Resection of small, residual retroperitoneal masses after chemotherapy for nonseminomatous testicular cancer: a decision analysis

BACKGROUND: After chemotherapy for metastatic, nonseminomatous testicular cancer, small, retroperitoneal lymph nodes still harbor mature teratoma or viable cancer cells in less than half of patients with normal tumor markers. Surgical resection is an effective treatment to remove residual masses, but observation may also be considered. METHODS: Using a decision analysis model, the authors estimated the survival achieved with either resection or observation for patients with residual masses measuring 0-20 mm. Prognostic estimates were obtained from an international data set containing 362 patients with masses < or =20 mm and from 10 clinical experts. RESULTS: According to the model, resection prolonged life expectancy by more than 2 years for masses 11-20 mm and by more than 1 year for masses 0-10 mm. The estimated gains in 5-year survival were 4.3% and 2.7%, respectively. In a sensitivity analysis, these results appeared rather robust for changes in the estimates of the experts. The magnitude of the gain in survival, however, depended on the probabilities of the residual histologies, which could be estimated with several well-known predictors, and the assumed benefit of resection for residual mature teratoma or cancer. CONCLUSIONS: Resection may on average be beneficial for patients with small, residual masses. The expected benefit depends on the probability and risks of residual malignancy, regarding which further research is required. For decision-making regarding individual patients, the morbidity and costs of resection and a patient's individual preferences should be considered in addition to any assumed gain in survival.     

Prediction models for the histology of residual masses after chemotherapy for metastatic testicular cancer. ReHiT Study Group

Patients with metastatic non-seminomatous testicular cancer can be cured by cisplatin-based chemotherapy. After chemotherapy, surgical resection is a generally accepted treatment to remove remnants of the initial metastases since residual tumor may still be present (mature teratoma or viable cancer cells). We review here several policies for the selection of patients for retroperitoneal lymph node dissection. We consider one simple policy as a reference, which bases the selection solely on the diameter of the residual mass (> or = 10 mm). Further, we distinguish 4 rule-based policies, which combine several clinical characteristics (e.g., primary tumor teratoma-positive or insufficient reduction in size), and 2 probability-based policies, where a regression or tree model is used that statistically combines well-known, important clinical predictors for the absence of residual tumor. The policies were evaluated in an international data set containing 716 patients. The reference policy would leave 204 masses < 10 mm unresected, where mature teratoma was present in 50 (25%) and cancer in 11 (5%). Compared with this policy, most of the rule-based policies left fewer patients with residual tumor unresected, at the expense of more resections. The probability-based policies could refine the selection without such an increase in the number of resections. Prediction models for the residual histology therefore merit wider application in clinical practice.     

Surgical management of complex residual masses following systemic chemotherapy for metastatic testicular germ cell tumours

BackgroundPost-chemotherapy retroperitoneal lymphadenectomy (PC-RPLND) represents the treatment of choice in patients with residual masses following chemotherapy for metastatic germ cell tumours. Involvement of major retroperitoneal vessels or thoracic/lumbar spine is rare and challenging but needs complete resection for curative intent. We report on our experience in the management of such complex cases.Patients and methodsA total of 185 patients underwent PC-RPLND and we identified 25 (13.5%) patients who needed complex adjunctive vascular (n = 16, 8.6%), skeletal (n = 5, 2.7%) and pancreaticoduodenal (n = 4, 2.2%) surgeries. We performed a retrospective analysis of treatment-associated complications according to the Clavien–Dindo classification. Progression-free, cancer-specific and overall survival was calculated.ResultsAll patients were of intermediate/poor prognosis according to IGCCCG. Median tumour diameter at time of surgery was 18.6 (9.0–35) cm. Sixteen (8.6%) underwent vascular surgery including aortic resection and replacement, complete or partial resection of the inferior vena cava with thrombectomy, and resection and replacement of the iliac vessels. In five patients, 1–2 metastatic lumbar vertebral bodies were resected, stabilized and replaced. Four patients underwent en-bloc resection of a suprahilar mass with pancreas and duodenum. Pathohistology revealed vital cancer in five patients; teratoma and malignant somatic transformation was identified in 12 and 6 patients, respectively. Complications occurred more often in the group of complex RPLND (41.7 versus 7.2%, P = 0.02) with the majority representing grade I–IIa. After a median follow-up of 28.5 months, four patients developed recurrent disease and one patient died of the disease.ConclusionsFew patients with advanced GCT need complex vascular, skeletal or intestinal surgery in an interdisciplinary setting with good functional and oncological outcome. Due to the complexity, treatment should be performed at specialized centres.     

Sequential resection of residual abdominal and thoracic masses after chemotherapy for metastatic non-seminomatous germ cell tumours.

Thirty-eight patients with advanced non-seminomatous germ cell tumours (NSGCTs) underwent multiple surgical interventions (two in 33 patients, three in four patients, four in one patient) after cisplatin-based chemotherapy. All patients had normal serum tumour markers but persistent radiographic masses. The larger mass was routinely resected first. Fifteen patients (39%) had dissimilar histological findings at sequential surgical procedures, 12 of whom demonstrated less favourable pathological features during the first operation and three at the second. Patients who underwent both retroperitoneal lymph node dissection (RPLND) and lung resection showed less favourable histological features in the retroperitoneum in nine cases and in the lung in three cases. Eight of 16 patients (50%) without mature teratoma in their primary tumours showed complete necrosis/fibrosis at all surgical interventions, whereas all patients whose primary tumour was classified as malignant teratoma intermediate demonstrated mature teratoma at least at one anatomical site. As histology of post-chemotherapy residual masses cannot be extrapolated from one anatomical site to another, patients usually are properly managed by excision of all residual masses. In particular, in patients with necrosis/fibrosis at lung resection omission of RPLND is not advised.     

Myocardial-infarction after adjuvant chemotherapy for resected stage-ii nonseminomatous testicular cancer

Although acute toxicity of cisplatin-based chemotherapy of germ cell tumors is considerable, major vascular complications have been reported infrequently. This report describes the case of a 36-year-old man developing myocardial infarction after the first cycle of adjuvant cisplatin-based chemotherapy for resected stage II testicular cancer. A close temporal association between the administration of chemotherapy and the vascular event suggests a cause and effect relationship. A drug-induced endothelial cell damage may be an important pathogenetic factor. Although reports on vascular accidents following treatment of testicular cancer raise concern with regard to the safety of chemotherapy, at present the very low incidence of such complications should not enter into therapeutic decisions.     

Surgical resection of residual tumor after chemotherapy in non-seminomatous testicular cancer

Fifteen patients with disseminated non-seminomatous testicular cancer, 13 of whom had advanced disease, underwent surgery for residual tumor after induction chemotherapy. Complete remissions were achieved in 7 of 9 patients with mediastinal or pulmonary metastases and in 2 of 6 patients with retroperitoneal metastases. Patients with alpha-fetoprotein (AFP) levels over 10⁴ng/ml at diagnosis and/or a positive AFP preoperatively failed to achieve complete remission. Complete remissions were obtained in all 8 patients who had resection of necrosis, mature teratoma, immature teratoma or mature teratoma with malignant foci, but in only 1 of 7 patients who had resection of embryonal carcinoma or yolk sac tumor with other components. Of 9 patients with complete remission, 8 have remained free of disease after a median follow-up time of 29 months (range 6–66 months) and one had a contralateral non-seminomatous testicular cancer removed after 60 months. In addition to being therapeutically successful, the combined use of chemotherapy followed by surgery for residual tumor may lead to a better understanding of the influence of chemotherapy on the biology of testicular carcinoma.     

Treatment of retroperitoneal residual tumor after PVB chemotherapy of nonseminomatous testicular tumors

Twenty-five patients with nonseminomatous testicular tumors stages IIB and IIC were treated at the Groningen University Hospital between January 1978 and April 1983. One patient died from his extensive tumor during chemotherapy. The remaining 24, treated by combination chemotherapy with cisplatin, vinblastine, and bleomycin as well as by surgery, are all alive after a mean follow-up period of 56 months. A laparotomy was performed after chemotherapy in each of the 24 cases. In four patients no residual tumor was found. Residual tumor was resected in 20 patients, in 13 the tumor contained only necrosis and fibrosis, 7 had mature teratoma. Comparison of the histologic features of the primary testicular tumor with those of the retroperitoneal residual tumor after chemotherapy, revealed that if the primary tumor did not contain a teratoma component the residual tumor showed only necrosis and/or fibrosis. When the primary tumor contained a teratoma component, mature teratoma was found in 50% (7/14) of the residual tumors.     

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.     

Adjuvant chemotherapy of stage-ii nonseminomatous testicular cancer

85 patients with resected stage II non-seminomatous testicular cancer were treated with adjuvant cisplatin-based chemotherapy. Only one patient developed a relapse 14 months after discontinuation of adjuvant chemotherapy, which was successfully treated with salvage chemotherapy. One patient developed a contralateral testicular tumor 6 years after primary therapy. After a median observation time of 6 years (range 2 months to 13 years) 84 patients are alive without evidence of testicular cancer; one died from an unrelated cause. In conclusion, adjuvant cisplatin-based chemotherapy for resected stage Il nonseminomatous testicular cancer almost always prevents relapse.     

Postchemotherapy retroperitoneal surgery remains necessary in patients with nonseminomatous testicular cancer and minimal residual tumor masses.

PURPOSE: To determine preoperative parameters that predict the histology of specimens obtained by retroperitoneal lymph node dissection (RPLND) in patients with nonseminomatous germ cell cancer (NSGCT) whose residual mass was 相似文献   

The surgery after. . . retroperitoneal lymph node dissection and surgery of the residual masses after chemotherapy for advanced testicular cancer

Thirty-six cases of retroperitoneal lymph node dissections for residual mass after chemotherapy for testicular cancer are reported. In a reference center, the recruitment is modified by the severity of the situations related to very big masses, tumors of poor prognosis and resistant tumors. Lymph node dissection is often atypical and surgery of metastatic residual masses is frequent (13 operations). The 8-year global survival remains stable, over 90%. The 5-year cumulated risk of recurrence is 20%, but these situations can be overtaken.     

Prognostic factors in unselected patients with nonseminomatous metastatic testicular cancer: a multicenter experience.

Between 1981 and 1986, 200 consecutive patients with metastatic nonseminomatous testicular cancer were entered into the Swedish Norwegian Testicular Cancer (SWENOTECA) project from 14 hospitals. The treatment plan was four chemotherapy cycles (cisplatin, vinblastine, and bleomycin) followed by surgical resection of residual tumor masses. After a median observation time of 75 months, the overall 5-year survival rate was 82%. In a univariate analysis, the following parameters influenced the prognosis significantly: the extent of the disease (Medical Research Council [MRC] grouping); the prechemotherapy levels of serum alpha-fetoprotein (AFP), human chorionic gonadotropin (HCG), and lactate dehydrogenase (LDH); the patients' age; the presence of extrapulmonary hematogeneous metastases; and/or particularly large lymph node metastases. Patients fared better when more than 3 weeks elapsed between orchiectomy and start of chemotherapy as compared with those who were treated within this interval. The place of treatment (a large oncology unit v smaller units) also represented a significant prognostic factor for patients with large-volume (LV) and very-large-volume (VLV) disease combined. Multivariate analysis (Cox regression proportional hazards model) performed in all 193 assessable patients showed the following adverse prognostic factors: high-volume metastatic burden, age older than 35 years, prechemotherapy AFP greater than 500 micrograms/L and/or HCG greater than 1,000 U/L, and an interval between orchiectomy and start of chemotherapy of less than 3 weeks. The place of treatment also significantly influenced the final outcome. If patients with LV and VLV disease were combined, the presence of two of the following risk factors represented an additional prognostic factor: AFP greater than 1,000 micrograms/L, HCG greater than 10,000 U/L, liver metastases, brain metastases, bone metastases, retroperitoneal tumor greater than or equal to 10 cm, and mediastinal tumor greater than or equal to 5 cm.     

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

PURPOSE: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.     

Hepatic resection following systemic chemotherapy for metastatic colorectal carcinoma.

Increasingly effective systemic chemotherapy has improved responses in patients with previously unresectable colorectal hepatic metastases. In the future, response to chemotherapy may define a new population of patients that may benefit from hepatic resection. A retrospective review to determine the safety and effectiveness of potentially curative hepatic resection of metastatic colorectal carcinoma after systemic chemotherapy identified 11 such patients with resections between July 1987 and October 1991. Five patients had unresectable disease confined to the liver, two had hepatic and limited extrahepatic metastases, two had hepatic recurrences after previous hepatic metastasectomy, and two had initially resectable liver metastases. These patients were resected after a mean of 8 months of systemic chemotherapy. Complications, usually minor, occurred in five patients (45%). There were no deaths. Three patients are disease free at 15, 18, and 31 months (mean 21) after hepatic resection. Eight patients have recurred with a median time to recurrence of 8 months. Five patients have subsequently died of recurrent disease. This study suggests that hepatic resection following systemic chemotherapy can be performed safely and may benefit selected patients.     

Early resection of residual tumor during cisplatin, vinblastine, bleomycin combination chemotherapy in stage III and bulky stage II nonseminomatous testicular cancer

Sixty consecutive patients with Stage III or bulky Stage II nonseminomatous germinal testis tumors were treated with cisplatin, vinblastine, bleomycin combination chemotherapy (PVB). One patient died of acute toxicity after the first course of therapy, 16 entered complete remission (CR) after two or three inductions, and 36 underwent surgery for removal of residual masses after the third cycle. No residual tumor was found in 16 cases, 10 had mature teratoma, and residual malignant tumor was completely resected in 8 of 10 patients. On the whole, 52 of 59 cases (88%) who completed the therapy entered CR, 34 (58%) with PVB and 18 (30%) with PVB and resection of the residual disease. The major beneficiaries of surgery were patients with bulky metastases (17 of 45, 38%) and those with primary teratocarcinoma (13 of 24, 54%). All of the patients who entered CR received two additional inductions and no maintenance. After a median follow-up period of greater than 3 years, 40 patients (68%) remain continuously disease-free, 1 died in CR, and 3 of the 11 who had relapse were salvaged. All of the 32 patients with lung deposits less than 5 cm and/or lymph node metastases less than 10 cm entered CR after the combined treatment modality, and 29 (91%) are alive disease-free. Also, 20 of 27 patients (74%) with far-advanced disease (lung and lymph node metastases larger than 5 and 10 cm, respectively, extrapulmonary disease) entered CR after PVB and surgery, but only 11 (41%) are continuously disease-free. Early resection of the residual tumor during PVB combination chemotherapy greatly increased the CR rate, but relapses were very frequent in patients with far-advanced disease.     

Sexual function after surgery and combination chemotherapy in men with disseminated nonseminomatous testicular cancer

Between 1978 and 1982 the sexual functions of 54 patients with a nonseminomatous testicular tumor stage II or III were assessed before and after treatment with surgery and combination chemotherapy. Two years after completing therapy 54% of the patients experienced sexual functional disorders. Greatly reduced or absent antegrade ejaculation was reported by 26 patients; 18 of them had been treated with more or less extensive retroperitoneal lymph node dissection, whereas 8 had not. This means that the chemotherapy might be responsible for ejaculatory disorders in 30% of the patients. Only two patients reported a change in the quality of erection; seven patients experienced a decidedly diminished libido, and five patients noticed their orgasm had changed in a negative sense. The appearance of the contralateral testis changed in 21 patients, who showed "atrophy" of this testis. The findings of this study indicate that sexual and ejaculatory disorders in particular are quite common in men treated for a disseminated nonseminomatous testicular tumor. Many of these disorders seem to be owing to causes other than surgical intervention.     

Nontraumatic osteonecrosis after chemotherapy for testicular cancer: a systematic review.

Nontraumatic osteonecrosis is a well-documented late complication of chemotherapy for hematologic malignancies, with prolonged corticosteroid exposure implicated. Reports of this treatment complication in patients treated with chemotherapy for solid tumors are sparse. We reviewed our institutional experience and the published medical literature to explore an association between chemotherapy for testicular cancer and the occurrence of nontraumatic osteonecrosis. Two databases of men with testicular cancer were reviewed. Search of the medical literature included MEDLINE, CANCERLIT, and EMBASE. Two of 107 men with testicular cancer treated with chemotherapy at our center were identified with nontraumatic osteonecrosis. Literature review identified 14 reports describing patients with 39 solid tumors with osteonecrosis after chemotherapy. Of 38 adults, 28 had testicular cancer and 6 had breast cancer. All patients with testicular cancer had received cisplatin, vinblastine, and bleomycin, or bleomycin, etoposide, and cisplatin. Twenty-seven of 28 had received corticosteroids. Diagnosis was subacute in three and delayed a mean of 26 months (range, 12-47 months) in 26. The femoral head was involved in 26 patients, with bilateral involvement in 18. Crude incidence was 1.5% (95% CI, 0.9-2.1). Nontraumatic osteonecrosis is an infrequent but disabling late complication of cancer chemotherapy reported most commonly in adult patients with testicular cancer. Corticosteroid exposure makes this association plausible.     

Postchemotherapy resections of residual masses from metastatic non-seminomatous testicular germ cell tumors

Purpose: To analyse the frequencies of histological findings, predictivefactors for the presence of undifferentiated tumor and variables influencingthe survival of patients with non-seminomatous germ cell tumors who underwentsecondary resection of residual masses after cisplatin-based combinationchemotherapy.Patients and methods: 134 patients with a median age of 26 years(15–47) undergoing at least one surgical intervention at HannoverUniversity Medical School were included. One hundred nine patients hadreceived first-line chemotherapy and 25 underwent surgery after second-linechemotherapy.Results: After first-line chemotherapy the distribution of histologicalfindings was 52% necrosis, 27% differentiated teratoma and21% undifferentiated tumor for 82 patients with marker negative PR(PRm–). Incompletely resected mass and failure to achieved completetumor marker normalisation were significantly associated with the finding ofundifferentiated tumor. Five-year progression-free survival rates accordingto histological findings were 78%, 67% and 66% fornecrosis, differentiated teratoma and undifferentiated tumor. Patients withundifferentiated tumor in the resected specimen routinely receivedpostoperative additional chemotherapy. Factors associated with a worse overallsurvival were progressive disease within three months, persistent AFPelevation prior to surgery, prechemotherapy elevated LDH levels or mediastinallymph node involvement at primary diagnosis. In 8 of 27 patients (30%)undergoing multiple resections at different sites a dissimilar histology wasfound. In the 25 patients operated after salvage chemotherapy undifferentiatedtumor was found in 80%. A five-year survival of 44% compared to80% after first-line chemotherapy was achieved.Conclusions: Resection of residual tumors after first-line chemotherapyremains essential in the treatment of metastatic testicular cancer.Undifferentiated tumor may still be found in 20% of patients despiteachieving PRm– after first-line chemotherapy. Necrosis is found in only50% of marker normalized patients after first-line and approximately30% after second-line chemotherapy. Future studies have to provewhether the combination of clinical prognostic factors and the use ofPET-scanning will allow to spare subsets of patients from secondary resection.     

Fertility after chemotherapy for testicular cancer

Sixty-nine patients with disseminated testicular cancer and no prior retroperitoneal lymphadenectomy treated with cisplatin, vinblastine, and bleomycin with or without doxorubicin were evaluated for semen analysis, serum gonadotropins, and testosterone. Since 1979, 41 men have been prospectively studied. Before treatment 77% were oligospermic, 17% were azoospermic, and only 6.6% could meet requirements for sperm banking. After 2 mo of therapy, 96% were azoospermic. A group of 28 patients treated between 1975 and 1979 were retrospectively evaluated. Normal sperm counts were found in 46% of those studied. Only 17% were azoospermic. Thirty-two percent have impregnated their wives, resulting in 5 healthy babies, 1 spontaneous abortion, and 3 ongoing pregnancies. These results show that (1) significant impairment of spermatogenesis exists before therapy, precluding the possibility of sperm banking in most patients, (2) combination chemotherapy in testicular cancer has substantial effects on gonadal function, rendering almost all patients azoospermic, and (3) a high degree of recovery of spermatogenesis occurs sometime after 2-3 yr from the initiation of treatment.