S. Ous

Cisplatin and 5-fluorouracil in advanced cancer of the penis

A total of 8 patients with advanced squamous cell carcinoma of the penis (Jackson stages III and IV) received chemotherapy with 100 mg./m2. cisplatin intravenously on day 1 and a 24-hour infusion of 1,000 mg./m.2 5-fluorouracil on days 1 to 5. Of the patients 2 (25%) achieved a partial response: 1 required a further operation and 1 required surgery with radiotherapy to achieve a complete response. These 2 patients were disease-free at 32+ and 57+ months. Nonresponders had a survival range of 2+ to 28 months after chemotherapy. Nausea and vomiting were the most frequent side effects of chemotherapy. Chemotherapy-related increase in serum creatinine occurred in 3 patients. Two patients had septicemia and 1 complained of tinnitus. Poor tolerability especially in the elderly was the main reason for discontinuing chemotherapy. The combination of cisplatin and 5-fluorouracil may have a role in the management of advanced penile cancer together with surgery and radiotherapy.

Histology of tumor residuals following chemotherapy in patients with advanced nonseminomatous testicular cancer

A total of 111 patients with advanced nonseminomatous testicular cancer underwent cisplatin-based combination chemotherapy, followed by surgical removal of residual masses in 101. Surgery included retroperitoneal lymph node dissection in 92 patients, thoracotomy in 19 and hepatic resection in 1 (11 patients underwent 2 operations). Complete necrosis and/or fibrosis was found in 52 operative specimens, mature teratoma in 37 and vital malignant tumor in 12. Of the 11 patients who underwent 2 operations 4 had complete necrosis and/or fibrosis in both histological specimens. After a median observation of 55 months 83 of 89 patients with complete necrosis and/or fibrosis or mature teratoma were without evidence of disease. Only 7 of 12 patients with vital malignant tumor in the operative specimen survived without evidence of disease. Relapses were observed in 16 patients, 4 of them in the retroperitoneal space. Of the 16 relapses 5 were in 12 patients with residual vital malignant tumor, 5 in 37 patients with post-chemotherapy mature teratoma and 4 in 52 patients with complete necrosis and/or fibrosis after chemotherapy. Two patients with recurrence did not undergo an operation. In patients in whom post-chemotherapy retroperitoneal lymph node dissection is considered complete necrosis and/or fibrosis can be predicted by the combination of several factors, including absence of teratomatous elements in the testicular tumor, complete response on post-chemotherapy computerized tomography, and normal alpha-fetoprotein and human chorionic gonadotropin levels after chemotherapy (sensitivity 83%, specificity 76% and correctly predicted 79%). With the knowledge of these factors it seems possible to omit post-chemotherapy retroperitoneal lymph node dissection in approximately 20% of the patients with advanced metastatic nonseminomatous testicular cancer with initial retroperitoneal tumors.

Post-chemotherapy lymph node histology in radiologically normal patients with metastatic nonseminomatous testicular cancer

A total of 37 patients with initially advanced metastatic nonseminomatous testicular cancer underwent retroperitoneal lymph node dissection after cisplatin-based combination chemotherapy. Abdominal computerized tomography was negative at retroperitoneal lymphadenectomy (lymph nodes not exceeding 10 mm. in the transverse computerized tomography plane). Complete necrosis and fibrosis were found in 25 patients. In 11 patients the retroperitoneal lymphadenectomy specimen showed a mature teratoma. Residual vital malignant tumor was observed in 1 patient. Neither the initial size of the retroperitoneal mass nor the histological status of the primary tumor was predictive of the histological findings in the retroperitoneal lymphadenectomy specimen. The high frequency of mature teratoma raises the question whether omitting post-chemotherapy surgery is a safe routine policy in patients with negative computerized tomography, especially if long-term followup is not feasible. We recommend a post-chemotherapy retroperitoneal operation as routine treatment even in patients with negative computerized tomography.

Bladder cancer definitive radiation therapy of muscle‐invasive bladder cancer: A retrospective analysis of 317 patients

Background. The role of radiation therapy as curative treatment of muscle‐invasive bladder cancer was to be analyzed.

Unilateral retroperitoneal lymph node dissection in patients with non-seminomatous testicular tumor in clinical stage I

19 of 53 patients (36%) with non-seminomatous testicular cancer, clinical stage I (CS I), had retroperitoneal lymph node metastases, pathological stage II (PS II), demonstrated by retroperitoneal lymph node dissection (RLND). RLND was done unilaterally in peroperatively tumor-free patients (PS I: 34 patients; PS II: 3 patients) and bilaterally if metastatic lymph nodes were found peroperatively. Patients with PS II received adjuvant cis-platinum containing combination chemotherapy. Postoperative tumor activity was observed in 3 patients (median observation time: 31 months). They were cured by salvage chemotherapy. 12-18 months after RLND no ejaculatory disturbances were observed in 28 of 36 unilaterally operated patients. After unilateral RLND, 7 patients fathered children. Unilateral RLND seems to be a sufficient diagnostic procedure in patients with non-seminomatous testicular cancer, CS I, who were found tumor-free during the operation. Fertility is preserved in the majority of the unilaterally operated patients.

Post-Chemotherapy Tumor Residuals in Patients with Advanced Nonseminomatous Testicular Cancer. Is it Necessary to Resect All Residual Masses?

A total of 15 patients with advanced nonseminomatous testicular cancer underwent 2 sequential operations (4 in 1 patient) to remove residual masses after cisplatin-based combination chemotherapy. All patients had normal human chorionic gonadotropin and alpha-fetoprotein levels but persistent radiographic masses after chemotherapy. The operations included retroperitoneal lymph node dissection in 13 patients, thoracotomy in 15, hepatic resection in 3 and craniotomy in 1. Histological comparison of the specimens resected during post-chemotherapy operations 1 and 2 demonstrated different patterns in 7 of 15 patients. Of these 7 patients 4 had less favorable pathological features in the specimen removed during the second procedure. Residual malignant tumor or mature teratoma was found in at least 1 site in 12 of the 15 patients and only 3 had complete necrosis or fibrosis in both specimens examined. These data indicate the favorable impact of excising all post-chemotherapy tumor residuals in patients with advanced nonseminomatous testicular cancer. However, in patients with no teratomatous elements in the testicular tumor and complete necrosis or fibrosis in the initial post-chemotherapy operation specimen the probability of complete necrosis or fibrosis in remaining tumors appears to be high.

Salvage treatment in male patients with germ cell tumours

The outcome of salvage treatment was reviewed in 55 patients relapsing during or after their primary chemotherapy for advanced malignant germ cell tumours. Fifty-two patients had been given cisplatin-based chemotherapy as their primary treatment, whereas three patients had received carboplatin-based chemotherapy. The median time to relapse was 2 months (range: 0-96 months) from discontinuation of the primary treatment. Two patients underwent radical surgery only, and one patient had radiotherapy to a brain metastasis as his only curatively intended salvage treatment. Six patients did not receive any treatment for their recurrent malignancy (refusal, terminal condition) except for purely palliative measures. The disease-free survival for the total group was 27% at 5 years. Complete response to primary treatment lasting for > or = 6 months was the only parameter which significantly predicted a favourable outcome (45% 5 year disease-free survival in 12 eligible patients).

DNA flow cytometry in human testicular cancer.

DNA flow cytometry revealed aneuploid tumour stemlines in 19 of 20 primary testicular cancers without significant difference of the ploidy values between seminomas and non-seminomas. In 7 of 8 analyzable histograms the S-phase activity was 22-51%. A metastatic mature teratoma had 6% cells in S-phase. These results support the clinical observation that testicular cancer is usually a rapidly growing human tumour. The high percentage of aneuploidy in testicular cancer may be of clinical value in the diagnosis of this malignancy.

Treatment and outcome of patients with extragonadal germ cell tumours - The Norwegian Radium Hospital's experience 1979-94

This report reviews 48 patients who from 1979 to 1994 were treated at the Norwegian Radium Hospital for newly diagnosed noncerebral extragonadal malignant germ cell tumour (EGGCT). Based on histology and/or serum tumour markers, 12 patients had a seminoma and 36 a non-seminoma. At diagnosis, 33 and 15 patients were classified as having abdominal and mediastinal EGGCT respectively. At the time of diagnosis 13 patients, all with non-seminomatous tumours, had metastases to bone, liver or brain. One patient with abdominal seminoma was cured by radiotherapy alone, whereas cisplatin-based chemotherapy (with or without surgery) was planned in the 47 remaining patients. Twenty-seven out of 42 patients receiving four or more chemotherapy cycles were rendered tumour free by induction chemotherapy, including 5 of the 13 patients with extralymphatic non-pulmonal disease. An additional tumour-free patient died of septicaemia after only two cycles of chemotherapy. Late relapses (after > 2 years) were observed in three patients, and a testicular primary was diagnosed during follow-up in three cases. Seven patients died of treatment-related complications, five of these because of neutropenic septicaemia. The median age of these patients was 52 years compared with 35 years in the remaining 41 patients (P < 0.05). The 5-year overall survival for all 48 patients was 60% (95% CI 46-74%) [cancer-specific 5-year survival 71% (95% CI 50-92%)]. EGGCT is a potentially curable disease, even in patients with very advanced disease. Special attention should, however, be devoted to patients above the age of 40 years because of an increased risk of treatment-related side-effects. Late relapses and the subsequent development of testicular tumours indicate the need for long-term follow-up.

The prognostic significance of deoxyribonucleic acid flow cytometry in muscle invasive bladder carcinoma treated with preoperative irradiation and cystectomy.

Deoxyribonucleic acid (DNA) flow cytometry measurements were performed in nuclear suspensions obtained from paraffin-embedded biopsies from 83 patients with stages T2, T3 and T4a bladder carcinoma. All patients were treated with preoperative radiotherapy and cystectomy from 1976 through 1985. Of the tumors 13 (16%) were diploid, 18 (22%) tetraploid and 52 (63%) aneuploid. A total of 19 tumors (23%) had 2 or 3 stemlines in addition to the diploid cells. Post-radiotherapy stage reduction (absence of muscle infiltration in the cystectomy specimen) occurred more often in tumors with only 1 nondiploid stemline than in diploid tumors or nondiploid tumors with multiple stemlines. The 5-year survival rate was significantly poorer for patients with a diploid (33%) than for those with a nondiploid (66%) tumor (p = 0.05), although this was only marginally retained in a multivariate analysis (p = 0.11). The clinical significance of DNA ploidy in muscle infiltrating bladder cancer seems not to be as evident as has been shown for superficial bladder tumors but it may be of value in selecting patients for preoperative radiotherapy.