Operative Management of Sacral Chordoma

Fuchs, Bruno MD, PhD; Dickey, Ian D. MD; Yaszemski, Michael J. MD, PhD; Inwards, Carrie Y. MD; Sim, Franklin H. MD

Journal of Bone & Joint Surgery - American Volume: October 2005 - Volume 87 - Issue 10 - p 2211–2216
doi: 10.2106/JBJS.D.02693
Scientific Articles

Background: Sacrococcygeal chordoma presents a difficult diagnostic and therapeutic problem, with a high rate of local recurrence. The purpose of this report is to define the importance of adequate surgical treatment for optimum outcome and survival.

Methods: Fifty-two patients underwent surgical treatment for sacrococcygeal chordoma between 1980 and 2001. The series included eighteen female patients and thirty-four male patients, with an average age of fifty-six years (range, thirteen to seventy-six years) at the time of the diagnosis. The surgical approach depended on the level and extent of the lesion, with a posterior approach performed in twenty-two patients and a combined anteroposterior approach used in thirty. A wide surgical margin was achieved in twenty-one patients.

Results: At an average of 7.8 years (range, 2.1 to twenty-three years) postoperatively, twenty-three patients were alive with no evidence of disease. Twenty-three patients (44%) had local recurrence. The rate of recurrence-free survival was 59% at five years and 46% at ten years. The overall survival rates were 74%, 52%, and 47% at five years, ten years, and fifteen years, respectively. The most important predictor of survival was a wide margin. All patients with a wide margin survived, and this survival rate was significantly different from that for patients who had had either marginal or intralesional excision (p = 0.0001). Of the twenty-one patients with a wide margin, seventeen (81%) had undergone a combined anteroposterior approach and only four had been treated with a posterior approach.

Conclusions: A wide surgical margin is the most important predictor of survival and of local recurrence in patients with sacrococcygeal chordoma. Use of a combined anteroposterior approach increases the likelihood of obtaining a wide margin.

Level of Evidence: Therapeutic Level IV. See Instructions to Authors for a complete description of levels of evidence.

1 Balgrist University Hospital, Forchstrasse 340, 8008 Zurich, Switzerland

2 Eastern Maine Medical Center, 417 State Street, Suite 209, Bangor, ME 04401

3 Departments of Orthopedics (M.J.Y. and F.H.S.) and Surgical Pathology (C.Y.I.), Mayo Clinic, 200 First Street S.W., Rochester, MN 55905. E-mail address for F.H. Sim: sim.franklin@mayo.edu

Article Outline

Chordomas are rare malignant neoplasms of the vertebral column. It is believed that these lesions arise from malignant degeneration of notochordal rests. The majority of chordomas develop in the sacrococcygeal region (40% to 50%) or the base of the skull (35% to 40%), and only a small proportion are found in the vertebral bodies (15% to 20%)1. Although chordomas are low to intermediate-grade malignant lesions, they are very difficult to treat. Symptoms are often vague and indolent and can be confused with those of a variety of other conditions, leading to a delay in diagnosis. Sacral chordomas often reach a large size before diagnosis, and their poor margination and the complex pelvic anatomy make treatment difficult. Achieving long-term survival remains a challenge and is probably influenced by local tumor control2-5. Still, too often, chordomas are excised with curettage or are biopsied through the rectal wall, procedures that compromise outcome. Chordomas are insensitive to chemotherapy, and complete surgical excision is the mainstay of treatment6-8. However, neurogenic dysfunction and pelvic instability are frequent consequences of adequate surgical removal and these complications correlate with the level of resection. A radical surgical approach therefore remains controversial. The goal of this study was to analyze the outcomes in a large series of patients with sacrococcygeal chordoma in order to help to define the role of surgery and its relationship to local recurrences.

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Materials and Methods

The cases of all patients diagnosed with sacrococcygeal chordoma who presented to the Mayo Clinic between 1980 and 2001 were identified and reviewed retrospectively. Patients who had undergone previous surgical treatment were excluded from the review. Fifty-two patients (eighteen female and thirty-four male) with an average age of fifty-six years (range, thirteen to seventy-six years; median, sixty-one years) at the time of the diagnosis were included in the study.

Follow-up included a reevaluation of the tumor at three to four months for the first two years, at six-month intervals for the next three years, and once a year after five years. Clinic visits were complemented by letters and questionnaires provided by our institutional cancer registry. The information included in this report was retrieved from the patients' charts and from the registry. For the purpose of this study, data on the cephalad anatomic extent of the tumor, size of the tumor, type of surgical approach, surgical margins, type of adjuvant treatment, local recurrence, metastasis, disease status at the time of the latest follow-up, and major complications associated with treatment were collected and analyzed for each patient.

The histologic features, as seen on hematoxylin and eosin-stained sections from each tumor, were reviewed. The “classic” chordoma morphology was confirmed, and the tumors were evaluated for the presence and degree of nuclear pleomorphism (defined as moderate or high), spindling of the tumor cells, necrosis, and chondroid differentiation and dedifferentiation. On the average, four microscopic slides (range, one to fifteen) were reviewed for each patient.

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Statistical Analysis

Kaplan-Meier curves were utilized to analyze the rates of overall survival, survival without local recurrence, and metastasis-free survival. Risk factors for these end points were compared with use of the log-rank test. Continuous and time-dependent variables were assessed with use of Cox proportional-hazards models. Chi-square analysis was utilized for comparisons of proportions. The level of significance was a probability value of <0.05.

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Results

Clinical Presentations

Local pain was the chief presenting symptom in almost every case. Neurological deficits, including bladder or bowel symptoms or radiculopathies, were less frequently observed. The typically long duration of symptoms for patients with chordoma was confirmed in this study, in which it averaged twenty-seven months (range, one to 180 months). The tumors were usually large, with a mean diameter of 9 cm (with two tumors measuring >15 cm), and a mean volume of 219 cm3. In two-thirds of the patients, the cephalad extent of the lesion reached the S2 or S3 level (Table I).

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Treatment

A posterior surgical approach was used in twenty-two patients (42%), and a combined anteroposterior approach was used in thirty (58%). All patients in whom the lesion extended above S2 underwent a combined anteroposterior approach, and those in whom the lesion was below S3 had only a posterior approach. Of the patients with a lesion extending to S2 or S3, seventeen had a posterior approach and seventeen had a combined anteroposterior approach. In this group, sixteen patients were treated in the 1980s and eighteen, in the 1990s. Interestingly, the posterior approach was used more frequently in the first decade of the study period than in the second decade (twelve patients compared with five patients), whereas the combined approach was used more often in the second decade of the study period (four patients in the 1980s compared with thirteen patients in the 1990s). This difference was significant (p = 0.04) and suggests that, during the study period, there was a shift toward performing more extensive surgery for lesions extending to the S2 or S3 level.

A wide margin was defined as a cuff of normal tissue around the tumor except anteriorly, where the tumor was covered by the presacral fascia and was separated easily from the rectum without any evidence of infiltration. If there was dorsal expansion, a cuff of muscle was resected with the specimen. Superiorly, on the basis of precise preoperative imaging, at least 1 to 2 cm of normal bone was obtained at the level of the osteotomy. A wide margin was obtained in twenty-one patients (40%), seventeen of whom had a combined anteroposterior approach and only four of whom had a posterior approach alone. An inadequate margin (marginal or intralesional) was obtained in thirty-one patients (60%), eighteen of whom had a posterior approach alone and thirteen of whom had a combined anteroposterior approach.

In this series, radiation therapy was reserved for local recurrences and for patients in whom a contaminated margin was obtained during surgery. Overall, radiation was administered to twenty-two (42%) of the fifty-two patients, at an average dose of 47 Gy (range, 15 to 60 Gy). Only seven patients received the radiation because the resection margin for the primary tumor was inadequate. Of these patients, five had died and two were alive at the time of final follow-up. The remaining fifteen patients received radiation because of a local recurrence. Of these fifteen patients, eleven had died and four were alive without evidence of disease at the time of final follow-up.

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Outcome

After a mean duration of follow-up of 7.8 years (range, 2.1 to twenty-three years), twenty-nine patients were alive and twenty-three patients had died (Table II). The overall survival rate in the entire group was 74% at five years, 52% at ten years, and 47% at fifteen years (Fig. 1). Twenty-three (44%) of the fifty-two patients had a local recurrence. The recurrence-free survival rate for the entire group was 59% at five years and 46% at ten years (Fig. 2). The survival rate for the patients without a local recurrence appeared to be better than the rate for those with a recurrence (73% compared with 40% at ten years) (Fig. 3). However, this difference did not reach significance (p = 0.2) when the Kaplan-Meier curves were compared, most likely because of the wide range of follow-up times. Nevertheless, a chi-square test comparing the local recurrence rate with the survival status showed that significantly more patients without a recurrence than patients with a recurrence were alive at the time of follow-up (p = 0.01; Table III).

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.

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Complications

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.

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Discussion

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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