Surgery for Disseminated Abdominal Sarcoma Constantine P. Karakousis,
PhD, Leslie E. Blumenson, PhD, Giuseppe Canavese, Uma Rao, MD, Buffab, NW York
MD,
Seventy-two consecutive patients with disseminated soft tissue sarcoma in the abdomen were prospectively placed in a program of debulking surgery. The tumor was completely resectable in 64% of the patients. Following the first exploration, the median survival was 23 months for those with resection of metastases and 9 months for those without resection (p 50.01); th e f ormer group had a survival rate of 28% at 3 years, 18% at 4 years, and 4% at 5 years (44%, 37%, and lo%, respectively, for low-grade sarcomas, i.e., grade I or II sarcomas), whereas in the latter group, none survived for 3 years. In the group with resection, patients with grade III tumors had a median survival longer by 6 months, and those with low-grade tumors by 28 months (p 10.001), over the respective median survival of patients with unresec table tumors. Metastasectomy appeared to prolong survival in all patients and significantly so in patients with lowgrade tumors and those with long disease-free intervals.
MD,
he most common sites of initial recurrence in soft T tissue sarcomas are the primary site and the lungs [I]. Of the patients with hematogenous metastasis, the lungs are involved in more than 80% and are the only organ initially affected by metastatic disease in 70% [2]. This peculiarity in the biologic behavior of these tumors provides the justification for resection of pulmonary metastases. Patients with isolated pulmonary metastases rendered free of disease with metastasectomy thus attain an actuarial 3-year survival rate of 38% [3]. However, this pattern of distant recurrence concerns the overall population of soft tissue sarcomas that occur primarily in the extremities (in 49% to 70%) [2,4] and other extra-abdominal sites. In a compilation of several series, the incidence of sarcomas in the trunk and retroperitoneum was 32% [5] of the total population of soft tissue sarcomas. Our experience with intra-abdominal sarcomas suggests that they have a different pattern of metastasis, often recurring locally and at multiple intra-abdominal sites. Extra-abdominal sites, such as the lungs, are involved infrequently and later in the course of these neoplasms. Since the majority of the patients with intra-abdominal dissemination do not have extra-abdominal disease, it was thought that debulking surgery might prove of some benefit, and it was prospectively evaluated in a series of 72 consecutive patients. PATIENTS AND METHODS
From the Departments of Surgical Oncology (CPK, GC), Biomathe matics (LEB), and Pathology (UR), Roswell Park Cancer Institute, Buffalo, New York. Requests for reprints should be addressed to Constantine P. Karakousis, MD, PhD, Surgical Oncology Department, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, New York 14263. Manuscript submitted January 9, 1991, and accepted in revised form April 251991.
560
THE AMERICAN JOURNAL OF SURGERY
A total of 72 patients with disseminated intra-abdominal sarcomas were managed in the period from February 1978 to January 1990 at Roswell Park Cancer Institute (RPCI). All these patients had previously had their primary tumor resected completely. There were 39 females (54%) and 33 males (46%). The mean age was 5 1, and the median age was 55 years (range: 14 to 82 years). The most common histologic type was leiomyosarcoma (63%) followed by liposarcoma (13%), malignant fibrous histiocytoma (8%), malignant mesenchymoma (3%), rhabdomyosarcoma, fibrosarcoma, malignant schwannoma, hemangiopericytoma, and neurogenic sarcoma (1% incidence each), and other types of sarcoma (7%). The grade of the tumor was I in 18 (25%), II in 13 (18%), and III in 41 (57%). The location of the original tumor was: (1) intraperitoneal in 34 (47%); (2) retroperitoneal in 13 (18%); (3) in the abdominal wall in 2 (3%); or (4) in other intra-abdominal sites such as the pelvis or diaphragm in 23 (32%). In 49 patients with available information as to the size of the original tumor, the latter had a mean diameter of 15 cm and median diameter of 14 cm.
VOLUME 163 JUNE 1992
SURGERY FOR DISSEMINATED
At the time of diagnosis of disseminated disease, the tumor was metastatic to several abdominal sites in 64 patients (89%) and was metastatic to several abdominal and extra-abdominal sites in 8 (11%). At the time of exploration for metastatic disease, the number of abdominal sites was countable in 43 patients (60%) and too large to count in 29 (40%). The smallest number of metastatic nodules found was four. The lesions were considered “uncountable*’ when they exceeded 15. The liver was involved in 29 (40%) patients. In only 1 of these 29 patients were the metastases confiied to the liver. At the first operation for disseminated disease at RPCI, removal of all metastatic lesions was possible in 46 (64%) patients, whereas, in 26 (36%) patients, only a portion of the metastatic lesions was removed. Most of the lesions were resected. Occasionally, when small lesions, approximately 1 to 2 mm in diameter, were numerous, they were simply cauterized. In patients with complete debulking, there was no evidence of any residual macroscopic tumor under the most meticulous examination at the end of the procedure. Chemotherapy was used postoperatively in 55 patients (76%), whereas the remaining 17 patients (24%) did not have chemotherapy mainly because, in their cases, all common drugs for these tumors had already been used unsuccessfully. Chemotherapy protocols commonly used were those of doxorubicin and dacarbaxine, ifosfamide, and c&platinum (the last either intravenously or intraperitoneally) in standard doses. There was no discernible difference in the type of protocols used between patients with complete debulking and those with incomplete or no debulking. Patients were followed up closely with a physical examination and computed tomographic scan at 2- to 3month intervals. This allowed the evaluation of the response to treatment (for those with unresectable disease) or the detection of recurrence (for those with complete debulking at the previous operation). Patients found to have unresectable disease at the first or subsequent operation had no further attempts at debulking operations, and any further operation was directed only to palliate a mechanical problem (mainly bowel obstruction). On the other hand, patients who had a complete debulking operation were reoperated upon with the intention of debulking at the frost evidence of recurrence, and this was repeated until such time as the tumor was no longer completely resectable. A total of 138 procedures were performed with the intention of debulking, which includes all debulking operations and the first procedure in which debulking was not possible. The mean number of such procedures per patient was two, and the median was two (range: one to seven). Long-term survivors had an average of two procedures annually. The total number of operations including those performed for palliation was 150. Four patients died within 1 month from the operation (operative mortality rate: 3%). One of these deaths was due to pulmonary embolism, two to pneumonia in association with cachexia and advanced
THE AMERICAN
ABDOMINAL
SARCOMA
age, and one to a small bowel fistula and sepsis. Only 1 postoperative death occurred after 112 operations of complete debulking performed in 46 patients. The median stay in the first three procedures was 21, 19, and 17 days, respectively. Each stay often included a period of hyperalimentation and/or a course of chemotherapy in addition to the postoperative recovery time. The estimated survival distributions were calculated by the method of Kaplan and Meier [6’j.Tests of significance with respect to survival distributions were based on the log-rank test [7]. Survival time was estimated from the time of diagnosis and from the first operation at RPCI for disseminated abdominal disease. RESULTS At a median follow-up of 15 months since the first debulking operation, 56 (78%) patients have died of their disease, 2 (3%) have died of other causes, 8 (11%) are alive with disease, and 6 (8%) are alive without disease. During the course of the illness, the disease remained confined in the abdomen in 52 patients (72%) whereas it spread to extra-abdominal sites in 20 (28%). The median survival time from the date of diagnosis of the primary tumor to last follow-up or death was 39 months, whereas that from the first attempt at debulking surgery at RPCI was 15 months. There was a significant difference (p = 0.02) in median survival from diagnosis of the primary tumor between men (median survival: 32 months) and women (median survival: 42 months), but there was no significant difference from the first debullcing operation (median survival: 13 months for men, 15 months for women). There was a mean interval of 29 months (median: 15 months) between diagnosis of the primary tumor and the first debulking operation. Corresponding intervals for the patients with resection of their metastases were 27 and 15 months, and for those without resection 31 and 16 months, respectively. Although all these patients eventually developed metastatic disease, their time to death followed a fairly indolent course. Patients with resection of their metastases and those with unresectable metastatic disease had respective median survivals from initial diagnosis of 40 and 34 months, estimated j-year survival rates of 29% and 27%, and 8-year survival rates of 29% and 9%, respectively. These two survival curves were not significantly different. Patients who had a successful debulking operation at the first attempt had no significant differences from those for whom the operation was not successful in removing their metastases with regard to sex, age, histologic grade, or tumor grade. In fact, patients with complete resection had a slightly higher percentage of high-grade tumors (27 of 46 or 59%) compared with patients who had no resection (14 of 26 or 54%). However, only 11 of 46 (24%) in the debulked group had liver metastases, whereas 18 of 26 (69%) of the group with tumors not completely resectable had liver metastases (p
PhD, Leslie E. Blumenson, PhD, Giuseppe Canavese, Uma Rao, MD, Buffab, NW York
MD,
Seventy-two consecutive patients with disseminated soft tissue sarcoma in the abdomen were prospectively placed in a program of debulking surgery. The tumor was completely resectable in 64% of the patients. Following the first exploration, the median survival was 23 months for those with resection of metastases and 9 months for those without resection (p 50.01); th e f ormer group had a survival rate of 28% at 3 years, 18% at 4 years, and 4% at 5 years (44%, 37%, and lo%, respectively, for low-grade sarcomas, i.e., grade I or II sarcomas), whereas in the latter group, none survived for 3 years. In the group with resection, patients with grade III tumors had a median survival longer by 6 months, and those with low-grade tumors by 28 months (p 10.001), over the respective median survival of patients with unresec table tumors. Metastasectomy appeared to prolong survival in all patients and significantly so in patients with lowgrade tumors and those with long disease-free intervals.
MD,
he most common sites of initial recurrence in soft T tissue sarcomas are the primary site and the lungs [I]. Of the patients with hematogenous metastasis, the lungs are involved in more than 80% and are the only organ initially affected by metastatic disease in 70% [2]. This peculiarity in the biologic behavior of these tumors provides the justification for resection of pulmonary metastases. Patients with isolated pulmonary metastases rendered free of disease with metastasectomy thus attain an actuarial 3-year survival rate of 38% [3]. However, this pattern of distant recurrence concerns the overall population of soft tissue sarcomas that occur primarily in the extremities (in 49% to 70%) [2,4] and other extra-abdominal sites. In a compilation of several series, the incidence of sarcomas in the trunk and retroperitoneum was 32% [5] of the total population of soft tissue sarcomas. Our experience with intra-abdominal sarcomas suggests that they have a different pattern of metastasis, often recurring locally and at multiple intra-abdominal sites. Extra-abdominal sites, such as the lungs, are involved infrequently and later in the course of these neoplasms. Since the majority of the patients with intra-abdominal dissemination do not have extra-abdominal disease, it was thought that debulking surgery might prove of some benefit, and it was prospectively evaluated in a series of 72 consecutive patients. PATIENTS AND METHODS
From the Departments of Surgical Oncology (CPK, GC), Biomathe matics (LEB), and Pathology (UR), Roswell Park Cancer Institute, Buffalo, New York. Requests for reprints should be addressed to Constantine P. Karakousis, MD, PhD, Surgical Oncology Department, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, New York 14263. Manuscript submitted January 9, 1991, and accepted in revised form April 251991.
560
THE AMERICAN JOURNAL OF SURGERY
A total of 72 patients with disseminated intra-abdominal sarcomas were managed in the period from February 1978 to January 1990 at Roswell Park Cancer Institute (RPCI). All these patients had previously had their primary tumor resected completely. There were 39 females (54%) and 33 males (46%). The mean age was 5 1, and the median age was 55 years (range: 14 to 82 years). The most common histologic type was leiomyosarcoma (63%) followed by liposarcoma (13%), malignant fibrous histiocytoma (8%), malignant mesenchymoma (3%), rhabdomyosarcoma, fibrosarcoma, malignant schwannoma, hemangiopericytoma, and neurogenic sarcoma (1% incidence each), and other types of sarcoma (7%). The grade of the tumor was I in 18 (25%), II in 13 (18%), and III in 41 (57%). The location of the original tumor was: (1) intraperitoneal in 34 (47%); (2) retroperitoneal in 13 (18%); (3) in the abdominal wall in 2 (3%); or (4) in other intra-abdominal sites such as the pelvis or diaphragm in 23 (32%). In 49 patients with available information as to the size of the original tumor, the latter had a mean diameter of 15 cm and median diameter of 14 cm.
VOLUME 163 JUNE 1992
SURGERY FOR DISSEMINATED
At the time of diagnosis of disseminated disease, the tumor was metastatic to several abdominal sites in 64 patients (89%) and was metastatic to several abdominal and extra-abdominal sites in 8 (11%). At the time of exploration for metastatic disease, the number of abdominal sites was countable in 43 patients (60%) and too large to count in 29 (40%). The smallest number of metastatic nodules found was four. The lesions were considered “uncountable*’ when they exceeded 15. The liver was involved in 29 (40%) patients. In only 1 of these 29 patients were the metastases confiied to the liver. At the first operation for disseminated disease at RPCI, removal of all metastatic lesions was possible in 46 (64%) patients, whereas, in 26 (36%) patients, only a portion of the metastatic lesions was removed. Most of the lesions were resected. Occasionally, when small lesions, approximately 1 to 2 mm in diameter, were numerous, they were simply cauterized. In patients with complete debulking, there was no evidence of any residual macroscopic tumor under the most meticulous examination at the end of the procedure. Chemotherapy was used postoperatively in 55 patients (76%), whereas the remaining 17 patients (24%) did not have chemotherapy mainly because, in their cases, all common drugs for these tumors had already been used unsuccessfully. Chemotherapy protocols commonly used were those of doxorubicin and dacarbaxine, ifosfamide, and c&platinum (the last either intravenously or intraperitoneally) in standard doses. There was no discernible difference in the type of protocols used between patients with complete debulking and those with incomplete or no debulking. Patients were followed up closely with a physical examination and computed tomographic scan at 2- to 3month intervals. This allowed the evaluation of the response to treatment (for those with unresectable disease) or the detection of recurrence (for those with complete debulking at the previous operation). Patients found to have unresectable disease at the first or subsequent operation had no further attempts at debulking operations, and any further operation was directed only to palliate a mechanical problem (mainly bowel obstruction). On the other hand, patients who had a complete debulking operation were reoperated upon with the intention of debulking at the frost evidence of recurrence, and this was repeated until such time as the tumor was no longer completely resectable. A total of 138 procedures were performed with the intention of debulking, which includes all debulking operations and the first procedure in which debulking was not possible. The mean number of such procedures per patient was two, and the median was two (range: one to seven). Long-term survivors had an average of two procedures annually. The total number of operations including those performed for palliation was 150. Four patients died within 1 month from the operation (operative mortality rate: 3%). One of these deaths was due to pulmonary embolism, two to pneumonia in association with cachexia and advanced
THE AMERICAN
ABDOMINAL
SARCOMA
age, and one to a small bowel fistula and sepsis. Only 1 postoperative death occurred after 112 operations of complete debulking performed in 46 patients. The median stay in the first three procedures was 21, 19, and 17 days, respectively. Each stay often included a period of hyperalimentation and/or a course of chemotherapy in addition to the postoperative recovery time. The estimated survival distributions were calculated by the method of Kaplan and Meier [6’j.Tests of significance with respect to survival distributions were based on the log-rank test [7]. Survival time was estimated from the time of diagnosis and from the first operation at RPCI for disseminated abdominal disease. RESULTS At a median follow-up of 15 months since the first debulking operation, 56 (78%) patients have died of their disease, 2 (3%) have died of other causes, 8 (11%) are alive with disease, and 6 (8%) are alive without disease. During the course of the illness, the disease remained confined in the abdomen in 52 patients (72%) whereas it spread to extra-abdominal sites in 20 (28%). The median survival time from the date of diagnosis of the primary tumor to last follow-up or death was 39 months, whereas that from the first attempt at debulking surgery at RPCI was 15 months. There was a significant difference (p = 0.02) in median survival from diagnosis of the primary tumor between men (median survival: 32 months) and women (median survival: 42 months), but there was no significant difference from the first debullcing operation (median survival: 13 months for men, 15 months for women). There was a mean interval of 29 months (median: 15 months) between diagnosis of the primary tumor and the first debulking operation. Corresponding intervals for the patients with resection of their metastases were 27 and 15 months, and for those without resection 31 and 16 months, respectively. Although all these patients eventually developed metastatic disease, their time to death followed a fairly indolent course. Patients with resection of their metastases and those with unresectable metastatic disease had respective median survivals from initial diagnosis of 40 and 34 months, estimated j-year survival rates of 29% and 27%, and 8-year survival rates of 29% and 9%, respectively. These two survival curves were not significantly different. Patients who had a successful debulking operation at the first attempt had no significant differences from those for whom the operation was not successful in removing their metastases with regard to sex, age, histologic grade, or tumor grade. In fact, patients with complete resection had a slightly higher percentage of high-grade tumors (27 of 46 or 59%) compared with patients who had no resection (14 of 26 or 54%). However, only 11 of 46 (24%) in the debulked group had liver metastases, whereas 18 of 26 (69%) of the group with tumors not completely resectable had liver metastases (p
