Advanced Nonseminomatous Testicular Cancer Research Articles

Postchemotherapy Retroperitoneal Lymph Node Dissection in Patients With Nonseminomatous Testicular Cancer: A Single Center Experiences.

Background:Testicular cancer accounts for about 1 - 1.5% of all malignancies in men. Radical orchiectomy is curative in 75% of patients with stage I disease, but advance stage with retroperitoneal lymph node involvement needs chemotherapy. All patients who have residual masses ≥ 1 cm after chemotherapy should undergo postchemotherapy retroperitoneal lymph node dissection (PC-RPLND).Objectives:Treatment of advanced nonseminomatous testicular cancer is usually a combination of chemotherapy and surgery. We described our experience about postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) in our center.Patients and Methods:In a retrospective cross-sectional study between 2006 and 2011, patients with a history of postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) in Imam Khomeini hospital were evaluated. All patients had normal postchemotherapy serum tumor markers and primary nonseminomatous cancer. We reviewed retrospectively clinical, pathological, and surgical parameters associated with PC-RPLND in our center.Results:Twenty-one patients underwent bilateral PC-RPLND. Mean age was 26.3 years (ranged 16 - 47). Mean size of retroperitoneal mass after chemotherapy was 7.6 cm. Mean operative time was 198 minutes (120 - 246 minutes). Mean follow-up time was 38.6 months. Pathologic review showed presence of fibrosis/necrosis, viable germ cell tumor and teratoma in 8 (38.1%), 10 (47.6%) and 3 (14.28%) patients, respectively. One patient in postoperative period of surgery and three patients in two first years after surgery were expired. Of 17 alive patients, only two (11.8%) had not retrograde ejaculation.Conclusions:PC-RPLND is one the major operations in the field of urology, which is associated with significant adjunctive surgeries. In appropriate cases, PC-RPLND was associated with good cancer specific survival in tertiary oncology center.

Surgery and chemotherapy for advanced nonseminomatous testicular cancer

Surgery and chemotherapy for advanced nonseminomatous testicular cancer

Retroperitoneal surgery in patients with nonseminomatous testicular cancer and minimal residual tumor

In the period 1980-1991, 78 patients with advanced nonseminomatous testicular cancer underwent retroperitoneal lymphadenectomy for post-chemotherapy residual masses less than 2 cm. To decrease the frequency of "dry ejaculation" in these patients with no or limited residual disease, the extent of dissection was reduced during the period, with bilateral dissections (49 cases, 1980-1986) being initially replaced by unilateral procedures (19 cases, 1983-1990) and subsequently by nerve-sparing techniques (10 cases, 1990-1991). As expected, a higher total number of lymph nodes was found in the retroperitoneal specimens after bilateral (44 (13-100)) than after unilateral (21 (7-35)) and nerve-sparing (18 (7-60)) procedures. The number of lymph nodes with pathological changes was low, with 3 (1-16) after bilateral, 2 (1-9) after unilateral, and 2 (1-4) after nerve-sparing operations. Histological examination revealed only necrosis/fibrosis in 65% of the patients, elements of mature teratoma in 28%, and remnants of viable malignant tumor in 6%. There were no major postoperative complications. "Dry ejaculation" was reported by 84% of the patients with bilateral operations, but was generally avoided after the unilateral (16%) and nerve-sparing (nil) procedures. After a mean follow-up of 83 (5-138) months, 6 patients have developed a recurrence, only one of them primarily in the retroperitoneal space. It is concluded that in patients with minimal residual retroperitoneal tumor, postchemotherapy lymphadenectomy using a unilateral or nerve-sparing technique seems to offer an effective therapeutic alternative with acceptable postoperative morbidity and preserved ejaculation.

Is postchemotherapy retroperitoneal surgery necessary in patients with nonseminomatous testicular cancer and minimal residual tumor masses?

At least one third of the patients with metastatic testicular cancer are rendered tumor-free by cisplatin-based chemotherapy. One may question, therefore, the routine use of postchemotherapy retroperitoneal lymph node dissection (RLND), especially if the residual masses are less than 20 mm in diameter. To define the role of such surgery, we analyzed the postchemotherapy histology in testicular cancer patients with minimal residual disease. Seventy-eight patients with advanced nonseminomatous testicular cancer underwent RLND after three to four cycles of cisplatin- or carboplatin-based chemotherapy. In all patients, the largest diameter of the residual retroperitoneal mass was less than 20 mm. Complete fibrosis/necrosis was found in 51 patients, mature teratoma in 22, and vital malignant germ cell tumor in five. In two of the latter five patients, alphafetoprotein (AFP) had increased immediately before RLND. In the 76 patients with normal pre-RLND tumor markers, the presence of undifferentiated malignant teratoma (MTU) in the primary tumor and normal prechemotherapy tumor markers were independent parameters predicting complete fibrosis/necrosis, which was demonstrated in all 15 patients with these two pretreatment parameters. Postchemotherapy RLND can be omitted in patients with MTU in the primary tumor who have normal AFP/human chorionic gonadotropin (AFP/HCG) before chemotherapy and whose residual retroperitoneal mass is less than 20 mm in diameter. If the pre-RLND tumor markers are normal, RLND should be performed in all other patients with small residual masses, even in the presence of a normal computed tomography (CT) and particularly if regular follow-up of the patients is not guaranteed.

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 α-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.

Editorial Comments

No AccessJournal of Urology1 Nov 1989Editorial Commentsis accompanied byHistology of Tumor Residuals Following Chemotherapy in Patients with Advanced Nonseminomatous Testicular Cancer John P. Donohue John P. DonohueJohn P. Donohue More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(17)54847-8AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "Editorial Comments." The Journal of Urology, 142(5), p. 1242 © 1989 by The American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsRelated articlesJournal of UrologyNov 13, 2018, 1:51:06 AMHistology of Tumor Residuals Following Chemotherapy in Patients with Advanced Nonseminomatous Testicular Cancer Volume 142Issue 5November 1989Page: 1242 Advertisement Copyright & Permissions© 1989 by The American Urological Association Education and Research, Inc.MetricsAuthor Information John P. Donohue More articles by this author Expand All Advertisement PDF DownloadLoading ...

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 α-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. (J. Urol., 142:1239-1242, 1989)

Prognostic factors in advanced nonseminomatous testicular cancer a multivariate logistic regression analysis

In order to define prognostic factors for advanced stage of nonseminomatous germ cell tumors (NSGCT) of the testis, the authors reviewed 84 patients treated from 1978 through 1985. The survival rate was 51% at 3 years. Patients with elevated seric levels of human chorionic gonadotropin (HCG) and/or alpha-fetoprotein (AFP), or the presence of an abdominal mass had significantly worse survival. Only HCG and AFP levels retained their significance when multivariate Cox analysis was performed. The probability that a patient achieves a complete remission (CR) was assessed by a function of certain patient characteristics using a multivariate logistic regression analysis. The significant variables were a function of HCG and AFP values. Since both variables are related to the CR rate and survival the authors define the obtention of a CR as a unique outcome of interest. The probability of a CR greater than 70% adequately separates the patients into two prognostic subgroups. This model currently is being used to enrole NSGCT patients in a prospective modulated clinical trial according to these prognostic factors.

Treatment of Poor Prognosis Nonseminomatous Testicular Cancer with a “High-Dose” Platinum Combination Chemotherapy Regimen

A new intensive four drug combination chemotherapy regimen, termed PVeBV, consisting of cis-platinum, vinblastine, bleomycin, and VP-16, was administered to six previously untreated patients with poor prognosis advanced nonseminomatous testicular cancer and to four patients who had relapsed on primary platinum based regimens. The cis-platinum was administered in 250 ml of 3% saline at twice the dose (40 mg/m2 IV days 1–5 every three weeks) used in other treatment schedules. All six previously untreated patients achieved a complete remission. Four achieved a complete remission with three cycles of PVeBV while the other two patients achieved a complete remission with an additional cycle of cisplatinum and VP-16 at 200 mg/m2 IV × five followed by autologous bone marrow infusion. All four relapsed patients responded to PVeBV (two complete remissions and two partial remissions). There were no deaths associated with PVeBV therapy; however, myelosuppression was severe. There has been no renal toxicity (other than hypomagnesemia) observed with 35 cycles of high-dose platinum therapy in previously untreated patients. These results indicate that PVeBV is a promising chemotherapy regimen for the treatment of poor prognosis testicular cancer patients. Furthermore, it appears that cis-platinum can be administered at higher doses than previously used without an increase in renal toxicity if administered in hypertonic saline. The high-dose cis-platinum schedule, as used in PVeBV, warrants evaluation in other tumors which respond to standard-dose platinum therapy.

Treatment of poor prognosis nonseminomatous testicular cancer with a "high-dose" platinum combination chemotherapy regimen.

A new intensive four drug combination chemotherapy regimen, termed PVeBV, consisting of cis-platinum, vinblastine, bleomycin, and VP-16, was administered to six previously untreated patients with poor prognosis advanced nonseminomatous testicular cancer and to four patients who had relapsed on primary platinum based regimens. The cis-platinum was administered in 250 ml of 3% saline at twice the dose (40 mg/m2 IV days 1-5 every three weeks) used in other treatment schedules. All six previously untreated patients achieved a complete remission. Four achieved a complete remission with three cycles of PVeBV while the other two patients achieved a complete remission with an additional cycle of cisplatinum and VP-16 at 200 mg/m2 IV X five followed by autologous bone marrow infusion. All four relapsed patients responded to PVeBV (two complete remissions and two partial remissions). There were no deaths associated with PVeBV therapy; however, myelosuppression was severe. There has been no renal toxicity (other than hypomagnesemia) observed with 35 cycles of high-dose platinum therapy in previously untreated patients. These results indicate that PVeBV is a promising chemotherapy regimen for the treatment of poor prognosis testicular cancer patients. Furthermore, it appears that cis-platinum can be administered at higher doses than previously used without an increase in renal toxicity if administered in hypertonic saline. The high-dose cis-platinum schedule, as used in PVeBV, warrants evaluation in other tumors which respond to standard-dose platinum therapy.

Tumor markers in advanced nonseminomatous testicular cancer.

The serum levels of human chorionic gonadotropin (HCG), alphafetoprotein (AFP), lactic dehydrogenase (LDH), and carcinoembryonic antigen (CEA) were measured in 62 men with advanced nonseminomatous germ-cell testicular tumors. The HCG level was elevated in 64%, the AFP level in 67%, and the LDH level in 62%, including three of the six men with normal levels of the other two markers. At least one of these three markers was elevated in 91% of patients. Sustained or rising levels of HCG or AFP always were accompanied by persistent or recurrent tumor. Carcinoembryonic antigen was found not to be a useful marker in testicular cancer. Patients whose tumors contained yolk-sac elements always had elevated AFP levels, and patients with choriocarcinoma always had elevated levels of HCG. However, absence of these histologic types did not preclude elevations of the respective markers. Tumor markers are indispensable in the management of patients with testicular cancer, and several markers must be measured repeatedly if the greatest percentage of patients is to benefit.

A phase II study of oral VP-16-213 in non-seminomatous testicular cancer

In a disease-oriented phase II study, thirty-three patients with advanced non-seminomatous testicular cancer were treated with oral VP-16-213 175 mg/m2/day for three consecutive days repeated every week. All patients had previously received extensive chemotherapy and twenty patients also had prior radiotherapy, Of 30 evaluable patients, 6 experienced partial remission for a median duration of 3.5 months, whereas minor regression or stabilization of the disease was achieved in 7 patients for a median duration of 2.5 months. Leukopenia was dose-limiting and resulted in dose reduction or treatment delay in 55% of the scheduled courses. The definite antitumor activity of VP-16-213 in non-seminomatous testicular cancer warrants its incorporation into combination chemotherapy for this disease.