James J. Daly

Non-invasive papillary carcinoma of the bladder associated with carcinoma in situ.

We evaluated 129 patients with low grade, low stage transitional cell carcinoma of the bladder with a minimum followup of 5 years. In addition to the phenomena recognized as indicators of a serious clinical problem (grade greater than I, rapid recurrence, multiple tumors and lamina propria invasion) the identification of carcinoma in situ and/or atypia in normal, incidentally resected mucosa adjacent to the tumor was found to be a positive predictor for subsequent muscle invasion. Ten of 12 patients with carcinoma in situ and 9 of 25 patients with atypia were among 39 who experienced invasion.

Photodynamic therapy with hematoporphyrin derivative in the treatment of superficial transitional-cell carcinoma of the bladder

Photodynamic therapy involves light-induced destruction of tumors containing a photosensitizer such as hematoporphyrin derivative. We conducted a collaborative study to evaluate the efficacy of this form of therapy in treating superficial transitional-cell carcinoma of the bladder. Thirty-seven patients were evaluated and 20 were selected for treatment. A total of 50 papillary tumors and 3 areas of carcinoma in situ were treated. All except two tumors were smaller than 2.5 cm. Assessments for treatment response and toxicity were carried out three months after treatment. The initial diagnosis of one patient was revised after the biopsy material was reviewed, and this patient was not included in the analysis. Complete eradication of all tumors was observed in 9 of 19 patients (47 percent), including those with carcinoma in situ. In the remaining 10 of these 19 patients, 13 tumors could not be eradicated (the overall eradication rate was 37 of 50 tumors [74 percent]), but 9 of the 10 patients had a reduction in tumor size, number, or both of 50 percent or more. We conclude that photodynamic therapy is useful in the treatment of superficial transitional-cell carcinoma of the bladder, but controlled trials will be required to define its place in the treatment of cancer.

Nodal Involvement as A Prognostic Indicator in Patients with Prostatic Carcinoma

Between 1969 and 1976, 92 patients with proved prostatic carcinoma in stages T0 and T4 underwent pelvic lymphadenectomy. Median followup has been 43 months. All patients had normal serum acid phosphatase levels and no clinical evidence of metastases as determined by physical examination, bone scans and metastatic bone surveys. Pelvic lymph node metastases were noted in 32 cases. Radical prostatectomy was done in 34 cases and 45 patients received radiotherapy, 11 of whom had 125iodine seeds implanted. Progression of the neoplastic process, almost exclusively in the form of bony metastases, occurred in 18 of the 32 patients who had positive pelvic nodes and in 6 of the 60 patients with negative nodes (p less than 0.001). Patients with poorly differentiated carcinoma were more likely to have progression of the disease than those with moderately differentiated carcinoma (p less than 0.01) and no patient with a well differentiated carcinoma had disease progression.

Prognostic Factors in Carcinoma of the Ureter

The records and pathological slides of 60 patients with ureteral cancer were reviewed with particular attention being paid to the tumor-adjacent mucosa. Mucosal abnormalities increased as grade and stage increased but their presence did not correlate with survival nor with the presence of urothelial tumors elsewhere, that is previous, concomitant and subsequent tumors. Patients with papillary and solid tumors survived equally well. Survival among patients with stage B tumors was better than that reported previously (82 per cent survived 5 years).

Prognosis of clinically undiagnosed prostatic carcinoma and the influence of endocrine therapy.

A 10-year series of 100 patients with clinically undiagnosed prostatic adenocarcinoma is presented. In 50 per cent of these patients the tumor was well differentiated and the survival was normal, while the remainder of the patients had moderately to poorly differentiated tumors and survival rates significantly less than normal. Of 8 deaths caused by cancer 7 were associated with less-than-well differentiated tumor. Patients who received endocrine therapy and died of causes other than cancer had a significantly shorter interval to death and a higher incidence of cardiovascular deaths than those who were untreated. While the majority of patients with incidental, clinically undiagnosed prostatic carcinoma is not at risk from the disease a minority exists who may benefit from radical therapy.

Carcinoma in situ of the urinary bladder with and without associated vesical neoplasms

Of 99 patients who had carcinoma‐in situ (TIS) at least once between 1970 and 1980,84 were subjected to detailed analysis and pathologic review. They may be classified into four groups: (Group 1) 14 patients, who presented with invasive bladder carcinoma (TCC) associated with TIS; (Group 2) 15 patients who, subsequent to the diagnosis of TIS with or without another superficial TCC developed muscle invasion (12 patients) or metastases without muscle invasion (three patients); (Group 3) 29 patients who underwent cystectomy for superficial TCC (Ta or T1, or TIS alone). Twenty (69%) had extravesical superficial extension. Two patients developed metastases subsequent to undergoing cystectomy; and (Group 4) 26 patients with TIS proven at least once who have not developed muscle invasion, metastases nor have undergone cystectomy. Nineteen had previous non‐TIS superficial TCC. All patients in Groups 2 and 4 were treated conservatively (TUR +/‐ intravesical chemotherapy) when the initial diagnosis of TIS was made. Twelve patients in Group 3 underwent cystectomy within a month of the diagnosis of TIS. When 38 patients found to have TIS in association with the first diagnosis of superficial transitional cell carcinoma of the bladder were compared with 32 patients who had TIS diagnosed subsequent to their initial diagnosis of transitional cell carcinoma, the former group fared significantly worse (P < 0.01) in regard to muscle invasion, metastases, or clinical indications for cystectomy.

Prostatic Cancer and Sch-13521: II. Histological Alterations and the Pituitary Gonadal Axis

We herein report on the results of treatment of 13 men with stage D prostatic carcinoma with a non-steroidal compound, SCH-13521 (flutamide). The dosage of the drug was 750 mg. in 3 divided doses daily and treatment extended for 2 to 20 months. Two patients failed to respond in any fashion, 7 had objective evidence of response and the others had varying degrees of subjective response. Plasma testosterone was never suppressed and sexual potency was not altered by the drug. Gynecomastia occurred in several patients, 1 patient had intractable vomiting and 2 had thromboembolic disease. In tissue biopsies after therapy, cytotoxic changes in some acinar cells were noted but healthy-appearing neoplastic cells were always abundant. These observations suggest the pre-treatment existence of autonomous cells that no conventional hormonal manipulation will succeed in destorying. However, the palliation that flutamide seems to afford makes it important to conduct an appropriately designed study that will compare it in a suitable fashion to the effectiveness of diethylstilbestrol.

Biopsy of apparently normal urothelium in patients with bladder carcinoma.

We obtained 246 cold cup biopsies from pre-selected sites of apparently non-tumor-bearing bladder urothelium from 82 patients who presented with bladder cancer for the first time. Of 75 patients with transitional cell carcinoma 32 (43 per cent) suffered coincidental urothelial abnormalities, the most common being atypia. Significant abnormalities occurred more commonly (77 per cent) in association with high grade tumors than with low grade tumors (15 per cent).

Vascular invasion as a prognosticator of metastatic disease in nonseminomatous germ cell tumors of the testis. Importance in “surveillance only” protocols

Forty‐five nonseminomatous germ cell carcinomas of the testis were evaluated retrospectively to define the biologic features associated with the occurrence of metastatic disease. A statistical analysis of several pertinent clinical and pathologic factors was performed. The factors evaluated included: duration of symptoms before diagnosis, serum level of alpha‐fetoprotein, serum or urinary level of human chorionic gonadotropin, testicular weight, extent of local tumor (pathologic T stage), and vascular invasion at the primary site. In each case, metastases were documented by a retroperitoneal node dissection, other biopsies, or by chest films. In 29 tumors with vascular invasion, 25 patients were seen with metastatic disease. In 16 tumors without vascular invasion, 3 patients demonstrated metastasis. The presence or absence of vascular invasion was strongly correlated with concomitant lymph node involvement or subsequent appearance of other metastatic disease (chi‐square = 17.19). Additionally, vascular invasion in bifactoral analysis with tumor size and pathologic T stage proved a significant prognosticator even in low‐staged (chi‐square = 8.48) and small tumors (chi‐square = 8.13). The implications of these findings, both as an adjunct to the staging of nonseminomatous germ cell tumors and in the management of clinical Stage I lesions, are discussed.

Intravesical Therapy of Low Stage Bladder Carcinoma with Mitomycin C: Comparison of Results in Untreated and Previously Treated Patients

There were 28 patients with superficial bladder carcinoma (Ta, Tl or TIS) entered into protocols for intravesical therapy with mitomycin C. Of the 28 patients 16 had failed previously on thio-tepa (group A), 7 had responded successfully to thio-tepa (group B) and 5 had never received thio-tepa (group C). There were 5 complete responses and 9 failures to mitomycin C therapy in group A. There were 5 and 4 complete responses to mitomycin C therapy in groups B and C, respectively. The treatment plan consisted of the instillation of 40 mg. mitomycin C in 40 cc water weekly for 8 weeks. Because of severe local irritative symptoms 3 of the 28 patients did not complete the course of therapy. In another patient a diffuse body rash developed after the third instillation. Mitomycin C seems effective in ablating low stage bladder carcinoma, although it is less effective in patients who have failed prior thio-tepa therapy.