated in vivo and in vitro using four MBT cell lines (40 drug responses). Using the optimum criteria for drug response, the TCA accurately predicted drug responses in the murine model 65% of the time with a true-positive predictive rate of 54% and a true-negative predictive rate of 70%. Drug testing tumor cells immediately on removal from the mouse resulted in a true-positive predictive rate of 77% and a true-negative predictive rate of 100%. The authors conclude that the TCA can predict response to chemotherapy in the MBT model and may be useful in screening investigation compounds for the subsequent evaluation in this murine bladder tumor model.
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Patients with advanced prostate carcinoma that had been stabilized by orchiectomy (ORCH) or hormone therapy for at least 3 months, were randomized to either diethylstilbestrol (DES) alone or DES plus Cytoxan or DES plus Emcyt. A total of 188 patients were randomized between July, 1976 and February, 1982 of which 161 were evaluable for objective response to treatment. Objective response rates, response duration, or survival experiences were not demonstrably different between treatment arms, either for all patients or within good or poor prognosis groups determined by initial pain or acid phosphatase level. Subjective improvements in performance status were small for each treatment. Pain relief was somewhat greater in the chemotherapy-hormone combinations than in the DES/ORCH, but the advantage was not statistically significant. Side effects were primarily nausea and vomiting and leukopenia, mostly in the DES + Cytoxan arm. The duration of stabilization prior to entry did not influence response overall, although there were opposing trends within each of the two chemotherapy arms. The premise for combining antitumor agents with hormones before hormone failure is still felt to be a more logical approach than waiting for the ultimate hormone failure, and a combination of hormones plus two antitumor agents is being evaluated in a subsequent ongoing trial where a more rigid design limits the duration of the preentry period of hormone stabilization.