Germ cell tumors (GCT) are uncommon neoplasms

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1 ORIGINAL ARTICLES: GENERAL THORACIC Pulmonary Metastasectomy for Testicular Germ Cell Tumors: A 28-Year Experience David Liu, MD, Amir Abolhoda, MD, Michael E. Burt, MD, PhD, Nael Martini, MD, Manjit S. Bains, MD, Robert J. Downey, MD, Valerie W. Rusch, MD, George J. Bosl, MD, and Robert J. Ginsberg, MD Thoracic Service, Department of Surgery, Genitourinary Oncology Service, Division of Solid Tumor Oncology, and Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York Background. The role of surgery in patients with pulmonary metastatic germ cell tumors has been evolving since the 1970s. To evaluate the results of pulmonary resection, we reviewed our 28-year experience. Methods. Between July 1967 and May 1995, 157 patients with testicular germ cell tumors underwent pulmonary resections for suspected metastases. Their clinical and pathological data were reviewed. Kaplan-Meier and Cox regression models were used to analyze prognostic factors for survival after resection of metastatic disease. Results. All patients were male with median age of 27 years (range 15 65). Complete resection was accomplished in 155 (99%) patients. Viable carcinoma was present in 44% (70) of the patients. Forty-one (26%) patients had metastases to other sites after pulmonary metastasectomy. The overall actuarial survival 5 years after pulmonary resection was 68% for the entire group and 82% for patients diagnosed after On multivariate analysis, the adverse prognostic factors were metastases to nonpulmonary visceral sites (p ) and the presence of viable carcinoma in the resected specimen (p < ). Conclusions. With current chemotherapy regimens, almost 85% of the patients with testicular germ cell tumors undergoing complete resection of their pulmonary metastases can be expected to achieve long-term survival. (Ann Thorac Surg 1998;66: ) 1998 by The Society of Thoracic Surgeons Germ cell tumors (GCT) are uncommon neoplasms accounting for 1% of all cancers, but are the most common malignancy in young adult males between the ages of 15 and 35 years [1]. Ninety percent of these tumors arise from the testes. The current annual incidence of GCT is approximately 5 cases per 100,000. While the incidence of GCT has been steadily increasing, the mortality rate from GCT has declined [2] which has been attributed to the advent of an effective multimodality approach consisting primarily of cisplatin-based chemotherapy and surgery. The prognosis of patients with GCT, including those patients with distant metastatic spread (most commonly lung [3]), is excellent. Surgical resection of residual disease after chemotherapy plays an important adjunctive role in the management of germ cell tumors. We report our experience with pulmonary metastasectomy and its role in the multimodality therapy of GCT. Material and Methods Between July 1967 and May 1995, 2,138 patients with newly diagnosed GCT were seen at the Memorial Sloan- Presented at the Thirty-fourth Annual Meeting of The Society of Thoracic Surgeons, New Orleans, LA, Jan 26 28, Address reprint requests to Dr Ginsberg, Division of Thoracic Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, C-881, New York, NY ( GinsbergR@mskcc.org). Kettering Cancer Center. One thousand eight hundred patients had testicular primaries. Approximately 30% of these patients developed intrathoracic lesions. During this time period, 168 patients with testicular GCT had radiographic evidence of intrathoracic abnormalities after chemotherapy and underwent thoracic exploration with either diagnostic or therapeutic intentions. We excluded patients who had mediastinal disease and identified 157 patients with intrathoracic lesions limited to the lungs who are the subjects of this study. Operative indications were as follows: patients who had (1) complete serologic response with residual pulmonary lesions, (2) evidence of persistent intrathoracic disease with elevated tumor markers despite a full course of chemotherapy, or (3) lesions which did not respond or progressed while on chemotherapy. Complete clinical and pathologic data were reviewed. Serum tumor markers, -fetoprotein (AFP) and human chorionic gonadotropin (HCG), were recorded if obtained within 3 weeks before their surgery. Clinical outcome was measured from the time of the first thoracic operation to the date of the first recurrence and to the date of either the last follow-up or death. Categories at the time of the last follow-up were no evidence of disease, alive with disease, died of other causes, and died of disease. All statistical analyses were performed using SPSS 6.1 for Windows (SPSS Inc, Chicago, IL). The Kaplan-Meier and Cox regression methods were used to analyze prognostic factors for survival after resection of metastatic 1998 by The Society of Thoracic Surgeons /98/$19.00 Published by Elsevier Science Inc PII S (98)

2 1710 LIU ET AL Ann Thorac Surg PULMONARY METASTASECTOMY FOR TESTICULAR GCT 1998;66: Table 1. Histology of the Testicular Primary and Resected Pulmonary Lesions Histologic Type Viable Tumor Fibrosis/ Necrosis Mature Teratoma No. of patients Nonseminomas Pure embryonal cell Teratocarcinoma Mature teratoma Mixed type Seminomas Total disease. A p value of less than 0.05 was regarded as statistically significant. Diagnosis All patients were male. Their ages ranged from 15 to 65 years, with a median of 27 years. Ninety-seven percent of the testicular primary tumors (n 153) were nonseminomas. Forty-nine patients had pure embryonal cell carcinoma which accounted for almost one third of all histologies, 46 had a mixed pattern, 34 had teratocarcinomas, and 24 had mature teratomas (Table 1). Nearly half the patients (n 71) presented with synchronous metastases. For those patients who developed metastases subsequently, the median interval from the time of initial diagnosis was 8 months with a range from 1 to 175 months. Forty-three patients had solitary metastases. The remainder had 2 or more metastases with a median number of 4 and a range of 2 to 27. Of the patients with multiple lesions, 61 had lesions confined to one lung, and 53 had lesions involving both lungs. Treatment All 157 patients in this review had undergone an inguinal orchiectomy for their primary testicular lesion and 153 patients were then treated with systemic chemotherapy. Of these, 143 patients received cisplatin-based chemotherapy. Four patients received only external radiation to the retroperitoneum and inguinal regions after orchiectomy. In addition to chemotherapy, 85 patients underwent retroperitoneal lymph node dissections, 25 of which were performed either concurrently with their pulmonary resections or during the same hospital stay. Nineteen patients had disease involving other organs and local control was obtained before undergoing pulmonary resection. The remaining 138 patients had hematogenous spread limited to the lung. One hundred two patients had serum tumor markers assessed within 3 weeks before their surgery. The serology was normal in 94 patients. Eight patients had elevated serum tumor markers defined by AFP 15 ng/ml, HCG 2 ng/ml or 2.2 miu/ml. Viable tumor in the resected specimens was found in 5 (63%) of 8 patients with positive serologies compared with only 11 (12%) of 94 patients with normal serum tumor markers. The operative approach at the initial thoracotomy was unilateral in 104 patients and bilateral in the remainder either by a median sternotomy (n 20), clamshell (n 22), or staged bilateral thoracotomies (n 11). Conservation of pulmonary parenchyma when possible was the rule reflected by the fact that most resections were confined to wedge excisions (n 141). Fourteen patients had a lobectomy and 2 patients required a pneumonectomy. All patients underwent resection with curative intent except for 2 patients who were found to have unsuspected mediastinal disease in addition to their pulmonary lesions. There was one postoperative death secondary to pneumonia. Ten patients had complications after surgery, the most common being prolonged air leaks (n 5). Other complications included one aortic injury, one partial esophageal tear, one stroke, and two septic complications. The overall mortality rate was 0.6% and morbidity rate 6%. Results Histology Histologic examination of the resected pulmonary specimens revealed viable tumor in 70 patients, necrosis/ fibrosis in 47 patients, and mature teratoma in 40 patients. Sixty-three patients (40%) had histology from their resected pulmonary lesions that agreed with the histology from their testicular primary (Table 1). Interestingly, mature teratoma in the resected pulmonary lesions was found in 7 patients who had pure embryonal carcinoma in their primary histology. Of the 25 patients who underwent RPLN dissection and pulmonary resection either simultaneously or during the same hospital stay, 6 (24%) had discordant pathologies between the pulmonary and retroperitoneal specimens. Recurrence Seventy-three patients remained disease free after their first thoracic operation and 58 patients developed recurrences with the majority being located in the lungs. Nonpulmonary visceral sites of recurrence included brain, retroperitoneum, neck, liver, and other sites (Table 2). Seventy-four percent of patients (n 43) who had recurrence of disease did so within 1 year (median, 5 months). Thirty-three patients (58%) who had recurrences and both patients who had unresectable disease died. Table 2. Site of Recurrences After Pulmonary Resection (n 58 patients) Location No. of sites Lung 34 Brain 10 Retroperitoneum 8 Neck 4 Intraabdominal 4 Liver 4 Bone 3 Other (atrium, testis) 4

3 Ann Thorac Surg LIU ET AL 1998;66: PULMONARY METASTASECTOMY FOR TESTICULAR GCT 1711 Fig 1. Overall survival of patients after pulmonary resection. Fig 2. Overall survival according to histology of resected specimens. Survival The overall survival at 5 years was 68% and remained essentially unchanged thereafter (Fig 1). One hundred patients are currently alive without evidence of disease (NED) and 6 with recurrent disease. Forty-seven patients died of disease and 3 patients died of other causes including sepsis, complications of acute myelogenous leukemia, and bladder carcinoma. The median follow-up was 38 months. Since 1975, all chemotherapy was cisplatin-based. The 143 patients who received this chemotherapy had a 5-year survival rate of 71% whereas the 14 patients who received a non cisplatin-based regimen or no chemotherapy had a 5-year survival rate of 42% ( p ). Serum tumor markers within 3 weeks of surgery were recorded in 102 patients. Five (62%) of 8 patients with positive serologies and 75 (80%) of 94 patients with negative serologies were alive without disease with a median follow-up time of 82 months and 46 months, respectively ( p 0.21). Patients with residual viable tumor had a significantly worse prognosis when compared with patients who had findings of necrosis/fibrosis or mature teratoma. Overall 10-year survival for patients with viable carcinoma was 43% compared with 86% and 84% for patients with necrosis/fibrosis and mature teratoma, respectively ( p ) (Fig 2). One hundred sixteen patients had metastatic disease that was limited to either the lungs or lungs and retroperitoneum. The 5-year survival rate in this group was 77%. The remaining 41 patients who had involvement at sites other than lungs or the retroperitoneum had a significantly lower 5-year survival rate of 47% ( p ) (Fig 3). Various factors were analyzed for prognostic significance. These include age, disease-free interval after treatment of primary, primary histology, preoperative serum tumor markers, number of pulmonary metastases, number of lesions with viable tumor, location of metastases, presentation of pulmonary metastases (synchronous versus metachronous), extent of disease, type of chemotherapy, and pathology of resected pulmonary lesions (Table 3). On univariate analysis, the factors which were significant for worse survival were patients more than 25 years of age ( p 0.048), patients who did not receive cisplatin-based chemotherapy ( p ), patients who had cancer in their resected pulmonary lesions ( p ), and patients who had extrathoracic involvement as well, other than the retroperitoneum ( p ). On multivariate analysis, only patients who had viable tumor in their lungs at the time of thoracotomy ( p ) and patients who had nonpulmonary visceral metastases (p ) had significantly worse survival rates. Comment The lung is the most common site of metastases in patients with disseminated disease from testicular GCTs. These patients undergoing pulmonary resection have the best survival when compared with patients with metastases from other tumor types including epithelial tumors, sarcomas, and melanomas, resulting in 5-year survival rates of 68% [25]. For such patients, resection of metastases is routinely considered after completion of cisplatin-based chemotherapy. Surgical resection of residual pulmonary disease has an important role in determining the response to chemotherapy and identifying those patients that should receive additional chemotherapy (ie, presence of viable malignant tumor). Fig 3. Overall survival according to metastatic sites involved.

4 1712 LIU ET AL Ann Thorac Surg PULMONARY METASTASECTOMY FOR TESTICULAR GCT 1998;66: Table 3. Results of Univariate and Multivariate Analysis Variables No. of Patients Univariate Multivariate p Value p Value Age (y) Disease-free interval (mo) Primary histology Seminoma Nonseminoma 153 Cisplatin-based chemotherapy Yes No 14 Preoperative tumor markers Normal Elevated 18 No. of pulmonary metastases Solitary Multiple 114 Lesions with viable tumor Solitary Multiple 42 Location of metastases Unilateral Bilateral 53 Presentation of metastases Synchronous Metachronous 86 Extent of disseminated disease Lung only Lung other sites (brain, 41 neck, liver, gastrointestinal, bone) Pathology of resected lesions Cancer Mature teratoma 40 Fibrosis/necrosis 47 The role of pulmonary metastasectomy in the treatment of testicular GCT has been evolving with the introduction of cisplatin to chemotherapy regimens in the mid-1970s. Further advances were made in the mid- 1980s with the introduction of new technology, better detection methods, and treatment protocols. The improvements in the overall survival of patients undergoing pulmonary resection for their metastatic lesions reflects these periods. In the pre-cisplatin era ( ), the 5-year survival rate for patients after pulmonary resection was 41%. After cisplatin was introduced and became a standard component in the medical treatment of patients with metastatic disease, the 5-year survival rate improved to 65%. Patients diagnosed after 1985 had a 5-year survival rate of 82% ( p ) (Fig 4). This latter improvement is most likely due to stage migration [4]. Fig 4. Overall survival of patients according to year of primary diagnosis. One of the significant prognostic factors in our analysis was the pathology of the resected pulmonary specimens. Numerous studies have demonstrated the prognostic value of the histology of the resected residual lesions. Toner and colleagues examined 185 patients who underwent surgery within 6 months of completing chemotherapy [5]. In 157 patients who underwent retroperitoneal resections after chemotherapy, patients who had residual malignancy fared worse than patients who had necrotic debris or teratoma in their resected specimens. Einhorn and colleagues examined the role of surgical resection in disseminated testicular cancer after chemotherapeutic cytoreduction [6]. Twenty-one patients underwent surgical resection for residual pulmonary lesions and 41 patients underwent lymphadenectomy for persistent retroperitoneal disease. Thirty-five of 39 patients with benign pathology remained continuously free of disease with a minimum postoperative follow-up time of 6 months. In contrast, only 2 of 22 patients with resected carcinomas remained continuously free of disease. Similarly, in a study by Fosså and associates, 83 of 89 patients with benign pathology were without evidence of disease after a median observation of 55 months [7]. Only 7 of 12 patients with malignant tumor in the operative specimen survived without evidence of disease. In our study, 73 (84%) of 87 patients with complete necrosis and/or fibrosis or mature teratoma are alive and well, whereas only 27 (39%) of 70 patients with viable malignant tumor in their resected lesions are alive and well at last follow-up with a median observation of 38 months (Table 4). About 15% to 20% of all resected residual masses (pulmonary and retroperitoneal) contain viable GCT, and the remainder contain either necrosis/fibrosis or mature teratoma in about equal percentages [5, 8]. Interestingly, the percent of residual masses containing viable tumor is higher in pulmonary residual lesions than in retroperitoneal masses [6, 9 11]. In these studies, carcinoma accounted for approximately 31% to 52% of all pathologies compared with 42% in our study. Several studies have attempted to predict the histology of the residual lesions preoperatively in order to spare

5 Ann Thorac Surg LIU ET AL 1998;66: PULMONARY METASTASECTOMY FOR TESTICULAR GCT 1713 Table 4. Status of Patients According to Histology of Resected Specimens Viable Tumor Necrosis/Fibrosis Mature Teratoma AWD DOC DOD NED Total AWD alive with disease, DOC died of other causes, DOD died of disease, NED no evidence of disease. those patients with benign pathology from operation [7, 12 15]. Various predictor factors have been assessed including size of lesion before and after chemotherapy, histology of primary tumor, tumor markers, findings on computed tomographic scan, and most recently positron emission tomography scan. None have demonstrated a reliability in predicting preoperatively which masses contain necrosis/fibrosis, mature teratoma, or viable malignant tumor. When the pathologies between the retroperitoneal residual thoracic masses were compared, there were discordant findings ranging from 25% to 46% [11, 16 18]. In our study, 6 of 27 patients had dissimilar pathologies for a discordant rate of 22%. Therefore, pathologic findings from one site cannot be reliably used to predict the histology of another site. It is unclear however, whether or not resection of all lesions is necessary. Watchful waiting may be another option. Traditionally, patients with elevated serum markers, indicative of persistent disease were believed to be unresectable and not considered for surgical resection. However, a few studies have demonstrated the potential for cure with salvage surgery in a select group of patients. Patients who were most likely to benefit from pulmonary resection of chemoresistant disease had lesions which were limited to one site and completely resectable. In a study by Murphy and colleagues, 3 of 4 patients with disease limited to the lung parenchyma and 1 of 2 patients with mediastinal nodal disease only, had no evidence of disease with a minimal follow-up time of 31 months [19]. In another report by Wood and colleagues [20], 3 patients with lung metastases and 1 with mediastinal disease were resected. Two were free of disease 16 months later. Eight patients in our study had persistently elevated serum tumor markers after chemotherapy prior to undergoing pulmonary resection. Five were alive without evidence of disease, 3 of whom are considered to be cured with follow-up times greater than 15 years. While the number of patients in this group is too small to draw definitive conclusions, long-term disease free status is possible with salvage surgery. The other significant prognostic factor of outcome in our study was involvement of extrathoracic sites other than the retroperitoneum. It is generally recognized that the lung and retroperitoneum are favorable sites for metastases whereas nonpulmonary visceral metastases predict poor prognosis. Various staging systems including one proposed by the International Germ Cell Cancer Collaborative Group have designated patients with nonpulmonary visceral metastases as being in the poor risk category [21]. In their study, the presence of liver, bone, brain, or other nonpulmonary visceral metastases were each associated with 5-year survival rates below 50%. When grouped together, patients with any nonlung visceral metastases had an overall 5-year survival rate of 41% compared with 83% for patients who had disease limited to the lung or retroperitoneum. In our study, 125 patients had metastatic disease limited to either the lungs alone or lungs and retroperitoneum. The 5-year survival rate in this group was 77%. The remaining 43 patients who had involvement at sites other than lungs or retroperitoneum had a significantly lower 5-year survival rate of 40% (Fig 3). Our current treatment of good-risk GCT patients with pulmonary metastases consists initially of combination cisplatin-based chemotherapy [22, 23]. Of the patients who relapse from a complete remission, fewer than 25% can be salvaged by ifosfamide and cisplatin-based regimens [24]. A significant number of patients with pulmonary metastases manifest residual radiographic abnormalities in the lung despite normal markers after chemotherapy. Because there is no reliable method of predicting the histology of the residual lesions, surgical resection of all sites of metastatic disease is indicated in this select group of patients. Postoperative management depends on the pathology of all resected masses. No further treatment is warranted with pathological confirmation of fibrosis/necrosis and mature teratomas. Approximately 90% of these patients will be cured with resection alone. The identification of viable malignant tumor in any resected lesion necessitates further treatment with chemotherapy [6]. Sixty to 70% of patients are cured with this approach. The 30% of patients who fail treatment have a poor prognosis and should be considered for experimental high-dose chemotherapy trials or other innovative treatment strategies. Salvage surgery should only be considered for the very rare patients with persistently elevated serum tumor markers after a full course of chemotherapy who have resectable metastases limited to the lung. Conclusions Currently, patients with testicular germ cell tumors undergoing complete resection of pulmonary metastases after cisplatin-based chemotherapy are expected to achieve long-term survival. Patients with nonpulmonary metastases, persistently elevated tumors markers, or viable tumor at the time of thoracotomy have a worse prognosis. Pulmonary resection has an important role in salvage surgery for patients with chemorefractory tumors and in identifying those patients with persisting viable tumor requiring further treatment. References 1. Devesa SS, Blot WJ, Stone BJ, et al. Recent cancer trends in the United States. J Natl Cancer Inst 1995;2:970 3.

6 1714 LIU ET AL Ann Thorac Surg PULMONARY METASTASECTOMY FOR TESTICULAR GCT 1998;66: Kosary Cl, Gloeckler Ries LA, Miller BA, et al, eds. SEER cancer statistics review, Bethesda, U.S. Department of Health and Human Services, Lee M, Hendrickson FR. Analysis of pattern of recurrence in non-seminomatous testicular tumor. Radiol 1978;127: Bosl GJ, Geller NL, Chan EY. Stage migration and the increasing proportion of complete responders in patients with advanced germ cell tumors. Cancer Res 1988;48: Toner GC, Panicek DM, Heelan RT, et al. Adjunctive surgery after chemotherapy for nonseminomatous germ cell tumor: recommendations for patients selection. J Clin Oncol 1990;8: Einhorn LH, Williams SD, Mandelbaum I, Donohue JP. Surgical resection in disseminated testicular cancer following chemotherapeutic cytoreduction. Cancer 1981;48: Fosså SD, Aass N, Ous S, et al. Histology of tumor residuals following chemotherapy in patients with advanced nonseminomatous testicular cancer. J Urol 1989;142: Mulder PFA, Oosterhol GON, Boetes C, et al. The importance of prognostic factors in the individual treatment of patients with disseminated germ cell tumors. Br J Urol 1990; 66: Carsky S, Ondrus D, Schnorrer M, et al. Germ cell testicular tumours with lung metastases: chemotherapy and surgical treatment. Int Urol Nephrol 1992;24: Bracken RB, Johnson DE, Frazier OH, et al. The role of surgery following chemotherapy in stage III germ cell neoplasms. J Urol 1983;129: Mandelbaum I, Yaw P, Einhorn L, et al. The importance of one-stage median sternotomy and retroperitoneal node dissection in disseminated testicular cancer. Ann Thorac Surg 1983;36: Tait D, Peckhan MJ, Hendry WF, et al. Post-chemotherapy surgery in advanced non-seminomatous germ cell testicular tumors: the significance of histology with particular reference to differentiated (mature) teratoma. Br J Cancer 1984;50: Donohue JP, Rowland RG, Kopecky K, et al. Correlation of computerized tomographic changes and histological findings in 80 patients having radical retroperitoneal lymph node dissection after chemotherapy for testis cancer. J Urol 1987;137: Steyerberg EW, Keizer SD, Fossa DT, et al. Prediction of residual retroperitoneal mass histology after chemotherapy for metastatic nonsemionmatous germ cell tumor: multivariate analysis of individual patient data from six study groups. J Clin Oncol 1995;13: 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 1996;14: Brenner PC, Herr HW, Morse MJ, et al. Simultaneous retroperitoneal, thoracic, and cervical resection of postchemotherapy residual masses in patients with metastatic nonseminomatous germ cell tumors of the testis. J Clin Oncol 1996;14: Tiffany P, Morse MJ, Bosl GH, et al. Sequential excision of residual thoracic and retroperitoneal masses after chemotherapy for stage III germ cell tumors. Cancer 1986;57: Qvist HL, Fosså SD, Ous S, et al. Post-chemotherapy tumor residuals in patients with advanced nonseminomatous testicular cancer. Is it necessary to resect all residual masses? J Urol 1991;145: Murphy BR, Breeden ES, Donohue JP, et al. Surgical salvage of chemorefractory germ cell tumors. J Clin Onc 1993;11: Wood DP, Herr HW, Motzer RJ, et al. Surgical resection of solitary metastases after chemotherapy in patients with nonseminomatous germ cell tumors and elevated serum tumor markers. Cancer 1992;70: The International Germ Cell Cancer Collaborative Group. International germ cell consensus classification: a prognostic factor-based system for metastatic germ cell cancers. J Clin Oncol 1997;15: Einhorn LH, William SD, Loehrer PJ, et al. Evaluation of optimal duration of chemotherapy in favorable-prognosis disseminated germ cell tumors: a Southeastern Cancer Study Group protocol. J Clin Oncol 1989;7: Bosl GJ, Geller NL, Bajorin D, et al. A randomized trial of etopside cisplatin versus vinblastine bleomycin cisplatin cyclophosphamide dactinomycin in patients with good prognosis germ cell tumors. J Clin Oncol 1988;6: Loehrer PJ, Lauer R, Roth BJ, et al. Salvage therapy in recurrent germ cell cancer: ifosfamide and cisplatin plus either vinblastine or etoposide. Ann Intern Med 1988;109: The International Registry of Lung Metastases. Long-term results of lung metastasectomy: prognostic analyses based on 5206 cases. J Thorac Cardiovasc Surg 1997;113: DISCUSSION DR HARVEY I. PASS (Detroit, MI): I am curious as to whether you can decrease your operations and predict whether you have fibrosis or no viable tumor. At your institution, do you have any data prospectively in these patients of preoperative positron emission tomography scanning and then correlative pathology after you have operated on these patients to see if positron emission tomography scanning could predict who was really going to have a viable tumor or not? Thank you. DR LIU: There has been a study done looking at the use of positron emission tomography scanning to predict the histology of the pulmonary lesions. Other investigators have looked at various modalities and factors including computed tomography scans, the histology of the primary, and the histology from the retroperitoneal node dissections. None of them have been able to demonstrate a reliable way of predicting the histology of the pulmonary lesions.

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