Clinical Relevance of “Late” in the Management of Late Relapse After Treatment for a Germ Cell Tumor

Purpose To define the incidence, clinical features, and outcome to salvage chemotherapy in patients with late-relapse germ cell tumor (GCT) after a complete response to first-line chemotherapy. Patients and Methods Two patient populations were examined. First, retrospective analysis of 246 patients treated on a clinical trial with salvage chemotherapy was performed; 29 patients with late-relapse GCT were identified and evaluated for treatment outcome and survival. Salvage regimens included paclitaxel, ifosfamide, and cisplatin, single agents, or a high-dose chemotherapy program. Second, the incidence of late relapse was assessed by retrospective analysis of 551 patients after a complete response (CR) to first-line chemotherapy. Results Twenty-nine patients received salvage chemotherapy on a clinical trial for late relapse GCT. The median survival was 23.9 months. At a median follow-up of 50.6 months, there were nine survivors. The chemotherapy regimens varied, but the only CRs were observed in patients treated with paclitaxel, ifosfamide, and cisplatin. Seven (50%) of 14 patients treated with paclitaxel, ifosfamide, and cisplatin achieved a continuous CR. Among the second population of 551 patients who had previously achieved a CR to a first-line chemotherapy trial, 17 were identified as having a late relapse (3%). The median time to relapse for these 17 patients was 7.8 years. Conclusion Late-relapse GCT is uncommon and is associated with a poor prognosis resulting from a high degree of resistance to chemotherapy. Chemotherapy with paclitaxel, ifosfamide, and cisplatin followed by surgery may be effective in patients with late-relapse GCT who are not considered candidates for primary surgery.

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Clinical characteristics and outcome of late relapse after cisplatin-based chemotherapy of germ cell tumor. An update

Journal of Clinical Oncology ◽

10.1200/jco.2004.22.14_suppl.4529 ◽

2004 ◽

Vol 22 (14_suppl) ◽

pp. 4529-4529

Author(s):

A. Gerl ◽

M. Hentrich ◽

N. Weber ◽

M. Schlemmer ◽

R. Hartenstein ◽

...

Keyword(s):

Germ Cell ◽

Germ Cell Tumor ◽

Clinical Characteristics ◽

Cell Tumor ◽

Late Relapse

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A 10-year retrospective review of germ cell tumors not cured with cisplatin-based chemotherapy.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.6_suppl.325 ◽

2013 ◽

Vol 31 (6_suppl) ◽

pp. 325-325

Author(s):

Elizabeth O'Donnell ◽

Kathryn P. Gray ◽

Michelle S. Hirsch ◽

Praful Ravi ◽

Clair Beard ◽

...

Keyword(s):

Germ Cell ◽

Germ Cell Tumor ◽

Retrospective Review ◽

Clinical Stage ◽

Germ Cell Tumors ◽

Disease Free Survival ◽

Cell Tumor ◽

Smoking History ◽

Late Relapse ◽

High Dose

325 Background: In 2011, there were about 8260 cases of Germ Cell Tumor (GCT) diagnosed in the US, of those, 350 or 4% will die of their disease. We sought to review our experience with a 10-year cohort of 819 patients treated for GCT at Dana-Farber and synthesize the cumulative findings of those who died from their disease specifically looking for different sub-types of incurable GCTs. Methods: Retrospective review of 819 germ-cell tumors treated in our center between 2000 and 2010 to identify patients not cured with cisplatin-based chemotherapy. Inclusion criteria were men over the age of 18 treated for malignant germ cell tumor between 2000 and 2010 at the Dana-Farber Cancer Institute that died from their disease. The outcomes of interest were smoking history, extent of disease at diagnosis, primary site of disease, histology, presence of lymphovascular invasion, outcomes to first- and second-line therapies, treatment with high dose chemotherapy (HDC), late relapse, brain metastases, and presence or absence of transformed teratoma as cause of death. Results: 38 men were identified. Median age 35. More than half had a smoking history. 3 presented with clinical stage 1 disease, 8 good-risk metastatic disease, 4 intermediate-risk and 22 poor-risk at diagnosis. The majority (28) had testicular primaries, 7 mediastinal, one pituitary, one retroperitoneal and one unknown. 21 of 48 had complete responses to first-line therapy. 4 received HDC for relapsed disease. 10 relapsed after 2 years of disease-free survival. 7 died of transformed teratoma. 63% progressed directly through cisplatin-based chemotherapy and died as a result of non-teratomatous germ cell tumor burden. 18% died from unresectable or transformed teratoma and 26% died after suffering a late relapse of disease. Conclusions: Within the cohort of patient who died from their GCTs there are three distinct biological subtypes – the majority is platinum-refractory germ cell tumor while unresectable/transformed teratoma and late relapse make up the remainder. Understanding the unique biology of these disease states compared with curable disease may provide informative insights into chemotherapy resistance for cancer in general.

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Gene Expression Profiling of Early- and Late-Relapse Nonseminomatous Germ Cell Tumor and Primitive Neuroectodermal Tumor of the Testis

The Journal of Urology ◽

10.1097/01.ju.0000180085.66337.f3 ◽

2005 ◽

Vol 174 (5) ◽

pp. 1826-1827 ◽

Cited By ~ 1

Author(s):

Jerome P. Richie

Keyword(s):

Gene Expression ◽

Germ Cell ◽

Gene Expression Profiling ◽

Germ Cell Tumor ◽

Expression Profiling ◽

Primitive Neuroectodermal Tumor ◽

Cell Tumor ◽

Neuroectodermal Tumor ◽

Late Relapse ◽

Nonseminomatous Germ Cell Tumor

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Clinical Outcome and Predictors of Survival in Late Relapse of Germ Cell Tumor

Journal of Clinical Oncology ◽

10.1200/jco.2007.15.7453 ◽

2008 ◽

Vol 26 (34) ◽

pp. 5524-5529 ◽

Cited By ~ 74

Author(s):

David S. Sharp ◽

Brett S. Carver ◽

Scott E. Eggener ◽

G. Varuni Kondagunta ◽

Robert J. Motzer ◽

...

Keyword(s):

Germ Cell ◽

Germ Cell Tumor ◽

Multivariable Analysis ◽

Cell Tumor ◽

Late Relapse ◽

Retroperitoneal Lymph Node Dissection ◽

Prior History ◽

Cancer Specific Survival ◽

Complete Surgical Excision ◽

Multifocal Disease

Purpose Late relapse (LR) of germ cell tumor (GCT) is a well recognized entity associated with poor survival. We report on our experience with LR and determine predictors of survival. Patients and Methods From 1990 to 2004, 75 patients were managed for LR of GCT at our institution. Clinical and pathologic parameters were reviewed. Estimates of cancer-specific survival were generated using the Kaplan-Meier method, and a Cox proportional hazards model was used to assess potential predictors of outcome. Results The median time to LR was 6.9 years (range, 2.1 to 37.7 years). Overall, 56 patients (75%) had LR in the retroperitoneum, including 25 (93%) of 27 patients initially managed without retroperitoneal lymph node dissection. The 5-year cancer-specific survival (CSS) was 60% (95% CI, 46% to 71%). Patients who underwent complete surgical resection at time of LR (n = 45) had a 5-year CSS of 79% versus 36% for patients without complete resection (n = 30; P < .0001). The 5-year CSS for chemotherapy-naive patients was significantly greater than patients with a prior history of chemotherapy as part of their initial management (5-year CSS, 93% v 49%, respectively). In multivariable analysis of pretreatment parameters available at the time of LR, the presence of symptoms (hazard ratio [HR] = 4.9) and multifocal disease (HR = 3.0) were associated with an inferior CSS. Conclusion The data suggest that meticulous control of the retroperitoneum is critical to prevent LR in the retroperitoneum. In multivariable analysis, patients with a symptomatic presentation and those with multifocal disease have a significantly decreased survival. Survival is greatly improved if complete surgical excision of disease is attained.

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