Clinical parameters that predict histology of postchemotherapy retroperitoneal lymph node mass in testicular cancer

BACKGROUND: Since the advent of cisplatin-based chemotherapy, the majority of metastatic testicular cancers can be cured by chemotherapy followed by retroperitoneal lymph node dissection (RPLND). However, postchemotherapy RPLND confers no therapeutic benefit if the residual mass contains no viable cells. Therefore, to determine which parameters predict a patient's likelihood of having only necrosis in the residual mass, we retrospectively analyzed clinical parameters of patients who underwent postchemotherapy RPLND. METHODS: Data from 27 patients with metastatic testicular cancer were analyzed. The histology of the primary tumor was seminoma in 11 cases and non-seminoma in 16 cases. All of the patients with non-seminoma showed a normalization of tumor markers after chemotherapy. Analysis of clinical parameters included data for the initial histology, pretreatment tumor marker levels, postchemotherapy retroperitoneal mass size, and the histology of the dissected RPLNs. RESULTS: Histological examination of dissected RPLNs showed residual tumor in 27% of seminoma patients and 38% of non-seminoma patients. In seminoma patients, no viable cells were found in all six patients with pretreatment lactate dehydrogenase (LDH) levels below 7.5 times the upper limit of normal, or in all five of the patients with postchemotherapy RPLNs less than 2.5 cm. In non-seminoma patients, no viable cells were found in nine of 10 patients with pretreatment alpha-fetoprotein (AFP) levels less than 2700 ng/mL, or in eight of nine patients with residual mass less than 2.5 cm. CONCLUSIONS: Both postchemotherapy RPLN mass size and pretreatment tumor marker levels are possible predictors for necrosis of the residual mass in testicular cancer patients.     

Prognostic analysis of Japanese men with metastatic germ cell tumors showing favorable response to bleomycin, etoposide and cisplatin as first-line chemotherapy

The objective of this study was to evaluate the efficacy of first-line bleomycin, etoposide and cisplatin (BEP) chemotherapy in Japanese patients with metastatic germ cell tumors (GCTs). Between 1996 and 2006, 88 male patients with metastatic GCTs were treated with first-line BEP at our institution. Of these 88, 47 (16, seminoma; 31, nonseminoma), who did not receive high-dose chemotherapy following BEP because of the normalization of serum tumor markers, were included in this study. The primary site was the testis in 42 patients, retroperitoneum in 3, and mediastinum in 2. The full-dose regimen used for BEP consisted of cisplatin 20 mg/m2 on days 1 to 5, etoposide 100 mg/m2 on days 1 to 5, and bleomycin on days 2, 9 and 16. Therapeutic outcome was assessed according to several clinicopathological parameters. Following 2 to 4 cycles of BEP (median, 4 cycles), alpha-fetoprotein, beta-human chorionic gonadotropin and lactate dehydrogenase were normalized in all 47 patients. Eighteen patients (38.3%) achieved a complete response (CR) after BEP alone, while BEP resulted in a partial response and stable disease in the remaining 23 (48.9%) and 6 (12.8%), respectively. In addition, surgical resection of the residual tumors following BEP was performed in 15 patients, of whom 12 (80.0%) and 3 (20.0%) achieved pathological and surgical CR, respectively. At a median follow-up of 27 months, all patients were alive; however, disease recurrence occurred in 5 (seminoma, 1; nonseminoma, 4), and all these 5 were subsequently treated with high-dose chemotherapy as salvage therapy. In this series, 1-, 3- and 5-year recurrence-free survival rates were 95.0, 91.4 and 79.2%, respectively, and, there was no significant difference in recurrence-free survival between patients with seminoma and those with nonseminoma. These findings suggested that patients with metastatic GCTs, regardless of histological subtype (i.e., seminoma or nonseminoma), who showed favorable response to first-line BEP chemotherapy, could achieve an excellent prognostic outcome.     

Late relapse of testicular germ cell neoplasms: a descriptive analysis of 122 cases

PURPOSE: The problem of late relapse of testicular germ cell tumor (GCT) is poorly understood. No more than approximately 300 cases have been reported to date. It appears that late relapse (L/R) of GCT involves a more aggressive biology than virginal GCT. In the present study we increased the understanding of L/R by analyzing these events in a large patient sample. MATERIALS AND METHODS: Late relapse was defined as recurrence of disease more than 2 years after completion of primary treatment. A total of 122 patients (50 with pure seminoma and 72 with nonseminoma) were retrospectively studied. Several parameters were analyzed including age, clinical stage, treatment at primary presentation, occurrence of prior early relapse, interval to L/R, tumor markers, site of relapse, and mode and outcome of L/R treatment. Possible effects of various clinical parameters on treatment results were studied by multivariate statistical analysis. RESULTS: Median age at first presentation was 34 years and 26.5 years in patients with seminoma and nonseminoma, respectively. The intervals to L/R were 42 months (range 25 to 276) in seminoma and 64.5 months (range 28 to 216) in nonseminoma. A total of 75% of nonseminomas but only 20% of seminomas had disseminated disease at first presentation, while 51 patients with nonseminoma had initially received chemotherapy. alpha-Fetoprotein was increased in 45 patients (of 59 eligible) with nonseminoma at L/R, human chorionic gonadotropin in 12 cases. alpha-Fetoprotein levels greater than 100 U/l indicated poor prognosis. Topographically relapses were mainly confined to lymph nodes of the abdomen, chest and neck. Of 72 patients with nonseminoma cure failed in 37 in contrast to only 6 patients with seminoma (of 48 eligible). Inclusion of surgery increased the chance of cure (RR 4.0, 95% confidence interval 0.9-18.5). CONCLUSIONS: Late relapses of GCT are biologically and clinically distinct from virginal GCT. These events occur in nonseminoma and seminoma, but clinical features are quite different in the 2 groups. Increase of alpha-fetoprotein is typical in late relapsing nonseminoma and levels of more than 100 U/l appear to indicate poor prognosis. Anatomically L/R presents as lymphadenopathy of abdomen, chest or neck. Treatment should include surgery in nonseminoma. Seminomas and otherwise chemotherapy naive cases might respond to chemotherapy only. Particular risk groups for late relapse are nonseminoma with prior early relapse, patients receiving chemotherapy for disseminated disease at first presentation and those with pure teratoma. These latter subgroups should be followed with annual health examinations for at least 10 years.     

Results of surgical treatment for pimary germcell tumors of the mediastinum

Primary germ cell tumors of the mediastinum are relatively rare with complicated backgrounds including various pathology with mixed types and characteristics. The primary treatment for mature teratoma is surgical resection. It is sometimes difficult because of the giant tumor size and severe adhesion. Pneumonectomy is sometimes necessary to resect a tumor completely. In elderly patients, mature teratomas possibly involve epithelial malignant transformation. Cisplatin-based chemotherapy plays an important role in the treatment of both seminoma and nonseminoma. In our institution, 10-year survival rates are 91.7% for seminoma and 53.0% for nonseminoma. In terms of survival, nonseminoma has a worse prognosis compared with seminoma. Cases with pleural dissemination or metastasis also have a worse prognosis, with a median survival time of 5 months. The reasons for the poor prognosis in nonseminoma are the inclusion of patients in whom chemotherapy is not effective and those with advanced disease with metastasis. It would be possible to improve the prognosis with the establishment of a standard treatment regimen, development of new agents for the treatment of tumors resistant to current chemotherapy regimens, and detection of more tumors in the early stage.     

Size and status of metastases after inductive chemotherapy of germ-cell tumors

Summary Secondary resection of metastases remaining after inductive chemotherapy of advanced germ-cell tumors has thus far been obligatory. The absence of malignant components in one-third of all residual tumors and the high risk of the operation have led several authors to reconsider the criteria for this approach. In a retrospective study of 153 cases (127 evaluable) we investigated the histology of the primary tumor and the size of the residual tumor with regard to residual histology and outcome. Patients were divided into the following three groups according to the histology of the primary tumor: group I, pure seminoma (16 patients); group II, nonseminoma without teratoma (32 patients); and group III, nonseminoma with teratoma (79 patients). Among the 16 purely seminomatous tumors, the residual masses ranged from 2 to 12 cm; 12 consisted of necrotic tissue only, 3 contained malignant germ-cell elements, and 1 contained adult teratoma. The residuals of primarily teratoma-free nonseminomas measured 2–16 cm; the smallest residual tumor containing active malignant elements measured 4 cm, and the diameter of the largest necrotic residue was 6 cm. Four residuals contained mature teratoma. The size of residuals from teratomatous primary tumors was 3–24 cm; the smallest malignant tumor measured 5 cm, and the diamter of the largest purely necrotic mass was 8 cm. According to our results, a secondary operation may be omitted if the residual mass of a primary seminoma is smaller than 5 cm or if that of a primary nonseminoma without teratoma is less than 3 cm in diameter. However, firm conclusions can be drawn only after these criteria have been confirmed by an ongoing multicenter trial.     

Oncological Outcomes in Japanese Men Undergoing Orchiectomy for Stage I Testicular Germ Cell Tumor

Background

The objective of this study was to retrospectively review oncological outcomes in patients with stage I testicular germ cell tumor (GCT).

Patients and Methods

This study included 265 consecutive Japanese men undergoing orchiectomy for stage I testicular GCT, and a retrospective review of their records was performed.

Results

Of these 265 patients, 192 and 73 were pathologically classified with seminoma and nonseminoma, respectively. Prophylactic radiation and chemotherapy were performed in 62 patients with seminoma and 6 with nonseminoma, respectively. Disease recurrence occurred in 12 seminoma patients, of whom 11 had not received prophylactic radiation therapy; however, all 12 achieved a complete response to bleomycin, etoposide and cisplatin therapy. Of the nonseminoma patients, 19 experienced disease recurrence and were then treated with bleomycin, etoposide and cisplatin followed additionally by the surgical resection of residual tumors and salvage chemotherapy in 7 and 4, respectively. There was no cancer-specific death in the 265 patients, and 5-year recurrence-free survival rates in patients with seminoma and nonseminoma were 92.6 and 72.8%, respectively. Furthermore, following factors appeared to be significantly associated with recurrence-free survival in these patients: age, T classification, microvascular invasion and adjuvant therapy for those with seminoma, and microvascular invasion for those with nonseminoma.

Conclusions

Despite a generally favorable prognosis in Japanese men with stage I testicular GCT, intensive follow-up or prophylactic therapy should be considered for men with possible risk factors of disease recurrence.Key Words: Stage I testicular germ cell tumor, Seminoma, Nonseminoma     

Management of advanced germ-cell tumors of the testis

Advanced tumors of the testis are curable. Standard treatment includes chemotherapy with a combination of bleomycin, etoposide and cisplatin, followed by surgical resection of residual tumor. The number of cycles of chemotherapy needed depends on prognostic factors such as the primary site, histology, presence of visceral metastases, and serum levels of tumor markers. Patients with a favorable risk profile receive three cycles of chemotherapy, and those with increased risk receive four cycles. After chemotherapy, resection of all residual local disease and systematic retroperitoneal dissection of bulky lymph-node disease are mandatory for patients with nonseminoma germ-cell tumors. In patients with seminoma, surgery is required when residual disease is either bulky or functional on (18)fluorodeoxyglucose-PET scan. When complete resection of necrosis, teratoma and/or active germ-cell cancer has been done, no further treatment is needed. The consequences of therapy are complex: treatment could affect fertility, sexuality, metabolic status and renal and neurological function. Secondary malignancies are reported, as well as contralateral germ-cell tumors. Owing to the complexity of treatment and the multidisciplinary approach required, patients with advanced germ-cell tumors should be managed in high-volume centers with experience of treating large numbers of patients.     

蒙古族睾丸肿瘤35例临床分析

目的:提高对蒙古族睾丸肿瘤的诊断和治疗水平。方法:多中心回顾性分析1990年2月~2004年12月35例蒙古族睾丸肿瘤患者的临床资料。结果:主要症状为无痛性睾丸肿大或结节。平均延误诊断(40.03±53.45)周,16例(45.7%)延迟诊断6个月~5年。睾丸肿瘤病理类型:精原细胞瘤21例(60%),占生殖细胞瘤的67.7%(21/31),非精原细胞瘤10例(28.6%),恶性淋巴瘤2例(5.7%),神经纤维瘤和平滑肌瘤各1例(5.7%)。生殖细胞瘤I期22例,II期2例,III期5例。治疗手段以睾丸肿瘤根治性切除和放疗及化疗为主。随访29例睾丸恶性肿瘤患者2个月~10年,其中精原细胞瘤20例,3、5年生存率分别为95.0%、95.0%;非精原细胞瘤7例,3、5年生存率分别为57.1%、42.8%;2例恶性淋巴瘤患者,1例健在,1例化疗中。结论:本组蒙古族睾丸肿瘤患者精原细胞瘤比例高于一般人群,平均延误诊断时间较长。非精原细胞瘤患者3、5年生存率均低于精原细胞瘤患者。睾丸肿瘤知识的宣教和诊疗技术的提高,有助于改善睾丸肿瘤患者的疗效和预后。     

Role of postchemotherapy surgery in the management of patients with liver metastases from germ cell tumors

OBJECTIVE: To evaluate the role of postchemotherapy adjunctive surgery in patients with liver metastases from germ cell cancer (GCT). PATIENTS AND METHODS: Forty-three male patients with nonseminoma were treated in different multicenter treatment protocols between 1990 and 1999, and they underwent hepatic surgery. The results of postchemotherapy surgical resection, histologic findings found during postchemotherapy surgery, and prognostic factors for survival were assessed. RESULTS: Thirty-five of 43 patients (81%) were initially diagnosed with liver metastases and advanced GCT, and 8 patients (19%) presented with metachronous liver metastases after a median interval of 16 months (range, 6-103 months). Twelve patients (28%) had isolated liver metastases after completion of chemotherapy, while 31 patients (72%) had additional residual extrahepatic tumor masses. Liver surgery included tumor excision or segmentectomy in 32 patients (74%) and hepatectomy (right/left) or resection of multiple segments in 11 patients (26%). Histologic analysis of postchemotherapy resected residua yielded necrosis in 67%, teratoma in 12%, and viable cancer in 21%. Additional resections at other sites have been performed in 31 patients revealing necrosis in 61% (n = 19), teratoma in 29% (n = 9), and vital carcinoma in 10% (n = 3). In 39% of patients, histologic findings differed among liver and other resection sites. Refractoriness to chemotherapy was associated with a shorter survival after surgery, and a trend was seen in patients with elevation of AFP. CONCLUSION: The high rate of viable cancer and teratoma found in liver specimens, differing histologic results at residual tumor locations, and the high survival rate achieved support a multidisciplinary approach including resection of liver masses since no accurate selection of patients can narrow the use of surgery.     

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.     

Predictors of residual mass requiring surgical resection after chemotherapy of stage III testicular cancer. A prospective study.

In a prospective study, 63 patients with histopathologically proved Stage III nonseminomatous testicular cancer (NSTC) were analyzed to predict the need for surgical resection of residual masses after cis-platinum-based chemotherapy. Of these 63 patients, 23 (37%) had residual masses after cis-platinum-based chemotherapy requiring surgical resection. Of the 23 patients undergoing surgical resections for their residual masses, 18 patients (78%) had matured teratoma, 3 (13%) had fibrosis with necrosis, and 2 (9%) had residual tumors. Twenty of the 23 (91%) patients with residual disease had either teratomatous elements in primary tumor or bulky metastatic disease at the time of initial chemotherapy. Two patients had incomplete resection of the metastatic disease containing teratoma and required additional resection of recurrent growing matured teratomas. We conclude that teratomatous elements in primary tumor having also bulky metastatic disease are strong predictors of residual disease after initial chemotherapy requiring surgery (21 of 23 or 91%).     

Predictors of residual mass histologyafter chemotherapy for advanced testis cancer

The records of 15 patients with Stage B3 or B2/C germ cell testis tumors who underwent full surgical debulking of a residual mass after completion of chemotherapy were reviewed retrospectively to look for predictors of residual mass histology. The density, character, and change in volume of the retroperitoneal mass on computerized tomography before and after chemotherapy were compared with the histology in the primary tumor and in the residual mass. One of 6 patients without teratoma in the primary tumor had a 97 percent reduction in the mass which contained residual teratoma. Two patients with residual seminoma had a 50 percent decrease in tumor volume, and both patients died of tumor progression despite salvage chemotherapy. Two patients with pure seminomas had only residual fibrosis in masses that decreased in volume by 77 and 75 percent, respectively. One of these masses was discrete and the other was diffuse. Seven of 9 patients (78%) with teratoma in the primary tumor had either teratoma (4 of 9, 44%) or carcinoma (3 of 9, 33%) in the residual mass, and the change in mass volume ranged from a 93 percent decrease to a 540 percent increase in size. All 7 patients with residual teratoma and/or carcinoma remain free of disease after observation or further chemotherapy. For the entire series, the mass density and character did not correlate consistently with the primary tumor or residual mass histology. Residual fibrosis alone or teratoma and/or carcinoma were seen with least (0 to 50%) and greatest (more than 90%) decreases in mass volume.     

The role of surgery following chemotherapy in stage III germ cell neoplasms

After curative chemotherapy 58 patients with metastatic germinal tumors and 2 with extragonadal germinal tumors underwent an operation either to confirm a clinical complete response or to remove a residual mass. Biomarker status was converted to negative in all patients. Retroperitoneal lymphadenectomy was done in 22 patients after a complete clinical response was achieved and in 23 after an apparent complete response was achieved except for a residual retroperitoneal mass. Thoracotomy was done for a residual mass in 13 patients, while 2 underwent bilateral thoracotomy. Scarring was found in 25 patients (42 per cent), teratoma in 14 (23 per cent) and active tumor in 17 (28 per cent). One patient with scarring and primary seminoma died of disseminated seminoma, while 1 with primary teratocarcinoma died of disseminated disease, for a false negative rate of 3 per cent. Four patients with a residual mass showed unexpected findings: 2 had granulomas in the lung, 1 had carcinoid of the lung and 1 had retroperitoneal neurofibroma. Thus, there was a 7 per cent incidence of a mass being other than scar, teratoma or residual tumor. There was 1 operative death and 10 deaths of tumor, for an 18 per cent death rate. Of the 17 patients with active tumor 9 responded to salvage chemotherapy with stable complete remission and a minimum followup of 18 months. In addition to the 60 patients the advanced disease in 10 was surgically debulked after failure of chemotherapy and this procedure was followed by salvage chemotherapy. All 10 patients died, with a median survival of 7 months. The lack of responsiveness to chemotherapy was not improved by incomplete removal of tumor.     

睾丸生殖细胞肿瘤中CD117的表达及其对精原细胞瘤的鉴别意义

目的:探讨CD117在睾丸生殖细胞肿瘤中的表达及其在鉴别睾丸精原细胞瘤和非精原细胞瘤中的价值和生物学意义。方法:采用CD117单克隆抗体对74例睾丸生殖细胞肿瘤和20例正常睾丸组织进行免疫组化染色,测定不同组织中CD117表达的阳性率、染色密度和染色强度,采用免疫反应积分(IRS)对结果进行分析比较。结果:74例睾丸生殖细胞肿瘤中,45例(60.8%)CD117表达阳性,IRS为(3.89±3.41)分。32例精原细胞瘤中,CD117阳性表达31例,阳性率为96.9%,IRS(6.82±2.76)分,表达部位以细胞膜为主;11例混合性精原细胞瘤中,CD117阳性表达10例,阳性率为90.9%,均为在精原细胞瘤成分中呈弱阳性表达,IRS为(1.25±0.42)分;31例非精原细胞瘤中CD117表达阳性者仅4例,阳性率为12.9%,并且均为胞质内弱阳性染色,IRS仅为(0.60±0.16)分。不同组织来源的睾丸生殖细胞肿瘤两两之间CD117表达差异均有统计学意义(P<0.05)。20例正常睾丸组织CD117均为阳性表达,IRS为(7.30±1.89)分。结论:CD117在睾丸精原细胞瘤细胞膜上有较为特异的表达,其在睾丸生殖细胞肿瘤中的表达对于鉴别精原细胞瘤和非精原细胞瘤有重要价值。     

Postchemotherapy retroperitoneal residual mass in infantile yolk sac tumor

BACKGROUND: Persistent postchemotherapy retroperitoneal residual mass with normalization of alpha-fetoprotein (AFP) in infantile yolk sac tumor is rare. METHODS/RESULTS: A 38-month-old boy with recurrent yolk sac tumor was treated with cisplatin-based combination chemotherapy. After chemotherapy, the retroperitoneal lymph node metastasis, 7 x 6 cm in size, decreased to 2 x 2 cm. Serum AFP levels returned to normal. The retroperitoneal residual mass was resected and histologically showed complete necrosis without viable cancer cells. CONCLUSION: The patient has remained free of disease for 36 months after operation.     

Clinicopathological features predicting nodal metastasis of testicular seminoma: results from 100 cases in a single institute

BACKGROUND/AIMS: To investigate the clinical and pathological features which predict nodal metastasis and/or the prognosis of testicular seminoma and to evaluate the current treatment strategy in a single institute. METHODS: We retrospectively analyzed 100 patients who had been pathologically diagnosed as having testicular seminoma in our institute. Ninety-one patients (91%) had stage I disease, 9 patients (9%) were stage II and none stage III. The median follow-up was 63.2 months (range 0.5-249). RESULTS: The duration between the tumor recognition and the first outpatient visit ranged from 0 to 144 weeks, with a median of 5 weeks, which did not influence the clinical stage. The tumor diameter and the preoperative serum lactate dehydrogenase (LDH) level were the significant predictors of stage II disease. Following orchiectomy, 68 patients (74.7%) with stage I disease received radiotherapy. Only 1 patient who had not received adjuvant radiotherapy died from the recurrent disease. The 5-year survival was 100% for the irradiation group but 95% for the surveillance group, although the difference was not statistically significant. All the stage II patients were successfully treated with chemotherapy following orchiectomy. CONCLUSION: The maximum tumor diameter and the preoperative serum LDH level were the significant predictors of nodal metastasis. Adjuvant radiotherapy in patients with stage I seminoma did not influence the survival. Systemic chemotherapy promised good survival for the seminoma, even with nodal metastasis, in this series. Our results support the good prognosis of testicular seminoma with the current treatment strategy.     

Delayed surgical resection of central nervous system germ cell tumors

OBJECTIVE: To determine the value of delayed surgical resection in patients with central nervous system germ cell tumors who exhibit less than complete radiographic response despite declining serum and cerebrospinal fluid (CSF) tumor markers after initial chemotherapy. METHODS: We retrospectively analyzed 126 patients enrolled on two international multicenter clinical trials (the First and Second International Central Nervous System Germ Cell Tumor Studies) for patients with newly diagnosed central nervous system germ cell tumors. After at least three cycles of chemotherapy, 10 of these patients underwent delayed surgical resection owing to evidence of residual radiographic abnormalities despite declining or completely normalized serum and CSF levels of alpha-fetoprotein and human chorionic gonadotropin. RESULTS: Eight of these patients demonstrated nongerminomatous germ cell tumor elements at the time of initial diagnosis. In these patients, either serum or CSF tumor markers were elevated initially. Two patients demonstrated pure germinomas with normal levels of serum and CSF tumor markers. After chemotherapy, radiographic evaluation revealed a partial response in seven patients, a minor response in one patient, and stable disease in two patients. All 10 patients had either normal or decreasing levels of serum and CSF tumor markers before second-look surgery. At delayed surgical resection, 7 of the 10 patients underwent gross total resection, and 3 patients underwent subtotal resection of residual lesions. Pathological findings at second-look surgery demonstrated three patients to have mature teratomas, two with immature teratomas, and five with necrotic or scar tissue alone. To date, 7 of the 10 patients have had no recurrence during an average follow-up time of 36.9 months (range, 3-96 mo). Three of four patients with nongerminomatous germ cell tumors who had tumor markers that were decreased, but not normalized, before second-look surgery eventually developed tumor dissemination/progression, and they required subsequent radiation therapy despite having teratoma or necrosis/scar tissue at delayed surgery. In contrast, three of four patients with nongerminomatous germ cell tumors and completely normalized markers did not progress and did not require radiation therapy. CONCLUSION: Delayed surgical resection should be considered in patients with central nervous system germ cell tumors who have residual radiographic abnormalities and normalized tumor markers, because these lesions are likely to be teratoma or necrosis/scar tissue. However, second-look surgery should be avoided in patients whose tumor markers have not normalized completely.     

Efficacy of routine follow-up after first-line treatment for testicular cancer

To define guidelines for the follow-up management of patients treated for testicular germ cell tumor this study assessed characteristics of patients with recurrent disease. The charts of 505 patients with testicular cancer treated and followed-up at the University Medical Centre Nijmegen between 1982–2000 were reviewed retrospectively. In 42 patients disease recurrence was found during routine follow-up. In a subset of patients no recurrences were seen after first-line treatment: (a) pathological stage IIa nonseminoma patients who were adjuvantly treated with chemotherapy and (b) histologically confirmed complete responders after primary chemotherapy. Furthermore, in low-stage disease no intra-abdominal recurrences were seen in (a) pathological stage I nonseminoma patients and (b) low-stage seminoma patients who received radiotherapy. The risk of recurrent testicular cancer depends on primary therapy and efficacy of it; these results indicate a limited role for follow-up in pathological stage II nonseminoma patients adjuvantly treated with chemotherapy and in histologically confirmed complete responders after chemotherapy. Abdominal computed tomography does not appear necessary in routine follow-up of patients treated for low-stage testicular cancer.     

Salvage surgery of chemorefractory germ cell tumors with elevated tumor markers

PURPOSE: We evaluated the prognostic criteria for salvage surgery in patients with persistent marker elevation after chemotherapy for metastatic germ cell tumors. MATERIALS AND METHODS: Of 125 men who underwent post-chemotherapeutic resection of residual tumors 30 had persistent marker elevation at surgery. This group was subdivided into 17 patients with no evidence of disease, 7 dead of disease and 6 others. Outcome analysis was performed in the subgroups with regard to preoperative and postoperative parameters. Mean followup was 120.3 months (range 1 to 228) after surgery. RESULTS: Of the 30 patients 17 (57%) with persistently elevated tumor markers after chemotherapy were long-term survivors after salvage surgery. Overall persistent viable cancer and teratomatous elements were identified in 64% and 11% of cases, respectively. Significantly more patients died of disease who had a poor prognosis according to International Germ Cell Cancer Collaborative Group guidelines. Embryonal carcinoma was the predominant initial histology in this group and residual disease was more often located at various sites, for example the viscera, with a lower chance of complete surgical resection. Marker status before surgery, and chemotherapeutic pretreatment and postoperative histological findings did not differ significantly in patients with no evidence of disease and those dead of disease. CONCLUSIONS: Salvage surgery results in long-term success in greater than 50% of patients. Complete resection is the most important single parameter for a favorable outcome. Even patients with visceral metastasis benefit from surgery. Our data do not justify omitting surgery in certain subgroups.     

Postchemotherapy retroperitoneal surgery remains necessary in patients with nonseminomatous testicular cancer and minimal residual tumor masses: Oldenburg J,Alfsen GC,Lien HH,Aass N,Waehre H,Fossa SD,Department of Medical Oncology,The Norwegian Radium Hospital,Montebello, Oslo,Norway.

J Clin Oncol 2003;21:3310–7PurposeTo 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 ≤20 mm in diameter after modern cisplatin-based induction chemotherapy.Patients and methodsEighty-seven patients with metastatic NSGCT underwent RPLND after having received cisplatin- or carboplatin-based induction chemotherapy. In all patients, the largest diameter of the residual mass on the transaxial plane was ≤20 mm, as assessed by abdominal computed tomography (CT) immediately before RPLND.ResultsComplete fibrosis or necrosis was found in 58 patients (67%), teratoma was found in 23 patients (26%), and vital malignant germ cell tumor was found in six patients (7%), including one patient with rhabdomyosarcoma in the RPLND specimen. In five of the six latter patients, the residual lesion was ≤10 mm at pre-RPLND CT. No pre- or postchemotherapy clinical or radiologic parameter was identified that significantly predicted the histology of the residual mass.ConclusionOne-third of retroperitoneal postchemotherapy lesions ≤20 mm contained residual vital tumor tissue, despite modern chemotherapy regimens. Therefore, postchemotherapy RPLND remains necessary in patients with minimal-size residual lesions to facilitate easy and safe follow-up and initiate additional therapy as early as possible, thus avoiding recurrences.