To our knowledge, this study was the first to assess and compare distinct symptom subgroups based on symptoms by seven cancer diagnoses (i.e., prostate, non-small cell lung, NHL, breast, uterine, cervical, and colorectal cancer) in a large sample of cancer survivors using LCPA and a validated symptom measure (PROMIS®), ensuring reliable representations of distressing symptoms common or distinct to different cancers. Analyzing across cancers may unveil shared underlying mechanisms for more targeted interventions to pro-inflammatory status in cancers. Addressing shared inflammatory mechanisms could lead to targeted interventions.

Our study showed variability in the number and types of latent class subgroups based on the specific cancer diagnosis, indicating different symptom experiences among these groups. In prostate, lung, NHL, and breast cancers, four distinct latent classes of patients were identified (WNL, Fatigue/SD/Pain, Fatigue/SD/Depression, and All Symptoms). Fewer distinct symptom patterns were identified in uterine and cervical cancer (three latent classes) and colorectal cancer (two latent classes) compared to the previously mentioned cancer types. These findings have important implications for the management and care of patients across different cancer types. Common latent class subgroups across these seven cancer populations are WNL and All Symptoms groups. The most common four latent classes identified in prostate, lung, NHL, and breast cancers are consistent with previous literature. Our study findings in lung cancer different differ from a previous study on lung cancer survivors [22]. In a study of 378 lung cancer survivors based on pain, fatigue, sleep disturbance, depression, and cognitive impairment, all low and all high-symptom groups were identified [22]. These differences could be due to different sample sizes and instruments compared to our study. Despite fatigue, depression, anxiety, and sleep disturbance are prevalent symptoms in prostate cancer [23] and NHL [24], there is no previous study identified that specifically analyzes latent classes based on symptoms in prostate cancer and NHL. Therefore, our study shed light on the prevalence of these common symptom subgroups (i.e., Fatigue/SD/Pain, Fatigue/SD/Depression, and All Symptoms) in prostate cancer and NHL populations.

We found pain with fatigue and sleep disturbances and depression with fatigue and sleep disturbances were common latent classes across the cancer types, specifically for prostate, lung, NHL, and breast cancers. In 84 cancer patients with multiple cancer diagnoses, pain predicted fatigue and sleep disturbances and sleep disturbances mediated the link of pain with fatigue [24]. Among four common types of latent classes across prostate, lung, NHL, and breast cancers in our study, pain, and depression were associated with fatigue and sleep disturbances. Numerous studies in the literature have indicated a robust correlation between depression, fatigue, and sleep disturbances in cancer survivors [25,26,27]. Cancer-related fatigue is a distressing and persistent symptom frequently experienced by cancer survivors, often resulting from disrupted sleep patterns [26, 27]. The prevalence of fatigue and depression in cancer patients has been extensively researched, with a significant number of survivors reporting elevated depressive symptoms and experiencing fatigue [25]. Additionally, sleep disturbances are common among cancer patients, and studies have shown that these symptoms tend to co-occur, implying a potential shared underlying mechanisms such as proinflammatory cytokines [26]. While causal pathways for whether pain or depression predicts fatigue and sleep disturbances or vice versa are unknown, managing these interconnected symptoms is crucial for enhancing the quality of life and overall well-being of cancer survivors. Our findings showing pain or depression as a distinguishable factor of two latent classes (Fatigue/SD/Pain and Fatigue/SD/Depression) suggest addressing either pain or depression may help to alleviate co-occurring fatigue and sleep disturbances and improve the overall health of cancer survivors.

In uterine cancer survivors, Fatigue/SD/Pain symptom cluster was identified in our study. Pain is one of the most distressing and prevalent symptoms for women with uterine cancer [27]. Furthermore, a 24-month longitudinal study of gynecologic cancer patients found that pain persisted for up to 6-month post-cancer treatments [28]. Of note, women with gynecologic cancers with pain have reported subsequent psychological distress such as depression, anxiety, and fatigue [29]. Inflammation may play a significant role in pain experiences among uterine cancer survivors. Pain sensitization and perpetuation of symptoms are linked to cytokines, which activate both peripheral and central nervous system pathways. These mechanisms involve increased stimulation of the autonomic nervous system, cytokine release by brain glia, and localized and systemic actions of prostaglandins. Proinflammatory cytokines found in the bloodstream have been associated with pain symptoms in various populations, including those with chronic pain disorders and cancer [28]. Therefore, uterine cancer survivors may face an increased risk of inflammation-related pain due to the secretion of pro-inflammatory biomarkers, such as interleukin (IL)-6, by uterine tumors. Furthermore, proinflammatory cytokines are released in response to tissue damage from treatments like chemotherapy, radiation therapy, and surgery. Uterine cancer patients have reported various types of pain such as uterine cramps, pelvic pressure, and abdominal pain [30]. Therefore, types of pain experiences will be further investigated in future studies to better manage pain and pain-related symptom subgroups.

In our study, we found two latent classes (WNL and All Symptoms) in colorectal cancer survivors. Gastrointestinal symptom toxicities such as diarrhea, constipation, abdominal pain, bloating, nausea, and fecal leakage, after cancer treatments are prevalent and severe in colorectal cancer survivors, compared to non-gastrointestinal cancer types [31, 32]. Colorectal cancer survivors with high gastrointestinal symptoms also reported high psychoneurological symptoms [31,32,33]. Thus, further research to identify latent classes including gastrointestinal symptoms is warranted to better capture the complex symptom experiences in colorectal cancer survivors.

In our second aim, we investigated the relationships of sociodemographic and clinical factors with latent classes by cancer diagnosis to understand better the potential contributing factors of distinct latent classes that differ by cancer diagnosis. The research findings confirm that symptom experiences may differ across the various cancer types due to cancer-related specific factors such as cancer sites, cancer stages, as well as different cancer treatment regimens (e.g., surgery, chemotherapy, radiotherapy). Furthermore, our results indicating younger age groups with higher symptom burdens are consistent with previous findings [34]. Younger cancer survivors may experience a higher symptom burden compared to older patients due to their additional life responsibilities and potentially higher resilience levels. Younger individuals often juggle work, family, and caregiving responsibilities, which can exacerbate the impact of cancer-related symptoms [34]. Older patients, on the other hand, may have fewer external stressors and greater acceptance of their health conditions, leading to a perceived lower symptom burden. However, it is essential to consider individual variations in symptom experiences and coping mechanisms across different age groups. Our study findings align with previous research indicating a potentially high symptom burden among cancer survivors with unfavorable social determinants of health (SDOH) status, such as racial/ethnic minorities, low education, low-income status, or poor social support [35]. These factors may contribute to disparities in health outcomes and healthcare access, leading to poorer health literacy and exacerbating symptom experiences [36]. Addressing these disparities is crucial for improving the overall well-being and quality of life of cancer survivors [35].

Based on our research findings, clinicians should consider that addressing one symptom in isolation given a specific cancer diagnosis may not be sufficient to manage a patient's overall symptom burden. Instead, a holistic approach is needed to comprehensively manage distinct subgroups based on symptoms. Furthermore, approximately 33-58% of cancer survivors in our study experience moderate-to-severe symptom burden, which significantly affects their quality of life. Clinicians should be attentive to these individuals and proactively identify patients with high symptom burdens. Symptom interventions need to be multi-faceted, addressing multiple symptoms simultaneously. For example, lifestyle interventions that incorporate improved sleep hygiene, exercise, and nutrition may positively impact sleep, fatigue, pain, and depression levels, by adopting an integrated approach. The similarities and differences in patterns of symptom subgroups observed in this study raise important theoretical and practical considerations that warrant further investigation. Lastly, understanding sociodemographic and cancer-specific factors can aid in tailoring interventions to meet the diverse needs related to symptom management, in particular, underserved cancer survivors.

Our study has several limitations. Our study might have focused on specific seven cancer types or populations (e.g., Whites, female predominant samples), which could limit the generalizability of the findings to other cancer types or patient groups. The heterogeneity of cancer types and treatment regimens might impact symptom experiences differently in various patient populations. Secondly, the use of a cross-sectional design might limit the ability to establish causality and track the changes in symptom subgroups over time. Longitudinal studies would provide a more comprehensive understanding of the dynamic nature of symptom experiences in cancer survivors. Third, we used subjective symptom measures, thus symptom reports might vary based on individual perceptions and reporting biases. Some symptoms may be underreported or overlooked, affecting the accuracy of the identified symptom subgroups. The selected symptom domains for analysis might not capture the full spectrum of symptoms experienced by cancer survivors with various types of cancer diagnoses. Additional symptoms relevant to specific cancer types or treatments might be omitted, potentially influencing the psychoneurological symptoms (e.g., respiratory symptoms in lung cancer, gastrointestinal symptoms in colorectal cancer, and pelvic pain in uterine cancer).