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.
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.
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).
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.
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.
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.
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. ?