0022-5347/91/1452-0300$03.00/0 Vol. 145, 300-303, February 1991 Printed in U. S. A.
THE JOURNAL OF UROLOGY Copyright © 1991 by AMERICAN UROLOGICAL ASSOCIATION, INC.
POST-CHEMOTHERAPY TUMOR RESIDUALS IN PATIENTS WITH ADVANCED NONSEMINOMATOUS TESTICULAR CANCER. IS IT NECESSARY TO RESECT ALL RESIDUAL MASSES? HANNE LOTHERINGTON QVIST, SOPHIE D. FossA, SIGURD OUS, JOHAN H0IE, ANNA E. STENWIG AND KARL-ERIK GIERCKSKY From the Departments of Surgical Oncology, Medical Oncology and Radiotherapy, and Pathology, The Norwegian Radium Hospital, Oslo, Norway
ABSTRACT
A total of 15 patients with advanced nonseminomatous testicular cancer underwent 2 sequentia.l operations (4 in 1 patient) to remove residual masses after cisplatin-based combination chemotherapy. All patients had normal human chorionic gonadotropin and a-fetoprotein levels but persistent radiographic masses after chemotherapy. The operations included retroperitoneal lymph node dissection in 13 patients, thoracotomy in 15, hepatic resection in 3 and craniotomy in 1. Histological comparison of the specimens resected during post-chemotherapy operations 1 and 2 demonstrated different patterns in 7 of 15 patients. Of these 7 patients 4 had less favorable pathological features in the specimen removed during the second procedure. Residual malignant tumor or mature teratoma was found in at least 1 site in 12 of the 15 patients and only 3 had complete necrosis or fibrosis in both specimens examined. These data indicate the favorable impact of excising all post-chemotherapy tumor residuals in patients with advanced nonseminomatous testicular cancer. However, in patients with no teratomatous elements in the testicular tumor and complete necrosis or fibrosis in the initial post-chemotherapy operation specimen the probability of complete necrosis or fibrosis in remaining tumors appears to be high. KEY WORDS:
testis, carcinoma, testicular neoplasms, drug therapy
of the tumor as evidenced by abdominal and, in most cases, thoracic computerized tomography (CT). · All visible residual tumors were routinely removed, excising the larger tumor first. Retroperitoneal lymph node dissection was performed even when initially enlarged retroperitoneal lymph nodes had regained normal size after chemotherapy. Retroperitoneal lymph node dissection was performed in 13 patients, thoracotomy (12 lung resections and 3 removals of residuals in the mediastinum) in 13, hepatic resection in 3 and craniotomy in 1 (see table). All patients underwent at least 2 operations: 11 had retroperitoneal lymph node dissection plus thoracotomy, 1 had retroperitoneal lymph node dissection plus hepatic resection, 1 underwent 2 thoracotomies, 1 underwent hepatic resection plus craniotomy, and 1 underwent retroperitoneal lymph node dissection, hepatic resection and 2 thoracotomies. Histological classification of the primary tumor and the postchemotherapy operation specimens was performed according to the method of Collins and Pugh. 9 According to this classification several subgroups of nonseminomatous testicular tumors were identified: differentiated teratoma, intermediate malignant teratoma, trophoblastic malignant teratoma (all 3 types with teratomatous elements) and undifferentiated malignant teratoma (the only type without teratomatous elements). The histological response of the residual tumor to chemotherapy was classified as complete necrosis or fibrosis, mature teratoma or vital malignant tumor.
Cisplatin-based combination chemotherapy followed by resection of residual tumor is currently regarded as optimal treatment of advanced nonseminomatous testicular cancer. 1- 5 Retroperitoneal lymph node dissection and thoracotomy are the most commonly required procedures but a few patients require excision of tumor manifestations at other sites, such as the liver and brain. In some patients nothing but complete necrosis or fibrosis is found in all operative specimens, suggesting a possible over-treatment in these patients. This raises the question of whether complete necrosis or fibrosis can be predicted in patients when multiple operations are considered to reduce safely the number of surgical interventions. When the present treatment policy was launched in 1981 (Swedish-Norwegian testicular cancer project-SWENOTECA6 ) it was decided that "if a complete remission is not achieved after 4 cycles (of chemotherapy) every attempt must be made to resect the remaining tumor tissue" and that "retroperitoneal lymph node extirpation should be performed even if a clinical complete remission is achieved with chemotherapy alone." Patients with advanced nonseminomatous testicular cancer routinely have undergone sequential excisions of post-chemotherapy residual tumor at multiple sites. To determine the necessity for multiple operations the histological response of the residual tumors was compared. MATERIAL AND METHODS
From 1980 to 1989, 15 patients with advanced nonseminomatous testicular cancer (clinical stage III or IV according to the Royal Marsden Hospital classification system?) underwent 2 or more post-chemotherapy operations for removal of residual tumor (see table). At operation all patients had undergone at least 4 cycles of chemotherapy. Details of the chemotherapy regimen have been described previously. 8 They had attained normal levels of serum tumor markers (a-fetoprotein and human chorionic gonadotropin) but no or only partial remission Accepted for publication July 19, 1990.
RESULTS
The histological status of the primary testicular tumor and post-chemotherapy operative specimens for all patients is listed in the table. Of the 15 primary tumors 2 were classified as differentiated teratoma, 7 as intermediate malignant teratoma, 3 as trophoblastic malignant teratoma and 3 as undifferentiated malignant teratoma. Histological examination of specimens from the initial post-chemotherapy operation demonstrated complete necrosis or fibrosis in 6, while mature teratoma and malignant tumor were found in 8 and 1, respectively. The
300
Teratoma, differentiated Teratoma, differentiated Malignant teratoma, intermediate Malignant teratoma, intermediate Malignant teratoma, intermediate Malignant teratoma, intermediate Malignant teratoma, intermediate Malignant teratoma, intermediate Malignant teratoma, intermediate Malignant teratoma, trophoblastic Malignant teratoma, trophoblastic Malignant teratoma, trophoblastic Malignant teratoma, undifferentiated Malignant teratoma, undifferentiated Malignant teratoma, undifferentiated
2
4 5 6
7
8 9
10 11 12 13 14 15
IV IV III IV IV III IV IV IV IV IV
Metastasis Operations
Histology of Metastasis
Retroperitoneal lymphadenectomy, thoracotomy Retroperitoneal lymphadenectomy, thoracotomy Retroperitoneal lymphadenectomy, thoracotomy Thoracotomy, retroperitoneal lymphadenectomy Retroperitoneal lymphadenectomy, thoracotomy Retroperitoneal lymphadenectomy, thoracotomy Retroperitoneal lymphadenectomy, thoracotomy Retroperitoneal lymphadenectomy, thoracotomy Retroperitoneal lymphadenectomy, hepatotomy, thoracotomy x2 Thoracotomy X2
Mature teratoma, necrosis
Retroperitoneal lymphadenectomy, thoracotomy Hepatotomy, craniotomy
IV III
Thoracotomy, retroperitoneal lymphadenectomy Retroperitoneal lymphadenectomy, hepatotomy Retroperitoneal lymphadenectomy, thoracotomy
IV IV
mc9.ll.gnanlt tumor was taken from a . . neal 3) and a germ Such nongerm malignancies probably arise within teratomatous foci and are regarded as malignant transformations. 10 During post-chemotherapy 2 there was CO]mlJllet~e necrosis or fibrosis in 5 3 of which with necrosis or also in the specimen. Mature teratoma was found in 8 and malignant tumor in 2. The tumors were taken from the mediastinum 6) brain In the former case the constituted a minor component of the consisted of mature teratoma, and the free of tumor The latter of the brain metastases. Since necrosis or fibrosis both resected relnalnlng 12 all had tumor or mature teratoma in at least 1 site. Of these 5 teratoma both '·VV\r' ....... n than
Mature teratoma X2 Malignant tumor, mature teratoma Mature teratoma, necrosis Mature teratoma X2 Mature teratoma, malignant tumor Necrosis, mature teratoma Mature teratoma X2 Mature teratoma X4 Necrosis X2 Necrosis, mature teratoma Necrosis, malignant tumor Necrosis x2 Mature teratoma X2 Necrosis x2
.n1r- .... r'Y),r' .... '1-A.
Y),n1r-' ..." ....... 1,..l""I
In,.,,..n.VT,,,,,,,,.,lvT
DISCUSSION
Y),Ao1r-r,Y),.n.-".o1r-'T7,oIT7
l""IY),A"\ ......
sp4~clmE~ns and acteristics Residual ("~ at various anatomical sites: 2 3 8 of 12, m
THE JOURNAL OF UROLOGY Copyright © 1991 by AMERICAN UROLOGICAL ASSOCIATION, INC.
POST-CHEMOTHERAPY TUMOR RESIDUALS IN PATIENTS WITH ADVANCED NONSEMINOMATOUS TESTICULAR CANCER. IS IT NECESSARY TO RESECT ALL RESIDUAL MASSES? HANNE LOTHERINGTON QVIST, SOPHIE D. FossA, SIGURD OUS, JOHAN H0IE, ANNA E. STENWIG AND KARL-ERIK GIERCKSKY From the Departments of Surgical Oncology, Medical Oncology and Radiotherapy, and Pathology, The Norwegian Radium Hospital, Oslo, Norway
ABSTRACT
A total of 15 patients with advanced nonseminomatous testicular cancer underwent 2 sequentia.l operations (4 in 1 patient) to remove residual masses after cisplatin-based combination chemotherapy. All patients had normal human chorionic gonadotropin and a-fetoprotein levels but persistent radiographic masses after chemotherapy. The operations included retroperitoneal lymph node dissection in 13 patients, thoracotomy in 15, hepatic resection in 3 and craniotomy in 1. Histological comparison of the specimens resected during post-chemotherapy operations 1 and 2 demonstrated different patterns in 7 of 15 patients. Of these 7 patients 4 had less favorable pathological features in the specimen removed during the second procedure. Residual malignant tumor or mature teratoma was found in at least 1 site in 12 of the 15 patients and only 3 had complete necrosis or fibrosis in both specimens examined. These data indicate the favorable impact of excising all post-chemotherapy tumor residuals in patients with advanced nonseminomatous testicular cancer. However, in patients with no teratomatous elements in the testicular tumor and complete necrosis or fibrosis in the initial post-chemotherapy operation specimen the probability of complete necrosis or fibrosis in remaining tumors appears to be high. KEY WORDS:
testis, carcinoma, testicular neoplasms, drug therapy
of the tumor as evidenced by abdominal and, in most cases, thoracic computerized tomography (CT). · All visible residual tumors were routinely removed, excising the larger tumor first. Retroperitoneal lymph node dissection was performed even when initially enlarged retroperitoneal lymph nodes had regained normal size after chemotherapy. Retroperitoneal lymph node dissection was performed in 13 patients, thoracotomy (12 lung resections and 3 removals of residuals in the mediastinum) in 13, hepatic resection in 3 and craniotomy in 1 (see table). All patients underwent at least 2 operations: 11 had retroperitoneal lymph node dissection plus thoracotomy, 1 had retroperitoneal lymph node dissection plus hepatic resection, 1 underwent 2 thoracotomies, 1 underwent hepatic resection plus craniotomy, and 1 underwent retroperitoneal lymph node dissection, hepatic resection and 2 thoracotomies. Histological classification of the primary tumor and the postchemotherapy operation specimens was performed according to the method of Collins and Pugh. 9 According to this classification several subgroups of nonseminomatous testicular tumors were identified: differentiated teratoma, intermediate malignant teratoma, trophoblastic malignant teratoma (all 3 types with teratomatous elements) and undifferentiated malignant teratoma (the only type without teratomatous elements). The histological response of the residual tumor to chemotherapy was classified as complete necrosis or fibrosis, mature teratoma or vital malignant tumor.
Cisplatin-based combination chemotherapy followed by resection of residual tumor is currently regarded as optimal treatment of advanced nonseminomatous testicular cancer. 1- 5 Retroperitoneal lymph node dissection and thoracotomy are the most commonly required procedures but a few patients require excision of tumor manifestations at other sites, such as the liver and brain. In some patients nothing but complete necrosis or fibrosis is found in all operative specimens, suggesting a possible over-treatment in these patients. This raises the question of whether complete necrosis or fibrosis can be predicted in patients when multiple operations are considered to reduce safely the number of surgical interventions. When the present treatment policy was launched in 1981 (Swedish-Norwegian testicular cancer project-SWENOTECA6 ) it was decided that "if a complete remission is not achieved after 4 cycles (of chemotherapy) every attempt must be made to resect the remaining tumor tissue" and that "retroperitoneal lymph node extirpation should be performed even if a clinical complete remission is achieved with chemotherapy alone." Patients with advanced nonseminomatous testicular cancer routinely have undergone sequential excisions of post-chemotherapy residual tumor at multiple sites. To determine the necessity for multiple operations the histological response of the residual tumors was compared. MATERIAL AND METHODS
From 1980 to 1989, 15 patients with advanced nonseminomatous testicular cancer (clinical stage III or IV according to the Royal Marsden Hospital classification system?) underwent 2 or more post-chemotherapy operations for removal of residual tumor (see table). At operation all patients had undergone at least 4 cycles of chemotherapy. Details of the chemotherapy regimen have been described previously. 8 They had attained normal levels of serum tumor markers (a-fetoprotein and human chorionic gonadotropin) but no or only partial remission Accepted for publication July 19, 1990.
RESULTS
The histological status of the primary testicular tumor and post-chemotherapy operative specimens for all patients is listed in the table. Of the 15 primary tumors 2 were classified as differentiated teratoma, 7 as intermediate malignant teratoma, 3 as trophoblastic malignant teratoma and 3 as undifferentiated malignant teratoma. Histological examination of specimens from the initial post-chemotherapy operation demonstrated complete necrosis or fibrosis in 6, while mature teratoma and malignant tumor were found in 8 and 1, respectively. The
300
Teratoma, differentiated Teratoma, differentiated Malignant teratoma, intermediate Malignant teratoma, intermediate Malignant teratoma, intermediate Malignant teratoma, intermediate Malignant teratoma, intermediate Malignant teratoma, intermediate Malignant teratoma, intermediate Malignant teratoma, trophoblastic Malignant teratoma, trophoblastic Malignant teratoma, trophoblastic Malignant teratoma, undifferentiated Malignant teratoma, undifferentiated Malignant teratoma, undifferentiated
2
4 5 6
7
8 9
10 11 12 13 14 15
IV IV III IV IV III IV IV IV IV IV
Metastasis Operations
Histology of Metastasis
Retroperitoneal lymphadenectomy, thoracotomy Retroperitoneal lymphadenectomy, thoracotomy Retroperitoneal lymphadenectomy, thoracotomy Thoracotomy, retroperitoneal lymphadenectomy Retroperitoneal lymphadenectomy, thoracotomy Retroperitoneal lymphadenectomy, thoracotomy Retroperitoneal lymphadenectomy, thoracotomy Retroperitoneal lymphadenectomy, thoracotomy Retroperitoneal lymphadenectomy, hepatotomy, thoracotomy x2 Thoracotomy X2
Mature teratoma, necrosis
Retroperitoneal lymphadenectomy, thoracotomy Hepatotomy, craniotomy
IV III
Thoracotomy, retroperitoneal lymphadenectomy Retroperitoneal lymphadenectomy, hepatotomy Retroperitoneal lymphadenectomy, thoracotomy
IV IV
mc9.ll.gnanlt tumor was taken from a . . neal 3) and a germ Such nongerm malignancies probably arise within teratomatous foci and are regarded as malignant transformations. 10 During post-chemotherapy 2 there was CO]mlJllet~e necrosis or fibrosis in 5 3 of which with necrosis or also in the specimen. Mature teratoma was found in 8 and malignant tumor in 2. The tumors were taken from the mediastinum 6) brain In the former case the constituted a minor component of the consisted of mature teratoma, and the free of tumor The latter of the brain metastases. Since necrosis or fibrosis both resected relnalnlng 12 all had tumor or mature teratoma in at least 1 site. Of these 5 teratoma both '·VV\r' ....... n than
Mature teratoma X2 Malignant tumor, mature teratoma Mature teratoma, necrosis Mature teratoma X2 Mature teratoma, malignant tumor Necrosis, mature teratoma Mature teratoma X2 Mature teratoma X4 Necrosis X2 Necrosis, mature teratoma Necrosis, malignant tumor Necrosis x2 Mature teratoma X2 Necrosis x2
.n1r- .... r'Y),r' .... '1-A.
Y),n1r-' ..." ....... 1,..l""I
In,.,,..n.VT,,,,,,,,.,lvT
DISCUSSION
Y),Ao1r-r,Y),.n.-".o1r-'T7,oIT7
l""IY),A"\ ......
sp4~clmE~ns and acteristics Residual ("~ at various anatomical sites: 2 3 8 of 12, m
