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Stage II nonseminomatous germ cell tumors of the testis: an analysis of treatment options in patients with low volume retroperitoneal disease.

The management of patients with nonseminomatous germ cell tumors of the testis and low volume retroperitoneal disease remains controversial. We analyzed the treatment modalities of 56 patients divided into 3 groups: group I--18 clinical stage I cancer patients who had pathological stage II disease after retroperitoneal lymph node dissection, group II--31 patients with abdominopelvic computerized tomography abnormalities of 5 cm. or less with or without positive biological markers and group III--7 patients with persistently positive biological markers after orchiectomy with normal abdominopelvic computerized tomography scans. In group I 4 of 18 patients received chemotherapy after retroperitoneal lymph node dissection. Two patients met criteria for post-dissection chemotherapy, but they did not receive it and subsequently had relapse. Of the remaining 12 patients who were observed after dissection only 1 (8 per cent) had relapse. In group II 19 of 31 patients were treated with initial chemotherapy: 13 (68 per cent) achieved a complete response, while 6 required retroperitoneal lymph node dissection after chemotherapy. Of 31 patients 12 were treated with initial retroperitoneal lymph node dissection and 9 (75 per cent) received post-dissection chemotherapy. In group III 5 of 7 patients were treated with initial retroperitoneal lymph node dissection and 3 of the 5 subsequently required chemotherapy. Of the 7 patients 2 received initial chemotherapy and achieved a complete response. All 56 patients are without disease at 4+ to 106+ months (median 28 months). We conclude that patients with the characteristics of groups II and III should be managed initially with chemotherapy, with retroperitoneal lymph node dissection reserved for patients who fail to achieve a complete response. In group I retroperitoneal lymph node dissection is sufficient initial treatment if pathological evaluation of the retroperitoneal lymph nodes does not meet our criteria for post-dissection adjuvant chemotherapy.

Antineoplastic Combined Chemotherapy Protocols

Is adjuvant chemotherapy necessary for patients with stage B1 testicular cancer?

Controversy exists concerning the role of adjunctive chemotherapy in patients with regional nodal involvement. A randomized study reported a 48% relapse rate for patients with positive nodes (stage B1 or stage B2), all of whom were salvaged by full-dose platinum-based chemotherapy. In a series of patients with positive nodes who received two cycles of adjunctive chemotherapy postoperatively, the relapse rate was only 2%. In order to evaluate the effect of retroperitoneal lymph node dissection on relapse rates in patients with stage B1 testicular cancer, a retrospective review of a series of 39 patients was performed. Criteria for inclusion included pathologic stage B1 (less than six positive nodes, located in the primary landing site, with no node greater than 2 cm in diameter and no extracapsular lymph node extension). Patients who fulfilled the criteria along with normalization of tumor markers were followed-up expectantly after retroperitoneal lymph node dissection. Thirty-nine patients were followed from 1 to 10 years with the median duration of follow-up of 3.5 years. Ten of the 39 patients had modified retroperitoneal lymph node dissections with preservation of antegrade ejaculation. The other 29 had full retroperitoneal lymph node dissections. Three relapses were seen, one patient with retrocrural and pulmonary metastases and two patients with pulmonary metastases only for a relapse rate of 8% (three of 39). Patients with stage B2 disease received adjunctive chemotherapy with two or three cycles of platinum-based chemotherapy. We conclude that retroperitoneal lymph node dissection alone is adequate treatment for the majority of patients with pathologic stage B1 testicular cancer. In that subset of patients, adjunctive chemotherapy should be reserved for relapse.

Cisplatin

Non-seminomatous testis tumors: a plan of management based in 96 patients to improve survival in all stages by combine therapeutic modalities.

To develop a plan of management based on the clinical and pathologic stage of the tumor the results of treatment of 96 consecutive patients with non-seminomatous testis tumors have been analyzed. There were no exclusions and all patients were treated, including 17 with advanced stage C disease. All patients underwent retroperitoneal lymph node dissection as primary treatment but the judicious use of adjuvant therapeutic modalities improved survival in all stages of disease. Chemotherapy was the most important adjuvant and postoperative radiation therapy was reserved for patients with extensive retroperitoneal metastatic disease. Results indicate that a modified unilateral thoracoabdominal retroperitoneal lymph node dissection can effectively remove the retroperitoneal nodes. Of 57 patients 50 with stage A or B tumor survived after lymph node dissection without radiation therapy. Compared to an operation alone prophylactic adjuvant chemotherapy improved survival from 82 to 93 per cent for patients with minimal disease (stage A or B1). Postoperative irradiation therapy combined with cyclic chemotherapy improved survival for patients with advanced retroperitoneal disease compared to an operation and radiation alone or an operation and chemotherapy alone. An aggressive approach that combined operation with chemotherapy, radiation therapy or both, has salvaged 8 of 17 patients with disseminated metastatic disease (stage C). The over-all survival rate for these 96 patients is 78 per cent. A plan of management has evolved, which is based on retroperitoneal lymph node dissection followed by the judicious use of adjuvant chemotherapy and radiation therapy as determined by pathologic findings.

Choriocarcinoma

Management of yolk sac carcinoma of the testis clinical stage I: lymphadenectomy vs. no lymphadenectomy.

Thirty seven patients with Stage I yolk sac tumor of the testis were registered at the Instituto Nacional de Enfermedades Neoplasicas (I.N.E.N.), Lima-Peru from 1962 through 1980. Eighteen patients underwent retroperitoneal Lymph node dissection. The age incidence was 5 to 29 months except for two patients 50 and 84 months of age each. Bilateral retroperitoneal lymph node dissection was performed in seventeen patients; unilateral dissection was performed in one patient. In two patients both had one positive node at lymphadenectomy (2/18: 11%). Eleven patients (61.11%) are alive and with no evidence of disease in between 7 to 26 years post lymphadenectomy. Seven patients (38.89%) died: 4/18 (22.22%) because of progression of the disease and three patients because of no neoplastic cause. Nineteen patients did not have retroperitoneal lymph node dissection: seven patients (36.84%) are alive with no evidence of disease and 12 patients (63.16%) died: 8/19 (42.10%) because of progression of the disease and 4/19 (21%) with no neoplastic disease. In conclusion, patients with localized disease (Clinical Stage I) benefit from retroperitoneal lymph node dissection when compared to a similar group of patients not submitted to lymphadenectomy.

Child, Preschool

Localization of solitary and multiple metastases in stage II nonseminomatous testis tumor as basis for a modified staging lymph node dissection in stage I.

Because of a continuing need for pathological staging of clinical stage I testicular tumors an investigation was performed to determine the primary sites of metastatic involvement of the retroperitoneal lymph nodes and to define narrowly limited ipsilateral areas of lymph node dissection strictly for the purpose of staging. Surgical/pathological localization of solitary metastases provides the most direct evidence of primary lymphatic spread. There were 214 consecutive patients with stage II disease (excluding bulky disease) evaluated with respect to localization relative to the side of the involved testis and the number of metastases up to 5 cm. Solitary metastases of 5 cm. or less were found in 74 patients, 53 patients had 5 or less lymph nodes of 2 cm. or less and 87 patients had more than 5 lymph nodes of between 2 and 5 cm. Solitary nodes of the right testis tumor were located with decreasing frequency in the upper and lower interaortocaval, lower paracaval and precaval, upper precaval and right common iliac, upper paracaval and upper preaortic zones. Primary deposits of the left testis tumor were seen predominantly in the upper para-aortic zone. Upper preaortic and lower para-aortic zones were involved infrequently, and other areas were affected only in rare cases. These data contradict the assumption of a testicular lymph center located at the openings of the testicular veins into the vena cava and left renal vein, respectively. Multiple metastases were spread over the entire retroperitoneum, except for the external iliac regions. Hilar/suprahilar metastases were seen infrequently. Ipsilateral areas are defined according to primary involvement. A modified retroperitoneal lymph node dissection within ipsilateral areas is proposed as a staging operation for clinical stage I disease and a radical retroperitoneal lymph node dissection is indicated for pathological stage II disease.

Humans

[Clinical studies of testicular tumor. II. Analysis of 30 patients with nonseminomatous testicular tumor].

Clinical findings and results of various treatments were discussed for 30 patients with nonseminomatous testicular tumor (NSTT) who had been treated from August, 1968 to March, 1985. Radioimmunoassays were positive for AFP in 19 of the 22 evaluated patients (86.4%) and were positive in 14 of the 19 evaluated patients (73.7%). These positive rates are consistent with those reported by others. Abnormal pre-treatment level of hCG-beta did not always indicate poor clinical courses, since in patients under stage III A pre-treatment level of hCG-beta did not correlate to either treatment results or clinical courses, even in patients with bulky metastasis such as stage IIIB1, B2 or C their treatment results and clinical courses seemed to be primarily determined by the size and extent of metastasis. However, pre-treatment measurement of hCG-beta was useful to predict in primary and/or metastatic tumor the presence of choriocarcinoma element which could not be found with conventional histopathological studies. Most of our 14 patients at stage I were subjected to radical orchiectomy and retroperitoneal lymph node dissection followed by post-surgical management with radiotherapy or chemotherapy. With these treatments only one of the stage I patients had a recurrence. However, adjuvant therapy may not be necessary for them because of a low recurrence rate following retroperitoneal lymph node dissection and the high cure rate with intensive chemotherapy including CDDP for the early stage of recurrence, when a close follow-up would be possible. We treated only 2 patients at stage II A. One of these 2 patients became free of the disease by intensive chemotherapy including CDDP (24 months after the start of treatment). In stage II A, a high recurrence rate has been reported, following retroperitoneal lymph node dissection without post-surgical adjuvant chemotherapy, which indicates that these patients should be treated with adjuvant chemotherapy, including CDDP. All 4 patients in stage II B or III treated mainly by chemotherapy without CDDP died of the disease at around one year after treatment. However, the five-year survival rate was improved to 40% in 10 advanced patients with these stages who had been treated mainly with recent chemotherapy regimen including CDDP. The recent development of chemotherapy regimen including CDDP has been able to lead many patients with advanced stage to a curable status. However, the appropriate treatment for some patients with bulky and extensive metastasis remains to be established. More aggressive treatment such as cytoreductive surgery may be necessary for such patients.

Choriocarcinoma

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.

Adolescent

Paratesticular rhabdomyosarcomas and leiomyosarcomas: a clinicopathological review.

One case of embryonal paratesticular sarcoma and 2 cases of leiomyosarcomas are reported. The 13-year-old boy with embryonal sarcoma is well after an orchiectomy and high ligation of the spermatic cord followed by radiotherapy and chemotherapy. A 66-year-old man has been doing well after orchiectomy and hemiscrotectomy for a paratesticular leiomyosarcoma. The third patient had a highly pleomorphic leiomyosarcoma and died 2 months postoperatively. The clinical and histological diagnosis of paratesticular rhabdomyosarcomas and leiomyosarcomas is reviewed and the various therapeutic approaches to these neoplasms are discussed. Retroperitoneal lymph node dissection, radiotherapy and chemotherapy are important adjuncts to orchiectomy in the management of rhabdomyosarcomas. On the contrary, retroperitoneal lymph node dissection and radiotherapy are not indicated in leiomyosarcomas, since these neoplasms tend to metastasize by the hematogenous route and are radioresistant. At the present time we are unable to evaluate chemotherapy in the management of paratesticular leiomyosarcomas.

Aged

Surgical aspects in the treatment of patients with testicular cancer.

We sit at a crossroads in the therapeutic treatment of patients with low-stage testicular cancer. The luxury of effective chemotherapy has allowed achievement of virtually 100% survival rates in patients with low-stage testicular cancer. The goal of urologists and oncologists in concert should be to minimize the long-term morbidity and to reduce the amount of therapy necessary to achieve these high survival rates. Patients with a low risk of lymphatic or disseminated metastases, such as those with low-stage tumors, without vascular invasion and with favorable histologic features (teratoma), are clearly candidates for observation protocols to be carried out in well-defined centers. It should be emphasized, however, that observation needs to be an active surveillance program for a minimum of 2 to 3 years after orchiectomy, with frequent chest roentgenography, tumor marker studies, and CT scanning. In the majority of patients with low-stage tumors, however, modified retroperitoneal lymph node dissection allows definitive staging, thus allowing treatment with a lesser amount of chemotherapy. Patients with bulky stage II disease require chemotherapy in hopes of avoiding the need for retroperitoneal lymph node dissection. In the group of patients with stage II disease with minimal retroperitoneal involvement (less than 3 cm in maximal diameter, stage IIA), approximately half of the patients can be treated by surgical approaches alone, although half will require postoperative chemotherapy. Testicular cancer at this time is one of the most successfully treated solid tumors. Although diagnostic tools are available, successful diagnosis still relies upon suspicion and physical findings. Staging techniques have improved but still have vast limitations, especially in patients with low-stage disease. By careful application of multimodal therapy, long-term survival and cure are likely in the majority of patients. Continued long-term observation is necessary, however, especially in patients with residual teratoma that has been resected. As we look to the 1990s, emphasis can be placed on finding less morbid treatments yet still maintaining the high success rates enjoyed in the treatment of this once nearly uniformly fatal tumor.

Adult

Chylous ascites following retroperitoneal lymphadenectomy: report of 2 cases with guidelines for diagnosis and treatment.

Two cases of chylous ascites following retroperitoneal lymphadenectomy are presented. The first case, a 3-year-old girl, undersent a right radical nephrectomy and retroperitoneal lymph node dissection for Wilms' tumor. Chylous ascites developed postoperatively and resolved after 3 months of supportive therapy. The second case, a 45-year-old woman, underwent a right radical nephrectomy and retroperitoneal lymph node dissection for renal carcinoma. Chylous ascites occurred postoperatively and resolved after a single paracentesis. Diagnosis, evaluation, and therapeutic modalities are outlined and the literature is reviewed.

Adenocarcinoma

[Germinal testicular tumors].

Characteristic for the germinal cell tumors of the testis is their great variety. Collins and Pugh gave a classification of testis tumors under consideration of the genesis of the tumor and the clinical progressing. The staging should be done according to the TNM-system which is based on the UICC recommendations of 1973. If a tumor is suspected an exploration of the testis must be performed. After definitive histological diagnosis via immediate section for microscopic examination during surgery an enlarged orchiectomy and local lymph node dissection has to be performed. In cases of seminoma a 5-year-survival-rate of 90 to 97 per cent can be achieved by radiation of two fields (4 fields in case metastases are suspected). Because of the radio resistance of the teratoid tumors a retroperitoneal lymph node dissection has to follow the enlarged orchiectomy. With a subtile operating technique all the lymph nodes between diaphragm and aortic bifuraction can be removed in case of operability. Postoperative radiation therapy is only recommended in case of excessive lymph node metastases. By an adjuvant chemotherapy following retroperitoneal lymph node dissection a 5-year-survival-rate of more than 80 per cent can be obtained in cases of teratoid tumors.

Antineoplastic Agents

[A case of advanced paratesticular rhabdomyosarcoma].

A case of paratesticular rhabdomyosarcoma is presented. An 18-year-old male was admitted with the complaint of giant scrotal swelling and abdominal fullness on September 5, 1986. Left radical orchiectomy was performed with the pathologic diagnosis of alveolar rhabdomyosarcoma. The tumor was paratesticular in location and had invaded a spermatic cord. Radiological examination showed a gross metastatic mass in retroperitoneal lymph nodes, supraclavicular lymph nodes and Douglas pouch. The patient received induction chemotherapy containing vincristine, actinomycin-D, cyclophosphamide, bleomycin, CDDP and VP-16. After 3 courses, he had no mass in Douglas pouch and supraclavicular lesion. He received retroperitoneal lymph node dissection for residual retroperitoneal mass, and postoperative radiotherapy was given. However, recurrent disease was developed in the paraaortic region with malignant ascites. He was treated with salvage chemotherapy, had without any significant effect. He died of liver dysfunction due to progressive mass in hepatic hilum. A review of the current approach of paratesticular rhabdomyosarcoma with the usefulness of combination chemotherapy is given.

Adolescent

Testicular germ-cell neoplasms: curative approaches.

Approximately 80 per cent of all patients with testis cancer will present with low-volume disease. If they are pathologic stage I, there is virtually a 100 per cent cure rate even though 5 to 10 per cent will relapse after node dissection. Those who have relapsed have been salvaged with systemic chemotherapy. If clinical stage I patients are followed on observation protocols, 20 to 30 per cent of the patients will relapse. Unfortunately, a small percentage of these patients will not be salvaged with chemotherapy because they have more advanced disease at the time that the relapse is discovered. The main objection to retroperitoneal lymph node dissection in patients with low-stage disease has been the issue of infertility induced by the procedure. This problem has been alleviated by the development of the prospective nerve-sparing procedures. Long-term follow-up is still required to make certain that the relapse rate is not significantly higher than with a full retroperitoneal lymph node dissection. Experience has demonstrated that patients with stage II disease will achieve a 98 to 99 per cent cure rate regardless of whether they have adjuvant chemotherapy after surgery, or full-course chemotherapy should they relapse (approximately 50 per cent). Advanced disease is best treated initially by systemic chemotherapy. The emphasis in the last few years has been on a reduction in the toxicity of chemotherapy while maintaining the high degree of efficacy. Surgery is used as an adjunct to chemotherapy in those patients who achieve a partial remission. Careful follow-up cannot be over emphasized in patients with any form of treatment for testis cancer. It is especially important that those patients who have teratoma present in the surgical specimens obtained at the time of a postchemotherapy lymph node dissection have prolonged follow-up, because recurrences have been noted as long as 6 to 8 years after the initial event. Although primary retroperitoneal or mediastinal germ-cell tumors do exist, the vast majority arise from the testis. If the diagnosis of germ-cell tumor has been made by some means other than orchiectomy, a careful review of the patient's history and physical findings is needed to guide the physician to the possible testicular site of origin. If no physical findings are present, scrotal ultrasound may be helpful in localizing a primary tumor of the testis. If such localization is possible, then a radical orchiectomy should be performed to prevent future seeding from persistent tumor in the testicle.(ABSTRACT TRUNCATED AT 400 WORDS)

Dysgerminoma

Bilateral synchronous testis tumors of different histology in a patient with the acquired immunodeficiency syndrome related complex.

The incidence of bilateral testis tumors is approximately 1.5%. Of these cases the majority have the same histological status and few occur synchronously. Recently, an increased number of nonseminomatous germ cell tumors have been reported in the acquired immunodeficiency syndrome population. We describe a rare case of bilateral synchronous testis tumors of different histological status (seminoma and embryonal cell carcinoma) in a patient with the acquired immunodeficiency syndrome related complex. The patient was managed with bilateral orchiectomy and retroperitoneal lymph node dissection. Pathological stage was B1. The treatment was complicated by the fact that the patient is on azidothymidine, a drug that causes bone marrow suppression as a side effect. Because of persistent neutropenia no chemotherapy was given. The patient had no evidence of disease almost 1 year after retroperitoneal lymph node dissection.

AIDS-Related Complex

Adjuvant chemotherapy of metastatic stage II nonseminomatous testis tumor.

In a prospective randomized trial, 225 patients with stage IIB nonseminomatous testis tumor after radical retroperitoneal lymph node dissection received 2 versus 4 courses (arms 1 and 2, respectively) of adjuvant chemotherapy with cis-platinum, vinblastine and bleomycin. With a median followup of 43 months, a total of 7 relapses occurred; 6 in arm 1 and 1 in arm 2. Three patients died: 2 during adjuvant chemotherapy and 1 of progressive disease. The difference in relapse rates between arms 1 and 2 is not statistically significant. Patient compliance differed: chemotherapy was administered according to protocol in 83% and 50% of the cases in arms 1 and 2, respectively. Most frequent side effects observed were nausea, vomiting and alopecia. No significant differences regarding these or other side effects were obtained. Patients with stage IIB nonseminomatous testis tumor after retroperitoneal lymph node dissection are treated sufficiently with 2 courses of adjuvant cis-platinum-containing chemotherapy.

Adolescent

Fertility status of patients with clinical stage I testis tumors on a surveillance protocol.

A potential benefit of a surveillance protocol for the management of patients with clinical stage I testis tumors is the avoidance of ejaculatory disturbances and infertility resulting from retroperitoneal lymph node dissection, the standard treatment for patients with this stage of disease. To address this issue we evaluated 22 patients with clinical stage I testis tumors on a surveillance protocol with history, physical examination and semen analysis. Previous fertility was unknown or it had not been tested in the majority of the patients (74 per cent). Ten patients (45 per cent) had abnormal spermatogenesis on the basis of a low sperm count or sperm motility. Of 6 patients with oligospermia or azoospermia 3 had recovered normal spermatogenesis when they were re-evaluated 4 to 19 months later. Although in this group of carefully staged cases the incidence of subfertile sperm counts seems to be similar to those with higher stage disease, some patients with abnormal counts clearly recover. The avoidance of retroperitoneal lymph node dissection seems to spare fertility in at least a small percentage of these patients.

Adult

Clinical usefulness of serum ferritin measurements in patients with testicular germ cell tumors.

In 50 patients with seminoma and in 50 with nonseminomatous germ cell tumors of the testis, serum levels of conventional markers (CEA, AFP, hCG) and ferritin were measured at the time of admission and during management. The conventional markers behaved as reported previously. After orchiectomy, elevated levels of ferritin were found in the presence as well as in the absence of tumor; the extent of these elevations was highly variable. Serial determinations of serum ferritin showed two patterns of variation. First, in patients treated with retroperitoneal lymph node dissection, irradiation, and chemotherapy regimens without platinum, decreasing levels of the conventional markers and serum ferritin were associated with response to therapy and increasing levels with relapse of tumor. Second, in patients treated with chemotherapy regimens containing cis-diamminedichloroplatinum, the conventional markers returned to normal values while the ferritin level doubled or tripled and returned to pretreatment or normal values only several weeks after therapy. Thus, it appears that hyperferritinemia was a sensitive index of platinum toxicity. We conclude that the serum ferritin level has no value in staging after orchiectomy but is a useful index of response to therapy during treatment with retroperitoneal lymph node dissection, irradiation or chemotherapy without platinum or relapse of tumor. During treatment with platinum, elevated levels might be explained as a possible toxic side effect of this drug.

Adolescent