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Pulmonary metastasectomy as secondary treatment for testicular tumors
Pulmonary Metastasectomy as Secondary Treatment for Testicular Tumors Enyeribe Anyanwu, MD, Sabine Krysa, MD, Heinrich Buelzebruck, PhD, and Ingolf Vogt-Moykopf, MD Departments of Surgery and Medical Documentation, Chest Hospital, Heidelberg-Rohrbach, Germany
Patients presenting with synchronous and metachronous metastases of nonseminomatous testicular tumors are candidates for pulmonary metastasectomy after receiving definitive primary treatment, which includes semicastration, eventually retroperitoneal lymphadenectomy, and definitely chemotherapy. One hundred four such patients (age, 14 to 79 years; median age, 27 years) underwent pulmonary metastasectomy from 1972 to 1990, representing 15.8% of the pulmonary metastasectomies performed during the same period. Of the 117 operations performed, eight were repeat operations. Median sternotomy, posterolateral and, later, transverse thoracotomies were the standard surgical approaches used to remove the single and multiple metastases randomly
distributed in both lungs. Wedge resections and atypical segmentectomies (66%), lobectomies (15%), anatomic segmentectomies (9%), pneumonectomies (3%), bilolbectomies (3%), and mediastinal lymphadenectoniies (65.4%) were the various procedures performed. Of the 104 patients, metastasectomy was complete in 80 and incomplete in 24. The 30-day mortality was 2.0%. Life table analysis revealed a survival rate of 77%, 70%, 66%, and 59% at 1, 2, 3, and 5 years, respectively. Of all prognostic factors examined, complete resection of the metastases seems to be the most significant factor influencing the prognosis.
A
diagnosed or within 1 year of the diagnosis. Pulmoriary metastases developed in 62 patients (60%) after 1 year. One patient presented with a right-sided mediastinal mass and pulmonary metastases, which were shown histologically to be a germ cell tumor. Subsequent clinical investigations showed the primary tumor was located in a hypoplastic undescended testis in the small pelvis. In another patient, the removal of a paravertebral tumor called attention to the malignant testicular teratoima, which was treated conventionally. Pulmonary metastases later developed in this patient. Almost all the other patients had received definitive treatment before they were referred for pulmonary metastasectomy. This consisted of semicastration and retroperitoneal lymphadenectomy combined with chemotherapy (102 of 104)or radiotherapy (8 of 104). Two patients had received no chemotherapy before metastasectomy was performed. During the period of study, a total of 757 pulmonary metastasectomies were performed, 117 of which were on the 104 patients with metastases of testicular tumors. A subset of 12 patients underwent more than one operation. Four of these were elective operations for the management of metastases of the contralateral lung, the other lung having been operated on a few weeks earlier through a posterolateral thoracotomy. Seven patients underwent a repeat operation because of recurrence. One patient underwent two repeat operations, the last of which was for the involvement of the chest wall. Similarly, 1 of the 4 patients who underwent sequential posterolateral thoracotomies went on to suffer a chest wall involvement that required chest wall resection. Ninety-two patients had only one operation.
pproximately 95% of all testicular tumors are germ cell tumors [l], which constitutes about 2% of all malignancies [2]. They rank as the fourth leading cause of death in the male population between 18 and 34 years of age, after leukemia, Hodgkin’s disease, and cerebral tumors [l]. During the past 50 years, medical science has been able to document increasing chances of cure of from 10% in the 1960s to 50% in the 1970s, to currently about 85% [3-91. This dramatically changing picture has resulted from the combined surgical, chemotherapeutic, and radiologic approaches to the treatment of the disease. Einhorn [3] has amply characterized testicular tumors as “a model for a curable neoplasm.” The role of operation in the fight against these malignancies was the subject of this study.
Material and Methods From 1972 to 1990, a total of 656 patients referred from other hospitals underwent 757 pulmonary metastasectomies in our hospital (Chest Hospital, Heidelberg-Rohrbuch). Of these, 104 males presented with metastases of nonseminomatous testicular tumors. The youngest patient was 14 years old and the oldest, 79 (median age, 27 years). Most of our patients (53%)were between 20 and 30 years of age; 87% were younger than 40 years. The tumor was rare beyond the sixth decade (Table 1). In 41 patients (39%),pulmonary metastases were diagnosed either at the time when the primary tumor was Accepted for publication Aug 25, 1993. Address reprint requests to Dr Anyanwu, Chest Hospital, HeidelbergRohrbach, Amalienstrasse 5, 69126 Heidelberg, Germany.
0 1994 by The Society of Thoracic Surgeons
(Ann Thoruc Surg 1994;57:1222-8)
0003-4975/94/$:7.00
ANYANWU ET AL RESECTION OF PULMONARY TESTICULAR TUMORS
Ann Thorac Surg 1994;57: 1222-8
Table 1. Aae Distribution Number
Percentage
11 55 25 9 2 2
10 53 24 9 2 2
0-19 20-29 30-39 4c-49 50-59 >60
After chemotherapy, all the patients' cancers were restaged using the algorithm shown in Figure 1. The tumor markers alpha-fetoprotein, human chorionic gonadotropin, beta-human chorionic gonadotropin, lactic dehydrogenase, and placental alkaline phosphatase were assessed. Those patients who had elevated tumor markers received chemotherapy until normal tumor marker levels were attained. Bronchoscopy was performed in all patients to rule out endobronchial tumor involvement or extraluminal compression of the bronchial system by tumor. Cavography and pulmonary angiography were not regarded as mandatory investigations, and were reserved for those presenting with clinical signs of obstruction of the superior vena cava and for those patients whose computed tomoCase history
Laboratory investigations Tumor markers
f
Chest X-ray ap and
t
3
1 # lateral
Abdomi na 1
t
Transesophageal
1
\
+
conventional lung tomography CT: Chest and abdomen
-e
(Magnetic resonance imaging)
U
*
Bone scan
(Esophagoscopy)
1
1
Invasive' radiology
Pulmonary angiography
The tracheobronchial tree was involved in 17 of the 104 patients (16.3%).Nine of these patients had compression of the tracheobronchial wall. This finding indicates enlargement of the mediastinal lymph nodes but does not allow any conclusion as to the integrity of the nodes. However, on histological examination, some of these nodes were found to be involved by metastases. In the remaining 8 patients, the metastases involved the lumen of the tracheobronchial system, which required lobectomies alone or in combination with sleeve resections. One patient underwent a sleeve pneumonectomy and another sleeve resection of the trachea.
Table 2. Surgical Treatment
BRONCHOSCOPY
Cavography
Median sternotomy was the most frequently used surgical approach (66%), followed by posterolateral thoracotomy on the right side (28%) and on the left side (4%), and finally by transverse thoracotomy (2%).Wedge and atypical segment resections were the most frequently carried out procedures (66%),followed by lobectomies (15%)and anatomic segmentectomies (9%). Bilobectomies (3%)and pneumonectomies (3%) were less frequently performed. The other five operations (4%) were for chest wall involvement and mediastinal metastases (Table 2). Sixty-eight patients (65.4%) underwent mediastinal lymphadenectomy. In 1patient, the operation was extended to include a segment of the superior vena cava, which was reconstructed with a vascular prosthesis. In 2 other patients, the superior vena cava was partially resected and reconstructed without a vascular prosthesis. Metastasectomy was complete in 80 patients and incomplete in 24. Postoperative mapping of the location of the metastases in the lungs revealed a haphazard distribution. The patients were followed up from 1972 until September 30, 1991. The life table was calculated according to the statistical model of Kaplan and Meier [lo]. The log rank test [ll]was used to verify the prognostic significance of the parameters examined.
Results
Barium meal
SONOGRAPHY
graphic scans or conventional tomograms suggested tumor invasion of the wall of the superior vena cava or the pulmonary artery. In the same way, aortography was performed only when invasion of the wall of the aorta was suspected. The operative risks were assessed using differentiated pulmonary function studies and cardiovascular investigations.
Surgical Approach
Restaging and Assessment of Operative Risks
kPhysical examination
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Type of Resection
t
Aortography
Fig I . Algorithm for restaging after chemotherapy or radiotherapy. (ap = anteroposterior; CT = computed tomography.)
-
Wedge/atypical segmentectomy Lobectomy I
_
Anatomic segmentectomy
Number
Percentage
77 18 11
66
Bilobectomy
3
Pneumonectomy
3 5
Others
15 9 3 3 4
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ANYANWU ET AL RESECTION OF PULMONARY TESTICULAR TUMORS
Ann Thorac Surg 1994;571222-8
Table 3. Pathology of Resected Metastases Pathology
Number
Percentage
38 27
36.5 26.0
15
14.4
3
3.0
3
3.0
2
2.0
1 11 2
10.5 2.0
2
2.0
Viable tumor cells Necrosis and fibrosis (fibronecrosis) Fibronecrosis + viable tumor cells (same metastases) Segregated metastases Fibronecrosis” and viable tumor cells” Fibronecrosis + viable tumor cells” and viable tumor cells” Fibronecrosis” and viable tumor cells“ and teratomaa Fibronecrosis” and teratomaa Viable tumor cells” and teratomaa Fibronecrosis + viable tumor cells“ and teratomaa Fibronecrosisa and fibronecrosis + viable tumor cellsa Total a
1.0
100
104
Differing histology in different metastases from same patients.
The number of metastases seen at operation varied greatly. Solitary metastases were found during 34 operations, two to three metastases in 22, four to five metastases in 13, and more than five metastases in 48 operations. The number of metastases found during the operation agreed with the preoperative diagnoses in 50 of the 117 operations (43%).More metastases were found during 30 of 117 operations (26%)and fewer were found during 37 of 117 operations (32%) than were suggested by the preoperative assessment findings. The pathologic characteristics of the resected specimens were varied. The metastases consisted entirely of viable tumor cells in 36.5% of the patients, 26% had outright necrosis and fibrosis, and 14.5%had necrosis and fibrosis with viable tumor cells at the periphery of the metastases. All the other patients had findings suggesting segregation of the different tumor cell populations. Thus, in 11 patients, the metastases from one part of the lung consisted of viable tumor cells only, whereas teratoma was observed in metastases from another part. The different combinations found during the pathohistologic assess-
Table 4. Changes Under Chemotherapy From
To
Adult teratoma Adult teratoma Adult teratoma Adult teratomaa + embryonal” carcinoma Embryonal carcinoma Teratocarcinoma Embryonal carcinoma Seminoma Seminoma Yolk sack tumor Teratocarcinoma Choriocarcinoma
Embryonal carcinoma Teratocarcinoma Choriocarcinoma Embryonal carcinoma
a
Differing histology in different metastases from same patient.
Number 11 4 1 1 9 1 1 1
ment of the specimens are listed in Table 3. In those instances in which combinations of necrosis, fibrosis, and viable tumor cells were observed, the viable tumor cells were usually located at the periphery of the metastases. Those segregated metastases consisting of viable tumor cells were usually less than 1 cm in diameter. Table 4 summarizes the changes observed as the result of chemotherapy. Embyronal carcinoma matured more frequently into adult teratoma than did teratocarcinoma. Furthermore, 8.6% of the embryonal carcinoma developed into teratocarcinoma. Two patients were diagnosed with seminoma. A comparison of the preoperative and postoperative histology revealed that the incidence of teratocarcinoma was practically unchanged by chemotherapy. The incidence of embyronal carcinoma decreased from 39.4‘%to 13.5%,whereas the incidence of teratoma rose from 9.6% to 23.0%. Chemotherapy was so effective in 11 patients that the tumor cells were devitalized beyond recognition (Table 5). Of the 68 patients who underwent mediastinal lymphadenectomy, 29 (43%)were found to have positive lymph nodes. The resected metastases from the 4 patients who underwent a second posterolateral thoracotomy and lrom those who underwent repeat operations were analyzed histologically. In 2 of the former patients, the histology was identical to that seen at the previous operakion performed on the contralateral side. Fibronecrosis was identified in the third patient, which represented an improvement over the histologic finding on the contralatera1 side. In the fourth patient, adult teratoma was cliagnosed. This was also an improvement over the histology seen at the previous operation (viable tumor cells). Of the 8 patients who underwent repeat operatitons, only 1 proved to have fibronecrosis; 4 had necrosis centrally and viable tumor cells at the periphery of the metastases. In 2 of these 4 patients, the metastases were segregated such that some were composed of viable tumor cells and others were adult teratomas. Similarly, 1 patient had teratoma and metastases with central necrosis and viable tumor cells located at the periphery. These viable tumor cells proved to be rhabdomyosarcoma. Of the last 2 patients, 1 had viable tumor cells and the other
Table 5. Comparison of Preoperative and Postoperative Histolorn in 104 Patients Histology Teratocarcinoma Embryonal carcinoma Teratoma Choriocarcinoma Yolk sack tumor Sertoli cell tumor Seminoma Necrosis and fibrosis” a
Preoperatively
Postoperatively
43 41 10
47 14 24 5 1 1 1 11
8
1 1
...
...
Cells devitalized beyond recognition.
-
:
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ANYANWU ET AL RESECTION OF PULMONARY TESTICULAR TUMORS
Ann Thorac Surg 1994;571222-8
sis, followed by those who have two to three metastases. Those presenting with more than five metastases have a much less favorable prognosis.
-
(n 104)
90%
Complications 60% 50%
40% 30%
20% 10% 1
0%
The surgical complications were within acceptable limits. Postoperative hemorrhage led to reoperation in 4 of 117 cases (3%). Secondary closed chest tube drainage was necessary in 6 cases (5%).Wound infection was seen in 4 cases (3%).Respiratory complications were manifested as the need for mechanical ventilation for more than 24 hours, and retention of bronchial secretions requiring endoscopic suction occurred in 5 postoperative cases (4%).
Comment an adult teratoma, which developed into a highly malignant metastasizing rhabdomyosarcoma, that spelled a downhill course for him after the repeat operation. No tumor cells were found in the specimens of the 2 patients who had a chest wall resection. The postoperative (30-day) mortality was 2% (2 of 104). The survival rate after 1 year was 77%, 70% after 2 years, 66% after 3 years, and 59% after 5 years (Fig 2). The median survival rate cannot be computed yet because of the good prognosis. A discriminatory calculation of the rate of survival shows that 83% of those patients whose metastases were completely resected were still alive after 1 year, 77% after 2 years, 71% after 3 years, and 65%after 5 years. On the other hand, 53% of those who underwent incomplete resection survived the first year, 48%the third year, and “only” 39% the fifth year (Fig 3). Even if this study were not randomized, the difference in the survival rate is noteworthy. Those who had a mature teratoma exhibited a higher survival rate than did those who had other histologic types. The difference between the two groups is, however, not statistically significant (Fig 4). Analysis of the survival curve also showed that patients presenting with single metastases have the best progno-
I
The therapy for testicular tumors has shifted from the empirical to a multimodal approach, which has caused them to be the most successfully treated malignancy of the present time. The success rate achieved by chemotherapy [12-141 has not detracted from the importance of secondary operation, which is required to excise residual masses in roughly 10% to 30% of the patients who receive chemotherapy [3, 15, 161. About 20% to 27% of these masses in the thoracic or retroperitoneal areas, or both, will show residual malignancy [13, 15-18]. The histologic assessment of the same metastases documented the presence of residual malignancy in 14% of our patients. However, if the segregated metastases are also considered, the percentage of patients with residual malignancy increases to a more realistic 37%.Because of the increased chances of cure, as represented by the higher longevity, we are seeing patients who require a repeat pulmonary metastasectomy as a result of recurrence. Other authors report a similar experience [19]. This rather aggressive surgical approach to the mediastinal and pulmonary metastases of testicular tumors [20] has paid off in terms of patient survival and cure. The survival rate in our patients is similar to that cited by other authors [19, 201, even though their calculations were based on relatively small series of patients. This emphasizes the salutary effects of combined therapy.
I
60% 60%
50% 40%
:
30%
others
~
-
(n 80)
‘
~
~
1
10% 0% 10% 0
6
12
18
24
30
36
42
48
54
60
months
Fig 3. Survival rate computed according to whether metastasectomy was complete or not.
0%’ 0
6
12
18
24
30
36
42
48
months
Fig 4. Survival rate: teratoma versus other histologic types.
54
60
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ANYANWU ET AL RESECTION OF PULMONARY TESTICULAR TUMORS
The segregation of tumor cell populations observed in some of our patients is particularly intriguing. Metastases containing only fibronecrotic tissue, viable tumor cells, or teratomas were found in areas sharing the same lymphatics (ie, in the same segment) as well as in distinctly different anatomic units. Thus, they could be located in different segments or lobes of the same lung or the contralateral lung. One patient had fibronecrosis in the metastases excised from the right lung and rhabdomyosarcoma in those excised from the lingular lobe during the same operation. In another patient, viable metastases of a teratogenic carcinoma were identified in the right lower lobe, whereas the histologic characteristics of the metastases excised from the left lower lobe suggested a bronchogenic cyst. In yet another patient, who presented with embryonal carcinoma with components of teratocarcinoma and chorioepithelioma, the metastases excised through a median sternotomy demonstrated fibronecrosis on the left side and biologically highly active tumor cells on the right side. We observed such a dissociated biologic behavior in 24 of 104 (23%)of our patients. The explanation for this is highly speculative. The combination of fibronecrosis and teratoma can be explained on the basis of cisplatin-based chemotherapy, and the resultant "selection" of resistant cell lines. On the other hand, the same chemotherapeutic regimen was found to produce sterilization of the metastases in 1 patient, while the cells of the same histologic type in another patient seemed "unimpressed." The clinical significance of mature teratomas is difficult to assess. Less clear is the mechanism underlying their maturation process. Cisplatin-based combination chemotherapy could induce the differentiation of germ cells in vivo into mature teratoma, a suggestion negated by some authors [21, 221. However, chemotherapy could also selectively destroy the nonteratomatous elements and allow the growth of the chemoresistant teratomatous elements. Furthermore, it could reduce the tumor burden by way of cytoreduction, thus allowing the patient to survive for long enough to permit differentiation of the immature germ cell element into teratomas [16]. Other authors have speculated about metastases containing immature germ cells being able to differentiate into mature teratomas independent of the therapy instituted [23]. Mature teratomas have been found during histologic analyses of the excised metastases of testicular cancer, but their incidence differs from one center to the other [18,24, 251. Excluding those patients in whom teratoma was observed as part of tumor cell segregation, 23% of our patients had mature teratoma. The proportion rapidly increases to 38% if we add the former. Our results show that the cohort of patients with teratomas had a better prognosis than the group with other histologic types (see Fig 4), but this difference does not reach statistical significance. However, other investigators consider patients with mature teratomas to have an extremely good prognosis [17, 251. Perhaps the most pertinent question to answer about teratomas regards their unpredictable clinical behavior. We had 1 patient in whom the metastatic disease took the form of continuously expanding multiple
Ann Thorac Surg 1994;5?1222-8
mediastinal masses that extended into the supraclavicular region and caused superior vena caval obstruction. In 2 other patients, the teratomas "dedifferentiated" into frank rhabdomyosarcoma, which bore no histologic resemblance to the original germ cell tumor. This secondary malignancy dictated the further clinical course of the patients. They all received cisplatin-based polychemotherapy. Other authors have reported similar ob,;cervations. Roth and associates [8] reported on 3 patients who sustained a secondary malignancy. One of these patients suffered multiple intraabdominal angiosarcoma after total abdominal radiotherapy [8]. Ahlgren and co-workers [26] reported on 1 patient presenting with embryonal rhabdomyosarcoma as a retroperitoneal metastasis. Two cases of sarcomatous transformation of mixed germ cell tumors were reported by Ritchey and colleagues [27]. Ulbright and associates [28] reported 11 cases of malignancy in germ cell tumors. Perhaps the largest number of malignant transformation of teratomas up to 1984 was reported from the Memorial Sloan-Kettering Cancer Center. Of more than 580 males with germ cell tumors treated over a 10-year period (1972-1982), 17 cases (3%) of malignant transformation of teratomas were documented histologically [29]. Even if the incidence of malignant transformation is not very high, these partly anecdotal examples suggest that one should accept the benignity of teratomas with some doubt and aim at complete excision of all the lesions. Only those patients who undergo complete resection benefit from the combined therapy and are less likely to experience a relapse [17]. A comparison of the number of pulmonary metastases found during the operation with the number diagnosed preoperatively confirms congruence in 43% of the cases. More metastases were found in 26% and fewer in 31% of the operations. Even though these data differ slightly from those we published earlier [30, 311, they confirm the divergence in the number of metastases diagnosed preoperatively and intraoperatively. This discrepancy has led to the liberal use of median sternotomy as the preferred standard approach for pulmonary metastasectomy, as reflected in our series. For the past 2 years, we have increasingly employed transverse thoracotomy for the same purpose, especially when multiple resections are anticipated in the left lower lobe. This approach reduces the pull on the hilum and the mechanical irritation of the heart, thus attenuating the negative cardiovascular effects of these maneuvers. The two-stage operation performed through posterolateral thoracotomies is reserved for poorrisk patients, those with a heavy tumor burden, and those undergoing laser metastasectomy, as well as those urtdergoing repeat operations, when bilateral exploration of the thoracic cavity is judged to be too hazardous for the patient. In 16% of the patients studied, we observed direct and indirect involvement of the tracheobroncheal tree that led to such therapeutic consequences as sleeve resections, lobectomies, and pneumonectomies. We have observed similar clinical findings in the setting of other tumors, especially colorectal tumors, hypernephroma, and breast cancer. For this reason, bronchoscopy is performed as
ANYANWU ET AL RESECTION OF PULMONARY TESTICULAR TUMORS
Ann Thorac Surg 1994;571222-8
Table 6 . Comparative Survival Rate After Metastasectomy for !Selected Tumors Testicular Breast Colorectal Kidney Osteosarcoma Melanoma
104 68 78 84 71 22
77 80 80 74 62 50
66 47 42 41 22 15
59 30 31 27
17 10
part of the preoperative assessment to rule out endobronlchial tumor invasion or extraluminal compression of the bronchial system. Because testicular tumors metastasize through lymphatic and hematogenous routes, we do not expect only pulmonary metastases. The mediastinal and scalene lymph nodes may be the first sites of metastases before the lung tissue becomes involved. Our data show that 43% of the patients in whom lymphadenectomies were performed had positive lymph nodes. For this reason, we believe that metastasectomy is incomplete without a systema tic and thorough lymphadenectomy. Moreover, there is no way of establishing the absence of nodal involvement beyond a doubt, except by removing the lymph nodes and examining them histologically. Admittedly, lymphadenectomy prolongs the operation by 15 to 30 minutes. Generally, this is tolerated well by the young patients. The extent of mediastinal lymphadenectomy has not been a problem for repeat operations. If performed thoroughly at the first operation, it does not need to be repeated. It could be a problem, however, if it is postponed to the second operation. We examined a number of prognostic factors. These consisted of the interval between the diagnosis of the primary tumor and the diagnosis of pulmonary metastases, the size of the metastases, their distribution pattern in the lungs, their number, the synchronous diagnosis of mediastinal and pulmonary metastases, and finally the completeness of metastasectomy. Complete resection turned out to be the most consistent factor that significantly influenced survival ( p = 0.006) (see Fig 3). Other authors also agree that those patients who undergo complete surgical excision of the metastases benefit most from the combination of cisplatin-based cytoreduction and resection of the residual tumor [16]. On the other hand, debulking operations seem to be a wasteful exercise, even when followed by salvage chemotherapy [24]. The second significant prognostic factor is the number of metastases, which reflects the extent of the tumor burden and the limitation of complete resection. The results of secondary surgery for the management of metastases of testicular tumors were compared with the results for a few other selected tumors. The data used for comparison came from studies conducted under similar clinical conditions. The differences in the chances of survival among patients presenting with metastases of breast cancer, colorectal carcinoma, and nonseminomatous testicular tumors in the first year are minor. The prognosis for melanoma does not compare favorably with that for other tumors. After 3 years, the prognosis for
1227
testicular tumors was found to be superior to that for all the others; the prognosis for breast cancer, colorectal cancer, and hypernephroma does not differ significantly. After 5 years, the prognosis for testicular tumors is significantly better than that for the others. Melanoma and osteosarcoma carry the worst prognosis (Table 6). In summary, the curative treatment of disseminated testicular tumors is best guaranteed by a multidisciplinary approach. Surgical removal is regarded as a secondary option after curative cisplatin-based combination chemotherapy. Its object is the complete resection of residual tumors and, by so doing, achieving complete remission. For this reason, mediastinal lymphadenectomy should be a part of the surgical procedure. In conjunction with histopathologic analysis, areas of viable tumor cells, scar tissue, or necrosis can be identified at surgery; the effectiveness of chemotherapy can be assessed; and changes in the tumor cell population can be determined. It definitely leads to an improved survival rate and is attended by low morbidity and mortality.
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24. Bracken RB, Johnson DE, Frazier OH, Logothetis CJ, Trindade A, Samuels ML. The role of surgery following chemotherapy in stage 111 germ cell neoplasms. J Urol 1983;129: 39-43. 25. Einhorn LH, Williams SD, Mandelbaum I, Donohue JP. Surgical resection in disseminated testicular cancer following chemotherapeutic cytoreduction. Cancer 1981;48:9044. 26. Ahlgren AD, Simrell CR, Triche TJ, Ozols R, Barsky SH. Sarcoma arising in a residual testicular teratoma after cytoreductive chemotherapy. Cancer 1984;54:201!%8. 27. Ritchey ML, Bagnall JW, McDonald EC, Sago AL. Development of non-germ cell malignancies in nonseminonnatous germ cell tumors. J Urol 1985;13414&9. 28. Ulbright TM, Loeher PJ, Roth LM, Einhorn LH, Williams DD, Clark SA. The development of nongerm malignancies within germ cell tumors: a clinical pathological study of 11 cases. Cancer 1984;54:1824-33. 29. Ahmed T, Bosl GJ, Hajdu SI. Teratoma with malignant transformation in germ cell tumors in men. Cancer 1985;56: 860-3. 30. Anyanwu E, Probst G, Branscheid D, Krysa S, Biilzebruck H, Vogt-Moykopf I. Operative Therapie von Lungenmetastasen-Technik und Ergebnisse. In: Drings P, Vogt-Moyltopf I, eds. Thoraxtumoren: Diagnostik-Staging-gegenwartiges Therapiekonzept. Berlin, Heidelberg, New York: SpringerVerlag, 1991:452-75. 31. Vogt-Moykopf I, Meyer G, Biilzebruck H, Merkle NM, Langsdorf M. Indications and long-term results in surgery of pulmonary metastases. Contrib Oncol 1988a;20:76-107.
Patients presenting with synchronous and metachronous metastases of nonseminomatous testicular tumors are candidates for pulmonary metastasectomy after receiving definitive primary treatment, which includes semicastration, eventually retroperitoneal lymphadenectomy, and definitely chemotherapy. One hundred four such patients (age, 14 to 79 years; median age, 27 years) underwent pulmonary metastasectomy from 1972 to 1990, representing 15.8% of the pulmonary metastasectomies performed during the same period. Of the 117 operations performed, eight were repeat operations. Median sternotomy, posterolateral and, later, transverse thoracotomies were the standard surgical approaches used to remove the single and multiple metastases randomly
distributed in both lungs. Wedge resections and atypical segmentectomies (66%), lobectomies (15%), anatomic segmentectomies (9%), pneumonectomies (3%), bilolbectomies (3%), and mediastinal lymphadenectoniies (65.4%) were the various procedures performed. Of the 104 patients, metastasectomy was complete in 80 and incomplete in 24. The 30-day mortality was 2.0%. Life table analysis revealed a survival rate of 77%, 70%, 66%, and 59% at 1, 2, 3, and 5 years, respectively. Of all prognostic factors examined, complete resection of the metastases seems to be the most significant factor influencing the prognosis.
A
diagnosed or within 1 year of the diagnosis. Pulmoriary metastases developed in 62 patients (60%) after 1 year. One patient presented with a right-sided mediastinal mass and pulmonary metastases, which were shown histologically to be a germ cell tumor. Subsequent clinical investigations showed the primary tumor was located in a hypoplastic undescended testis in the small pelvis. In another patient, the removal of a paravertebral tumor called attention to the malignant testicular teratoima, which was treated conventionally. Pulmonary metastases later developed in this patient. Almost all the other patients had received definitive treatment before they were referred for pulmonary metastasectomy. This consisted of semicastration and retroperitoneal lymphadenectomy combined with chemotherapy (102 of 104)or radiotherapy (8 of 104). Two patients had received no chemotherapy before metastasectomy was performed. During the period of study, a total of 757 pulmonary metastasectomies were performed, 117 of which were on the 104 patients with metastases of testicular tumors. A subset of 12 patients underwent more than one operation. Four of these were elective operations for the management of metastases of the contralateral lung, the other lung having been operated on a few weeks earlier through a posterolateral thoracotomy. Seven patients underwent a repeat operation because of recurrence. One patient underwent two repeat operations, the last of which was for the involvement of the chest wall. Similarly, 1 of the 4 patients who underwent sequential posterolateral thoracotomies went on to suffer a chest wall involvement that required chest wall resection. Ninety-two patients had only one operation.
pproximately 95% of all testicular tumors are germ cell tumors [l], which constitutes about 2% of all malignancies [2]. They rank as the fourth leading cause of death in the male population between 18 and 34 years of age, after leukemia, Hodgkin’s disease, and cerebral tumors [l]. During the past 50 years, medical science has been able to document increasing chances of cure of from 10% in the 1960s to 50% in the 1970s, to currently about 85% [3-91. This dramatically changing picture has resulted from the combined surgical, chemotherapeutic, and radiologic approaches to the treatment of the disease. Einhorn [3] has amply characterized testicular tumors as “a model for a curable neoplasm.” The role of operation in the fight against these malignancies was the subject of this study.
Material and Methods From 1972 to 1990, a total of 656 patients referred from other hospitals underwent 757 pulmonary metastasectomies in our hospital (Chest Hospital, Heidelberg-Rohrbuch). Of these, 104 males presented with metastases of nonseminomatous testicular tumors. The youngest patient was 14 years old and the oldest, 79 (median age, 27 years). Most of our patients (53%)were between 20 and 30 years of age; 87% were younger than 40 years. The tumor was rare beyond the sixth decade (Table 1). In 41 patients (39%),pulmonary metastases were diagnosed either at the time when the primary tumor was Accepted for publication Aug 25, 1993. Address reprint requests to Dr Anyanwu, Chest Hospital, HeidelbergRohrbach, Amalienstrasse 5, 69126 Heidelberg, Germany.
0 1994 by The Society of Thoracic Surgeons
(Ann Thoruc Surg 1994;57:1222-8)
0003-4975/94/$:7.00
ANYANWU ET AL RESECTION OF PULMONARY TESTICULAR TUMORS
Ann Thorac Surg 1994;57: 1222-8
Table 1. Aae Distribution Number
Percentage
11 55 25 9 2 2
10 53 24 9 2 2
0-19 20-29 30-39 4c-49 50-59 >60
After chemotherapy, all the patients' cancers were restaged using the algorithm shown in Figure 1. The tumor markers alpha-fetoprotein, human chorionic gonadotropin, beta-human chorionic gonadotropin, lactic dehydrogenase, and placental alkaline phosphatase were assessed. Those patients who had elevated tumor markers received chemotherapy until normal tumor marker levels were attained. Bronchoscopy was performed in all patients to rule out endobronchial tumor involvement or extraluminal compression of the bronchial system by tumor. Cavography and pulmonary angiography were not regarded as mandatory investigations, and were reserved for those presenting with clinical signs of obstruction of the superior vena cava and for those patients whose computed tomoCase history
Laboratory investigations Tumor markers
f
Chest X-ray ap and
t
3
1 # lateral
Abdomi na 1
t
Transesophageal
1
\
+
conventional lung tomography CT: Chest and abdomen
-e
(Magnetic resonance imaging)
U
*
Bone scan
(Esophagoscopy)
1
1
Invasive' radiology
Pulmonary angiography
The tracheobronchial tree was involved in 17 of the 104 patients (16.3%).Nine of these patients had compression of the tracheobronchial wall. This finding indicates enlargement of the mediastinal lymph nodes but does not allow any conclusion as to the integrity of the nodes. However, on histological examination, some of these nodes were found to be involved by metastases. In the remaining 8 patients, the metastases involved the lumen of the tracheobronchial system, which required lobectomies alone or in combination with sleeve resections. One patient underwent a sleeve pneumonectomy and another sleeve resection of the trachea.
Table 2. Surgical Treatment
BRONCHOSCOPY
Cavography
Median sternotomy was the most frequently used surgical approach (66%), followed by posterolateral thoracotomy on the right side (28%) and on the left side (4%), and finally by transverse thoracotomy (2%).Wedge and atypical segment resections were the most frequently carried out procedures (66%),followed by lobectomies (15%)and anatomic segmentectomies (9%). Bilobectomies (3%)and pneumonectomies (3%) were less frequently performed. The other five operations (4%) were for chest wall involvement and mediastinal metastases (Table 2). Sixty-eight patients (65.4%) underwent mediastinal lymphadenectomy. In 1patient, the operation was extended to include a segment of the superior vena cava, which was reconstructed with a vascular prosthesis. In 2 other patients, the superior vena cava was partially resected and reconstructed without a vascular prosthesis. Metastasectomy was complete in 80 patients and incomplete in 24. Postoperative mapping of the location of the metastases in the lungs revealed a haphazard distribution. The patients were followed up from 1972 until September 30, 1991. The life table was calculated according to the statistical model of Kaplan and Meier [lo]. The log rank test [ll]was used to verify the prognostic significance of the parameters examined.
Results
Barium meal
SONOGRAPHY
graphic scans or conventional tomograms suggested tumor invasion of the wall of the superior vena cava or the pulmonary artery. In the same way, aortography was performed only when invasion of the wall of the aorta was suspected. The operative risks were assessed using differentiated pulmonary function studies and cardiovascular investigations.
Surgical Approach
Restaging and Assessment of Operative Risks
kPhysical examination
1223
Type of Resection
t
Aortography
Fig I . Algorithm for restaging after chemotherapy or radiotherapy. (ap = anteroposterior; CT = computed tomography.)
-
Wedge/atypical segmentectomy Lobectomy I
_
Anatomic segmentectomy
Number
Percentage
77 18 11
66
Bilobectomy
3
Pneumonectomy
3 5
Others
15 9 3 3 4
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ANYANWU ET AL RESECTION OF PULMONARY TESTICULAR TUMORS
Ann Thorac Surg 1994;571222-8
Table 3. Pathology of Resected Metastases Pathology
Number
Percentage
38 27
36.5 26.0
15
14.4
3
3.0
3
3.0
2
2.0
1 11 2
10.5 2.0
2
2.0
Viable tumor cells Necrosis and fibrosis (fibronecrosis) Fibronecrosis + viable tumor cells (same metastases) Segregated metastases Fibronecrosis” and viable tumor cells” Fibronecrosis + viable tumor cells” and viable tumor cells” Fibronecrosis” and viable tumor cells“ and teratomaa Fibronecrosis” and teratomaa Viable tumor cells” and teratomaa Fibronecrosis + viable tumor cells“ and teratomaa Fibronecrosisa and fibronecrosis + viable tumor cellsa Total a
1.0
100
104
Differing histology in different metastases from same patients.
The number of metastases seen at operation varied greatly. Solitary metastases were found during 34 operations, two to three metastases in 22, four to five metastases in 13, and more than five metastases in 48 operations. The number of metastases found during the operation agreed with the preoperative diagnoses in 50 of the 117 operations (43%).More metastases were found during 30 of 117 operations (26%)and fewer were found during 37 of 117 operations (32%) than were suggested by the preoperative assessment findings. The pathologic characteristics of the resected specimens were varied. The metastases consisted entirely of viable tumor cells in 36.5% of the patients, 26% had outright necrosis and fibrosis, and 14.5%had necrosis and fibrosis with viable tumor cells at the periphery of the metastases. All the other patients had findings suggesting segregation of the different tumor cell populations. Thus, in 11 patients, the metastases from one part of the lung consisted of viable tumor cells only, whereas teratoma was observed in metastases from another part. The different combinations found during the pathohistologic assess-
Table 4. Changes Under Chemotherapy From
To
Adult teratoma Adult teratoma Adult teratoma Adult teratomaa + embryonal” carcinoma Embryonal carcinoma Teratocarcinoma Embryonal carcinoma Seminoma Seminoma Yolk sack tumor Teratocarcinoma Choriocarcinoma
Embryonal carcinoma Teratocarcinoma Choriocarcinoma Embryonal carcinoma
a
Differing histology in different metastases from same patient.
Number 11 4 1 1 9 1 1 1
ment of the specimens are listed in Table 3. In those instances in which combinations of necrosis, fibrosis, and viable tumor cells were observed, the viable tumor cells were usually located at the periphery of the metastases. Those segregated metastases consisting of viable tumor cells were usually less than 1 cm in diameter. Table 4 summarizes the changes observed as the result of chemotherapy. Embyronal carcinoma matured more frequently into adult teratoma than did teratocarcinoma. Furthermore, 8.6% of the embryonal carcinoma developed into teratocarcinoma. Two patients were diagnosed with seminoma. A comparison of the preoperative and postoperative histology revealed that the incidence of teratocarcinoma was practically unchanged by chemotherapy. The incidence of embyronal carcinoma decreased from 39.4‘%to 13.5%,whereas the incidence of teratoma rose from 9.6% to 23.0%. Chemotherapy was so effective in 11 patients that the tumor cells were devitalized beyond recognition (Table 5). Of the 68 patients who underwent mediastinal lymphadenectomy, 29 (43%)were found to have positive lymph nodes. The resected metastases from the 4 patients who underwent a second posterolateral thoracotomy and lrom those who underwent repeat operations were analyzed histologically. In 2 of the former patients, the histology was identical to that seen at the previous operakion performed on the contralateral side. Fibronecrosis was identified in the third patient, which represented an improvement over the histologic finding on the contralatera1 side. In the fourth patient, adult teratoma was cliagnosed. This was also an improvement over the histology seen at the previous operation (viable tumor cells). Of the 8 patients who underwent repeat operatitons, only 1 proved to have fibronecrosis; 4 had necrosis centrally and viable tumor cells at the periphery of the metastases. In 2 of these 4 patients, the metastases were segregated such that some were composed of viable tumor cells and others were adult teratomas. Similarly, 1 patient had teratoma and metastases with central necrosis and viable tumor cells located at the periphery. These viable tumor cells proved to be rhabdomyosarcoma. Of the last 2 patients, 1 had viable tumor cells and the other
Table 5. Comparison of Preoperative and Postoperative Histolorn in 104 Patients Histology Teratocarcinoma Embryonal carcinoma Teratoma Choriocarcinoma Yolk sack tumor Sertoli cell tumor Seminoma Necrosis and fibrosis” a
Preoperatively
Postoperatively
43 41 10
47 14 24 5 1 1 1 11
8
1 1
...
...
Cells devitalized beyond recognition.
-
:
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ANYANWU ET AL RESECTION OF PULMONARY TESTICULAR TUMORS
Ann Thorac Surg 1994;571222-8
sis, followed by those who have two to three metastases. Those presenting with more than five metastases have a much less favorable prognosis.
-
(n 104)
90%
Complications 60% 50%
40% 30%
20% 10% 1
0%
The surgical complications were within acceptable limits. Postoperative hemorrhage led to reoperation in 4 of 117 cases (3%). Secondary closed chest tube drainage was necessary in 6 cases (5%).Wound infection was seen in 4 cases (3%).Respiratory complications were manifested as the need for mechanical ventilation for more than 24 hours, and retention of bronchial secretions requiring endoscopic suction occurred in 5 postoperative cases (4%).
Comment an adult teratoma, which developed into a highly malignant metastasizing rhabdomyosarcoma, that spelled a downhill course for him after the repeat operation. No tumor cells were found in the specimens of the 2 patients who had a chest wall resection. The postoperative (30-day) mortality was 2% (2 of 104). The survival rate after 1 year was 77%, 70% after 2 years, 66% after 3 years, and 59% after 5 years (Fig 2). The median survival rate cannot be computed yet because of the good prognosis. A discriminatory calculation of the rate of survival shows that 83% of those patients whose metastases were completely resected were still alive after 1 year, 77% after 2 years, 71% after 3 years, and 65%after 5 years. On the other hand, 53% of those who underwent incomplete resection survived the first year, 48%the third year, and “only” 39% the fifth year (Fig 3). Even if this study were not randomized, the difference in the survival rate is noteworthy. Those who had a mature teratoma exhibited a higher survival rate than did those who had other histologic types. The difference between the two groups is, however, not statistically significant (Fig 4). Analysis of the survival curve also showed that patients presenting with single metastases have the best progno-
I
The therapy for testicular tumors has shifted from the empirical to a multimodal approach, which has caused them to be the most successfully treated malignancy of the present time. The success rate achieved by chemotherapy [12-141 has not detracted from the importance of secondary operation, which is required to excise residual masses in roughly 10% to 30% of the patients who receive chemotherapy [3, 15, 161. About 20% to 27% of these masses in the thoracic or retroperitoneal areas, or both, will show residual malignancy [13, 15-18]. The histologic assessment of the same metastases documented the presence of residual malignancy in 14% of our patients. However, if the segregated metastases are also considered, the percentage of patients with residual malignancy increases to a more realistic 37%.Because of the increased chances of cure, as represented by the higher longevity, we are seeing patients who require a repeat pulmonary metastasectomy as a result of recurrence. Other authors report a similar experience [19]. This rather aggressive surgical approach to the mediastinal and pulmonary metastases of testicular tumors [20] has paid off in terms of patient survival and cure. The survival rate in our patients is similar to that cited by other authors [19, 201, even though their calculations were based on relatively small series of patients. This emphasizes the salutary effects of combined therapy.
I
60% 60%
50% 40%
:
30%
others
~
-
(n 80)
‘
~
~
1
10% 0% 10% 0
6
12
18
24
30
36
42
48
54
60
months
Fig 3. Survival rate computed according to whether metastasectomy was complete or not.
0%’ 0
6
12
18
24
30
36
42
48
months
Fig 4. Survival rate: teratoma versus other histologic types.
54
60
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ANYANWU ET AL RESECTION OF PULMONARY TESTICULAR TUMORS
The segregation of tumor cell populations observed in some of our patients is particularly intriguing. Metastases containing only fibronecrotic tissue, viable tumor cells, or teratomas were found in areas sharing the same lymphatics (ie, in the same segment) as well as in distinctly different anatomic units. Thus, they could be located in different segments or lobes of the same lung or the contralateral lung. One patient had fibronecrosis in the metastases excised from the right lung and rhabdomyosarcoma in those excised from the lingular lobe during the same operation. In another patient, viable metastases of a teratogenic carcinoma were identified in the right lower lobe, whereas the histologic characteristics of the metastases excised from the left lower lobe suggested a bronchogenic cyst. In yet another patient, who presented with embryonal carcinoma with components of teratocarcinoma and chorioepithelioma, the metastases excised through a median sternotomy demonstrated fibronecrosis on the left side and biologically highly active tumor cells on the right side. We observed such a dissociated biologic behavior in 24 of 104 (23%)of our patients. The explanation for this is highly speculative. The combination of fibronecrosis and teratoma can be explained on the basis of cisplatin-based chemotherapy, and the resultant "selection" of resistant cell lines. On the other hand, the same chemotherapeutic regimen was found to produce sterilization of the metastases in 1 patient, while the cells of the same histologic type in another patient seemed "unimpressed." The clinical significance of mature teratomas is difficult to assess. Less clear is the mechanism underlying their maturation process. Cisplatin-based combination chemotherapy could induce the differentiation of germ cells in vivo into mature teratoma, a suggestion negated by some authors [21, 221. However, chemotherapy could also selectively destroy the nonteratomatous elements and allow the growth of the chemoresistant teratomatous elements. Furthermore, it could reduce the tumor burden by way of cytoreduction, thus allowing the patient to survive for long enough to permit differentiation of the immature germ cell element into teratomas [16]. Other authors have speculated about metastases containing immature germ cells being able to differentiate into mature teratomas independent of the therapy instituted [23]. Mature teratomas have been found during histologic analyses of the excised metastases of testicular cancer, but their incidence differs from one center to the other [18,24, 251. Excluding those patients in whom teratoma was observed as part of tumor cell segregation, 23% of our patients had mature teratoma. The proportion rapidly increases to 38% if we add the former. Our results show that the cohort of patients with teratomas had a better prognosis than the group with other histologic types (see Fig 4), but this difference does not reach statistical significance. However, other investigators consider patients with mature teratomas to have an extremely good prognosis [17, 251. Perhaps the most pertinent question to answer about teratomas regards their unpredictable clinical behavior. We had 1 patient in whom the metastatic disease took the form of continuously expanding multiple
Ann Thorac Surg 1994;5?1222-8
mediastinal masses that extended into the supraclavicular region and caused superior vena caval obstruction. In 2 other patients, the teratomas "dedifferentiated" into frank rhabdomyosarcoma, which bore no histologic resemblance to the original germ cell tumor. This secondary malignancy dictated the further clinical course of the patients. They all received cisplatin-based polychemotherapy. Other authors have reported similar ob,;cervations. Roth and associates [8] reported on 3 patients who sustained a secondary malignancy. One of these patients suffered multiple intraabdominal angiosarcoma after total abdominal radiotherapy [8]. Ahlgren and co-workers [26] reported on 1 patient presenting with embryonal rhabdomyosarcoma as a retroperitoneal metastasis. Two cases of sarcomatous transformation of mixed germ cell tumors were reported by Ritchey and colleagues [27]. Ulbright and associates [28] reported 11 cases of malignancy in germ cell tumors. Perhaps the largest number of malignant transformation of teratomas up to 1984 was reported from the Memorial Sloan-Kettering Cancer Center. Of more than 580 males with germ cell tumors treated over a 10-year period (1972-1982), 17 cases (3%) of malignant transformation of teratomas were documented histologically [29]. Even if the incidence of malignant transformation is not very high, these partly anecdotal examples suggest that one should accept the benignity of teratomas with some doubt and aim at complete excision of all the lesions. Only those patients who undergo complete resection benefit from the combined therapy and are less likely to experience a relapse [17]. A comparison of the number of pulmonary metastases found during the operation with the number diagnosed preoperatively confirms congruence in 43% of the cases. More metastases were found in 26% and fewer in 31% of the operations. Even though these data differ slightly from those we published earlier [30, 311, they confirm the divergence in the number of metastases diagnosed preoperatively and intraoperatively. This discrepancy has led to the liberal use of median sternotomy as the preferred standard approach for pulmonary metastasectomy, as reflected in our series. For the past 2 years, we have increasingly employed transverse thoracotomy for the same purpose, especially when multiple resections are anticipated in the left lower lobe. This approach reduces the pull on the hilum and the mechanical irritation of the heart, thus attenuating the negative cardiovascular effects of these maneuvers. The two-stage operation performed through posterolateral thoracotomies is reserved for poorrisk patients, those with a heavy tumor burden, and those undergoing laser metastasectomy, as well as those urtdergoing repeat operations, when bilateral exploration of the thoracic cavity is judged to be too hazardous for the patient. In 16% of the patients studied, we observed direct and indirect involvement of the tracheobroncheal tree that led to such therapeutic consequences as sleeve resections, lobectomies, and pneumonectomies. We have observed similar clinical findings in the setting of other tumors, especially colorectal tumors, hypernephroma, and breast cancer. For this reason, bronchoscopy is performed as
ANYANWU ET AL RESECTION OF PULMONARY TESTICULAR TUMORS
Ann Thorac Surg 1994;571222-8
Table 6 . Comparative Survival Rate After Metastasectomy for !Selected Tumors Testicular Breast Colorectal Kidney Osteosarcoma Melanoma
104 68 78 84 71 22
77 80 80 74 62 50
66 47 42 41 22 15
59 30 31 27
17 10
part of the preoperative assessment to rule out endobronlchial tumor invasion or extraluminal compression of the bronchial system. Because testicular tumors metastasize through lymphatic and hematogenous routes, we do not expect only pulmonary metastases. The mediastinal and scalene lymph nodes may be the first sites of metastases before the lung tissue becomes involved. Our data show that 43% of the patients in whom lymphadenectomies were performed had positive lymph nodes. For this reason, we believe that metastasectomy is incomplete without a systema tic and thorough lymphadenectomy. Moreover, there is no way of establishing the absence of nodal involvement beyond a doubt, except by removing the lymph nodes and examining them histologically. Admittedly, lymphadenectomy prolongs the operation by 15 to 30 minutes. Generally, this is tolerated well by the young patients. The extent of mediastinal lymphadenectomy has not been a problem for repeat operations. If performed thoroughly at the first operation, it does not need to be repeated. It could be a problem, however, if it is postponed to the second operation. We examined a number of prognostic factors. These consisted of the interval between the diagnosis of the primary tumor and the diagnosis of pulmonary metastases, the size of the metastases, their distribution pattern in the lungs, their number, the synchronous diagnosis of mediastinal and pulmonary metastases, and finally the completeness of metastasectomy. Complete resection turned out to be the most consistent factor that significantly influenced survival ( p = 0.006) (see Fig 3). Other authors also agree that those patients who undergo complete surgical excision of the metastases benefit most from the combination of cisplatin-based cytoreduction and resection of the residual tumor [16]. On the other hand, debulking operations seem to be a wasteful exercise, even when followed by salvage chemotherapy [24]. The second significant prognostic factor is the number of metastases, which reflects the extent of the tumor burden and the limitation of complete resection. The results of secondary surgery for the management of metastases of testicular tumors were compared with the results for a few other selected tumors. The data used for comparison came from studies conducted under similar clinical conditions. The differences in the chances of survival among patients presenting with metastases of breast cancer, colorectal carcinoma, and nonseminomatous testicular tumors in the first year are minor. The prognosis for melanoma does not compare favorably with that for other tumors. After 3 years, the prognosis for
1227
testicular tumors was found to be superior to that for all the others; the prognosis for breast cancer, colorectal cancer, and hypernephroma does not differ significantly. After 5 years, the prognosis for testicular tumors is significantly better than that for the others. Melanoma and osteosarcoma carry the worst prognosis (Table 6). In summary, the curative treatment of disseminated testicular tumors is best guaranteed by a multidisciplinary approach. Surgical removal is regarded as a secondary option after curative cisplatin-based combination chemotherapy. Its object is the complete resection of residual tumors and, by so doing, achieving complete remission. For this reason, mediastinal lymphadenectomy should be a part of the surgical procedure. In conjunction with histopathologic analysis, areas of viable tumor cells, scar tissue, or necrosis can be identified at surgery; the effectiveness of chemotherapy can be assessed; and changes in the tumor cell population can be determined. It definitely leads to an improved survival rate and is attended by low morbidity and mortality.
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ANYANWU ET AL RESECTION OF PULMONARY TESTICULAR TUMORS
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