Mark S. Soloway

Flow Cytometry Versus Urinary Cytology in the Evaluation of Patients with Bladder Cancer

We compared the roles of urinary cytology and flow cytometry in the evaluation of patients with bladder cancer in clinical practice situations at a large general hospital. Specimens included 105 bladder washings from patients being followed for urothelial carcinomas and 28 control washings from individuals undergoing cytoscopy for other reasons. Flow cytometry and cytology were performed on aliquots of the same specimen in all bladder cancer samples. When carcinoma was present at the time of specimen collection it was detected by positive cytology in 75 per cent and deoxyribonucleic acid aneuploidy in 78 per cent of the cases. Combination of flow cytometry and urinary cytology increased the diagnostic yield to 95 per cent. Flow cytometry was slightly more sensitive than urinary cytology for detection of abnormalities in specimens from noninvasive and untreated tumors but the only statistically significant difference between the 2 procedures occurred among specimens from treated invasive cancers in which flow cytometry was a less sensitive method than cytology. Abnormal deoxyribonucleic acid ploidy was documented in a few specimens from noncancer-bearing patients having diseases associated with high urothelial cell turnover rates but the concomitant urinary cytology was negative for neoplasia. When used in conjunction with urinary cytology, flow cytometry was a valuable procedure in the followup of patients with bladder cancer. The diagnostic yield with this combination was such that flow cytometry and cytology may be used to reduce the frequency of cystoscopy and biopsy during clinical management in selected situations.

Prognostic Factors in Survival Free of Progression After Androgen Deprivation Therapy for Treatment of Prostate Cancer

We analyzed 110 patients with metastatic prostate cancer (stage D2) to determine the associations between interval until progression and the pretreatment testosterone level, extent of bone metastases, performance status, race, age and pretreatment level of prostatic acid phosphatase. The median followup was 21 months (4 to 89 months). All patients received androgen deprivation therapy when metastases were identified. This multivariate analysis demonstrated that the pretreatment serum testosterone was the most significant variable (p less than 0.01) associated with interval until progression and the extent of bone metastases observed on the bone scan was the second most important variable (p less than 0.05). Age, race and prostatic acid phosphatase were not significantly correlated with the interval free of progression. Performance status was significantly correlated but it was nonsignificant in the multivariate analysis if the model already included testosterone level and extent of metastasis. Patients with a pretreatment testosterone level of less than 300 ng. per 100 ml. and more than 6 areas of increased uptake on the bone scan had the most rapid progression. We conclude that serum testosterone and extent of bone metastases are the most important of the analyzed factors in terms of interval to progression in patients with prostate cancer following androgen deprivation.

The importance of prognostic factors in advanced prostate cancer.

Three factors were identified in a multivariate analysis of prognostic factors in men with metastatic prostate cancer as significantly associated with their progressionfree survival: 1) extent of disease on the bone scan, 2) pretreatment serum testosterone, and 3) performance status. Men with less than six bone metastases, a pretreatment testosterone < 300 ng/100 ml, and an excellent performance status will have a progression‐free survival much longer than a man with more extensive bone metastases, a low testosterone prior to androgen deprivation, and a poor performance status. This information should be used to ensure proper stratification in randomized trials. It may also be helpful in identifying the patient unlikely to be helped by our current treatment. Such patients should be considered for alternative approaches with the aim of improving survival.

Invasive Bladder Cancer: Support for Screening

Of 297 patients with bladder cancer treated between 1975 and 1981, 90 (30 per cent) had histologic documentation of muscle invasion, 82 of whom (91 per cent) had invasion into the muscle at the time of presentation. Of these 82 patients 51 (62 per cent) had tumor localized to the bladder after clinical staging. Of 36 patients undergoing radical cystectomy 9 (25 per cent) had microscopic pelvic lymph node involvement. Nine patients underwent urinary diversion alone and 31 presented with perivesical or pelvic nodal tumor extension, or distant metastases. Only 8 of the 90 patients (9 per cent) had prior superficial bladder cancer. The mean survival for patients with stage B to C disease at diagnosis was 23 months and for those with stage D tumor it was 11 months. This experience indicates that the majority of patients with advanced bladder cancer are not identified at a stage when definitive therapy offers an excellent prognosis. More resources must be devoted to earlier detection.

Treatment of Superficial Bladder Cancer with Intravesical Mitomycin C: Analysis of Immediate and Long-Term Response in 70 Patients

A total of 70 patients received intravesical mitomycin C for treatment of superficial bladder cancer. The drug was instilled weekly for 8 weeks. Thirty-nine patients (56 per cent) had failed thiotepa therapy and 25 had high grade tumors. Of the patients 27 (39 per cent) had complete eradication of tumor at the initial 3-month evaluation and an additional 27 had a partial response. The response did not vary with initial tumor grade or stage. Followup averaged 28 months for the 70 patients. A muscle invasive tumor developed during followup in 7 per cent of the patients with an initial complete response, 15 per cent with a partial response and 25 per cent of the initial failures. To date 5 patients (7 per cent) have died of bladder cancer. Intravesical mitomycin C is an effective modality for treatment of superficial bladder cancer. Patients achieving a complete response are at little risk for progressive disease.

Bacillus Calmette-Guerin for Treatment of Superficial Transitional Cell Carcinoma of the Bladder in Patients who have failed Thiotepa and/or Mitomycin C

Thirty patients with stage Ta carcinoma in situ or T1 superficial bladder cancer received 6 weeks of intravesical bacillus Calmette-Guerin. All patients had persistent or recurrent tumor despite thiotepa and/or mitomycin C. Response was determined by the results of endoscopy, bladder wash cytology and biopsy performed 4 weeks after the last dose of bacillus Calmette-Guerin. Of the 30 patients 15 (50 per cent) had a complete response. The likelihood of a complete response was better for those with initial Ta lesions (62 per cent) and carcinoma in situ (56 per cent) than for patients with an initial T1 lesion (25 per cent). Although the longest followup is only 36 months (mean 16 months) patients with a complete response have a much better prognosis in terms of subsequent tumor, need for cystectomy and death of bladder cancer.

Bladder Cancer Induced by Noncarcinogenic Substances

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.

Thiotepa-induced Myelosuppression: Review of 670 Bladder Instillations

Intravesical chemotherapy is an integral part of the therapeutic strategy for patients with superficial bladder cancer. Despite the introduction of new agents thiotepa currently is used most owing to its low cost and moderate effectiveness. Myelosuppression is a side effect caused by absorption of the drug through the bladder mucosa. A review of 670 instillations of thiotepa in 72 patients at our medical center revealed a decrease in the white blood or platelet count below normal in 18 per cent of the patients (3.9 per cent of the instillations). In no case did this decrease lead to any problem other than a delay in therapy.

Malignant fibrous histiocytoma of the kidney.

We report on a 33-year-old woman with malignant fibrous histiocytoma of the kidney. This malignant mesenchymal tumor is indistinguishable clinically and radiologically from a renal cell carcinoma. In our patient the tumor recurred locally following nephrectomy and metastasized to the lung. Post-nephrectomy radiation and chemotherapy may not alter the poor prognosis.

The morphologic effects of mitomycin C in mammalian urinary bladder.

This investigation was intended to determine the morphologic changes of mitomycin C. It is part of a series of experiments designed to evaluate the cytologic and histologic effects of topical chemotherapeutic agents using the FANFT experimental model system in mice. The results for mitomycin C are very similar to those previously reported for thio‐tepa. They indicate that these chemicals produce few, if any, drug‐specific light microscopic alterations. Rather, mitomycin C and thio‐tepa apparently act as toxic substances, causing increased exfoliation, degeneration, and necrosis of urothelial cells. The implications of these findings and suggestions for future investigations are discussed.