Colorectal cancer (CRC) is one of the most common malignancies and has high morbidity and mortality rates (Song et al., 2020). In China, CRC ranks third among all cancers in terms of overall incidence, third for mortality in women, and fifth for mortality in men (Feng et al., 2019). CRC is the second leading cause of cancer-related death in patients aged 60–79 years and the third leading cause of death in patients aged 80 years and older (Hamed et al., 2022). However, regarding conventional medicine, there are still no guidelines for patients with advanced CRC (ACRC) who are aged ≥ 75 years because patients in this age group are usually excluded from clinical studies (Audisio and Papamichael, 2012). Nevertheless, some elderly patients with an Eastern Co-operative Oncology Group performance status (ECOG-PS) score of 0–1 may be suitable candidates for clinical studies in the Western medicine. Yet, the toxicity of the anti-cancer agents developed in the West is still greater in elderly patients than in their young counterparts, resulting in reduced quality of life and a shorter life expectancy (Shibutani et al., 2021).

Traditional Chinese medicine (TCM) has been used to treat various diseases for thousands of years in China. The history of treatment of CRC in China can be traced back thousands of years to a description of CRC and its treatment in the classic Chinese book “Huangdi Neijing” written 2,000 years ago. TCM is now covered by the medical insurance system in China and is very cost-effective. Therefore, it is readily accessible by the general population. Recent clinical studies have also confirmed that TCM has anti-tumor activity and prolongs survival without serious side effects (Sun et al., 2021). TCM can also improve quality of life, relieve symptoms, and reduce adverse events in patients with ACRC undergoing conventional chemotherapy (Zhang et al., 2018; Yan et al., 2021; Chen et al., 2022); Moreover, TCM can significantly prolong overall survival and progression-free survival (PFS) (Liu et al., 2020; Zhu et al., 2021). There are clinical cases reports of elderly patients with ACRC deriving benefit from TCM, with some taking TCM for up to 50 months. In view of these reports and the lack of data on TCM in elderly patients with CRC, the aim of our study was to explore the efficacy and safety of TCM in elderly patients with ACRC.

Currently, there’s no treatment guidelines exist for elderly patients with ACRC, mainly because patients aged ≥ 75 years are excluded from participation in clinical trials in the conventional medicine as a result of their high likelihood of comorbidities. Therefore, there is little information on treatment for ACRC and its efficacy in this age group. The limited literature available has focused on the short-term effects after surgery or on patients starting treatment at the age of 65–70 years (Cheng et al., 2022; Hashimoto et al., 2022), Or start at age 65 or 70 (Takahashi et al., 2021). Although there are some relevant clinical studies in patients aged ≥ 75 years, either the ECOG-PS score has been around 0–1 (Rosati et al., 2019), adverse events were severe (François et al., 2020), or there was only one metastatic site (Cuccia et al., 2021). Furthermore, most elderly participants in clinical research have undergone strict screening, requiring, for example, an ECOG-PS score of 0–1 or only one metastatic site for inclusion. Therefore, most clinical studies in the conventional Western medicine do not include patients aged ≥ 75 years with multiple metastases and an ECOG-PS score ≥ 2. Moreover, older adults may be more concerned about their quality of life and therapies that relieve their symptoms rather than receiving conventional curative Western chemotherapy, targeted therapy, or immunotherapy, which could have a high degree of toxicity and be burdensome for both patients and their families (Kemeny et al., 2003).

Patients treated with TCM do not need to be screened strictly for clinical research purposes. They can receive TCM provided that they can drink and are willing to do so. TCM is an independent factor affecting PFS (11); when combined with chemotherapy and cetuximab or bevacizumab, TCM has been shown to prolong PFS, improve quality of life, and reduce adverse reactions in patients with ACRC (11). Studies have shown that long-term use of TCM not only has a positive effect on survival in patients with CRC but also helps to reduce the risk of recurrence and metastasis (Wang et al., 2020). Pharmacological studies in animals or cell lines and network research have shown that TCM can prevent metastasis of CRC to the liver by down-regulating the activation of cancer-associated fibroblasts mediated by CRC-derived ITGBL1-loaded extracellular vesicles (Li et al., 2022); thus, TCM has the unique characteristics of being multi-targeted and multi-linked, and may have a comprehensive therapeutic effect. TCM can also inhibit epithelial–mesenchymal transition by downregulating trans-forming growth factor-beta, thereby inhibiting invasion and metastasis of CRC cells (Ge et al., 2022), inhibit progression of CRC by suppressing CCL2 and preserving progenitor Tex in an obese microenvironment (Xu et al., 2022) and suppress growth and metastasis of 5-fluorouracil-sensitive/resistant CRC by inhibiting the Wnt singling pathway (Zhang et al., 2022).

For the above reasons, this retrospective observational real-world study analyzed the clinical characteristics and survival data for patients aged ≥ 75 years with ACRC whose treatment included TCM. These patients had an overall median PFS of 4 months and a median TTCM of 5.5 months, which is in line with the PFS of 4.3 months reported for patients with wild-type KRAS metastatic CRC and frail older patients treated with panitumumab as a single agent in a study by the Spanish Digestive Oncology Collaborative Group (Sastre et al., 2015). However, the patients in that study were also strictly screened; the highest ECOG-PS score was 2% and 15.2% had adverse reactions that were grade ≥ 3. In contrast, our study included patients who did not undergo strict screening and was open to any patient who chose TCM and attended for follow-up. Our subgroup analysis found that patients without bone metastases had longer PFS and TTCM than those with bone metastases, which is also consistent with another recent report (Lavacchi et al., 2021). Due to the small sample size in our study, there were few patients with bone metastases; nevertheless, of the five patients with multiple bone metastases, four also had liver and lung metastases, pelvic metastases, and distant lymph node metastases. Therefore, no conclusions can be drawn regarding TCM and PFS in patients with CRC and bone metastases. Quality of life and survival in patients with bone metastases is markedly decreased due to pain, walking difficulties, pathological fractures, and neurological impairment (Rocha et al., 2022). Although TCM cannot reverse bone metastasis, it can have a positive effect on expression levels of markers of inflammation, apoptosis, and remission, thereby relieving pain and improving quality of life (Shen et al., 2022).

Studies have shown that patients with liver (Chuang et al., 2020) and peritoneal (Franko, 2018) metastases have a shorter survival time. However, our subgroup analysis found no significant difference in PFS or TTCM according to liver or peritoneal metastasis status. There are several possible explanations for these inconsistent findings. First, our sample size of 48 patients may have been too small to detect a statistically significant effect of TCM. Second, all our patients with liver metastases had metastases at multiple sites, including the lung, peritoneum, and distant lymph nodes. Similarly, patients with peritoneal metastasis also had metastases in the liver and abdominal and pelvic lymph nodes. Therefore, we cannot draw any conclusions regarding survival by simply analyzing liver and peritoneal metastases.

In our study, most of the patients who received TCM alone had an ECOG-PS score of 2–3 (n = 18) and most of those who received a combination of TCM and conventional anti-cancer treatment had an ECOG-PS score of 1 (n = 22). ECOG-PS is an important determinant of patient survival (LI, 2020), and also one of the important reasons for whether or not Western chemotherapy is recommended. With the exception of four patients who chose not to continue with conventional chemotherapy, those treated with TCM were not candidates for chemotherapy. Our subgroup analysis according to ECOG-PS score confirmed that the better the patient’s physical status, the longer the PFS and TTCM (Figure 5). This may be the main reason why PFS was shorter in our patients who were treated with TCM alone than in those treated with TCM in combination with conventional chemotherapy. Median PFS was 2.1 months in rigorously screened patients who received TAS-102 (Cicero et al., 2020). This value is similar to the median PFS of 3 months in our patients who received TCM alone, which had the additional advantages of low cost and fewer side effects. Overall, our research shows that TCM has advantages in treatment.

Surgery, radiotherapy, chemotherapy, targeted therapy, and immunotherapy remain the mainstay of treatment for CRC. However, for patients who have failed on or are ineligible for these treatments, TCM is their last chance for potentially helpful treatment. Most patients who choose TCM are in a poor physical state and seek TCM to alleviate the toxicity of conventional chemotherapy, have discontinued conventional anti-cancer treatments because of adverse reactions, or are not candidates for these therapies. All the patients in our study had multiple metastases, even if only one organ was involved. Furthermore, their ECOG-PS scores were worse than those in the clinical studies of Western anti-cancer treatments. More than half of our patients had an ECOG-PS score > 1. Many such patients attend for a medical consultation in a wheelchair, or are already bedridden, in which case their family members attend instead. However, even in these circumstances, the median PFS was still 4 months with a median TTCM of 5.5 months, which suggests that TCM is effective in prolonging survival and may improve quality of life.

This study has some advantages and limitations. The study found the potential benefits of TCM for elderly patients with ACRC who are physically weak and unable to receive conventional Western medicine treatment. In China, many elderly patients choose TCM treatment because they cannot tolerate conventional Western medicine treatment. In the course of clinical treatment and follow-up, we found that elderly patients with ACRC seem to benefit from TCM, but there is a lack of relevant data to prove a benefit of TCM for elderly patients with ACRC. Therefore, we carried out such a retrospective data summary analysis. Fortunately, we found a potential benefit of TCM in the elderly. TCM has a potential therapeutic value for the elderly patients with an ECOG score of 2-3 and who cannot tolerate conventional Western medicine treatment. Therefore, we would like to share this result in the hope that more studies can pay attention to this problem and better serve elderly patients.

However, there are still some shortcomings in this study. First, the study had a retrospective single-center design, which would have introduced a degree of bias. Second, although most elderly patients have comorbidities, these were not included in our analysis. Therefore, while some studies have shown that comorbidities have a marked impact on survival in the elderly (Canoui-Poitrine et al., 2022), we could not draw any conclusions in this regard. Third, the safety of TCM is also one of the topics of concern at present. Although no serious side effects of TCM were found in this study, the interaction between drugs should not be ignored. For this kind of study, we preliminarily found the potential benefits of TCM on elderly patients. However, due to the lack of rigor in design, more rigorous design, scientific statistical processing, strict inclusion of patients, and well follow-up information design is needed in future studies. Multicenter clinical studies in larger samples are required to determine the efficacy and safety of TCM in elderly patients with ACRC.

This retrospective observational real-world study suggests that TCM is potential effective in patients aged ≥ 75 years with advanced colorectal cancer. And TCM can be used safely in these patients, even if they have an ECOG-PS score of 2–3.