ISSN: 2754-8880
Published 00 11 0000
OPEN ACCESS
Edited by
A.Hussain
Submitted 30 Nov 2021
Accepted 04 Dec 2021
Citation
Matthew Mouat, Ashok
Gunawardene, Lisa
Sweetman, Elizabeth
Dennett, Peter Larsen.
Psoas Muscle
Cross-Sectional Area and
Outcomes Following
Colorectal Cancer Surgery:
BJOSS::2021:(1);39-45
Psoas Muscle Cross-Sectional Area and
Outcomes Following Colorectal Cancer Surgery
Matthew Mouat
1
, Ashok Gunawardene
2
, Lisa Sweetman
1
, Elizabeth Dennett
1,2
,
and Peter Larsen2*
*
Corresponding author: Associate Professor Peter Larsen, Department of Surgery Anaesthesia,
University of Otago Wellington, New Zealand. Peter.Larsen@otago.ac.nz.
1Capital & Coast District Health Board, New Zealand
2Department of Surgery and Anaesthesia, University of Otago, Wellington, New Zealand
ORIGINAL
Abstract
Background: Frailty and functional status are established risk factors for postoperative morbidity
and mortality, but new data also suggest a link between sarcopenia and longer-term oncological
outcomes in colorectal cancer. Cross-sectional imaging is performed routinely prior to elective
resection and provides a means to measure psoas muscle cross-sectional area, which in turn is a
surrogate marker of sarcopenia.
Methods: A retrospective cohort study of patients undergoing elective surgery with curative intent
for colorectal cancer. Using automated software, psoas muscle cross-sectional area was measured
and the relationship with five-year disease-free survival was evaluated using Kaplan-Meier survival
curves.
Results: A significant relationship was found among patients with a low (below median) psoas
muscle cross-sectional area, HR 1.57 (95% CI 1.1-2.5) p=0.04.
Conclusion: This study demonstrated a potential relationship between psoas muscle cross-
sectional area and disease-free survival, highlighting the further utility of pre-operative staging
CT in predicting prognosis in patients with colorectal cancer.
Introduction
Assessing the likelihood of postoperative morbidity and mortality is critical to informing the
decision-making of both surgical teams and patients. One of the more complex tasks for clinicians
is assessing the overall physical health of the preoperative patient, or when thinking about potential
adverse outcomes, their frailty. Frailty can be described as “a state of a reduced physiologic reserve
associated with increased susceptibility to disability” (
1
). Methods for measurement of frailty or
functional status have included many variables such as the patient’s ability to perform activities
of daily living, cognition, falls, anaemia, weight loss, physical fitness, and underlying medical
conditions (
1
;
2
;
3
;
4
;
5
). One aspect of frailty is the loss of lean muscle mass, and many studies have
shown that this can be used as a predictor of adverse post-surgical outcomes (
4
;
6
;
7
;
8
;
9
;
10
;
11
).
A simple and reproducible method for loss of muscle mass is a measurement of the cross-sectional
area of the psoas muscle in the lumbar spine (8;9;12).
Colorectal cancer is the second leading cause of cancer-related deaths in New Zealand. The
incidence of colorectal cancer progressively increases with age. Over ninety percent of cases
in New Zealand occur after the age of 50, and three-quarters of those patients are older than
65 (
13
). This age-related increase means that the greatest need for colorectal cancer surgery is in
older patients who are also more likely to be frail, conferring a higher risk of adverse postoperative
outcomes. Loss of lean muscle mass in this population has been associated with poor short-term
outcomes, but not with a longer-term prognosis. To determine whether loss of mean muscle mass
does predict longer-term outcomes, this study examined whether measurements of psoas muscle
cross-sectional area in colorectal cancer surgery patients was a predictor of 5-year disease-free
survival.
Methods
We retrospectively collated a cohort of all patients undergoing surgery with curative intent for
colorectal at Wellington Hospital over the years 2010, 2011, and 2012. Baseline demographics
and outcomes were recorded for all patients. Disease-free survival was defined as having neither
recurrence nor death. Time-to-recurrence was calculated from the date of surgery to either
histological confirmation or clinical-radiological evidence of loco-regional or metastatic disease
recurrence on review at a multi-disciplinary meeting, where the date of the meeting was taken as
the end-point (
14
). Patients that were alive and without evidence of disease recurrence on 1st
November 2016 were censored.
For each patient, we accessed preoperative CT imaging which had been performed either in
Wellington Hospital on 16 slice Siemens or GE CT scanners or by a local private radiology provider
on 32 or 64 slice CT scanners. The images for these CT scans were then uploaded onto the
workstation for the current 320 slices Toshiba Aquilion One Genesis CT at Wellington Hospital
and the images were evaluated using the Toshiba workstation software. This software allowed
for the region of interest (ROI) measurement of both psoas muscles at the level of the inferior
endplate of L3 using maximum and minimum Hounsfield unit (HU) thresholds Figure 1. The range
of values used for measurement of psoas cross-sectional area was between +150HU and -29
HU (
12
). Measurements were taken by a single observer, a final year diagnostic radiology trainee.
The ROI was defined manually using a drawing tool on the Toshiba software. Any operator error
that inadvertently included bone (vertebral body or osteophyte) or retroperitoneal fat within the
ROI was minimized by the HU threshold settings.
Figure 1. CT image for a representative subject at the inferior endplate of L3. The region of
interest was defined manually (defined here as the green line). The Toshiba software then
detected muscle tissue on the basis of HU threshold settings (area shaded pink), excluding
bone or retroperitoneal fat.
Measurement error was further minimized by using multi-planar reconstruction software to
account for curvature (anteroposterior or lateral) of the patient’s lumbar spine, to standardize
the level of measurement to the inferior endplate of L3. Repeat measurements were performed
on images for 10 subjects selected at random, with the investigator blinded to the original
measurement. The percentage variance between initial and repeat measurement averaged 1.7%,
with a maximum variance of 5.9%.
40/45
We took the average of left and right psoas muscle area and divided this by patient height to give
total psoas muscle (TPA) area (
15
). Sarcopenia was defined using gender-specific cutoff points of
<38.5cm²/m²for female patientsand <54.5cm²/m²for male patients based on an international
consensus group definition (16).
Statistical analysis
Continuous variables are expressed as mean + standard deviation, and categorical variables are
expressed as numbers (percentage). We examined disease-free survival based on quartiles and
median cut-points for BMI and TPA, and those with and without sarcopenia. P values >0.05 were
taken as statistically significant. Data analysis was performed using SPSS.
Results
During the study period, 237 patients underwent curative-intent surgery for the colorectal cancer
cohort. Of this group, 218 patients had preoperative CT scans that were accessible and were
included in the study. Demographic features of the patient cohort are given in Table 1. The mean
age was 69, 49% were male, and 74% had colon cancer.
Table 1. Demographical and clinical characteristics of the patients
All (n=218)
Age 69 (12)
Male Gender 108 (49%)
BMI 27 (7)
CCI
0 117(54%)
1 46 (21%)
2 32 (15%)
3+ 23 (10%)
Tumour Location Colon 161 (74%)
Rectum 57 (26%)
Cancer Stage
1 37 (17%)
2 84 (39%)
3 87 (40%)
4 10 (5%)
Adjuvant Therapy 69 (32%)
The mean TPA in the cohort was 58.1 +/- 17.2 cm²/m²and the mean BMI was 27.2 +/- 6.9 kg/m².
While there was a correlation between BMI and TPA, this relationship was relatively weak (r=0.36,
p=0.0001, Pearson’s Correlation) Figure 2. There was a weak inverse relationship between TPA
and age, and TPA was greater in male patients (67.9 +/- 16.1 cm²/m²versus 47.4 +/- 11.1 cm²/m²,
p=0.0001, unpaired t-test). TPA was also greater in male patients than female patients and had a
weak inverse relationship with age (r=-0.22, p=0.001, Pearson’s Correlation). TPA did not differ
by cancer stage, or between patients with colon or rectal cancer.
Applying the consensus definition of sarcopenia to the population, 23 patients were defined as
sarcopenic. This group was older than the rest of the cohort (mean age 74+/-7 versus 69+/-12,
p=0.04) but did not differ from the rest of the cohort significantly by BMI.
At 5 years, disease free survival in the cohort was 62%. We examined rates of disease-free
survival against TPA by quartile and by median Figure 3 and observed that there was a statistical
difference in outcome in the group divided by median score. Those in the lower half had a 5-year
disease-free survival of 55% compared to 66% in those in the upper half, giving a hazard ratio of
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Figure 2. A shows the relationship between TPA in cm2/m2and BMI in kg/m2(r=0.36, p=0.0001,
Pearson’s Correlation). B shows the relationship between age and TPA (r=-0.22, p=0.001,
Pearson’s Correlation). C shows the difference in TPA between male and female patients
(p=0.0001, unpaired t-test)
1.57 (95% CI 1.1 to 2.5) associated with being in the lower half of TPA scores (p=0.04, Mantel-Cox
test). There was no significant difference in disease-free survival against BMI by either quartile
or by median Figure 4. In those with sarcopenia, we observed a 5-year disease-free survival
rate of 54%, compared to 62% in those nonsarcopenic. This difference was not statistically
significant Figure 5.
Figure 3. Disease free survival in the population segregated on the basis of TPA quartiles (A)
and by the median (B). There was a significant difference between the survival curves
segregated by the median, with a hazard ratio of 1.57 (95% CI 1.1 to 2.5) associated with being
in the lower half of TPA scores (p=0.04, Mantel-Cox test
Discussion
We have observed that low TPA is a predictor of poor 5-year disease-free survival in patients
with colorectal cancer and a similar trend observed in analysis by sarcopenia, but the rate of
sarcopenia was low and this result was not statistically significant. TPA did differ by gender, and
was correlated with BMI and inversely correlated with age although these were weak relationships.
We observed that preoperative TPA was a statistically significant predictor of 5-year disease-
free survival in colorectal cancer surgical patients. Patients in the high TPA group had a 66%
42/45
Figure 4. Disease free survival in the population segregated on the basis of BMI quartiles (A)
and by the median (B). There were no significant differences in survival between these groups
Figure 5. Disease free survival of groups with (n=23) and without (n=195) sarcopenia on the
basis of TPA measurement. There was no statistical difference in survival outcomes between
these groups
5-year survival compared with 55% in the low TPA group. While TPA was related to BMI, we did
not observe the same association between BMI and disease-free survival, indicating that TPA
measurement is providing information that is not gained from simple measurement of BMI.
The association between TPA and outcome is consistent with the findings of multiple previous
studies linking low preoperative TPA to poor short-term post-surgical outcomes (
4
;
6
;
7
;
9
;
11
).
While the majority of literature examining TPA in cancer patients has focused on short-term
outcomes, a previous study in oesophageal cancer patients observed that low TPA was associated
with worse 3-year survival (
17
). The only other study we are aware of to examine long term
outcomes in colorectal cancer patients found no significant survival differences between those
with and without sarcopenia, however, this was in a cohort of patients who had undergone liver
resection for metastatic colorectal cancer, as opposed to surgery for the primary mass (7).
The findings of this study suggest that in addition to the previously demonstrated increased
likelihood of adverse short-term outcomes, patients with low TPA have reduced 5-year survival.
This provides additional information to clinicians and patients for the purposes of operative
risk stratification and informed decision-making. It also reinforces the need to optimize patient
resilience (reduce frailty) prior to surgery whenever possible.
Measurement of TPA is simple to perform and multiple studies have shown high inter-observer
43/45
reliability with minimal training (
9
;
11
;
12
). Jones et al also demonstrated that a simplified two-axis
cross-sectional measurement significantly correlates with the measurements made using more
complex software, as used in this study (
9
). This further simplifies the quantification of TPA
and reduces additional software costs. The measurements take no more than a few minutes to
perform and could easily be included in a template report for colorectal cancer staging CT scans.
It is not clear what the optimal threshold for determining low TPA should be. The international
consensus document defines CT-based criteria for sarcopenia (
16
), but these come from a single
study examining sarcopenia in obese cancer patients (
15
). A variety of different thresholds have
been applied in the literature (
9
;
17
;
18
), and our quartile data suggest a graded risk may exist
across the spectrum of TPA. Routine reporting of TPA in colorectal staging CT scans would provide
large population data that could address how to quantify TPA. Gender and age-specific criteria
may be appropriate, as our data show a degree of correlation with these demographic variables.
The study has several limitations. The data were collected retrospectively, which may affect
its quality. Using only the area of the psoas muscles at the level of L3 as an indirect marker
of sarcopenia and therefore frailty provides an incomplete assessment of patient health and
functional status, and although it has been shown to correlate well with more comprehensive
measures of sarcopenia, the addition of more variables such as body fat (to evaluate for the
presence of sarcopenic obesity) may increase the predictive value (
9
;
15
). Another limitation is
that while the cohort is larger than some, with 218 patients, there were only 23 patients that met
the criteria for sarcopenia, limiting the power of the findings for this group. The study was also
insufficient in size to allow for detailed analysis of subgroups based on cancer stage, although
TPA did not differ by this variable suggesting that our observed results were not attributable to
the cancer stage alone.
Conclusion
Low TPA is a predictor of reduced 5-year survival in colorectal cancer surgical patients. Mea-
surement of TPA on CT is reliable, quick, and easy to perform, and could be used to assist in
preoperative risk assessment and planning.
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