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© 1999 American Society for Clinical Oncology Positron Emission Tomography Scans in the Evaluation of Postchemotherapy Residual Masses in Patients With SeminomaFrom the Department of Medicine, Division of Hematology/Oncology, Indiana University Medical Center, Indianapolis, IN. Address reprint requests to Lawrence H. Einhorn, MD, Indiana University, Indiana Cancer Pavilion, 535 Barnhill Dr, Route 473, Indianapolis, IN 46202.
PURPOSE: To assess the ability of positron emission tomography (PET) scans in differentiating between necrosis and viable seminoma in postchemotherapy (PC) residual disease. PATIENTS AND METHODS: We conducted a prospective study of 29 patients with seminoma at Indiana University. All patients had PC residual disease. Computed tomography and PET scans were performed for 19 patients after primary chemotherapy (group A) and for 10 patients after salvage chemotherapy (group B).
RESULTS: In group A, the PC masses were CONCLUSION: PET scans have no apparent benefit in PC evaluation of residual masses in bulky seminoma.
TESTICULAR GERM CELL tumors are rare but are the most common carcinoma in the age group of 15 to 35 years. Before the use of cisplatin, the cure rates were less than 10%. Today, germ cell tumors are highly curable, and effort should be made to decrease treatment-related morbidity. The management of postchemotherapy (PC) residual disease is well defined in nonseminomatous germ cell tumors (NSGCT). Most patients with PC residual masses undergo surgical resection. Approximately 45% have necrosis, 45% teratoma, and 10% residual carcinoma.1,2 No useful noninvasive method has been shown to be beneficial in the identification of patients with necrosis before surgery; therefore, most patients with residual masses should undergo surgical resection of persistent disease.
The treatment of patients with pure seminomas and PC residual disease is highly controversial. At Indiana University, such patients are monitored with serial computed tomography (CT) scans regardless of the size of the residual mass. At Memorial Sloan-Kettering Cancer Center (MSKCC), patients with a residual mass Gallium scan has been used in this setting and was not shown to be beneficial in differentiating between necrosis and viable seminoma.5 However, when positron emission tomography (PET) scans were used to detect PC residual disease in patients with NSGCT, a significant difference was observed between viable carcinoma and either teratoma or necrosis.6 Unfortunately, it did not distinguish between fibrosis and teratoma. However, pure seminomas do not contain teratomatous elements, thus, PET scans have the potential to determine whether a residual mass needs resection (seminoma) or merely observation (fibrosis). Therefore, this prospective study was conducted to assess the use of PET scans in the management analysis of PC residual disease in patients with bulky seminoma. Proof of the hypothesis would involve a PC resection of viable seminoma in a patient with a positive PET scan result.
Twenty-nine patients with a median age of 38 years (range, 24 to 67 years) were prospectively evaluated between February 1996 and March 1998. All histologic slides were reviewed at Indiana University, and the diagnosis of pure seminoma was confirmed. A staging work-up was performed with a plain chest radiograph or a chest CT scan and an abdominal CT scan. Only patients with bulky seminomas receiving chemotherapy were included in the study. All patients had baseline serum tumor markers with a beta-human chorionic gonadotropin and alpha-fetoprotein. Alpha-fetoprotein was normal in all patients. Nineteen of 29 patients were evaluated initially at the time of diagnosis (group A), and 10 patients were evaluated after relapse and at the time of salvage chemotherapy (group B). Patients who received prior radiotherapy to the assessable area were excluded. In group A, 11 patients had primary testicular seminoma, four had primary retroperitoneal seminoma, and four had primary anterior mediastinal seminoma. In group B, eight patients had primary testicular seminoma, and two had primary retroperitoneal seminoma.
All patients underwent CT and PET scans at the completion of therapy. The PET scanning was performed by injecting 10 mCi of F-18-fluorodeoxyglucose (FDG) and collecting the dynamic emission data for 1 hour. A single static emission scan at 1 hour was reconstructed, and regions of interest were placed over the residual abnormality. The location of the maximum FDG uptake was then determined. Standardized uptake values (SUVs), a quantitative measure of tumor uptake of the tracer-adjusted dose and body weight, were calculated for the region of maximal FDG uptake. Patients with an SUV Follow-up evaluation occurred every 2 months the first year, every 4 months the second year, every 6 months during the third, fourth, and fifth year, and annually thereafter. Follow-up included a chest radiograph, tumor markers, and physical examination. CT scans of the involved area were performed every 4 months during the first year and every 6 months during the second year. If the mass was stable or decreasing in size after the second year, then no further CT scans were performed. If the mass was enlarging or if the beta-human chorionic gonadotropin level was increasing, patients received salvage chemotherapy with either vinblastine and ifosfamide combination chemotherapy7 or high-dose chemotherapy and stem-cell transplant.
Patient characteristics are listed in Table 1. All patients in group A received three or four cycles of cisplatin/etoposide-containing regimens. They all had residual radiographic abnormalities after chemotherapy, including 14 with residual mass greater than 3 cm. All patients underwent CT and PET scans at the completion of chemotherapy. Seventeen patients had a negative PET scan results with no uptake, and two patients had minimal uptake (SUV, 2.4 and 3.3, respectively). None of these patients have relapsed (median follow-up duration, 11.5 months; range, 6 to 26 months). Five of 19 patients have stable CT scans, and 14 of 19 have a mass that is decreasing in size.
All patients in group B received three or four cycles of cisplatin and etoposide (with or without bleomycin) as initial chemotherapy. All treatments were administered at centers other than Indiana University. All but one patient had residual radiographic abnormalities after their initial chemotherapy. The median time to relapse was 4 months (range, 2 to 13 months). These patients were referred to Indiana University for salvage chemotherapy. Progressive disease in these 10 patients was primarily in the retroperitoneum. However, other sites of relapse included the posterior mediastinum (n = 2), liver (n = 1), lung (n = 1), and cervical nodes (n = 1). Seven of 10 patients received three or four cycles of vinblastine, ifosfamide, and cisplatin,7 and three underwent high-dose chemotherapy with peripheral stem-cell support. All 10 patients had a residual mass (sizes listed in Table 1). Only one patient had a positive PET scan result, with an SUV of 4.2 for a posterior mediastinal 2.5-cm mass. This patient's 5-cm retroperitoneal mass did not have any FDG uptake. He underwent a resection of the posterior mediastinal mass, which only showed necrosis. Nine months later, he had an enlarging retroperitoneal mass. The other nine patients had a negative PET scan result with no FDG uptake after salvage therapy. Five of nine patients have remained without evidence of disease (median follow-up duration, 8 months; range, 7 to 22 months). However, four other patients relapsed after a negative PET scan result: one had a 3-cm residual mass, two had a less than 3-cm mass, and one was undetermined. All patients relapsed with enlarging masses in the area of previous disease. Four of five patients relapsed in the retroperitoneum, and one relapsed in the peripancreatic area. All five patients who relapsed were further treated with high-dose chemotherapy and stem-cell support and are all currently without evidence of disease (median follow-up duration, 12 months; range, 2 to 26 months). In our study, the sensitivity of PET scan to detect seminoma in the residual PC mass was zero (zero of one), and the specificity to identify true negative was 96%.
PET scans have been used in different malignancies for staging. One of the first uses of PET scans in oncology was in the management of solitary pulmonary nodules. Lowe et al8 reported 89 patients with an indeterminate solitary pulmonary nodule after an evaluation with chest radiograph and CT scan. PET scan results were both reported by the calculated SUV value and by a visual scoring model. All patients underwent surgical resection, and the PET scans were compared with the pathology results. The SUV had a 92% sensitivity and a 90% specificity in the detection of malignant nodules. The visual method had a 98% sensitivity and a 69% specificity. PET scan has also been used to rule out lymph node metastasis and/or distant metastases in patients with non–small-cell lung cancer before curative surgery. Vansteenkiste et al9 compared the accuracy of CT scan with or without PET scanning in the detection of locoregional lymph node metastasis in 68 patients with non–small-cell lung cancer. All patients underwent a CT scan, a PET scan, and invasive surgical resection. CT scan correctly identified only 40 of 68 patients. PET scan plus CT scan was accurate in 59 patients but resulted in overstaging in four of 68 patients. PET scan has also been used in other situations, including staging of high-risk melanoma,10 detecting recurrent or persistent nasopharyngeal carcinoma,11,12and detecting recurrent resectable colon cancer in patients with an elevated carcinoembryonic antigen level.13 We previously evaluated PET scans in NSGCT6 and demonstrated that PET scan was useful in differentiating residual cancer from necrosis or teratoma. Other investigators have also evaluated PET scans in patients with germ cell tumors.14 There is limited value for PC management of residual masses in NSGCT because PET scan results are negative in both teratoma and necrosis. Therefore, a negative PET scan result would not dissuade a physician from recommending surgical resection of a persistent mass. However, a persistent PC residual abnormality in patients with pure seminoma should be either seminoma or necrosis. In this setting, a PET scan might determine the necessity for PC resection.
The management of PC residual disease in patients with advanced seminoma is controversial. The two management options include surgical resection versus observation. Primary chemotherapy with cisplatin/etoposide-containing regimens for advanced seminomas have a more than 90%curative potential. Almost all patients with bulky disease have a residual mass after completion of chemotherapy. In our experience, fewer than 10% of these patients will relapse, with most instances occurring in the first 2 years of follow-up. Therefore, effort should be made to reduce treatment-related morbidity by avoiding unnecessary invasive procedures. At MSKCC, patients with residual masses In this study, we performed a prospective analysis of PET scanning in the evaluation of PC residual masses in seminoma. No patient relapsed after receiving first-line chemotherapy. Five of 10 patients who received salvage chemotherapy relapsed. None of these patients had any FDG uptake in the residual mass, and they all relapsed in the same area. One of these patients had a positive PET scan in the mediastinum. However, resection of this mass showed only necrosis. Treatment of residual disease in patients after salvage chemotherapy is a difficult issue and should be decided on an individual basis. If the residual disease is in the same area of previous relapse, then surgical resection should be considered. However, if surgery has a high degree of morbidity secondary to either the size or location of the mass, then observation might be more reasonable. Unfortunately, PET scans failed to help resolve this problem. Therefore, we have found that PET scanning is not beneficial in distinguishing necrosis from viable seminoma, and we do not recommend the routine use of PET scans in the evaluation of residual PC masses in seminoma.
Supported in part by grant no. 2R35CA-39844-14 from the National Cancer Institute, Bethesda, MD, and the Walther Cancer Institute, Indianapolis, IN.
Presented in part at the Thirty-Fifth Annual Meeting of the American Society of Clinical Oncology, Atlanta, GA, May 15-18, 1999.
1. Fox EP, Weathers TD, Williams SD, et al: Outcome analysis for patients with persistent germ cell carcinoma in post-chemotherapy retroperitoneal lymph node dissection. J Clin Oncol11:1294-1299, 1993 2. Fossa S, Aass N, Ous S, et al: Histology of tumor residuals following chemotherapy in patients with advanced nonseminomatous testicular cancer. J Urol142:1239-1242, 1989[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 Oncol14:454-460, 1996 4. Herr HW, Sheinfeld J, Puc HS, et al: Surgery for a post-chemotherapy mass in seminoma. J Urol157:860-862, 1997[Medline] 5. Warren GP, Einhorn LH: Gallium scans in the evaluation of residual masses after chemotherapy for seminoma. J Clin Oncol13:2784-2788, 1995[Abstract]
6.
Stephens AW, Gonin R, Hutchins GD, et al: Positron emission tomography evaluation of residual radiographic abnormalities in postchemotherapy germ cell tumor patients. J Clin Oncol14:1637-1641, 1996 7. Miller KD, Loehrer PJ, Gonin R, et al: Salvage chemotherapy with vinblastine, ifosfamide, and cisplatin in recurrent seminoma. J Clin Oncol15:1427-1431, 1997[Abstract] 8. Lowe VJ, Fletcher JW, Gobar L, et al: Prospective investigation of positron emission tomography in lung nodules. J Clin Oncol16:1075-1084, 1998[Abstract] 9. Vansteenkiste JF, Stroobants SG, De Leyn RP, et al: Lymph node staging in non-small cell lung cancer with FDG-PET scan: A prospective study on 690 lymph node stations from 68 patients. J Clin Oncol16:2142-2149, 1998[Abstract] 10. Rinne D, Baum RP, Hor G, et al: Primary staging and follow-up of high risk melanoma patients with whole-body 18F-fluorodeoxyglucose postron emission tomography: Results of a prospective study of 100 patients. Cancer82:1664-1671, 1998[Medline]
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Anzai Y, Carrol WR, Quint DJ, et al: Recurrence of head and neck cancer after surgery or irradiation: Prospective comparison of 2-deoxy-2-[F-18]fluoro-D-glucose PET and MRI imaging diagnoses. Radiology200:135-141, 1996 12. Kao CH, Changlai SP, Chieng PU, et al: Detection of recurrent or persistent nasopharyngeal carcinomas after radiotherapy with 18-fluoro-2-deoxyglucose positron emission tomography and comparison with computed tomography. J Clin Oncol16:3550-3555, 1998[Abstract] 13. Valk PE, Abella-Columna E, Tesar RD, et al: Detection of recurrent colorectal cancer by FDG PET in patients with serum CEA elevation. J Nucl Med 39:135P, 1998
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Cremerius U, Effert PJ, Adam G, et al: FDG PET for detection and therapy control of metastatic germ cell tumor. J Nucl Med39:815-822, 1998 15. Schultz SM, Einhorn LH, Conces DJ, et al: Management of postchemotherapy residual mass in patients with advanced seminoma: Indiana University experience. J Clin Oncol7:1497-1503, 1989[Abstract] Submitted April 23, 1999; accepted July 8, 1999.
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Copyright © 1999 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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ABSTRACT
INTRODUCTION
3 cm in 14 patients, less than 3 cm in three patients, and not quantified in two patients. All of the patients in group A had negative PET scan results and have had stable or decreasing residual mass size (median follow-up duration, 11.5 months; range, 6 to 26 months). In group B, the PC masses were 
