Rapidly alternating chemotherapy and radiotherapy instead of cystectomy for the treatment of muscle-invasive carcinoma of the urinary bladder: long term results of a pilot study.

BACKGROUND: The authors studied rapidly alternating chemotherapy and radiotherapy as the initial treatment for patients with muscle-invasive transitional cell carcinomas of the urinary bladder whose advanced age and lack of strength precluded cystectomy. METHODS: Twenty-one patients with T2 (28%) or T3 (72%) NXM0 carcinomas were treated by transurethral resection followed by chemoradiotherapy. Their median age was 73 years. The chemotherapy (consisting of methotrexate, vinblastine, doxorubicin, and cisplatin) was given during Weeks 1, 4 and 7. Radiotherapy (1.8-2 Gray [Gy] twice a day, to a total dose of 18-20 Gy per week) was given during Weeks 2, 5 and 8, for a final dose of 40 Gy to the pelvis plus 14-20 Gy boost to the affected bladder. RESULTS: There was 1 treatment-related death (5% of patients), but otherwise the acute toxicity was relatively mild. Cystoscopy 1 month after chemoradiotherapy did not reveal invasive cancer in any patient. Subsequent cystoscopies detected recurrent invasive cancer in 3 patients after 30, 44, and 82 months, respectively. The observed survival rate after 5 years was 37%, the cause specific survival rate was 63%, the metastasis free rate was 71%, and the local control rate was 80%. Eighty-four percent of patients had normal bladder function. CONCLUSIONS: Transurethral resection plus chemoradiotherapy was successful in preserving bladder function in the majority of the patients. The survival and progression free rates compared favorably with what has been reported recently after radical cystectomy and chemotherapy, and they add to the growing body of evidence that chemoradiotherapy might be a safe, effective alternative to cystectomy for many patients with muscle-invasive carcinoma of the urinary bladder.

A pilot study of chemotherapy alternating with twice-a-day accelerated radiation therapy as an alternative to cystectomy in muscle infiltrating (stages T2 and T3) cancer of the bladder: preliminary results.

Laboratory studies have suggested that rapidly alternating chemotherapy and accelerated radiation therapy might act synergistically. We evaluated the toxicity and effectiveness of this approach in muscle infiltrating transitional cell carcinoma of the bladder in patients who were poor risks for or who refused cystectomy. We treated 18 men and 3 women with stage T2 or T3 transitional cell carcinoma of the bladder by transurethral resection, followed by 3 cycles of chemotherapy (during weeks 1, 4 and 7) rapidly alternating with 3 cycles of twice-a-day radiation therapy (during weeks 2, 5 and 8). Chemotherapy consisted of methotrexate, vinblastine, doxorubicin and cisplatin. The total dose of radiation therapy was 5,400 to 6,000 cGy, during 6 1/2 weeks and the total duration of chemotherapy and radiation therapy was 7 1/2 weeks. One patient died of hematological toxicity during treatment. With a median followup of 2 years (range 0.5 to 5.5 years) the observed survival rate was 72% at 2 years and 60% at 3 years. To date, only 1 patient (5%) had recurrence of invasive cancer in the pelvis. Only 3 others (15%) had carcinoma in situ but to date none has required cystectomy. Bladder function was normal in 15 of 18 evaluable patients (83.5%). This pilot study suggests that chemotherapy alternating with radiation therapy produced an encouraging survival rate without cystectomy and deserves further study. These patients require continued surveillance for carcinoma in situ.

Ureteral stump calculi.

We report 2 cases of ureteral stump calculi presenting years after nephrectomy. Stones in the ureteral stump are extremely uncommon, and their occurrence has led us to review the possible mechanisms underlying their etiology.

Histopathology of testis in acquired immune deficiency syndrome.

Histologic sections from the testes of 32 autopsied patients with acquired immune deficiency syndrome (AIDS) were examined. Almost invariably the testes displayed decreased spermatogenesis, and 20 of the 32 cases showed marked hypospermatogenesis with Sertoli cells predominantly lining the tubules. Although the seminiferous tubules were generally of normal size, the tunica propria at the periphery of the tubules was mildly to moderately thickened in 19 cases and markedly thickened in 10. The interstitial cells of Leydig were unaltered in most patients, with only 4 testes showing Leydig cell hyperplasia. The testicular blood vessels were slightly thickened in many patients, but 5 exhibited moderate to marked intimal proliferation with narrowing of the lumen. Mononuclear inflammatory infiltration of the testicular interstitium was slight in 11 cases, moderate in 6. Only 7 of the 28 AIDS patients with opportunistic infections had evidence of direct involvement of the testes by the infectious organisms. We concluded that the extragonadal endocrine balance of AIDS patients may be deranged due to the infectious process and so deserves clinical evaluation.

Contraindications to needle aspiration of a solid renal mass: tumor dissemination by renal needle aspiration.

We report a case of tumor dissemination via needle aspiration of a solid hypovascular renal mass. This case emphasizes how needle aspiration of these masses does not always lead to proper management and may be detrimental to the patient.

Prostatic biopsy in selected patients with carcinoma in situ of the bladder: preliminary report.

Transitional cell carcinoma was found in biopsies of grossly normal-appearing prostates in 4 of 40 patients with recurrent carcinoma in situ of the bladder. In selected patients prostatic biopsy may be warranted if conservative therapy does not control the bladder tumors and if cystectomy is contemplated.

Unresectable carcinoma of the bladder.

The clinical courses of 119 patients with unresectable bladder cancer were analyzed. All patients had a laparotomy with the intent of cystectomy. TN categorization postlaparotomy did not identify variables significantly influencing the natural history of the disease, although previous definitive irradiation or T4aNx-4 categories were associated with especially poor survival. T category correlated more closely with survival than did N category. Supravesical urinary diversion palliated patients with urinary symptoms and/or bilateral ureteral obstruction. Patients without compelling urinary symptoms at the time of laparotomy uncommonly needed diversion later. Pelvic irradiation and systemic chemotherapy available in the interval from 1961 to 1976 had minimal if any demonstrable effect on the time course of the disease.

Intravenous cisplatin for superficial bladder tumors.

Cisplatin, 1.25 mg/kg IV QM, was administered to 15 patients with recurrent flat carcinoma in situ and/or bladder tumors confined to the mucosa and lamina propria. All patients had a history of multiple transurethral resection and 4 had received prior irradiation and two prior intravesical thiophosphoramide. Response was evaluated by urinary cytologic findings, cystoscopy and biopsy. Of 14 adequately treated cases, four (28%) had disappearance of all visible lesions, cystoscopically, for a median of eight months (range, 8-18), and six exhibited transiently a greater than 50% decrease in the number of tumors. However, no patient demonstrated a complete remission--all had persistently positive urinary cytologies. Nausea and vomiting, even at this dose level, was significant and at times, severe. Cisplatin, in the dose and schedule used, was found to be ineffective in controlling low-stage bladder tumors.

Intravesical cisplatin for superficial bladder tumors.

Cisplatin, 50-150 mg in a maximum concentration of 1 mg/ml, was administered intravesically each week to 24 patients with multiple, recurrent carcinoma in situ and/or bladder tumors confined to the mucosa and lamina propria. All patients had a history of multiple transurethral resections and four had received prior chemotherapy. Response was evaluated by urinary cytology, cystoscopy, and biopsy. In a total of 237 weekly doses, toxicities included mild dysuria, pruritus, rash and in one patient, acute anaphylaxis. Only three (13%) patients were classified as achieving complete remission. Cisplatin, in the dose and schedule employed, is ineffective in controlling superficial bladder cancer.

Preoperative irradiation and cystectomy for bladder cancer.

Between 1971 and 1974, 101 patients at Memorial Sloan-Kettering Cancer Center underwent planned integrated treatment for bladder cancer with 2000 rads by megavoltage delivered to the whole pelvis over five consecutive days followed by radical cystectomy within a week. The overall five-year survival rate was 39%; the hospital mortality rate was 2%. In the pelvis alone tumor recurred in 9% of the patients. These results support other studies demonstrating the efficacy of this and other regimens of preoperative irradiation and cystectomy.

The influence of simultaneous resection of bladder tumors and prostate on the occurrence of prostatic urethral tumors.

The records of 137 patients who underwent simultaneous transurethral resection of bladder tumors and the prostate were compared to those of 150 patients who underwent transurethral resection of bladder tumors only. The data presented provide no evidence that simultaneous resection of bladder tumors with the prostate affects adversely the incidence of tumor occurrences in the prostatic urethra.

Adjuvant chemotherapy with VAB-3 of stage II-B testicular cancer.

A recent report from the Memorial Sloan-Kettering Cancer Center has indicated that patients with resected Stage IIB (N-2B and N-3) testicular cancer are at significant risk for relapse. Of patients with resected Stage IIB disease (N-2B, 19%; N-3, 54%), 34% relapsed after having undergone relatively mild adjuvant chemotherapy consisting of vinblastine, actinomycin D, bleomycin, and chlorambucil (VAB). In this study, 29 patients with resected Stage IIB testicular cancer underwent treatment with adjuvant VAB-3 which has been used as primary treatment for Stage III disease. All patients have remained in complete remission with a median follow-up time of 24 months. Three patients received broad spectrum antibiotics when fever and leukopenia developed. No patient experienced renal failure. The results of this study demonstrate the capability of aggressive adjuvant chemotherapy to prevent recurrence in the high-risk setting of resected Stage II (N-2B and N-3) disease. Optimal adjuvant treatment remains to be defined.

Adjuvant chemotherapy combination of vinblastine, actinomycin D, Bleomycin, and Chlorambucil following retroperitoneal lymph node dissection for stage II testis tumor.

In an attempt to reduce recurrence of nonseminomatous germ cell tumors of testis stage II, 62 patients were treated with vinblastine, actinomycin D, bleomycin, and chlorambucil after retroperitoneal lymph node dissection. Of the patients, 84% have remained in complete remission with median follow-up of three years: 33/33 stage II-A (N-1,N-2A) and 19/29 (66%) stage II-B (N-2B,N3). The relapse rate in patients who had histologic evidence of extranodal extension of the tumor (N-3) was 54% (7/13). This program did not cause any serious toxicity. Adjuvant chemotherapy is effective in reducing relapses. More recently, with the current availability of chemotherapy with a high efficacy for control of disseminated disease, patients with resected stage II-A (N-1,N2A) have been followed closely and treated only if they developed evidence of recurrence. Patients with resected stage II-B (N-2B,N-3) have been placed on a more aggressive adjuvant program.

Complications of ureteroileal conduit with radical cystectomy: review of 336 cases.

Review of complications of the ileal conduit in patients undergoing radical cystectomy for bladder cancer showed a statistically significant increase in renal calculi, ureteral obstruction, acute and chronic pyelonephritis and deterioration of renal function by 60 months postoperatively. Ureteroileal fistulas occurred in 3.3 per cent, stomal stenosis in 5.1 per cent, intestinal fistulas in 5.4 per cent, severe intestinal obstruction in 6 per cent and abdominal wound infection or dehiscence in 20.2 per cent of the cases. The over-all operative mortality was 13.7 per cent, with 8 per cent of the deaths attributed to complications from the ileal conduit. Comparison of colonic conduits to ileal conduits as a means of urinary diversion with radical cystectomy for bladder cancer demonstrated no convincing evidence of its superiority.

Resectoscope loop for urethral biopsy following cystectomy in the male patient.

A small resectoscope loop, sans scope, has been used to obtain tissue from the male urethral mucosa for diagnostic and therapeutic purposes.

Controversies concerning lymph node dissection for cancer of the penis.

Cancer of the penis represents one of the two genital cancers (testis cancer is the other) in which cure may frequently be effected in the presence of lymph node metastases. The questions that are raised include if and when therapeutic or prophylactic lymphadenectomy is indicated. Extended node dissection is governed, to an extent, by recognition of the seriousness of pelvic node involvement and by uncertainty regarding the status of the contralateral side with proof of disease on one side. The sentinel node theory, with its potential impact on the possible approach to these problems, must be confirmed or denied before our present therapeutic philosophy is modified.

Cryptorchidism and testicular cancer.

An analysis of 125 patients with a history or clinical evidence of cryptorchidism and testicular germinal tumor treated at our hospital from 1934 to 1975 is presented. Cryptorchidism was corrected ipsilaterally or contralaterally in 83 patients with intrascrotal testis cancer when they were from 4 to 42 years old, either spontaneously (21 patients), by orchiopexy (51 patients) or by hormonal therapy (11 patients). Forty-two cryptorchid patients (uncorrected cases) presented with either ipsilateral inguinal (24 patients), abdominal (14 patients) or contralateral intrascrotal tumors (4 patients). Tumor histologic types on orchiectomy were pure seminoma in 54 patients, embryonal carcinoma in 35, teratocarcinoma in 33 and pure choriocarcinoma in 3. The 5-year survival rates were 60 per cent for the corrected cases and 63 per cent for the uncorrected cases according to cryptorchid state, and they were 78 per cent in patients with pure seminoma and 48 per cent in patients with other germinomas according to histologic type. The majority (58 of 73) of 5-year survivors received regional lymphatic irradiation, in 39 patients with pure seminoma, and/or systemic chemotherapy, in 19 patients with germinal carcinomas, with or without regional lymphadenectomy.