The Importance of One-Stage Median Stemotomy and Retroperitoneal Node Dissection in Disseminated Testicular Cancer

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1 The Importance of One-Stage Median Stemotomy and Retroperitoneal Node Dissection in Disseminated Testicular Cancer Isidore Mandelbaum, M.D., Peter B. Yaw, M.D., Lawrence H. Einhorn, M.D., Stephen D. Williams, M.D., Randall G. Rowland, M.D., and John P. Donohue, M.D. ABSTRACT More than 350 patients with testicular germ cell cancer have been treated with cisplatin combination chemotherapy. Seventy-two with metastases to the thorax who had operation are discussed here. In a subgroup of 24 patients with additional retroperitoneal disease, a one-stage median sternotomy was performed in 18 patients, and a thoracotomy in 6, with retroperitoneal node dissection. Seventeen patients had similar pathological lesions in the thorax and retroperitoneum; in 7, the lesions differed. There was no operative mortality in the entire group. Overall, chemotherapy altered the metastases to mature teratoma in 28 patients, and 27 are long-term survivors. Among 22 patients with fibrotic, necrotic masses, 19 are long-term survivors; 6 of the 22 with persistent carcinoma had chemotherapy postoperatively and are long-term survivors. The overall cure rate for patients with disseminated testicular cancer is approximately 80%. Among those who had a one-stage thoracoretroperitoneal procedure, long-term survival is 83%; for the entire thoracic surgical group, it is 74%. Within the last seven years, 72 patients with germ cell testicular carcinoma metastatic to the chest have been treated surgically. Our early experience with 22 patients was documented previously [l] and encouraged us to continue our original protocol, which consisted of vigorous chemotherapy followed by operation in selected patients. Overall, approximately 350 patients From the Department of Surgery, Division of Thoracic Surgery, Department of Medicine, Section of Oncology, and Department of Urology, Indiana University School of Medicine, Indianapolis, IN. Presented at the Nineteenth Annual Meeting of The Society of Thoracic Surgeons, San Francisco, CA, Jan 17-19, Address reprint requests to Dr. Mandelbaum, Department of Surgery, Indiana University Medical Center, Indianapolis, IN with disseminated testicular carcinoma have been treated at Indiana University Medical Center. The purpose of this paper is to present the results for 72 patients who required thoracic surgical intervention following chemotherapy and to highlight a unique subgroup of 24 who also had a retroperitoneal node dissection at the same time. Patients with extragonadal germ cell tumors of mediastinal origin are not included in this series. Material and Methods From April, 1975, to October, 1982, 72 patients were operated on for metastatic testicular carcinoma of the chest. The median age was 26 years (range, 13 to 52 years). The histological types of primary tumor included embryonal carcinoma, teratoma, seminoma, choriocarcinoma, yolk sac tumor, or combinations of these. All patients had a radical orchiectomy initially, and many had had a previous retroperitoneal lymph node dissection. All of them received an intensive course of cisplatin, vinblastine, and bleomycin therapy, the exact schedule of which has been detailed previously [2, 31. Indications for thoracic surgical intervention were limited to patients with a solitary pulmonary lesion that had recurred after initial chemotherapy induced remission or with thoracic lesions persisting after a full course of chemotherapy or those associated with persistent retroperitoneal disease. Operation usually was undertaken four to eight weeks after the last course of chemotherapy to ensure optimal preoperative health and recovery for the patient. To preserve as much pulmonary function as possible, wedge resections of the lesions were carried out in most patients. A lobectomy was performed in 2. The minimum postoperative follow-up on 524

2 525 Mandelbaum et al: Median Sternotomy and Node Dissection in Disseminated Testicular Cancer these patients was 12 months (range, 12 to 84 months). The median follow-up was 36 months. Results A posterolateral thoracotomy was performed in 29 patients for either a solitary lesion or multiple ipsilateral lesions, or a mediastinal lesion. In 19 patients with bilateral lung or mediastinal lesions, a median sternotomy was carried out in 18 and a bilateral thoracotomy, in 1. After completion of chemotherapy, an additional 24 patients had persistent thoracic as well as retroperitoneal disease. A median sternotomy was performed in 18 patients and a thoracotomy in 6, and all thoracic disease was excised. Our urological colleagues then carried out a midline celiotomy and a retroperitoneal node dissection at the same time (combined thoracoabdominal procedure). The number of lesions discovered during operation correlated well with preoperative wholelung tomograms. Computed tomographic (CT) scans of the chest were performed infrequently because tomography proved more accurate and less expensive for the patient. However, tomography failed to predict accurately the pathological histology-whether the tumor turned out to be a mature or immature teratoma, carcinoma, or masses of fibrotic, necrotic tissue. At the time of operation, most patients had lesions in the lung or mediastinum that could not be diagnosed by gross examination. Microscopic examination was essential. In many patients with multiple lung lesions, mature or immature teratomas coexisted with nodules composed of fibrotic, necrotic tissue. The same was true for some patients who were found to have a mixture of carcinoma with teratoma or of carcinoma with fibrotic, necrotic tissue. Of the 72 patients, 28 had teratoma, 22 had carcinoma, and 22 exhibited masses of necrosis and fibrosis without viable tumor. In 24 patients who had a combined thoracoretroperitoneal procedure, the pathological findings in both areas were similar in 17 and different in 7. In the overall analysis, a patient was designated as having carcinoma if he or she had viable malignancy in either the chest or abdomen; if a patient had teratoma and fibrous tissue, he or she was classified as having teratoma. ThoracovetroF7evitonerrl Dissectioii In the 24 patients who underwent a combined approach, the pathological findings in both sites were similar in 17 patients and dissimilar in the other 7. Ten were discovered to have mature teratomas in the retroperitoneum and thorax, 3 had carcinoma in both sites, and 4 had necrotic, fibrotic masses in both the retroperitoneum and thorax. Seven patients had different lesions in the retroperitoneum compared to the thorax. No preoperative studies (i.e., whole-lung tomograms, abdominal CT scans, or hormonal markers) were of value in predicting the histological type found in the chest or abdomen. Among these latter 7 patients, 1 had necrotic, fibrotic masses in the retroperitoneum and incompletely resected carcinoma in the lung. Another had teratomas in the retroperitoneum and teratomas associated with a single mass of carcinoma in the lung. Two patients had carcinoma in the retroperitoneum associated with masses of necrosis and fibrosis in the chest. Three patients had teratomas in the retroperitoneum and masses of necrotic, fibrotic tissue in the thorax. All of these 24 patients who underwent thoracoretroperitoneal dissection survived the operation and were discharged from the hospital in 10 to 14 days. Twenty were long-term survivors without evidence of disease. There were 4 late deaths: 3 patients with persistent cancer in the chest and retroperitoneum and 1 in whom retroperitoneal necrotic, fibrotic masses were resected, but carcinoma in the left lung was unresectable because the malignancy was adherent to the diaphragm. This patient s hormonal markers were normal preoperatively and postoperatively, and he received postoperative courses of cisplatin combination chemotherapy; however, he died of recurrent disease several months later. Two patients who had a combined surgical approach and had carcinoma in the retroperitoneum and 1 who had carcinoma in the thorax are among the long-term survivors. They each received two postoperative courses of cisplatin combination chemotherapy. Disease Limited to the Chest Forty-eight patients required a thoracotomy for unilateral thoracic disease or a median ster-

3 526 The Annals of Thoracic Surgery Vol 36 No 5 November 1983 notomy for bilateral involvement. There were no operative deaths, and there are 33 longterm survivors (69%), 32 with no evidence of disease. Seventeen patients had resection of mature teratomas. These patients had normal preoperative hormonal markers and required no postoperative chemotherapy. Sixteen are alive without evidence of disease. One late death occurred, the result of pulmonary failure secondary to bleomycin therapy. Fourteen patients were found to have discrete masses of necrosis and fibrosis. Twelve are long-term survivors with no evidence of disease. In the other 2 patients, the postoperative hormonal markers became elevated, and despite further chemotherapy, these patients eventually died of the malignancy. Seventeen patients had resection of persistent carcinoma in the lungs or mediastinum or both locations. Four remain disease free after two postoperative courses of chemotherapy. One is alive with evidence of disease. There were 2 operative complications. One patient with a mature teratoma had involvement of the left recurrent laryngeal nerve, and vocal cord paralysis developed postoperatively. He was treated with an injection of Teflon into the cord, and his condition improved. Another patient required reexploration for bleeding and had suture ligation of an arterial vessel. The postoperative course was smooth. As noted in our previous series [l], there was no relationship between long-term survival and the time interval from primary testicular resection to thoracic surgical intervention. It also was again true that all patients who proved to have mature teratomas had normal levels of human chorionic gonadotropin (HCG) and a-fetoprotein preoperatively. Many patients with carcinoma, on the other hand, had markedly elevated levels of these substances, although some showed normal values. Patients with fibrotic masses in the chest all had normal preoperative serum markers. While abnormal levels of HCG and a-fetoprotein indicated the presence of carcinoma, normal levels did not rule it out. Twenty-seven patients with teratomas and 19 of 22 with necrotic, fibrotic masses are free from disease. Six of 22 patients with carcinoma are long-term survivors, 4 with no evidence of disease and 2 with evidence of disease. Comment Our experience indicates that chemotherapy plays a major role in eradicating all evidence of metastatic disease in testicular cancer or possibly in altering the histological characteristics of a tumor from a virulent malignant carcinoma to mature (or immature) teratoma. The mechanisms of apparent retroconversion from carcinoma to mature teratoma is of great biological interest. However, an alternative hypothesis is that the teratoma may have been present initially in a mixed tumor and remained after chemotherapeutic eradication of other cellular elements. Teratoma usually does not metastasize, but it is not a benign lesion because it may cause death by local extension or may possibly convert back to a serologically positive carcinoma. The purposes of thoracic surgical intervention are to eradicate all disease in the chest and to determine the exact diagnosis and nature of the lesion. Because one lesion may be of a different type from another in a given patient, complete excision of all lesions is mandatory for optimal diagnostic and therapeutic results. This is especially true for the combined thoracoretroperitoneal group of lesions. For example, in 17 patients, persistent disease in the retroperitoneum and chest was the same, but in 7, the pathological findings differed. The prognosis for patients who have had resection of necrotic, fibrotic tissue or teratoma or both is excellent: 46 of 50 patients in our study are alive and continuously disease free (92% survival) with minimal follow-up of one year after operation. No postoperative chemotherapy is necessary for these patients. Interestingly, 2 in this group required a repeat thora- cotomy for resection of recurrent mature teratoma, and both are disease free more than two years following their last operation. In contrast, only 6 of 22 patients (27%) with resected carcinoma in the thorax are long-term survivors. Two recently have been found to have recurrent carcinoma. Numerous patients with carcinoma had been referred to us from other institutions after the patients had received multiple preoperative combination chemother-

4 527 Mandelbaum et al: Median Sternotomy and Node Dissection in Disseminated Testicular Cancer apy regimens. Many were refractory to cisplatin at the time of thoracotomy. Furthermore, several patients had incomplete resections or had rising levels of HCG or a-fetoprotein or both after operation prior to postoperative chemotherapy. It is encouraging that 4 of 6 patients who had complete resection of carcinoma with clear surgical margins and negative postoperative markers (HGG and a-fetoprotein) and received two postoperative courses of cisplatin combination chemotherapy are currently disease free. Based on our experience, there is probably no value in attempting surgical resection in any patient who has a rising serum marker after cisplatin chemotherapy; our current policy is not to operate on such patients. There were no operative deaths, either in the subset of 24 patients treated by one-stage thoracoretroperitoneal resection or in the entire thoracic surgical series. By the combined procedure, it was possible to remove abdominal and thoracic disease, determine the precise pathological characteristics of the lesions, and identify patients who required postoperative chemotherapy. There was little morbidity; some patients had a slightly prolonged intestinal ileus. The 10 to 14 days of hospitalization for the combined procedure was considerably shorter than if a retroperitoneal and then a thoracic procedure had been carried out on two separate occasions. The long-term survival in this combined group is 83% (20124). In our entire experience of 72 patients, there have been no operative deaths, and the overall long-term survival is 53 of 72 patients (74%). Twenty-four of 72 patients (33% of the entire group) who underwent a combined procedure had a slightly higher long-term survival-as mentioned, 20 of 24 patients (83%) have survived. At present the cure rate for disseminated testicular cancer is approximately 80%. About 20% of our patient population will require thoracic surgical intervention to achieve a disease-free status. In this series of 72 surgically treated patients, 33% required a one-stage thoracoretroperitoneal resection. Because the operative mortality has been nil and the long-term survival relatively good among the patients with limited thoracic disease as well as those with thoracic and retroperitoneal involvement, we recom- mend an aggressive surgical approach and excision of all disease in such patients. It is essential for them to have a first-line course of chemotherapy before operation and to have normal preoperative serum a-fetoprotein and P-HCG levels. Supported in part by Southeastern Cancer Study Group No. CA We thank Ms. D. Maria Moore for her diligence in the preparation of the manuscript. References 1. Mandelbaum I, Williams SD, Einhorn LH: Aggressive surgical management of testicular carcinoma metastatic to lungs and mediastinum. Ann Thorac Surg 30:224, Einhorn LH, Donohue J: Cis-diammine-dichloroplatinum, vinblastine, and bleomycin: combination chemotherapy in disseminated testicular cancer. Ann Intern Med 87:293, Einhorn LH, Williams SD, Troner M, et al: The role of maintenance therapy in disseminated testicular cancer. N Engl J Med , 1981 Discussion DR. E. CARMACK HOLMES (Los Angeles, CA): I compliment the authors on a very nice presentation and also compliment the physicians at the University of Indiana for pioneering the transition of a uniformly fatal disease to one that now enjoys a cure rate of 60 to 80%. It is quite a scenario, one that we would like to be able to emulate for other solid tumors. I certainly have no argument with the technique of median sternotomy and simultaneous retroperitoneal lymph node dissection. However, I must emphasize the difficulty in approaching the left lower lobe through a median sternotomy. Frequently it is not possible to reach this area with that technique. We all know that the double-lumen Robertshaw tube is necessary in all median sternotomies for the purpose of resection of pulmonary metastatic disease. Dr. Mandelbaum, have you found any evidence of extensive fibrosis in the tumors that have responded to chemotherapy? Do you have difficulty in dissecting the tumors from the pulmonary artery and other difficult structures? My associates and I have evaluated 25 patients, and our experience does indicate that with a similar approach, 60% of these patients can essentially be cured. The degree of differentiation of the tumor is very important in survival. Our experience has been that patients with multiple metastatic lesions do not do as well as patients with a single metastatic lesion. This is not the case for patients with metastatic sarcomas. Finally, it is of in-

5 528 The Annals of Thoracic Surgery Vol 36 No 5 November 1983 terest to note that the presence or absence of retroperitoneal disease, even though it may be massive, does not affect survival following thoracotomy and resection of metastatic disease to the lung. Clearly, the ability of a thoracic surgeon to develop an aggressive approach to disseminated malignancies is entirely dependent on the availability of effective chemotherapy. In an era when aggressive medical oncologists are besieging us daily to operate on patients with greatly advanced disseminated malignancies, it is very important that thoracic surgeons develop a better understanding of the availability of chemotherapy, the effectiveness of chemotherapy, the effects of chemotherapy on postoperative wound healing, and the intraoperative problems it can cause, because all patients referred to us by the medical oncologists are not surgical candidates, although we are frequently encouraged to operate on them. It behooves us to learn as much as we can about oncology, chemotherapy, and radiation therapy so we can make our own decisions regarding the indications for aggressive surgical attack on these lesions. DR. F. G. PEARSON (Toronto, Ont, Canada): I enjoyed this paper thoroughly and think it a very original contribution. I have a few queries for Dr. Mandelbaum about the incidence and location of the nodes in the mediastinum. I assume that some of the patients who had a median sternotomy had both pulmonary lesions and anterior mediastinal nodes. Did some of these patients also have paratracheal or middle and posterior mediastinal nodes? If so, did you find they presented a difficult technical problem in resection? DR. L. PENFIELD FABER (Chicago, IL): I congratulate Dr. Mandelbaum and his co-workers on their excellent results and even more on the very low mortality that was achieved. Preoperative chemotherapy in these patients usually includes bleomycin, a drug that has pulmonary toxicity as one of its major side effects. In our initial experience of operating on patients who had had prior treatment with bleomycin, there were 2 in whom adult respiratory distress syndrome developed 48 hours following the pulmonary resection. It was thought that this complication was related to the bleomycin. Subsequently we have employed a technique of continuous epidural anesthesia and morphine sedation for such patients. Intraoperative ventilation is carried out with room air. If the partial pressure of arterial oxygen falls below 50 mm Hg during the operation, we utilize high-frequency ventilation. Crystalloid fluid replacement is restricted, as recommended in the literature. Dr. Mandelbaum, would you outline for us your anesthetic techniques, including the recommended inspired oxygen fraction during the procedure, and postoperative fluid management in these patients who have received pulmonary-toxic drugs? DR. MANDELBAUM: I thank Dr. Holmes, Dr. Pearson, and Dr. Faber for their kind comments. With respect to Dr. Holmes s question concerning a median sternotomy approach to the left lower lobe of the lung, we have found that it is somewhat more difficult to expose the left lower lobe of the lung. However, we have resected many lesions from this area and have discovered that the median sternotomy approach is excellent in mobilizing the left lower lobe and bringing it into the operative field. With reference to mediastinal involvement and the necrotic, fibrotic masses that may be adherent to the pulmonary artery, we have seen a number of such masses and have found that with careful dissection they can be removed without any problem. Dr. Holmes also asked a question about the outcome of patients who have multiple metastases versus a single metastasis. In our experience, long-term survival does not depend on how many metastases the patient has but, and perhaps more importantly, on the histological nature of the lesion. A patient may have as many as eight mature teratomas in the chest and many others in the retroperitoneum, and the long-term survival will be excellent. However, if that same patient has fewer metastases but those are persistent carcinoma, then the patient will require postoperative chemotherapy and the long-term prognosis will be more guarded. Dr. Pearson brought up a question concerning excision of the numerous nodes that may be present in patients who have metastatic testicular cancer of the chest. In most patients, the lesions are confined to the pulmonary parenchyma. However, we have had a substantial number of patients with involved nodes. These nodes may include the azygos nodes, the paratracheal nodes, and, perhaps the most interesting, the nodes along the esophagus in the retrocardiac portion. Again, the median sternotomy does let us view the retrocardiac area, and often we can find an extension right through the diaphragm from the retroperitoneum and into the posterior mediastinum. With the help of the urologist, we can resect all these posterior lymph nodes. Dr. Faber asked about bleomycin toxicity. This is a multifaceted question. We have been fortunate in that the oncologists at our institution tend to use a low dose of bleomycin compared with that in some other institutions. I think this may be a major reason why we have an operative mortality of zero. During operation and in the postoperative period, we use an inspired oxygen fraction of around 30 to 407~. We employ fluid restriction so that the patient who has had bleomycin is not overloaded. However, we do not exaggerate this fluid restriction. Finally, I emphasize something Dr. Holmes mentioned: This is one disease that requires teamwork and very close cooperation between the oncologist and the thoracic surgeon.