John P. Donohue

Cis-Diamminedichloroplatinum, Vinblastine, and Bleomycin Combination Chemotherapy in Disseminated Testicular Cancer

Fifty patients with disseminated testicular cancer were treated with a three-drug combination consisting of cis-diamminedichloroplatinum, vinblastine, and bleomycin. Three patients were considered inevaluable due to early death. This chemotherapy regimen produced 74% complete and 26% partial remissions. Furthermore, five patients with partial remission became disease-free after surgical removal of residual disease, producing an overall 85% disease-free status. Toxicity, although significant during remission induction with cis-platinum, vinblastine, and bleomycin, was usually manageable, although there were two drug-related deaths during this period. Thirty-eight of these patients remain alive and 32 remain alive and disease-free at 6 + to 30 + months. We believe this regimen represents a major advance in the management of patients with disseminated testicular cancer.

Immediate Adjuvant Chemotherapy versus Observation with Treatment at Relapse in Pathological Stage II Testicular Cancer

Between 1979 and 1984, 195 evaluable patients were entered in an international multicenter study comparing two regimens for patients with completely resected pathological Stage II testicular cancer (that is, with positive retroperitoneal lymph nodes). All patients had undergone orchiectomy and dissection of the retroperitoneal lymph nodes. They were randomly assigned to be treated with two cycles of immediate adjuvant cisplatin-based chemotherapy or to be observed monthly with treatment at relapse. The median follow-up period was four years. Of the 97 patients assigned to adjuvant chemotherapy, 6 (6 percent) had a recurrence; however, only 1 had received adjuvant chemotherapy before the recurrence. Three died (one of testicular cancer), and 94 of the 97 survived. Of the 98 patients who were observed, 48 (49 percent) had a relapse. However, almost all patients with relapses were effectively treated, and 93 of the 98 are alive and disease-free; 3 have died of testicular cancer. No identifiable factors were strongly associated with the risk of relapse. We conclude that two courses of cisplatin-based adjuvant chemotherapy will almost always prevent relapse in pathological Stage II testicular cancer treated with orchiectomy and retroperitoneal-lymph-node dissection. However, when surgery, follow-up, and chemotherapy are optimal, observation with chemotherapy only for relapse will lead to equivalent cure rates.

Late relapse of testicular cancer.

PURPOSE This study analyzed a large group of patients with testicular germ cell cancer in complete remission, who relapsed more than 2 years after completion of treatment. PATIENTS AND METHODS A review of all patients treated at Indiana University Medical Center from 1979 through 1992 for late relapse was conducted. Eighty-one patients were treated for late relapse of testicular cancer. Forty-seven patients relapsed more than 5 years after successful management of their initial disease. RESULTS At initial diagnosis, 35 patients had clinical stage I, 18 stage II, and 28 stage III disease. Twenty-three of 35 stage I, all 18 stage II, and all 28 stage III patients were treated by chemotherapy before their late relapse. The median follow-up duration of patients post-management of late relapse was 4.8 years. Twenty-one patients (25.9%) are continuously disease-free. Nineteen of these 21 patients had surgical resection of carcinoma or teratoma as a component of their therapy. Of sixty-five patients treated for late relapse by chemotherapy, 17 (26.2%) had a complete response, but only two have been continuously disease-free with chemotherapy alone. These two never received prior chemotherapy. CONCLUSION Late relapse of testis cancer is more common than previously thought. Surgery is the preferred mode of therapy. Chemotherapy has only modest success in this entity, in contrast to the excellent results in de novo germ cell tumors. Patients treated for testicular germ cell cancer need annual follow-up evaluations throughout their life due to the possibility of late relapse.

Distribution of Nodal Metastases in Nonseminomatous Testis Cancer

AbstractThe distribution of 104 consecutive stage II (or B) nonseminomatous germinal cell testis tumor deposits in the retroperitoneal space has been analyzed and segregated into 11 anatomic zones of spread: 1) right para-caval, 2) right pre-caval, 3) inter aortocaval, 4) left pre-aortic, 5) left paraaortic, 6) right (renal) suprahilar, 7) left suprahilar, 8) right iliac, 9) left iliac, 10) inter iliac (pre-lumbosacral) and 11) gonadal vein. Each patient had no treatment after orchiectomy and before retroperitoneal lymph node dissection, that is no preoperative radiotherapy or chemotherapy, which may have influenced histologic analysis. Each patient had an extended bilateral retroperitoneal lymph node dissection, including both suprahilar zones. Tumor deposits in these 11 nodal zones were correlated with the side of the primary lesion (right versus left side) and the extent of metastatic disease (B1, B2 or B3).The inter aortocaval zone, just below the left renal vein, is the most common site of tumor depo...

Primary Aldosteronism: Diagnosis, Localization, and Treatment

New diagnostic techniques have enhanced the detection of primary aldosteronism. However, the response of blood pressure after operation in unilateral and bilateral adrenal disease is different. We have compared four localizing techniques--adrenal venography, adrenal isotopic scanning, a modified adrenal venous sampling for steroid measurements, and the anomalous postural decrease in plasma aldosterone concentration--in 51 patients with primary aldosteronism, all of whom had undergone operative confirmation. Adrenalectomy resulted in normal blood pressure in 59%, improvement in 25%, and no change in 16%. Correct localization of the lesion was obtained in 47% by the adrenal isotopic scan, in 66% by adrenal venography, and in 91% by the modified adrenal venous hormone technique despite four false-positives. Of the 26 patients with an anomalous postural decrease in plasma aldosterone, 88% had a unilateral lesion.

Retroperitoneal Lymphadenectomy for Clinical Stage a Testis Cancer (1965 to 1989): Modifications of Technique and Impact on Ejaculation

Results with primary retroperitoneal lymphadenectomy in 464 patients with clinical stage A nonseminomatous germ cell testis cancer (1965 to 1989) were reviewed. The false-negative staging error by clinical methods remains at 30%. The relapse rate in pathological stage A cancer patients was 11% (37 of 323), with 2 deaths. For pathological stage B disease 64% of the patients were cured by retroperitoneal lymphadenectomy alone. With modern adjuvant chemotherapy no stage B tumor relapsed since 1979 and the survival rate was 100%. For all 25 years (464 patients) the relapse rate was 14% and the survival rate was 98.9% (3 cancer and 2 noncancer deaths). Because these results are based on preoperative clinical staging, they are directly comparable with series using radiotherapy or surveillance.

Nerve-Sparing Retroperitoneal Lymphadenectomy with Preservation of Ejaculation

The feasibility of sparing postganglionic fibers of lumbar sympathetic nerves during the course of retroperitoneal lymphadenectomy has been investigated at our university medical center beginning in 1978. We selected 75 patients for nerve-sparing retroperitoneal lymphadenectomy in an effort to preserve ejaculatory function postoperatively. This cohort of patients was selected on the basis of clinical stage. Of the 75 patients 73 had clinical stage I disease. However, 14 of these 73 patients had pathological stage II cancer. No patient was treated with adjuvant chemotherapy after nerve-sparing retroperitoneal lymphadenectomy. Of these 14 patients with pathological stage II disease 4 had relapse: 1 with proved retroperitoneal recurrence, and 3 with serological elevations of tumor markers and questionable clinical findings as to anatomical site of relapse. All 4 patients are free of disease after chemotherapy and/or surgical (1) rescue. There were no local recurrences in the 61 patients with negative nodes. All 75 patients ejaculate and had no evidence of disease more than 2 years after nerve-sparing retroperitoneal lymphadenectomy. It is clear that nerve-sparing retroperitoneal lymphadenectomy is a feasible technique. As noted, it can even be applied to selected patients with low volume positive nodes, yet maintaining relapse and survival figures that are acceptable. Ejaculation is reliably preserved when this nerve-sparing technique is applied accurately in retroperitoneal lymphadenectomy.

Prediction of residual retroperitoneal mass histology after chemotherapy for metastatic nonseminomatous germ cell tumor: multivariate analysis of individual patient data from six study groups.

PURPOSE To develop a statistical model that predicts the histology (necrosis, mature teratoma, or cancer) after chemotherapy for metastatic nonseminomatous germ cell tumor (NSGCT). PATIENTS AND METHODS An international data set was collected comprising individual patient data from six study groups. Logistic regression analysis was used to estimate the probability of necrosis and the ratio of cancer and mature teratoma. RESULTS Of 556 patients, 250 (45%) had necrosis at resection, 236 (42%) had mature teratoma, and 70 (13%) had cancer. Predictors of necrosis were the absence of teratoma elements in the primary tumor, prechemotherapy normal alfa-fetoprotein (AFP), normal human chorionic gonadotropin (HCG), and elevated lactate dehydrogenase (LDH) levels, a small prechemotherapy or postchemotherapy mass, and a large shrinkage of the mass during chemotherapy. Multivariate combination of predictors yielded reliable models (goodness-of-fit tests, P > .20), which discriminated necrosis well from other histologies (area under the receiver operating characteristic (ROC) curve, .84), but which discriminated cancer only reasonably from mature teratoma (area, .66). Internal and external validation confirmed these findings. CONCLUSION The validated models estimate with high accuracy the histology at resection, especially necrosis, based on well-known and readily available predictors. The predicted probabilities may help to choose between immediate resection of a residual mass or follow-up, taking into account the expected benefits and risks of resection, feasibility of frequent follow-up, the financial costs, and the patients individual preferences.

Surgical salvage of chemorefractory germ cell tumors.

PURPOSE Patients with disseminated germ cell tumors who relapse after salvage chemotherapy, or who progress during cisplatin-based therapy, have chemorefractory disease and a very poor prognosis. A subset of these patients will have chemorefractory but resectable disease. We have therefore evaluated the role of salvage surgery in this patient population. PATIENTS AND METHODS We performed a retrospective review of all patients with disseminated germ cell tumors who were felt to have chemorefractory disease and underwent salvage surgery from 1977 to 1990 at Indiana University. All patients had elevated serum markers or other signs of progressive carcinoma. A total of 48 patients underwent surgery (33 retroperitoneal lymph node dissections [RPLNDs], six thoracotomies, three thoracoabdominal resections, and multiple asynchronous procedures in six patients). RESULTS Thirty-eight of 48 patients (79%) were rendered grossly free of disease and 29 (60%) obtained a serologic remission. Ten patients (21%) remain continuously disease-free with no postoperative treatment with a median follow-up of 46 months (range, 31 to 89). Six additional patients who relapsed after salvage surgery are currently disease-free with further treatment (four with repeat surgery and two with high-dose chemotherapy and autologous bone marrow transplantation [ABMT]). CONCLUSION Selected patients with chemorefractory but resectable germ cell tumors have definite potential for cure with salvage surgery.

Surgical resection in disseminated testicular cancer following chemotherapeutic cytoreduction.

Platinum combination chemotherapy will regularly produce a 70% complete response rate in testicular cancer. Many patients failing to achieve complete remission can still be rendered disease‐free with surgical resection of residual localized disease. Twenty‐one patients underwent resection for residual pulmonary lesions and 41 underwent lymphadenectomy for persistent retroperitoneal disease. There were no characteristic radiographic findings for fibrous tissue versus mature teratoma versus carcinoma. Although elevated HCG or AFP levels indicated the presence of carcinoma, negative HCG and AFP did not rule out such a diagnosis as 12 of 22 resected carcinoma patients were seronegative. Of 35 patients, 31 (89%) with fibrous tissue or mature teratomas and all four patients with immature teratomas have been continuously free of disease with a minimal postoperative follow‐up time of six months. However, only two of 22 patients with resected carcinomas have been continuously disease‐free. Postoperative chemotherapy for mature teratoma or fibrous tissue is probably not necessary. However, we feel that further aggressive chemotherapy is needed in the resected carcinoma patient with at least two courses of platinum combination chemotherapy. Surgical resection of residual disease following chemotherapy‐induced cytoreduction with platinum combination chemotherapy may be therapeutic in some cases and helps to define the optimal subsequent treatment strategy.