The average life expectancy in Japan is the second-highest worldwide for men, at 81.5 years, and the highest for women, at 86.9 years [13]. Furthermore, Japan has one of the highest proportions of elderly citizens (age ≥ 65), with a rate of 28.9% [14]. Therefore, the probable high rate of individuals with sarcopenia in Japan suggests that research on this condition is of utmost importance. Sarcopenia is broadly attributed to two primary causes: age-related physiological changes leading to a reduction in skeletal muscle mass and secondary changes resulting from chronic conditions such as chronic obstructive pulmonary disease (COPD), acquired immunodeficiency syndrome (AIDS), and various cancers, including CRC. Notably, the presence of sarcopenia in cancer patients is associated with worse prognoses compared to those without sarcopenia [2, 15]. Indeed, sarcopenia is recognized as an adverse prognostic factor for many malignant tumors, with HRs ranging from 1.11 to 2.12 [16]. Additionally, sarcopenia has a negative impact on outcomes and reduces quality of life (QOL), increases susceptibility to depression, and has other adverse effects [17].
Cancer patients who overcome sarcopenia following surgery tend to have improved outcomes compared to those who continue to be affected by sarcopenia [18]. These findings emphasize the importance of identifying sarcopenia in cancer patients. Consequently, our focus in this study was to explore how to identify sarcopenia in CRC cases. There are various methods for diagnosis of sarcopenia, including CT, MRI, ultrasound, DXA, and BIA [19–21]. Each method has its benefits and drawbacks, including the need for specialized equipment, radiation exposure, ease of use for medical staff, and patient convenience. Among these methods, CT has been widely used in the past few years for measurement of PA at the L3 vertebral level,. In the current study, we examined the PV method, which utilizes CT data to determine the volume of the psoas major muscle, rather than just its cross-sectional area. This method is relatively new, but is considered to be useful. A few studies have compared the PV and PA methods in a range of patients and diseases, including pelvic fractures, lung cancer, liver diseases, and gastrointestinal cancers.
In CRC, there are reports on use of PV and PA for post-chemoradiotherapy rectal cancer and postoperative complications [22–26], but we could not find any studies on long-term prognosis and 5-year survival rate in elderly patients with CRC. In this regard, our study is novel in addressing these perspectives. In previous reports, Horie et al. have suggested that evaluating PV may have higher reliability than PA since it involves measuring a broader range of the muscle, thereby reducing errors [22]. In PA measurement, the measured height may not correspond to the maximum area, and significant variations can occur depending on the level of measurement [23, 24]. So et al. argued that 3D assessments in patients with hip fractures are more accurate for evaluating muscle mass compared to 2D methods [25]. On the other hand, one report suggested that both PA and PV are effective [26]. We considered how these approaches may be applicable in elderly individuals with spinal curvature, and we concluded that volume assessment (PV) would allow for more accurate diagnosis of skeletal muscle mass (i.e., sarcopenia) compared to PA. We also note that preoperative CT scans for CRC were performed in all cases, and the data were simply imported into a 3D-CT workstation, on which PV could be automatically determined. This process is convenient and efficient for both medical staff and patients, and it also reduces radiation exposure.
In comparing the PV and PA methods for diagnosis of sarcopenia in the same 150 cases, one striking observation was the notable difference in the proportion of sarcopenia cases between the two methods: 10.0% with PV vs. 34.7% with PA. Generally, the rate of sarcopenia in older adults with various types of cancer, including CRC, ranges from 18.5–83.0% [3], making our PV data appear notably low. One of the reasons for this discrepancy may be the newness of the PV method, with definitive cutoff values yet to be established. Psoas muscle volumes are influenced by factors such as height, weight, and ethnicity, requiring the need for normalization by dividing by height. However, there are methods involving height squared and cubed for this purpose, and as a result, cutoff values remain uncertain. It is possible that the cutoff used in this study was somewhat stringent [6, 22, 23]. We also found a strong correlation between PVI and PAI (r = 0.66), as illustrated in Fig. 2. This was expected since both methods diagnose sarcopenia, implying that they both should identify the same group of patients with sarcopenia. In fact, Womer et al. have reported that PA and PV are both important parameters [26].
The question arises with regard to which method is more appropriate. To determine this, we assessed whether cases identified as having sarcopenia by both methods had the expected worse prognosis, using statistical analyses, survival curves (Figs. 3 and 4) and Cox proportional hazards models (Table 5). The results clearly showed that sarcopenia cases identified by the PV method had a significantly worse prognosis than those identified by the PA method. In Cox proportional hazard analysis, the adverse prognostic factors were sarcopenia with the PV method, and age and gender with the PA method. It is reasonable that older age is associated with a shorter lifespan and overall functional decline, and age is viewed as an adverse prognostic factor in this context. Concerning gender, females with CRC are generally considered to have a poorer prognosis than males. This is partially attributable to the higher incidence of right-sided CRC in females, which, compared to left-sided CRC, often exhibits features such as microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and BRAF mutations, which contribute to a poorer prognosis. For ASA and tumor location, the p-values were relatively small (< 0.10) with the PV and PA methods, whereas other factors (GPS, TNM Stage, LN dissection) had relatively large p-values in multivariate analysis. These factors are commonly associated with adverse prognosis, but were relatively unimportant compared to sarcopenia, age, and sex in this study. Thus, while TNM Stage and LN dissection are generally expected to influence CRC prognosis, under the specific conditions in this study (elderly patients with CRC aged 80 or above, excluding TNM Stage 4) the influence of sarcopenia, age, and gender may have masked the effects of TNM Stage and LN dissection. These findings suggest that the PV method is superior to the PA method for identification of sarcopenia.
It is also important to understand the mechanisms underlying the well-established effects of sarcopenia in worsening the prognosis of malignancies [2, 15]. One explanation is that sarcopenia is related to immunological deterioration and aging, which in turn may promote cancer progression and increase systemic inflammation [22, 28]. It is also important to recognize that skeletal muscles support movement and support, and also serve as secretory organs. Skeletal muscles produce and release hundreds of peptides and proteins, which are referred to as myokines and cytokines. Among these, myostatin is associated with transforming growth factor-β, interleukin-15, NK cells, CD3, and CD8 T cells, all of which are linked to tumor progression. A decline in skeletal muscle mass can disrupt the balance of cytokines, potentially contributing to cancer progression and recurrence [23, 29–31]. For these reasons, the coexistence of sarcopenia in cancer has been associated with progression and a worsened prognosis, which includes a poorer survival curve.
This study has several limitations. First, it is a single-center study with a relatively small number of cases. Additionally, older cases were included for which calculation of PV using the workstation software was not possible due to limitations in CT data handling. Second, the study is retrospective. Third, it is uncertain whether the cutoff values for PVI and PAI were appropriate. As mentioned above, cutoff values in this field are not universally established, both internationally and domestically, which is a challenge for future research. However, the cutoffs used in the study were chosen carefully, as they are tailored for the relatively smaller body size of the Japanese population, with a particular focus on the elderly, in contrast to the larger body sizes found in other countries. If the cutoff value for PA was set more strictly, it could be as important a factor as PV, and one study has found that both PA and PV are important [26]. There is also an issue regarding the diagnostic criteria for sarcopenia. The diagnostic approach recommended in Asia, including Japan, is comprehensive, assessing both loss of skeletal muscle mass and of muscle strength and physical performance, including handgrip strength, 6-meter walk, the Short Physical Performance Battery (SPPB), and the 5-time chair stand test [32]. In Europe, there is emphasis on the importance of "low strength" in the criteria [33]. In this retrospective study, collecting data beyond skeletal muscle CT scans was challenging. As in many studies, we focused on skeletal muscle mass, which is the fundamental and critical component of sarcopenia criteria, but this limitation warrants acknowledgment. Moving forward, it will be important to amass prospective data encompassing both muscle mass and muscle strength and physical performance, with significant implications for clinical applications.