Several factors were analyzed to assess their impact on survival. Neither the tumor volume (p = 0.13) nor the level of the resection affected survival. The type of surgical approach per se (posterior or anteroposterior) also did not seem to influence survival (p = 0.138), although a wide margin was obtained more often when the combined anteroposterior approach was used. The survival rate was significantly higher when an adequate (wide) margin had been achieved (Fig. 4). Multivariate analysis identified the surgical margin (p = 0.0001) and the age of the patient (p = 0.04) as independent predictors of survival. Therefore, the size of the tumor, level of resection, and surgical approach were not found to significantly influence survival, whereas the surgical margin was shown, by multivariate analysis, to be the single most important predictor of survival.
A significant relationship (p = 0.0001) was found between the local recurrence rate and the margin that had been achieved during the surgery (Table IV). Overall, lung metastasis developed in sixteen (31%) of the fifty-two patients, and all but three of those patients also had a local recurrence. The overall metastasis-free survival rate was 63% at five years and 46% at ten years (Fig. 5). Patients who had metastasis had a significantly worse survival rate than those in whom metastasis did not develop (p = 0.05) (Fig. 6). Of the four patients in whom the tumor diameter was >15 cm or the cephalad extent of the tumor was to L5, two had an adequate margin and the other two did not. Three of the four were alive at the time of the last follow-up.
Histologically, all of the tumors displayed the classic features of a conventional chordoma. At low magnification, they all showed a lobular growth pattern. The tumor cells were arranged in cords, nests, and sheets with variable amounts of pale blue mucoid or myxoid matrix. The level of cellularity varied within the individual tumors and among the different tumors. All of the tumors contained cells with round-to-oval nuclei with at least mild cytologic atypia surrounded by clear or eosinophilic cytoplasm. Although cytoplasmic vacuolization was variable, it was seen in all cases. In areas where the vacuolization was prominent, the tumor had a clear-cell appearance. In areas in which it was less prominent, the more abundant eosinophilic cytoplasm imparted an epithelioid appearance, particularly in tumors with lesser amounts of matrix production.
Moderate-to-marked nuclear pleomorphism was seen in sixteen (31%) of the tumors. Nine of the sixteen tumors contained focal (occupying <25% of the tumor) moderate pleomorphism, whereas pleomorphism was more prominent (occupying >50% of the tumor) in four. Three tumors contained areas of marked pleomorphism, which was focal in two and more diffuse in the third. Necrosis was seen histologically in twenty tumors (38%). Focal spindling of the tumor cells without increased nuclear pleomorphism was seen in five tumors. There was no evidence of chondroid matrix or dedifferentiation in any tumor. We were unable to correlate any of these histopathological findings with the clinical course.
The most common complication was local wound break-down, which required débridement in fifteen patients and local flap placement in two. Interestingly, 80% of these complications occurred early in the series, when a transverse rectus abdominis musculocutaneous flap was not routinely used. Stress fractures of the alae of the pelvis developed in three patients, two of whom had undergone radiation. Three other patients, all treated with an anteroposterior approach, had persistent stool incontinence, which required a delayed colostomy in each. One patient had a persistent cerebrospinal fluid leak, which required a reoperation. Another patient underwent a knee disarticulation because of an anesthetic nonhealing ulcer on the foot subsequent to surgical resection of and nerve-root involvement by the primary tumor.
Chordoma of the sacrum presents a diagnostic and therapeutic challenge. The overall survival of these patients is still relatively poor considering the low-grade nature of this malignant lesion1. As noted in the current series, the long duration of symptoms prior to diagnosis, the delay in diagnosis, and the large volume of the tumor may contribute to the relatively poor prognosis. Previous studies have shown five and ten-year survival rates of 45% to 77% and 28% to 50%, respectively9-11. The long-term survival rate of the patients in our series compares favorably with the rates in those reports; however, the mortality was still high (>50% at fifteen years). Local control issues probably are related to the poor survival. In this study, all but three patients with distant metastasis also had a local recurrence. The cumulative probability of local recurrence at five and ten years was 46% and 54%, respectively. We found the development of metastatic disease to be an indicator of a poor prognosis. Several studies have shown that the risk of metastatic disease ranges from 10% to 40%12. Samson et al. reported a ten-year cumulative probability of metastasis of 50%, which is similar to our finding9. The recurrence rate in this study may be lower than those in other reports, but it is still high2-5,13.
Local recurrence is of great concern because of its inverse relationship with survival2,3,13-15. There is general agreement that complete surgical resection with wide, tumor-free margins is the treatment of choice for a chordoma6-8. However, the extent of the resection directly correlates with the resulting functional deficits16-22. Therefore, meticulous preoperative planning and discussion of potential neurogenic dysfunction with the patient are essential17.
Several surgical approaches can be utilized to remove a sacral chordoma, and it is unclear whether some approaches may increase the probability of obtaining a wide margin. The posterior approach was described as being most appropriate for lesions at S3 and below23. This approach offers the advantage of a single operation, shorter operative time, and less morbidity. Disadvantages include a potential for hemorrhage and possible violation of the pelvic viscera or ureters during removal of specimens. We reserve the posterior approach for lesions at S3 and below. For lesions above S3, we prefer to use the combined anteroposterior approach. At some centers, a simultaneous anteroposterior approach is preferred to visualize the anterior structures during osteotomy. We used a sequential approach, thereby accepting the disadvantage of not visualizing the anterior structures during the sacral osteotomy24-26. The anterior approach allows exposure of the entire sacrum with mobilization of the rectum, ureter, and major vessels. Ligation of the internal iliac arteries may have helped reduce bleeding during mobilization of the specimen from posteriorly. Laparoscopic mobilization of the anterior structures has also been used. However, an anterior open approach is more popular and allows the harvest of a pedicled rectus abdominis flap to assist final wound closure posteriorly.
In our study, the single most important predictor of survival and local recurrence was the margin obtained during the surgery. All patients with a wide margin survived. The local recurrence rate in our series was still high, and it seems to have been related to the frequent use of the posterior approach alone during the early years of the study. Interestingly, the majority of patients (81%) in whom a wide margin was achieved had a combined anteroposterior approach. This finding may help surgeons to decide which approach to use, particularly for lesions at the S2 or S3 level (two-thirds of the tumors in our series). Because our results indicate that the combined approach increases the chances of obtaining a wide margin, we now are more likely to employ this approach for lesions at this level.
The role of radiation remains a subject of debate, and its value in controlling local disease is inconclusive. Although chordomas may be relatively resistant to adjuvant radiation1,6,27, the therapy may prolong the disease-free interval and decrease the symptoms of recurrent lesions28-30. Indications for radiation therapy may include surgically inaccessible lesions, contaminated surgical margins, or incomplete surgical excision of the tumor. Radiation therapy can also be used after removal of the primary tumor or when there is a local recurrence. Previous studies have demonstrated mixed results regarding the ability of early radiation therapy to improve the prognosis when the surgical margin is positive6,8,9,27,29,31. Our results did not demonstrate that radiation improved survival or disease status. However, fewer than half of the patients in our series received radiation, and, of these, two-thirds received it only for recurrence. The authors of a recent promising report found carbon-ion radiotherapy to be an effective treatment for chordomas32. Given the rarity of the tumor, the value of radiation therapy for its treatment needs to be addressed in future prospective multi-institutional studies.
Earlier diagnosis of chordomas is important and requires a high index of suspicion. The surgical margin is the most important predictor of survival, and aggressive surgery, including a combined anteroposterior approach, may help to achieve an adequate margin. Hopefully, one can expect more cures with earlier recognition and aggressive surgical treatment. ▪
The authors did not receive grants or outside funding in support of their research or preparation of this manuscript. They did not receive payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, educational institution, or other charitable or nonprofit organization with which the authors are affiliated or associated.
Investigation performed at the Departments of Orthopedics and Surgical Pathology, Mayo Clinic, Rochester, Minnesota
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