The Second Medical Research Council Study of Prognostic Factors in Nonseminomatous Germ Cell Tumors

In the report entitled, "The Second Medical Research Council Study of Prognostic Factors in Nonseminomatous Germ Cell Tumors" by Mead et al (J Clin Oncol 10:85–94, 1992), the second sentence in the Results section of the abstract should have read: "The independently adverse features proved to be (1) the presence of liver, bone, or brain metastases; (2) raised marker levels (alpha-fetoprotein [AFP] level > 1,000 kU/L or beta subunit of human chorionic gonadotropin [HCG] > 10,000 IU/L); (3) the presence of a mediastinal mass greater than 5 cm in diameter; (4) the presence of 20 or more lung metastases; (5) increasing age; and (6) absence of undifferentiated teratoma (embryonal carcinoma) or fibrous tissue from the primary tumor."

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The Second Medical Research Council study of prognostic factors in nonseminomatous germ cell tumors. Medical Research Council Testicular Tumour Working Party.

Journal of Clinical Oncology ◽

10.1200/jco.1992.10.1.85 ◽

1992 ◽

Vol 10 (1) ◽

pp. 85-94 ◽

Cited By ~ 135

Author(s):

G M Mead ◽

S P Stenning ◽

M C Parkinson ◽

A Horwich ◽

S D Fossa ◽

...

Keyword(s):

Prognostic Factors ◽

Germ Cell ◽

Medical Research ◽

Research Council ◽

Medical Research Council ◽

Lung Metastases ◽

Large Population ◽

Germ Cell Tumors ◽

Cox Regression Analysis ◽

Nonseminomatous Germ Cell Tumors

PURPOSE To assess prognostic factors in a large population of patients with metastatic nonseminomatous germ cell tumors (NSGCT) arising in gonadal or extragonadal sites. PATIENTS AND METHODS Data from 795 patients treated with chemotherapy between 1982 and 1986 in 13 centers were analyzed. Particular emphasis was placed on exact tumor measurements (eg, size of nodal masses, number of lung metastases), and the diagnostic pathology was also reviewed. Cox regression analysis was performed on these data. The patients were treated with a variety of cisplatin-containing chemotherapy regimens, 86% of which included etoposide. RESULTS With median follow-up of 45 months, overall 3-year survival is 85%. The independently adverse features proved to be (1) the presence of liver, bone, or brain metastases; (2) raised marker levels (alpha-fetoprotein [AFP] level greater than 1,000 kU/L or beta subunit of human chorionic gonadotropin [HCG] greater than 10,000 IU/L [corrected]); (3) the presence of a mediastinal mass greater than 5 cm in diameter; (4) the presence of 20 or more lung metastases; (5) increasing age; and (6) absence of undifferentiated teratoma (embryonal carcinoma) or fibrous tissue from the primary tumor. CONCLUSIONS The first four factors were used to define a simple prognostic classification. A good-prognosis group having none of these features comprised 67% of our patient population and had a 3-year survival of 93%. The remaining 33% of patients having at least one of these features had a 3-year survival rate of 68%. These patient groups are currently the subjects of international randomized clinical trials.

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Short-course adjuvant chemotherapy in high-risk stage I nonseminomatous germ cell tumors of the testis: a Medical Research Council report.

Journal of Clinical Oncology ◽

10.1200/jco.1996.14.4.1106 ◽

1996 ◽

Vol 14 (4) ◽

pp. 1106-1113 ◽

Cited By ~ 238

Author(s):

M H Cullen ◽

S P Stenning ◽

M C Parkinson ◽

S D Fossa ◽

S B Kaye ◽

...

Keyword(s):

High Risk ◽

Adjuvant Chemotherapy ◽

Germ Cell ◽

Medical Research ◽

Research Council ◽

Medical Research Council ◽

Germ Cell Tumors ◽

Stage I ◽

Nonseminomatous Germ Cell Tumors

PURPOSE This United Kingdom Medical Research Council (UK-MRC) study prospectively evaluated efficacy and long-term toxicity of adjuvant chemotherapy in high-risk stage I nonseminomatous germ cell tumors of the testis (NSGCTT). PATIENTS AND METHODS Eligible patients were those identified by the local histopathologist as having features confirmed in MRC surveillance studies to indicate an approximate 50% risk of relapse. Central histopathology review was undertaken. Chemotherapy consisted of two courses of cisplatin 100 mg/m2, bleomycin 30 mg weekly x 3, and etoposide 120 mg/m2 x 3, every 21 days (BEP). RESULTS One hundred fourteen eligible cases were enrolled. Median time of follow-up was 4 years, with 93 patients followed-up for at least 2 years. There have been two relapses, including one patient who did not have a germ cell tumor (GCT), according to the reference histopathologist. This patient is alive with active disease, the other has died. There was one death after a cerebrovascular accident during treatment. Assessment of fertility, lung function, and audiometry pretreatment and more than 9 months posttreatment indicated no clinically significant changes. A mean decrease in transfer factor coefficient (KCO) of 15% of the predicted value was noted, but no patient had symptomatic respiratory dysfunction. CONCLUSION There have been only two relapses among 114 cases of high-risk stage I NSGCTT treated with two courses of adjuvant BEP chemotherapy. The 95% confidence interval (CI) excludes a true relapse rate of more than 5%. Of 104 patients confirmed on histopathology review to have GCT, there has been only one relapse. Adjuvant chemotherapy is free from significant long-term toxicity, offering an effective alternative to surveillance or retroperitoneal lymph node dissection (RPLND) followed by surveillance, and may be preferred by some patients.

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Intensive induction-sequential chemotherapy with BOP/VIP-B compared with treatment with BEP/EP for poor-prognosis metastatic nonseminomatous germ cell tumor: a Randomized Medical Research Council/European Organization for Research and Treatment of Cancer study.

Journal of Clinical Oncology ◽

10.1200/jco.1998.16.2.692 ◽

1998 ◽

Vol 16 (2) ◽

pp. 692-701 ◽

Cited By ~ 139

Author(s):

S B Kaye ◽

G M Mead ◽

S Fossa ◽

M Cullen ◽

R deWit ◽

...

Keyword(s):

Germ Cell ◽

Medical Research ◽

Poor Prognosis ◽

Research Council ◽

Medical Research Council ◽

Lung Metastases ◽

Germ Cell Tumors ◽

Sequential Chemotherapy ◽

European Organization ◽

Significant Difference

PURPOSE The aim of this randomized trial was to assess the potential therapeutic advantage of an intensive induction-sequential chemotherapy schedule (bleomycin, vincristine, cisplatin [BOP])/etoposide, ifosfamide, cisplatin, and bleomycin [VIP-B]), compared with a regimen based on bleomycin, etoposide, and cisplatin (BEP) (BEP/etoposide and cisplatin [EP]) for the treatment of patients with poor-prognosis metastatic nonseminomatous germ cell tumors (NSGCTs). PATIENTS AND METHODS Patients had one or more of the following: a retroperitoneal mass > or = 10 cm in diameter; mediastinal or supraclavicular mass > or = 5 cm in diameter; at least 20 lung metastases (any size); liver, bone, or brain metastases; and serum beta human chorionic gonadotropin (betaHCG) > or = 10,000 IU/L or alfa fetoprotein (AFP) > or = 1,000 IU/L. A total of 380 patients were accrued between May 1990 and June 1994 into this joint Medical Research Council (MRC)/European Organization for Research and Treatment of Cancer (EORTC) trial; of these, nine patients were deemed ineligible. RESULTS There was no significant difference between the two arms in the proportion of patients who achieved a complete response (CR) with chemotherapy alone, ie, 79 of 185 assessable patients (57%) with BEP/EP and 72 of 186 (54%) with BOP/VIP-B (P = 0.687). With a median follow-up of 3.1 years (maximum, 5.8), a total of 107 patients (28%) had progressive disease. There was no significant difference in time to first disease progression, or failure-free or overall survival between the two arms (P = 0.21, 0.101, and 0.190, respectively). The 1-year failure-free survival rates for BEP/EP and BOP/VIP-B were 60% (95% confidence interval [CI], 53% to 67%) and 53% (95% CI, 47% to 61%). Grade 3 or 4 myelosuppression, febrile neutropenia, and weight loss were more pronounced with BOP/VIP-B than with BEP/EP, and there were more toxic deaths with BOP/VIP-B than BEP/EP (18 [9%] v nine [5%]). CONCLUSION The intensive BOP/VIP-B therapy was associated with more toxicity, but there was no evidence of an improvement in response rate or survival compared with treatment with BEP/EP.

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Prognostic Factors in Metastatic IMon-Seminomatous Germ Cell Tumours: The Medical Research Council Studies

European Urology ◽

10.1159/000474593 ◽

1993 ◽

Vol 23 (1) ◽

pp. 196-201 ◽

Cited By ~ 7

Author(s):

G.M. Mead ◽

S.P. Stenning

Keyword(s):

Prognostic Factors ◽

Germ Cell ◽

Medical Research ◽

Research Council ◽

Medical Research Council ◽

Germ Cell Tumours

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Predicting Outcomes in Men With Metastatic Nonseminomatous Germ Cell Tumors (NSGCT): Results From the IGCCCG Update Consortium

Journal of Clinical Oncology ◽

10.1200/jco.20.03296 ◽

2021 ◽

pp. JCO.20.03296

Author(s):

Silke Gillessen ◽

Nicolas Sauvé ◽

Laurence Collette ◽

Gedske Daugaard ◽

Ronald de Wit ◽

...

Keyword(s):

Prognostic Factors ◽

Germ Cell ◽

Prognostic Model ◽

Lung Metastases ◽

Cell Cancer ◽

Germ Cell Tumors ◽

Progression Free Survival ◽

Collaborative Group ◽

Data Set ◽

Nonseminomatous Germ Cell Tumors

PURPOSE The classification of the International Germ Cell Cancer Collaborative Group (IGCCCG) plays a pivotal role in the management of metastatic germ cell tumors but relies on data of patients treated between 1975 and 1990. MATERIALS AND METHODS Data on 9,728 men with metastatic nonseminomatous germ cell tumors treated with cisplatin- and etoposide-based first-line chemotherapy between 1990 and 2013 were collected from 30 institutions or collaborative groups in Europe, North America, and Australia. Clinical trial and registry data were included. Primary end points were progression-free survival (PFS) and overall survival (OS). The survival estimates were updated for the current era. Additionally, a novel prognostic model for PFS was developed in 3,543 patients with complete information on potentially relevant variables. The results were validated in an independent data set. RESULTS Compared with the original IGCCCG publication, 5-year PFS remained similar in patients with good prognosis with 89% (87%-91%) versus 90% (95% CI, 89 to 91), but the 5-year OS increased from 92% (90%-94%) to 96% (95%-96%). In patients with intermediate prognosis, PFS remained similar with 75% (71%-79%) versus 78% (76%-80%) and the OS increased from 80% (76%-84%) to 89% (88%-91%). In patients with poor prognosis, the PFS increased from 41% (95% CI, 35 to 47) to 54% (95% CI, 52 to 56) and the OS from 48% (95% CI, 42 to 54) to 67% (95% CI, 65 to 69). A more granular prognostic model was developed and independently validated. This model identified a new cutoff of lactate dehydrogenase at a 2.5 upper limit of normal and increasing age and presence of lung metastases as additional adverse prognostic factors. An online calculator is provided ( https://www.eortc.org/IGCCCG-Update ). CONCLUSION The IGCCCG Update model improves individual prognostication in metastatic nonseminomatous germ cell tumors. Increasing age and lung metastases add granularity to the original IGCCCG classification as adverse prognostic factors.

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