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Positron Emission Tomography Scans in Postchemotherapy Seminoma Patients With Residual Masses: A Retrospective Review From Indiana University Hospital

Division of Hematology-Oncology, Indiana University School of Medicine, Walther Cancer Institute, and Indiana University Center, Indianapolis, IN

Mark Tann

Division of Nuclear Medicine, Indiana University School of Medicine, Indianapolis, IN

Kenneth Kesler

Department of Surgery, Thoracic Division, Indiana University School of Medicine, Indianapolis, IN

Alan McCool, Richard S. Foster

Department of Urology, Indiana University School of Medicine, Indianapolis, IN

Lawrence H. Einhorn

Division of Hematology-Oncology, Indiana University School of Medicine, Walther Cancer Institute, and Indiana University Center, Indianapolis, IN

To the Editor:

Testicular cancer is highly curable, with 5-year survival rates over 95%.¹ Seminomas usually present as confined to the testis (clinical stage I). Small volume stage II disease (< 3 cm) is treated with abdominal radiotherapy. Bulky stage II and all stage III disease is treated with cisplatin-based chemotherapy. A confounding issue with seminoma is the evaluation of a postchemotherapy residual mass.² This usually represents fibrosis rather than persistent seminoma. Investigators at Memorial Sloan-Kettering (New York, NY) advocate surgery for all residual postchemotherapy masses larger than 3 cm.³ Other centers, including ours, have taken a more conservative approach given the high incidence of fibrosis. We perform serial computed tomography (CT) imaging and only intervene if there is progressive disease.⁴

Positron emission tomography (PET) scans have been used in an attempt to differentiate between fibrosis and persistent germ cell tumors. With nonseminomatous germ cell cancer, PET scans cannot distinguish fibrosis from teratoma as both are metabolically inert.⁵ For pure seminoma, where teratoma is not a factor, PET scans have been clinically utilized to predict the histology of residual masses. In the SEMPET trial, PET scans more accurately predicted which persistent lesions represented fibrosis versus persistent seminoma compared with CT scans.^6,7 We retrospectively assessed the accuracy of postchemotherapy PET scans in seminoma patients with residual masses. All PET scans were performed a minimum of 6 weeks from completion of chemotherapy in patients with residual postchemotherapy masses. Study was conducted from April 2002 to September 2004. A PET scan was considered true-positive if either the mass in question was proven to represent persistent seminoma by surgical pathology or if the patient clinically progressed. A study was considered false-positive if surgery done afterwards revealed fibrosis, necrosis, or inflammation. A study was considered true-negative if a patient remained disease free after the negative scan. A study was considered false-negative if a patient had a relapse of disease after a scan was interpreted as negative.

Twenty-four PET scans were reviewed from 19 patients who had received primary or salvage chemotherapy for seminoma. Fourteen PET scans were done after primary chemotherapy and 10 were done after salvage treatment. Twelve PET scans were read as negative. None of the patients with negative PET scans have relapsed with seminoma, thus giving PET scans a negative predictive value of 100%. These 12 patients have a median follow-up of 29+ months (range, 22+ to 38+ months). There were 12 PET scans read as positive. PET scans identified all eight patients who had persistent disease after chemotherapy, thus giving them a sensitivity of 100%. However, four positive PET scans led to surgical resections of residual masses revealing only fibrosis, necrosis, or inflammation (false-positive). The positive predictive value for PET scans was 67%.

Of the 24 PET scans, 11 evaluated residual masses larger than 3 cm on CT scans. Nine of 11 masses were correctly predicted by PET scan. This included two negative PET scans. There were two patients with residual masses larger than 3 cm in which PET scans were associated with a false-positive result. Thirteen patients had residual CT masses smaller than 3 cm. Ten patients had negative PET scans and three patients had positive PET scans. Two of three were false-positive.

Management of postchemotherapy residual masses in seminoma patients remains a confounding issue, with the primary dilemma being whether to resect or simply observe these lesions. Data from Memorial Sloan-Kettering has led to suggesting the resection of all lesions 3 cm or larger.³ A significant proportion of these surgeries yields only necrosis or inflammation. A literature review of residual masses in seminoma patients documented that of the 116 that were 3 cm or larger, only 11 of 64 (17%) resectable masses revealed viable disease.⁸

PET scans displayed a high negative predictive value in this study. This can be reassuring to both the clinician and a patient who after having a negative PET scan, the possibility of future relapse is highly unlikely. However, there were four false-positive PET scans including two patients in whom residual masses were larger than 3 cm. Utilizing the size criteria adopted by Memorial Sloan-Kettering, our PET scans obviated two surgeries, but also led to two unnecessary surgeries. As all PET scans were done at least 6 weeks after chemotherapy, the chances of these studies highlighting inflammation were minimized. Five of 10 postsalvage chemotherapy PET scans were positive compared with five of 14 PET scans being positive after initial chemotherapy.

PET scans are being used more frequently in treatment paradigms for various malignancies. However, as our data show, with respect to residual masses in postchemotherapy seminoma patients, positive PET scans have their limitations and should not be relied on solely to make decisions in this patient population. A negative PET scan indicates a low likelihood of persistent seminoma after chemotherapy. However, a positive PET scan does not translate to a similar high probability of persistent seminoma.

Authors' Disclosures of Potential Conflicts of Interest

Although all authors completed the disclosure declaration, the following author or immediate family members indicated a financial interest. No conflict exists for drugs or devices used in a study if they are not being evaluated as part of the investigation. For a detailed description of the disclosure categories, or for more information about ASCO's conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors.

Authors Employment Leadership Consultant Stock Honoraria Research Funds Testimony Other Lawrence H. Einhorn Amgen; Glaxo; SmithKline; Biogenidec

ACKNOWLEDGMENTS

This data was presented, in part, at the 41st Annual Meeting of the American Society of Clinical Oncology, Orlando, Florida, May 13-17, 2005.

REFERENCES

1. Ries LA, Eisner MP, Kosary CL, et al: SEER Cancer Statistics Review, 1975-2001. National Cancer Institute, Bethesda, MD, 2004

2. Quek ML, Simma-Chiang V, Stein JP, et al: Postchemotherapy residual masses in advanced seminoma: Current management and outcomes. Expert Rev Anticancer Ther 5:869-874, 2005[CrossRef][Medline]

3. Puc HS, Heelan R, Mazumdar M, et al: Management of residual mass in advanced seminoma: Results and recommendations from the Memorial Sloan-Kettering Cancer Center. J Clin Oncol 14:454-460, 1996[Abstract/Free Full Text]

4. Schultz SM, Einhorn LH, Conces DJ, et al: Management of postchemothreapy residual mass in patients with advanced seminoma: Indiana University experience. J Clin Oncol 7:1497-1503, 1989[Abstract]

5. Stephens AW, Gonin R, Hutchins GD, et al: Positron emission tomography evaluation of residual radiographic abnormalities in postchemotherapy germ cell tumor patients. J Clin Oncol 14:1637-1641, 1996[Abstract/Free Full Text]

6. De Santis M, Becherer A, Bokemeyer C, et al: 2-¹⁸fluoro-deoxy-D-glucose positron emission tomography is a reliable predictor for viable tumor in postchemotherapy seminoma: An update of the prospective multicentric SEMPET trial. J Clin Oncol 22:1034-1039, 2004[Abstract/Free Full Text]

7. Becherer A, De Santis M, Karanikas G, et al.: FDG PET is superior to CT in the prediction of viable tumor in post-chemotherapy seminoma residuals. Eur J Radiol 54:284-288, 2005[CrossRef][Medline]

8. Flechon A, Bompas E, Biron P, et al: Management of post-chemotherapy residual masses in advanced seminoma. J Urol 168:1975-1979, 2002[CrossRef][Medline]

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