Extragonadal and poor risk nonseminomatous germ cell tumors. Survival and prognostic features.

One hundred forty-nine patients with poor risk nonseminomatous germ cell tumors (NSGCT) treated between 1975 and 1988 were studied. Patients were considered poor risk if they had an extragonadal primary site or testicular NSGCT with low predicted probability of achieving a complete response (CR). Primary sites were the testis (99 patients), retroperitoneum (18 patients), and mediastinum (32 patients). Patients with mediastinal NSGCT had lower human chorionic gonadotropin (HCG) (P less than 0.0001) and lactate dehydrogenase (LDH) levels (P less than 0.0001), and more frequent yolk sac elements (P = 0.002). CR rates were 38% for mediastinal, 61% for retroperitoneal, and 38% for testicular primary sites. Mediastinal NSGCT patients more frequently required resection of residual malignancy to attain a CR (6 of 12). Mediastinal NSGCT had the worst event-free survival (P = 0.02). Cox regression analysis identified brain or liver metastases as the most important predictor of event-free survival in poor risk patients. Retroperitoneal NSGCT often have a poor outcome due to advanced presentation, but the likelihood of a CR to therapy can be predicted using criteria applicable to testicular primary tumors. Therefore, not all retroperitoneal NSGCT are poor risk, and retroperitoneal tumors are probably of occult testicular origin. Mediastinal NSGCT have distinct clinical and pathologic features, do not respond as well to chemotherapy, relapse more frequently, and have the worst survival. The likelihood of a CR cannot be predicted using criteria developed for primary testicular tumors, suggesting that mediastinal primary NSGCT is a distinct clinical entity.     

Is full bilateral retroperitoneal lymph node dissection always necessary for postchemotherapy residual tumor?

BACKGROUND: Traditionally, postchemotherapy (PC) surgery for metastatic nonseminomatous germ cell tumor (NSGCT) has used a full bilateral retroperitoneal lymph node dissection (RPLND) from the crus of the diaphragm to the bifurcation of the common iliac arteries, from ureter to ureter. With the primary landing zone well defined in low-volume retroperitoneal disease, the authors performed modified dissections in the PC setting in a select population; and, herein, they report disease outcome. METHODS: From 1991 to 2004, a retrospective review of the testicular cancer database at the authors' institution was performed to identify patients with NSGCT, normal serum tumor markers after cisplatin-based chemotherapy, and residual retroperitoneal tumor who underwent modified PC-RPLND. All patients had metastatic disease at initial presentation that was limited to the primary landing zone (left or right). RESULTS: One hundred patients were identified, including 43 who underwent a right modified template, 18 patients who underwent a left full modified template, and 39 patients who underwent a left modified template. Pathology revealed cancer in 2% of patients, teratoma in 62% of patients, and necrosis in 36% of patients. The 2- and 5-year disease-free survival rate was 95%, and the median follow-up was 31.9 months (range, 1-152 months). Four patients developed recurrent disease with a median time to recurrence of 8.25 months (range, 6-11 months). All recurrences were outside the boundaries of a full bilateral RPLND. CONCLUSIONS: Selected patients at PC surgery can be managed with modified PC-RPLND.     

Bilateral testicular germ cell tumors: twenty-year experience at M. D. Anderson Cancer Center

BACKGROUND: The incidence of testicular carcinoma in the United States has increased significantly over the last two decades. Germ cell tumors form the majority of malignant testicular tumors. With advances in diagnosis and therapeutic approaches, germ cell tumors are now highly sensitive to treatment, providing long-term survival. It has been speculated that the incidence of bilateral germ cell tumors may increase due to the improved survival of patients with unilateral germ cell tumors. In this report, the authors present a study of bilateral germ cell tumors of the testis in men who were treated at The University of Texas M. D. Anderson Cancer Center over a 20-year period with emphasis on their incidence, histologic features, and clinical features. METHODS: Between 1978 and 1999, 2431 patients with testicular germ cell tumors were treated at The University of Texas M. D. Anderson Cancer Center. Among these, 24 patients with bilateral germ cell tumors were identified. Clinical records and all available pathology slides of the tumors were reviewed. RESULTS: The overall incidence of bilateral germ cell tumors in the patients with testicular germ cell tumors was 1% (24 of 2431 patients). The incidence was 1.8% (14 of 776 patients) in patients with seminoma and 0.6% (10 of 1655 patients) in patients with nonseminomatous germ cell tumors. Patients with seminoma who were age 相似文献   

Long-term follow-up in patients with bilateral testicular germ cell tumors: a report of ten cases

Several risk factors have been identified for the development of testicular germ cell tumors with history of a testicular tumor in the contralateral testis being one of the most important factors; the incidence of bilateral tumors in large series ranges from 2% to 5%. The aim of this study was to evaluate the results of long-term follow-up in patients with bilateral testicular germ cell tumors. In a series of 247 patients with testicular germ cell tumors treated at Kobe University Hospital between 1966 and 1995, 10 patients (4.0%) had bilateral testicular tumors. Clinicopathological data are presented for these 10 patients and the literature is reviewed. Of the 10 patients with bilateral tumors, 2 had a simultaneous bilateral tumor, and in the remaining 8 patients, the second tumor was diagnosed after an interval of 2 months to 16 years. All 10 patients were diagnosed as stage I or II in both the initial and secondary tumors. Five patients had identical histological findings in both tumors. Eight patients were free of disease after a median observation period of 13.5 years, and the remaining 2 patients died of metastatic disease. The present results are essentially consistent with previous studies analyzing the features of bilateral testicular germ cell tumors. Considering these findings, close clinical follow-up and patient education appeared to be an appropriate follow-up strategy in patients with testicular tumors, as the secondary tumors can generally be cured with current treatment regimens. Received: August 7, 1998 / Accepted: January 5, 1999     

Positive expressions of N-acetylglucosaminyltransferase-V (GnT-V) and beta1-6 branching N-linked oligosaccharides in human testicular germ cells diminish during malignant transformation and progression

N-acetylglucosaminyltransferase-V (GnT-V) is an enzyme that catalyzes beta1-6 branching of N-acetylglucosamine on asparagines (N)-linked oligosaccharides of cell proteins. We examined the implication of GnT-V and beta1-6 branching N-linked oligosaccharide expression in human testicular germ cells during malignant transformation and cancer progression. We analyzed immuhistochemically orchiectomy specimens of 130 patients with testicular germ cell tumors (TGCT) using anti-GnT-V monoclonal antibody, and compared GnT-V expression with clinicopathological features. N-linked oligosaccharide structural analysis was also performed to confirm the oligosaccharide profile produced by GnT-V. GnT-V was positive in all normal testis samples. This positive incidence declined in TGCT according to clinical stage; 16/71 (22.5%) in stage I, and 3/59 (5.1%) in stage II/III (p=0.015, chi(2) test). When divided into pathological subtypes, GnT-V positive incidences in stage I seminoma, stage II/III seminoma, stage I non-seminomatous germ cell tumor (NSGCT), and stage II/III NSGCT were 3/43 (7%), 0/22 (0%), 13/28 (46.4%), and 3/37 (8.1%), respectively. In stage I NSGCT, patients with GnT-V-negative tumor samples were at a significantly higher risk of recurrence than those with GnT-V-positive tumors (p=0.015, log-rank test). N-linked oligosaccharide structural analysis revealed that a normal testis has three kinds of beta1-6 branching N-linked oligosaccharides, all of which are downregulated in TGCT tissues. These results suggest that GnT-V and beta1-6 branching N-linked oligosaccharide expressions are downregulated during carcinogenesis and progression of human TGCT. GnT-V may be a promising recurrence predictor for stage I NSGCT.     

Results of treatment of non seminomatous germ cell tumours; 122 consecutive cases in the West of Scotland, 1981-1985

Between January 1981 and December 1985, 122 patients with non-seminomatous germ cell tumours (NSGT) were seen at a regional referral centre. Of these, a total of 98 patients received chemotherapy for metastatic disease. Treatment was given within collaborative EORTC Urology group studies, all of which involved cis-platin-containing schedules. Ninety patients had tumours of testicular origin, and their 2 year actuarial survival rate is 91%; 8 had tumours of extragonadal origin and their 2 year actuarial survival is 25%. Patients with testicular tumours were subdivided by volume of metastatic disease using the recommendations of the Testicular Cancer Subgroup of the MRC Urological Cancer Working Party and survival was significantly worse in the group with very large volume metastatic disease (VLVM, 57%) compared with the groups with large volume metastases (LVM, 100%) and small volume metastases (SVM, 98%). There were 31 patients with Stage I disease at presentation; of these 6 were treated by prophylactic abdominal radiotherapy and 25 were managed by a policy of surveillance only. Seven of these Stage I patients (23%) relapsed with metastatic disease (median 8 months); all have been successfully treated with chemotherapy. These data confirm that the majority of patients now presenting with metastatic NSGCT are curable with chemotherapy, but that a small proportion with very large volume metastases or extragonadal tumours require alternative chemotherapy schedules.     

Late recurrences in long-term survivors of germ cell neoplasms

Patients with germ cell neoplasms who are in complete remission 2 years after treatment have a very high probability of cure, and reports of recurrences occurring after 2 years are rare. Of 81 testicular cancer patients treated for advanced disease at Vanderbilt University between 1970 and 1985, five developed a recurrent or metachronous germinal tumor 58 to 195 months after the initial treatment. Only two of these patients had received prior cisplatin-based combination chemotherapy. Four patients had unfavorable prognostic features when tumor recurrence was diagnosed. All five patients responded to salvage chemotherapy, although there were only two complete responses. The extent of disease was a significant factor in predicting response to salvage therapy. The possible mechanisms of development of a late recurrence of germinal neoplasms include the following: (1) malignant degeneration of mature teratoma to germinal malignancy; (2) growth of an occult testicular tumor not eliminated by chemotherapy due to the presence of a blood-testicular barrier; (3) development of a second primary germ cell neoplasm; or (4) late relapse due to persistent microscopic viable tumor with an atypical less aggressive biologic behavior. "Cured" germ cell tumor patients need careful follow-up beyond 2 years. At a minimum, these patients should be seen annually. Patients found to have teratomas following cisplatin-based chemotherapy should probably undergo more frequent evaluations.     

An analysis of surveillance for stage I combined teratoma--seminoma of the testis.

We analysed 973 patients with stage I testicular tumours presenting between 1983 and 1994. The median ages at presentation for non-seminomatous germ cell tumour (teratoma) were 27 years, seminoma 36 years and combined tumour 33 years. These differences were statistically significant (Mann-Whitney P < 0.05), suggesting that combined tumours may have a separate natural history. We, therefore, analysed all stage I patients managed with surveillance (530 in total) post orchidectomy. The actuarial 5 year relapse-free survival and anatomical patterns of relapse were identical for non-seminomatous germ cell tumour (NSGCT) and combined tumour and both were statistically distinct from seminoma (P = 0.01, log-rank test, chi-square test P = 0.001). The association of seminoma within a histologically confirmed NSGCT has no influence on the clinical outcome.     

Intensive induction chemotherapy with CBOP/BEP in patients with poor prognosis germ cell tumors.

PURPOSE: Despite a high cure rate in patients with testicular cancer, there remain patients in the poor prognosis group who have a less favorable outcome. Intensive induction chemotherapy using a regimen consisting of carboplatin, bleomycin, vincristine, and cisplatin, followed by bleomycin, etoposide, and cisplatin (CBOP/BEP), developed at the Royal Marsden Hospital, is designed to overcome the rapid proliferation seen in germ cell tumors. This study assesses the outcome of patients with poor-prognosis nonseminomatous germ cell tumors (NSGCT) treated with CBOP/BEP. PATIENTS AND METHODS: Patients with NSGCT from three centers, classified as poor prognosis according to International Germ Cell Classification Consensus Group criteria, were treated with CBOP/BEP regimen during the period from 1989 to 2000. Data on treatment toxicity, relapse-free survival (RFS), and overall survival (OS) were collected prospectively on a hospital database. RESULTS: Fifty-four male patients with poor prognosis NSGCT were treated with CBOP/BEP. The RFS at 3 and 5 years for all patients was 83.2% (95% confidence interval [CI], 68.8% to 91.3%). After a median follow-up of 4 years, the OS of the 54 patients was 91.5% (95% CI, 78.6% to 96.8%) at 3 years and 87.6% (95% CI, 71.3% to 94.9%) at 5 years. Three-year OS in patients with a primary mediastinal germ cell tumor was 77.1% (95% CI, 34.5% to 93.9%) compared with 95.4% (95% CI, 82.8% to 98.8%) in patients with a testicular primary tumor (P =.24). CONCLUSION: The results reported here compare favorably with the historical results of alternative regimens used in the management of poor-prognosis NSGCT. We suggest a phase III trial to confirm our findings.     

Late relapse of testicular cancer presenting as differentiated teratoma - report of a case and discussion of the clinical implications

This report describes the unusual case of a patient with late relapse of testicular cancer, histologically defined as differentiated teratoma occurring 76 months after primary therapy for metastatic non-seminomatous germ cell cancer. During initial treatment the patient received 4 cycles of cisplatin-based chemotherapy followed by secondary resection of residual retroperitoneal and pulmonary metastases which had histologically revealed necrotic tissue. The patient had been without evidence of disease during the follow-up until May 1994 when a cystic mass was noted in the left fossa obturatoria. There was no concomitant elevation of serum tumour markers, while alpha-fetoprotein (AFP) could be detected in fluid gained by fine-needle aspiration from inside the cystic structure. Histological resection showed a differentiated teratoma. Late relapses defined as tumour recurrences later than 24 months after primary chemotherapy for metastatic testicular cancer are rather rare and affect only 2-5% of patients. However, the prognosis of patients with late relapse is poor with only 20-30% of patients achieving a second remission after chemotherapy +/- surgery. Patients presenting with only differentiated teratoma at late relapse and in whom the tumour can be completely surgically resected have the best prognosis among the subgroup of patients with late relapses with a long-term survival in approximately 50% of patients. The incidence and clinical implications of late relapses after chemotherapy for testicular cancer are discussed in the current report.     

Recurrence of a germ cell tumor 12 years after initial treatment: a case report

Patients with testicular germ cell tumors who have disease-free remission for more than 2 years are usually considered to be cured of their disease. This report describes a case of a germ cell tumor recurring 12 years after initial diagnosis and its treatment in a 35-year-old man who developed a retroperitoneal mass adhering to the abdominal aorta with a bout of severe colic in the left flank. Although tumor markers were not elevated and histology of the biopsy specimen was initially diagnosed as adenocarcinoma, we finally concluded that the retroperitoneal tumor was teratoma developing as a recurrence of the germ cell tumor for the following reasons: (1) the histology of the specimen was similar to an epithelial component of teratoma found in the tissue resected 12 years before; (2) systemic survey failed to detect any other primary site; (3) the young age of this patient was consistent with germ cell tumor rather than adenocarcinoma; and (4) the retroperitoneum is the most frequent site of late recurrences of testicular cancer. He was treated successfully with combination chemotherapy of cisplatin, etoposide and bleomycin followed by surgery. It is important to differentiate this treatable disease from metastasis from an unknown primary, because the latter responds poorly to therapy and survival is usually short.      

Second-line high-dose chemotherapy in patients with mediastinal and retroperitoneal primary non-seminomatous germ cell tumors: the EBMT experience.

BACKGROUND: Results of second-line chemotherapy in patients with extragonadal non-seminomatous germ cell tumor (NSGCT) appear inferior to results in testicular NSGCT. Patients with retroperitoneal NSGCT achieve a comparable long-term survival rate of 30%, but the salvage rates of patients with mediastinal primary are less than 10%. We conducted a retrospective analysis on patients with mediastinal and retroperitoneal NSGCT treated with second-line high-dose chemotherapy (HDCT) registered with the European Group for Blood and Marrow Transplantation (EBMT). PATIENTS AND METHODS: Between 1987 and 1999, 59 registered patients with retroperitoneal (n=37) and mediastinal (n=22) primary NSGCT, median age 28 years (range 18-60), were treated with second-line HDCT. All had received cisplatin-containing chemotherapy as first-line treatment. RESULTS: Toxic death occurred in three cases (5%). With a median follow-up of 58 months (range 14-114), 18/59 patients (30%) continue to be disease-free. Of three patients who had a disease recurrence after HDCT, one patient achieved a disease-free status with further chemotherapy and surgery. In total, 19 patients (32%) are currently disease-free. Sixteen of 37 patients (43%) with retroperitoneal NSGCT, and three of 22 patients (14%) with mediastinal NSGCT are currently alive and disease-free. CONCLUSIONS: Second-line HDCT might represent a possible option for patients with retroperitoneal primary NSGCT. New salvage strategies are needed for patients with mediastinal NSGCT.     

Different risk factors and prognosis for early and late intrahepatic recurrence after resection of hepatocellular carcinoma

BACKGROUND: Recent studies have shown that the prognosis of recurrent hepatocellular carcinoma (HCC) after resection was dependent on the time of recurrence. The current study investigated whether early and late intrahepatic recurrences were associated with different risk factors and prognostic factors. METHODS: After curative resection of HCC, 246 patients were followed prospectively for recurrence. Intrahepatic recurrences were classified into early ( 1 year) recurrences. Risk factors for recurrence and prognostic factors for survival after recurrence in each group were analyzed. RESULTS: Early and late intrahepatic recurrences developed in 80 patients and 46 patients, respectively. By multivariate analysis, preoperative tumor rupture (P = 0.022) and venous invasion (P < 0.001) were independent risk factors for early recurrence, whereas cirrhosis (P = 0.018) was the only significant risk factor for late recurrence. By comparing histologic features of resected recurrent and primary tumors, 8 of 9 resected early recurrent tumors (89%) were classified as intrahepatic metastases, whereas all 6 resected late recurrent tumors (100%) were multicentric occurrences. Despite similar treatments, the prognosis for patients with early recurrence was worse than that of patients with late recurrence (median survival of 15.8 months vs. 29.6 months; P = 0.005). Independent prognostic factors for early recurrence were serum albumin level and initial tumor pTNM classification, whereas only serum bilirubin level was found to be an independent prognostic factor for late recurrence. CONCLUSIONS: Early and late intrahepatic recurrences after resection of HCC were associated with different risk factors and prognostic factors. Early recurrences appear to arise mainly from intrahepatic metastases, whereas late recurrences are more likely to be multicentric in origin. The current study suggests that different strategies may be needed for the prevention and management of early and late recurrences. Further studies based on genetic analysis of clonal origins of tumors are required to clarify fully the mechanism of early and late recurrences after resection of HCC.     

Management of patients with low-stage nonseminomatous germ cell testicular cancer

Management options for patients with clinical stage (CS) I nonseminomatous germ cell testicular cancer (NSGCT) include surveillance, retroperitoneal lymph node dissection (RPLND), or two cycles of bleomycin-etoposide-cisplatin (BEP x 2) chemotherapy. The optimal management of these patients is controversial, as cure rates of 97% or greater are reported with each of these treatment modalities. Patients without evidence of lymphovascular invasion, a predominant component of embryonal carcinoma, or advanced pathologic (p) T stage (pT 2 or greater) are at low risk for occult metastases and are optimal candidates for surveillance. Compliance with diagnostic testing and imaging is essential for a successful surveillance strategy to detect and treat metastases at an early stage. For patients who are not candidates for surveillance, RPLND offers several advantages over chemotherapy. RPLND alone is curative in 50% to 80% of CS I patients with pathologic stage (PS) II, and an estimated 75% of CS I patients avoid chemotherapy (as adjuvant therapy or for treatment of relapse). Virtually all patients are cured following two cycles of adjuvant chemotherapy for PS II disease, which is reserved for patients with high-volume (PN2-3) retroperitoneal disease. The poor outcome of patients with late retroperitoneal recurrence from unresected, chemorefractory germ cell testicular cancer indicates that RPLND is a vital component to the long-term cure of patients with NSGCT. Approximately 20% to 30% of patients with PS II disease have retroperitoneal teratoma (which is chemoresistant), and an estimated 5% of PS II patients have chemoresistant viable cancer following BEP x 2 as primary therapy. When RPLND is omitted, these patients are at risk for late recurrence with potentially lethal consequences. Patients who relapse after RPLND are "chemotherapy-na?ve" and cured in virtually all cases with good-risk chemotherapy regimens. When nerve-sparing techniques are employed to preserve ejaculation, RPLND is also associated with a more favorable long-term toxicity profile compared with chemotherapy. In the absence of conclusive evidence from a randomized trial, we believe RPLND is the treatment of choice for patients with CS I NSGCT who are not candidates for surveillance, as it offers the greatest likelihood of long-term cure with considerably less morbidity than primary chemotherapy.     

Primary germ cell tumors in the mediastinum: a 50-year experience at a single Japanese institution

BACKGROUND: Primary germ cell tumors (GCT) of the mediastinum share similar clinical and biologic characteristics, which are different from their testicular counterpart. The purpose of the current study was to review the authors' institutional experience of mediastinal GCT, emphasizing the clinical spectrum, time trends of treatment, and recent advances in therapeutic modalities for malignant GCT. METHODS: Between 1951 and 2000, 129 patients (70 males and 59 females) underwent surgical treatment for GCT, which accounted for 16.0% of the mediastinal tumors during the same period. There were 95 patients with mature teratomas, 13 patients with seminomas, and 21 patients with nonseminomatous germ cell tumors (NSGCT) with median ages of 26.4 years, 27.6 years, and 28.5 years, respectively. RESULTS: Adult patients with mature teratomas were less symptomatic (33.3%) than pediatric patients (52.4%). All patients with mature teratoma were cured by resection alone. Eight of the 13 patients (61.5%) with seminoma were symptomatic and 10 of 13 patients (83.3%) survived after surgery and radiation with/without chemotherapy. Nineteen of 21 patients (90.5%) with NSGCT had dyspnea, chest pain, and superior vena cava syndrome. Before 1985, patients received radical resection and/or chemoradiotherapy. However, all patients died due to disease progression, with a median survival period of 7.6 months. After 1986, six of eight patients received cisplatin-based chemotherapy, including three who received additional high-dose chemotherapy with a supporting peripheral blood stem cell transplantation until tumor markers normalized. Five patients who underwent salvage resection are currently disease free with a median survival period of 58.3 months. CONCLUSIONS: The institutional experience indicates the benign nature of mediastinal mature teratomas and the excellent prognosis for patients with seminomas after resection. An improved survival advantage was ensured with cisplatin-based preoperative chemotherapy in patients with NSGCT.     

Late breast recurrence after lumpectomy and irradiation

For 276 patients with early breast cancer followed from 10-21 years after lumpectomy and radiotherapy, the recurrence rate in the treated breast was 15.6%, and 7.2% developed contralateral breast cancer. Only 63% of breast recurrences occurred within 5 years, and the remainder were "late failures," with 5 of the 43 recurrences observed after 10 years. The proportion of failures occurring late was greater for T1 than for T2 tumors (53% vs 25%). Twenty-six percent of early recurrences were inoperable, and an adverse impact of early recurrence on 10-year survival was clearly demonstrable. Late recurrences were all operable and did not appear to be associated with decreased survival. Only 16 of the 36 patients (44%) with operable breast recurrence ever developed metastatic disease, and 5 year survival following salvage therapy was 62%. Although the treated breast remains at continuous cancer risk even beyond 5 year, the prognosis of late recurrence appears quite similar to that of contralateral breast cancer. We do not consider the phenomenon of late recurrence to lend support to a policy of primary mastectomy, just as the existence of contralateral breast cancer does not justify routine "prophylactic" contralateral mastectomy.     

Is the Blood–Brain Barrier Relevant in Metastatic Germ Cell Tumor?

PURPOSE: Germ cell tumors are uniquely chemosensitive and curable, even with advanced metastatic disease. Central nervous system recurrence can terminate a complete remission in other chemosensitive tumors, such as small cell lung cancer, because of the blood-brain barrier (BBB). We propose to document that the BBB is also relevant in germ cell tumors despite their dramatic chemosensitivity. METHODS AND MATERIALS: We present five cases illustrating the concept of the BBB in patients with metastatic testicular cancer treated with chemotherapy. RESULTS: In our large series of patients with metastatic testicular cancer treated with chemotherapy, we identified 5 unique patients. These patients were rendered free of disease only to experience relapse in the brain alone. This included 1 patient who initially had good-risk metastatic disease by means of the International Germ Cell Collaborative Group staging system at the onset of chemotherapy. CONCLUSIONS: The BBB is relevant in patients with metastatic testicular cancer.     

The management of stage I nonseminomatous testicular germ cell tumors

Testicular germ cell tumors represent the most common malignancies in young males; 70% of patients with seminomas and 50% of those with nonseminomatous germ cell tumors (NSGCT) have clinical stage I at diagnosis. Lymphovascular invasion, embryonal-cell carcinoma component, absence of yolk sac histology and MIB1 proliferation rate represent predictors of micrometastatic diseasein stage I NSGCT. Therapeutic options following orchiectomy in patients with stage I NSGCT comprise nerve-sparing retroperitoneal lymph node dissection, surveillance or adjuvant cisplatin-based chemotherapy. All available treatment modalities produce excellent results, with a long-term survival of almost 100%. Consequently, therapy-induced toxicity is an important concern in the management of these patients. An individually tailored approach that takes into account the prognostic factor profile as well as the patient's preferences and their ability to comply with each one of the modalities is the key to the management of stage I testicular cancer.     

Surveillance for stage I testicular germ cell tumours: results and cost benefit analysis of management options

Between 1979 and 1996 303 men with stage I testicular germ cell tumours (120 seminoma and 183 non-seminomatous germ cell tumours (NSGCT)) were enrolled onto a programme of surveillance. In our institutions the frequency of computed tomography (CT) scans is reduced compared with other centres. For all 303 men, the median follow-up is 5.1 years (range: 0.1-21.7 years) and there have only been 3 deaths (1 from disease, 1 from neutropenic sepsis and 1 from secondary leukaemia). 52/183 (28%) patients with NSGCT and 18/120 (15%) patients with seminoma have relapsed. The relapse-free survival at 5 years is 82% for seminoma and 69% for NSGCT (Logrank P=0.004). All men who relapsed, except 1 man with NSGCT, were in the International Germ Cell Cancer Collaborative Group good or intermediate prognosis group at relapse. Half of the seminoma relapses presented with symptoms and 31% of the NSGCT relapses. The remaining relapses were detected serologically or radiologically by the surveillance programme. 5 men (2%) on surveillance, 3 with initial diagnosis of seminoma and 2 with NSGCT, have developed second contralateral testis tumours (all stage I seminomas). In a well motivated centre a policy of surveillance for stage I testicular germ cell tumours (both NSGCT and seminoma) is associated with a low mortality rate (3/303, 1%) and may have the advantage of sparing overtreatment with potentially toxic therapies in this group of young men.     

A phase II trial of early intensive chemotherapy with autologous bone marrow transplantation in the treatment of poor prognosis non seminomatous germ cell tumors.

Twenty-eight patients with poor prognosis, advanced metastatic non seminomatous germ cell tumors (NSGCT) were treated with early high dose chemotherapy and autologous bone marrow transplantation (ABMT) rescue. The primary tumor was testicular in 19 patients and extragonadal in nine patients. For 19 patients with a testicular primary, the median probability of complete remission (CR) was 0.05 according to our prognostic mathematical model based on pretreatment levels of serum HCG and AFP. The same prognostic model was used for extragonadal primaries. Treatment consisted of two cycles of a modified double dose of cisplatin, vinblastine, bleomycin, VP-16 regimen (mPVeBV) followed by a high dose cisplatin-etoposide-cyclophosphamide regimen (PEC) followed by ABMT. Of the 28 patients, 17 (61%) achieved CR, one of which was surgical CR (sCR), five died of rapidly progressive disease early during the first cycle of mPVeBV, two had treatment-related deaths, three did not respond and one patient refused treatment. Of the 17 patients initially in CR, three relapsed after 4, 4 and 7 months respectively and have subsequently died. Two other patients died while still in CR: one committed suicide and one died of an infectious complication due to transfusion-related AIDS. Twelve patients are alive in CR after a median follow-up of 66 months (range 7-72 months). The non parametric 3-year survival rate is 40%. To demonstrate the effect of intensive chemotherapy with ABMT, a randomized multicenter French study was set up to evaluate the PVeBV regimen with or without high dose treatment and ABMT in poor risk NSGCT patients.