Metastatic Nonseminomatous Germ Cell Tumors Research Articles

Predicting Teratoma in the Retroperitoneum in Men Undergoing Post-Chemotherapy Retroperitoneal Lymph Node Dissection

The biological potential of teratoma remains unpredictable, therefore identifying its presence in the retroperitoneum remains important. We evaluated patients undergoing post-chemotherapy retroperitoneal lymph node dissection for nonseminomatous germ cell tumors to determine predictors of teratomatous elements in the retroperitoneum. We identified 532 patients from 1989 to 2003 who underwent retroperitoneal lymph node dissection following chemotherapy for nonseminomatous germ cell tumors at our institution. Multiple clinical and pathological variables were reviewed from our prospective retroperitoneal lymph node dissection database. A logistic regression model was designed based on preoperative variables to predict the presence of teratomatous elements in the retroperitoneal lymph node dissection specimen. Of the 532 patients in our series 450 (85%) received only induction chemotherapy and 82 (15%) required salvage chemotherapy. Teratomatous elements were identified in the orchiectomy specimen in 42% of patients. Retroperitoneal nodal pathology revealed teratomatous elements in 235 (44%) patients and only teratoma in 210 (40%) patients. By multivariate analysis testicular yolk sac tumor (p = 0.046), teratoma in the orchiectomy specimen (p <0.005), relative change in nodal size before and after chemotherapy (p <0.005), and no requirement for salvage chemotherapy (p = 0.03) were independent predictors for the presence of teratoma in the retroperitoneum. Teratoma remains a common histological finding in the retroperitoneal lymph nodes following chemotherapy. We have identified several pre-retroperitoneal lymph node dissection variables that predict the finding of teratoma in the retroperitoneum for men treated with chemotherapy for metastatic nonseminomatous germ cell tumors.

Short- and Long-Term Outcomes After Large Pulmonary Resection for Germ Cell Tumors After Bleomycin-Combination Chemotherapy

Abstract Background Treatment of nonseminomatous germ cell tumors frequently requires bleomycin-combination chemotherapy followed by resection of residual disease. Bleomycin administration however raises concerns with respect to postoperative respiratory complications, particularly for patients undergoing large pulmonary resections. We undertook an institutional review to determine the outcome of large pulmonary resections after bleomycin-combination chemotherapy. Methods Between 1981 and 2001, 530 patients presented to our institution for resection of residual intrathoracic disease for either metastatic testicular or primary mediastinal nonseminomatous germ cell tumors. We subsequently reviewed 32 of these patients who required pneumonectomy (n = 19; right=9, left=10) or bilobectomy (n = 13) after bleomycin-combination chemotherapy. Results There were four operative deaths (13%). All postoperative deaths occurred in patients undergoing right-sided resections (pneumonectomy, n=2; bilobectomy, n=2) as a consequence of pulmonary complications. Operative survivors had a pulmonary morbidity of 18%. Fourteen of 20 long-term survivors were found to have a satisfactory performance status at follow-up. Conclusions Otherwise young and healthy male nonseminomatous germ cell tumors patients requiring large pulmonary resections after bleomycin-combination chemotherapy appear to be at higher than anticipated risk for pulmonary-related morbidity and mortality. However long-term survivors report an acceptable functional status.

Nonseminomatous Germ Cell Tumor after Chemotherapy with Residual Mass Invading the Spine

Bony metastasis is a rare feature of metastatic nonseminomatous germ cell tumor. A 25 year-old man presented with back pain radiating down both legs, and a subsequent work-up demonstrated a right-sided testicular mass with bilateral retroperitoneal lymphadenopathy and tumor involvement of the L2 vertebra. Radical inguinal orchiectomy confirmed nonseminomatous germ cell tumor, and the patient underwent chemotherapy with a residual mass and vertebral involvement by MRI. Combined vertebral resection with spinal reconstruction and retroperitoneal lymph node dissection demonstrated residual fibrosis. While bony metastasis of nonseminomatous germ cell tumors is rare, resection with spinal reconstruction can be accomplished with acceptable morbidity.

Significance of elevated preoperative α-fetoprotein in postchemotherapy residual tumor resection for the disseminated germ cell tumors

The purpose of the study is to determine the significance of elevated serum alpha-fetoprotein (AFP) in the setting prior to residual tumor resection (RTR) following chemotherapy for metastatic germ cell tumor in terms of the prediction of histology of the specimen and postoperative survival. We conducted a retrospective review of 68 patients undergoing RTR for metastatic nonseminomatous germ cell tumor or extragonadal germ cell tumor after at least a first-line chemotherapy. Pretreatment and postchemotherapy serum markers were evaluated in association with other clinical findings including results of pathological examination of RTR specimen and surgical outcome. Of the 68 study patients, 54 (79%) and 45 (66%) had positive AFP and beta-human chorionic gonadotropin (beta-HCG) in pretreatment settings. Rates of presence of residual malignant cell in RTR specimen were similar between patients with normal AFP (7/28 or 25%) and with mildly elevated (10-30 ng/ml) AFP (3/11 or 27%). In 26 patients who had residual viable malignancy in RTR specimen, patients with preoperative positive AFP had significantly better survival (P = 0.02) compared to those with preoperative positive beta-HCG. Sole and mild elevation of AFP is not always associated with postoperative poor prognosis. It should be carefully considered individually whether a mild elevation of AFP after chemotherapy represents residual malignancy or benign pathogenesis.

Post-chemotherapy retroperitoneal lymph node dissection for non-seminomatous germ cell tumors: The impact of time

4581 Background: The integration of chemotherapy and surgery for metastatic non-seminomatous germ cell tumors (NSGCT) results in an overall survival of > 90%. We evaluated NSGCT patients (pts) undergoing post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) to assess for associations between year of treatment and clinical outcome. Methods: We evaluated 509 men who underwent PC-RPLND from 1989–2002 for NSGCT at our center. Pts were retrospectively allocated to 3 cohorts according to year of treatment from 1989 to 1992, 1993 to 1997, and 1998 to 2002. Data were obtained from our prospective surgical database and assessed for stage at diagnosis, IGCCCG risk classification, chemotherapy regimen, PC-RPLND histology, and disease free survival. Statistical analysis was performed using SPSS software; p-values < 0.05 were considered significant. Results: From 1989 to 1992, clinical stage IIa, IIb, IIc, and III NSGCT was seen in 3%, 12%, 25% and 54% of patients respectively, compared to 16%, 23%, 17%, and 37%, respectively from 1998 to 2002 (p < 0.001). The prevalence of good, intermediate, and poor risk disease remained similar over time but the need for salvage chemotherapy declined from 21% (1989–1992) to 9% (1998–2002, p = 0.002). Teratoma in the retroperitoneum increased from 34% (1989–1992) to 49% (1998–2002, p = 0.003), while the prevalence of teratoma in the orchiectomy specimen remained similar. The presence of viable NSGCT at the time of PC-RPLND decreased over time. From 1989–1992, 1993–1997, 1998–2002, 19%, 13%, and 6% of patients had persistent viable disease respectively (p = 0.001). Over time, the 5-year actuarial disease free survival has improved (Table). Conclusion: In more recent years men are presenting with less advanced metastatic NSGCT and a smaller percentage require salvage chemotherapy. This stage migration together with effective chemotherapy and surgery has resulted in an improved disease free survival. No significant financial relationships to disclose.

Postchemotherapy resections of residual masses from metastatic nonseminomatous testicular germ cell tumors. A Spanish Germ Cell Group study

4525 Background: After chemotherapy for metastatic testicular tumors masses may remain. We analyze factors influencing histology and long-term evolution of patients with post-chemotherapy residual masses. Methods: 352 patients with nonseminomatous germ cell tumors with postchemotherapy residual masses and negative tumor markers were selected from the database of the Spanish Germ Cell Group between December 94 and February 04. Our protocol recommends surgical resection of masses larger than 2 cm. Patients with masses between 1 and 2 cm were offered follow-up or surgical resection. Of them 292 were finally operated: IGCCCG class: 137 (47%), 72 and 83 (28%) for good, intermediate and bad prognosis group respectively. Results: Median follow-up: 4 yrs. Thirty patients need 2 resections, 8 patients 3 and 3 patients 4 surgical maneuvers. Histology of masses: necrosis in 116 (40%), teratoma in 135 (46%), malignant tumor in 41 (14%). IGCCCG and Royal Marsdem class, histology of the primary, age and prechemotherapy size were correlated (X2 test) with histology of the residual masses. Lesions >5 cm before chemo and intermediate or bad prognosis group of the IGCCCG significantly correlated with necrosis. Statistically significant factors predicting teratoma were primary containing teratomatous elements, patient belonging to the good prognosis group and lesions below 5 cm before treatment. We did not identify factors correlated to malignant tumor. Analysis for survival: both IGCCCG class and malignant tumor at surgery were statistically significant in the multivariate analysis (p<0.001), whereas size, Royal Marsdem Class or histology of the primary were not. Five-year survival was 75%, 93% and 95% if malignant tumor, teratoma or necrosis were found respectively. Good, intermediate and bad prognosis group had a 5-yr survival of 97, 87 and 81% respectively. Conclusions: Our results suggest that persistence of small lesions after chemotherapy together with teratomatous elements in the primary predicts teratoma at surgery. IGCCCG class and persistence of malignant cells at surgery are the strongest prognostic factors for survival after resection of residual masses. No significant financial relationships to disclose.

The Management and Outcome of Patients with Germ-cell Tumours Treated in the Edinburgh Cancer Centre Between 1988 and 2002

The aim of this retrospective analysis was to review the outcome of patients with germ-cell tumours treated in the Edinburgh Cancer Centre over the past 15 years, and to see whether there had been any changes over three 5-year cohorts. Patients referred with gonadal and extra-gonadal primary germ-cell tumours, between 1988 and 2002, were identified from the departmental database, and survival by stage and prognostic group was analysed. The proportion of patients with stage I seminoma has significantly increased. The good prognosis of patients with early stage disease is confirmed, with the outcome for some groups of patients being better than expected. There is a non-significant trend to improved results over the three 5-year cohorts. The outcome for patients with stage IV seminoma is worse than would be expected, but numbers are small. The poor prognosis of patients with non-seminomatous germ-cell tumours who fall into the International Germ Cell Consensus Classification (IGCCC) poor-prognostic group is confirmed. Failure of patients with metastatic non-seminomatous germ-cell tumours to achieve a complete response to initial therapy is shown to be a poor prognostic indicator.

A NONPARAMETRIC COMPARISON OF THE EFFECTIVENESS OF TREATMENTS: A MULTIVARIATE TOXICITY-PENALIZED APPROACH

ABSTRACT In cancer clinical trials, the amount of treatment dose actually received by a patient may be limited by severe toxicity or lack of efficacy. A nonparametric approach is proposed for comparing the effectiveness of treatments based on the bivariate relationship defined by the doses at which efficacy and toxicity are observed to occur. Simulation studies are used to contrast the performance of the new procedure with the usual method of comparing percentages of patients who have effective results. Data from a randomized clinical trial of patients with metastatic nonseminomatous germ cell tumors are used to illustrate the method.

Advances in the management of non-seminomatous germ cell tumors during the cisplatin era: a single-institution experience.

The objectives of the present study were to review chronological changes in the long-term survival of patients with non-seminomatous germ cell tumor (NSGCT) who were treated at a single institution after the introduction of cisplatin-based combination chemotherapy. One hundred and twenty patients with NSGCT who were treated between January 1978 and October 2001 were enrolled in this study. To evaluate chronological changes in treatment outcome between 1978 and 2001, data were analyzed according to the timing of initial treatment in two consecutive 12-year periods. The numbers of patients who were treated during 1978-1989 and 1990-2001 were 59 and 61, respectively. Patients were classified according to criteria of both the Japanese Urological Association (JUA classification) and the International Germ Cell Cancer Collaborative Group (IGCCCG classification). The mean follow up of surviving patients during the periods 1978-1989 and 1990-2001 was 84 months and 63 months, respectively. The overall 5-year survival rate of patients with NSGCT significantly increased from 72.8% during the period 1978-1989 to 83.6% during the period 1990-2001 (P = 0.02, log-rank test). A significant improvement in survival was found in the patients with stage III disease, according to the JUA classification, and in the patients with poor-risk disease, according to the IGCCCG classification (P = 0.004 and 0.05, respectively). The overall 5-year survival rate of patients with NSGCT increased significantly from 72.8% during 1978-1989 to 83.6% during 1990-2001. This improvement resulted mainly from an increased survival of patients with metastatic poor-risk NSGCT.

Reoperative retroperitoneal surgery for nonseminomatous germ cell tumor: clinical presentation, patterns of recurrence, an outcome: McKiernan JM, Motzer RJ, Bajorin DF, Bacik J, Bosl GJ, Sheinfeld J, Department of Urology, Memorial Sloan-Kettering Cancer Center, New York, NY.

Urology 2003;62:732–6 Objectives To describe the clinical characteristics and outcome of patients with metastatic nonseminomatous germ cell tumor requiring reoperative retroperitoneal surgery at the Memorial Sloan-Kettering Cancer Center, because such patients are poorly characterized. Methods The Memorial Sloan-Kettering Cancer Center germ cell tumor surgical database was reviewed from January 1989 through April 2001, and the clinical characteristics of patients undergoing reoperative retroperitoneal surgery for nonseminomatous germ cell tumor were identified. The initial presentation, histologic findings, morbidity, and survival were analyzed. Disease-specific survival was calculated using the Kaplan-Meier method. Results A total of 56 patients underwent 61 repeat operations: 22 after primary retroperitoneal lymph node dissection (RPLND) and 34 after postchemotherapy RPLND. Left testicular primary tumors were more common than right (33 versus 23), and the most common sites of disease prompting reoperation were the para-aortic and left hilar regions. Teratoma was the most common histologic finding at the time of reoperation. Of 56 patients, 37 (66%) required chemotherapy between the initial operation and reoperation. The overall perioperative complication rate was 27%, and median length of hospital stay was 8 days. Sixty-nine percent of patients required adjunctive procedures at the time of reoperation, the most common of which was thoracotomy. The 5-year disease-specific survival rate was 67% for the entire group (86% following reoperation after primary RPLND and 56% following reoperation after postchemotherapy RPLND). Conclusions Reoperative retroperitoneal surgery for nonseminomatous germ cell tumor can be performed with acceptable morbidity in select referral centers. Teratoma is highly prevalent in the retroperitoneum at the time of reoperation. A significant subset of these high-risk patients can be salvaged with complete resection.

The management of nonseminomatous testicular cancer.

Despite the fact that testis cancer accounts for only 1% of all male malignancies, it is the most common solid malignancy affecting males between the ages of 15 to 35 years. The management of germ cell tumors (GCT) of the testis has proved to be a model of success among solid tumors. This is due to tremendous advances during the past 2 decades, which have changed the once dismal prognosis for patients with advanced disease. Testicular cancer has, in fact, become one of the most curable of all solid neoplasms. Thirty years ago testicular cancer accounted for 11.4% of all cancer deaths in the 25 to 34 year age group, with an overall 5 year survival rate of 64%. The most recent five-year survival rate for GCT of the testis in the United States was recently reported as being in excess of 90%. Improved prospects for cure and long-term disease free survival rate, are related to a better understanding of the natural history of testicular tumors, improved staging methods and surgical techniques, as well as to the introduction of effective platinum based combination chemotherapy. Modifications to the surgical management of testis cancer have significantly reduced morbidity associated with the classical full bilateral retroperitoneal lymph node dissection. Template and nerve sparing retroperitoneal node dissections are now routinely employed in low stage nonseminomatous germ cell tumors (NSGCT), providing the patient with the benefit of accurate pathological staging combined with reduced morbidity. In addition, nerve sparing techniques have also been used in dissections for residual disease following chemotherapy. Chemotherapy for advanced GCT has undergone a number of important breakthroughs during the past three decades. In the 1960's the first major chemotherapeutic advance in metastatic NSGCT was described; a combination of chlorambucil, methotrexate and dactinomycin produced a response rate of 30%. By the 1970's combination therapies such as vinblastine and bleomycin had been shown to produce objective responses; 57% complete response rates and 45% long-term disease-free survival rates were reported. The discovery of cisplatin as a highly effective anti-neoplastic agent in 1965, and its later use in germ cell tumors of the testis (GCT), was another important breakthrough. In 1974 the combination of cisplatin, vinblastine and bleomycin was investigated by the Indiana group. Of the 47 patients in the initial phase II study, 100% achieved a response rate. Thirty five (74%) patients achieved complete remission, the remaining patients achieved a partial remission.

Reoperative retroperitoneal surgery for nonseminomatous germ cell tumor: clinical presentation, patterns of recurrence, and outcome

Objectives To describe the clinical characteristics and outcome of patients with metastatic nonseminomatous germ cell tumor requiring reoperative retroperitoneal surgery at the Memorial Sloan-Kettering Cancer Center, because such patients are poorly characterized. Methods The Memorial Sloan-Kettering Cancer Center germ cell tumor surgical database was reviewed from January 1989 through April 2001, and the clinical characteristics of patients undergoing reoperative retroperitoneal surgery for nonseminomatous germ cell tumor were identified. The initial presentation, histologic findings, morbidity, and survival were analyzed. Disease-specific survival was calculated using the Kaplan-Meier method. Results A total of 56 patients underwent 61 repeat operations: 22 after primary retroperitoneal lymph node dissection (RPLND) and 34 after postchemotherapy RPLND. Left testicular primary tumors were more common than right (33 versus 23), and the most common sites of disease prompting reoperation were the para-aortic and left hilar regions. Teratoma was the most common histologic finding at the time of reoperation. Of 56 patients, 37 (66%) required chemotherapy between the initial operation and reoperation. The overall perioperative complication rate was 27%, and median length of hospital stay was 8 days. Sixty-nine percent of patients required adjunctive procedures at the time of reoperation, the most common of which was thoracotomy. The 5-year disease-specific survival rate was 67% for the entire group (86% following reoperation after primary RPLND and 56% following reoperation after postchemotherapy RPLND). Conclusions Reoperative retroperitoneal surgery for nonseminomatous germ cell tumor can be performed with acceptable morbidity in select referral centers. Teratoma is highly prevalent in the retroperitoneum at the time of reoperation. A significant subset of these high-risk patients can be salvaged with complete resection.

Mediastinal metastases from testicular nonseminomatous germ cell tumors: Patterns of dissemination and predictors of long-term survival with surgery

Objectives: The purpose of this study was to determine the pattern of mediastinal dissemination of nonseminomatous germ cell tumors of testicular origin and evaluate variables that may influence survival with mediastinal dissection in patients with metastatic nonseminomatous germ cell tumors. Methods: From 1981 to 2000, a total of 421 patients were seen at our institution for extirpation of residual lung or mediastinal disease after cisplatin-based chemotherapy for metastatic testicular nonseminomatous germ cell tumors. We reviewed 268 of these patients, with a mean age of 26.8 years, who required at least one surgical procedure to remove residual mediastinal disease. Pathologic types of resected residual mediastinal disease were necrosis (15%), teratoma (59%), persistent nonseminomatous germ cell cancer (15%), and non-germ cell carcinomatous degeneration (11%). Twelve variables were evaluated by univariate analyses, and four variables potentially statistically significant at P <.10 were subsequently entered into a Cox regression model. Results: All patients demonstrated metastases to the visceral mediastinum. Fewer patients also demonstrated metastases to the paravertebral sulcus or anterior compartments (16% and 7%, respectively). Overall 5- and 10-year survivals were 86% ± 2% and 74% ± 4%, respectively. According to multivariate analysis, disease-related survival was negatively influenced by an elevated preoperative β-human chorionic gonadotropin level (P =.028) and adverse pathologic characteristics of residual mediastinal disease (P =.006). Conclusions: Testicular nonseminomatous germ cell tumors follow a predictable pattern of mediastinal dissemination, primarily following the course of the thoracic duct and its major tributaries. Patients who require surgery to remove residual mediastinal disease after cisplatin-based chemotherapy for metastatic nonseminomatous germ cell tumors have good to excellent long-term survivals. These results justify an aggressive surgical approach, including multiple surgical procedures if clinically indicated.J Thorac Cardiovasc Surg 2003;125:913-23

Treatment-induced anaemia and its potential clinical impact in patients receiving sequential high dose chemotherapy for metastatic testicular cancer.

First-line sequential high dose chemotherapy is under investigation in patients with ‘poor prognosis’ metastatic germ cell tumours in order to improve survival. Despite the use of autologous peripheral blood stem cell transplantation and granulocyte colony stimulating factor chemotherapy dose intensification is associated with severe haematotoxicity including anaemia, which may significantly affect quality of life and tolerability of chemotherapy. This study investigates the frequency and degree of anaemia in patients receiving first-line sequential high dose chemotherapy for metastatic testicular cancer and the impact of anaemia on treatment outcome. A total of 101 newly diagnosed patients with ‘poor prognosis’ metastatic nonseminomatous germ cell tumours were treated with one cycle of standard VIP followed by three cycles of HD-VIP-chemotherapy (etoposide, ifosfamide, cisplatin) within a large phase I/II study. Differential blood cell counts were taken prior, during and after every cycle of chemotherapy. Additionally, the numbers of red blood cell and platelet transfusions were recorded. Kaplan–Meier analyses were performed to correlate pre-treatment and post-treatment haemoglobin values to response and overall survival. Forty-eight per cent of the patients were classified anaemic (haemoglobin <12 g dl−1) prior to the start of chemotherapy. The application of sequential HD-VIP resulted in median haemoglobin nadirs between 7.8 g dl−1 (range 5.5–11.1 g dl−1) in the first cycle and 7.6 g dl−1 (range 6.0–11.4 g dl−1) in the third cycle despite the frequent use of red blood cell transfusions. Almost all patients (99%) had haemoglobin levels <10 g dl−1 at some timepoint during first-line sequential high dose chemotherapy. Overall, 97 patients received red blood cell transfusions with a median of 10 units (range 2–25) per patient during the four consecutive cycles of therapy. The time to first transfusion was shortest in patients with the lowest initial haemoglobin values. While there was no prediction of response or outcome by baseline haemoglobin-levels, a significant survival difference in favour of patients with a haemoglobin value >10.5 g dl−1 after completion of four cycles of therapy (at leukocyte recovery after the last cycle) compared to those with haemoglobin values <10.5 g dl−1 was found with 3-year overall survival rates of 87% vs 68%, respectively (P<0.05). Severe anaemia is a very frequent side effect of sequential dose intensive therapy in patients with germ cell cancer, with almost all patients becoming transfusion dependent. Despite the frequent use of red blood cell transfusions, median haemoglobin nadirs remained about 7.5–8 g dl−1 during therapy. A correlation of haemoglobin-values after completion of therapy to overall treatment outcome was found.British Journal of Cancer (2002) 87, 1066–1071. doi:10.1038/sj.bjc.6600629 www.bjcancer.com© 2002 Cancer Research UK

Resection of residual pulmonary masses after chemotherapy in patients with metastatic non-seminomatous germ cell tumours

Resection of residual pulmonary masses after chemotherapy in patients with metastatic non-seminomatous germ cell tumours

Loss of CD30 expression in metastatic embryonal carcinoma: the effects of chemotherapy?

CD30 has been shown to be consistently strongly expressed in embryonal carcinomas. Our aim was to examine changes in CD30 expression in embryonal carcinomas before and after treatment with chemotherapy. One hundred and eighteen retroperitoneal lymph node dissections from patients with metastatic germ cell tumours were reviewed. Seventeen contained embryonal carcinoma deposits. In nine cases, the matching pre-chemotherapy orchidectomy specimens were available. The cases were immunohistochemically stained for CD30. All nine pre- chemotherapy orchidectomy specimens showed embryonal carcinoma and stained strongly positively for CD30. However, only four out of nine of the matched post-chemotherapy retroperitoneal lymph node dissection specimens and a total of six out of 17 (35%) with embryonal carcinoma deposits stained for CD30. Ten seminomas were negative for CD30. Loss of CD30 did not appear to influence the relapse rate of the patients. Loss of CD30 expression occurs frequently in metastatic embryonal carcinomas after chemotherapy. This finding has implications in the use of CD30 in the diagnosis of metastatic non-seminomatous germ cell tumours and suggests that chemotherapy may alter the immunophenotype of embryonal carcinoma while retaining its characteristic histological appearances.

Prediction of relapse after lymph node dissection for germ cell tumours: can salvage chemotherapy be avoided?

Salvage chemotherapy has been used by some oncology centres for patients with residual malignant or immature elements in retroperitoneal lymph node dissections removed for metastatic non-seminomatous germ cell tumours. However, surveillance of these patients shows that many are cured by surgery alone. 118 retroperitoneal lymph node dissections for metastatic non-seminomatous germ cell tumours were reviewed and the morphology seen within them was quantified. 28 of these had immature or malignant elements and had been treated by surveillance before administration of further chemotherapy. The proliferation rate in these cases was assessed by immunochemistry. The proliferation index and the amount of embryonal carcinoma (EC) were both predictors of recurrence and therefore the need for further chemotherapy. Patients with greater than 25% of EC had an 84% chance of relapse and those with a Ki-67 index of greater than 50% had a 71% chance of relapse. The two tests had a positive predictive value of 83% and 71%, respectively. Patients with such a high risk of recurrence could be considered for post-operative adjuvant therapy at this point whilst others would be suitable for a watchful waiting approach. © 2001 Cancer Research Campaign http://www.bjcancer.com

Improved long term survival of patients with metastatic nonseminomatous testicular germ cell carcinoma in relation to prognostic classification systems during the cisplatin era

The current study reviews chronologic changes in the long term outcome of patients with metastatic nonseminomatous testicular germ cell tumors (NSTGCT) who were treated at a single institution during the past two decades. The 10-year survival of prognostic subgroups according to the classification of the International Germ Cell Consensus Classification Group (IGCCCG) and various other prognostic classifications is examined in time to evaluate whether cumulative experience has led to an improved outcome of patients with metastatic NSTGCT and to explore differences in outcome of prognostic subgroups. Two hundred ninety-nine patients with metastatic NSTGCT who were treated with cisplatin-based polychemotherapy during the period from 1977 to 1996 were staged retrospectively according to the Royal Marsden (RM) classification and the following prognostic classifications: IGCCCG, Indiana, Medical Research Council (MRC), and European Organization for Research and Treatment of Cancer (EORTC). The numbers of patients who were treated during the periods 1977-1986 and 1987-1996 were 146 and 153, respectively. Survival curves were constructed using the Kaplan-Meier method, and disease specific 10-year survival rates of prognostic subgroups treated during the two consecutive 10-year periods were compared using the log rank test. The median follow-up of surviving patients during the periods 1977-1986 and 1987-1996 was 14.7 years (range, 0.2-20.6 years) and 7.0 years (range, 0.4-11.4 years), respectively. The actuarial disease specific 10-year survival rate of patients with metastatic NSTGCT increased from 76% during the period 1977-1986 to 88% during the period 1987-1996 (relative risk [RR], 0.51; 95% confidence interval [95% CI], 0.29-0.89; P < 0.05). The 10-year survival rates of patients with good, intermediate, and poor prognoses according to the IGCCCG classification were 95%, 74%, and 37%, respectively, during the period 1977-1986 and 94%, 87%, and 66%, respectively, during the period 1987-1996. Patients with a poor prognosis according to the IGCCCG classification showed the greatest increase in 10-year survival (RR, 0.43; 95% CI, 0.18-1.04; P = 0.06). Analysis using the RM, Indiana, and EORTC classifications also showed an improved 10-year survival rate of patients with a poor prognosis who were treated during 1987-1996 compared with those who were treated during 1977-1986. The 10-year survival rate of patients with metastatic NSTGCT who were treated with cisplatin-based chemotherapy significantly increased from 76% during the period 1977-1986 to 88% during the period 1987-1996. This improvement during the cisplatin era resulted mainly from an increase in the survival of patients with metastatic disease who had a poor prognosis. These results indicate that the management of patients with NSTGCT is still improving.

RECOGNIZING ABNORMAL MARKER RESULTS THAT DO NOT REFLECT DISEASE IN PATIENTS WITH GERM CELL TUMORS

No AccessJournal of UrologyCLINICAL UROLOGY: Original Articles1 Mar 2000RECOGNIZING ABNORMAL MARKER RESULTS THAT DO NOT REFLECT DISEASE IN PATIENTS WITH GERM CELL TUMORS MICHAEL J. MORRIS, and GEORGE J. BOSL MICHAEL J. MORRISMICHAEL J. MORRIS More articles by this author , and GEORGE J. BOSLGEORGE J. BOSL More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(05)67807-XAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: The judicious use of serum α-fetoprotein (AFP), human chorionic gonadotropin (HCG) and lactate dehydrogenase is key to appropriate management of patients with germ cell tumors. Elevated AFP and/or HCG generally indicate active disease. We describe patients with germ cell tumors who had elevated serum AFP and/or HCG but no active disease, despite careful repeat evaluation. Materials and Methods: Histories of 6 cases of germ cell tumors that remained in remission despite abnormal serum AFP and/or HCG were reviewed. Results: Markers were only modestly elevated, remained constant or spontaneously normalized during repeat measurements, and there was no other clinical or radiographic evidence of disease. Patients were treated conservatively with physical examination, radiological tests and repeat marker assays, with no relapse to date. Conclusions: Stable, low increases in serum AFP and HCG may not represent active disease. Careful repeat evaluation will determine whether the markers increase. If no change is noted after appropriate studies have been reviewed by an experienced practitioner to exclude active disease from diagnosis, then consideration should be given to managing such cases with close surveillance to avoid unnecessary chemotherapy. References 1 : International Germ Cell Consensus Classification: a prognostic factor-based staging system for metastatic germ cell cancers. J Clin Oncol1997; 15: 594. Google Scholar 2 : Multivariate analysis of prognostic variables in patients with metastatic testicular cancer. Cancer Res1983; 43: 3403. Google Scholar 3 : Serum tumor marker half-life during chemotherapy allows early prediction of complete response and survival in nonseminomatous germ cell tumors. Cancer Res1990; 50: 5904. Google Scholar 4 : Does serum tumor marker half-life complement pretreatment risk stratification in metastatic nonseminomatous germ cell tumors?. Clin Cancer Res1996; 2: 1565. Google Scholar 5 : The role of tumour markers in the diagnosis and treatment of testicular germ cell cancers. Br J Urol1997; 79: 247. Google Scholar 6 : Microheterogeneity of human alphafetoprotein. Tumour Biol1988; 9: 3. Google Scholar 7 : Clinical relevance of alphafetoprotein microheterogeneity in alphafetoprotein-secreting tumors. Cancer Detect Prev1994; 18: 447. Google Scholar 8 : Alpha-fetoprotein-concanavalin. A binding as a marker to discriminate between germ cell tumours and liver diseases. Eur J Cancer1995; 31A: 2239. Google Scholar 9 : Falsely positive specific human chorionic gonadotropin assays in patients with testicular tumors: conversion to negative with testosterone administration. J Urol1979; 122: 126. Link, Google Scholar 10 : Pulsatile secretion of human chorionic gonadotropin in normal adults. N Engl J Med1987; 317: 1688. Google Scholar 11 : Commercial radioimmunoassay for beta subunit of human chorionic gonadotropin: falsely positive determinations due to elevated serum luteinizing hormone. Cancer1982; 49: 136. Google Scholar 12 : Gonadal function in men with testicular cancer. Semin Oncol1998; 25: 224. Google Scholar 13 : Gonadal dysfunction in patients treated for metastatic germ-cell tumors. J Clin Oncol1986; 4: 1500. Google Scholar 14 Bayer, Inc. Technicon Immuno 1 System Information. Publication No. DA4–1159J95, 1995 Google Scholar From the Department of Medicine, Division of Solid Tumor Oncology, Genitourinary Oncology Service, Memorial Sloan-Kettering Cancer Center and Department of Medicine, Weill Medical College of Cornell University, New York, New York© 2000 by American Urological Association, Inc.FiguresReferencesRelatedDetails Volume 163Issue 3March 2000Page: 796-801 Advertisement Copyright & Permissions© 2000 by American Urological Association, Inc.Keywordsalpha-fetoproteinschorionic gonadotropin, beta subunit, humantesticular neoplasmstumor markers, biologicalneoplasms, germ cell and embryonalMetricsAuthor Information MICHAEL J. MORRIS More articles by this author GEORGE J. BOSL More articles by this author Expand All Advertisement PDF DownloadLoading ...

Modified neck dissection for metastatic nonseminomatous testicular carcinoma.

To examine the role of neck dissection in the treatment of metastatic stage 3 nonseminomatous germ-cell tumors (NSGCTs) of testicular origin. A retrospective review was made of 45 patients with metastatic NSGCT who underwent 48 unilateral and 3 bilateral neck dissections. Only level III-VI nodes were dissected, often with concomitant or staged mediastinal dissection, thoracotomy, and/or retroperitoneal node dissection. Occasionally, resection of the clavicle, jugular vein, or subclavian artery, or a combination of these, was required to eradicate the disease. There were only four instances of recurrence in dissected necks. There was one case of dedifferentiation of mature teratoma to adenocarcinoma Patients who were followed for a mean period of 32 months had a disease-free survival of 72%. Prognosis for patients with stage 3 disease but negative preoperative tumor markers (alpha-fetoprotein and human chorionic gonadotropin) was excellent, with 97% of these patients having no evidence of disease at follow-up. Factors having a negative impact on survival included positive tumor markers, elements of germ-cell cancer in excised nodes, and a neck mass that represents late relapse of disease. Modified neck dissection has a demonstrated role in the treatment of metastatic NSGCT. It prevents reversion of mature teratoma to malignant germ cell tumor with minimal morbidity. Aggressive resection of disease is indicated, often in conjunction with thoracic surgery, to eradicate disease extending into the chest. There is an excellent prognosis in patients with negative preoperative serologic tumor markers.