Consistent evidence from large-scale prospective studies, including a major pooled analysis (9), indicates that individuals with higher levels of leisure-time physical activity experience a significantly lower risk—generally ranging from 10% to over 20%—for numerous cancers such as bladder, breast, colon, endometrial, esophageal adenocarcinoma, and kidney cancer, compared to those with the lowest activity levels. The Japan Public Health Center-based Prospective Study (JPHC Study) found that higher total daily physical activity was associated with lower overall cancer incidence (13% reduction in men and 16% reduction in women when comparing highest versus lowest activity groups) (10).

Further strengthening this evidence with objective measurements, a recent prospective analysis of the UK Biobank cohort using wrist-worn accelerometers found that greater total daily physical activity was significantly associated with a lower risk of developing a composite of 13 physical-activity-related cancers (HR per 1 SD increase: 0.85, 95% CI 0.81–0.89) (11).

The protective effects of physical activity against cancer development and progression are underpinned by a complex interplay of systemic and local biological modifications. While human studies provide correlative evidence, preclinical research, particularly utilizing murine models, has been instrumental in elucidating specific molecular and cellular pathways involved.

Enhanced Immune Surveillance and Modulation of the Tumor Microenvironment (TME): Physical activity robustly impacts anti-tumor immunity. Exercise has been shown to mobilize and enhance the trafficking and cytotoxic activity of immune cells crucial for tumor elimination, such as Natural Killer (NK) cells and CD8+ T cells. For instance, studies in mouse models demonstrate that voluntary wheel running can increase NK cell infiltration into tumors and impede tumor growth, partly mediated by exercise-induced epinephrine release which primes NK cells via IL-6 signaling from other immune cells (12). Furthermore, exercise demonstrably remodels the tumor immune microenvironment, critically enhancing the role of cytotoxic T lymphocytes. The work by Rundqvist et al. established in murine cancer models that voluntary exercise significantly increased the frequency of intratumoral CD8+ T cells, and crucially, that the exercise-induced suppression of tumor growth was dependent upon this CD8+ T cell population, as its depletion abrogated the beneficial effect (13). It is important to note that the aging process itself can alter the tumor microenvironment, for example, by increasing the burden of senescent cells which contribute to a pro-inflammatory state. Exercise may counteract these age-specific changes, although this is a developing area of research. While these preclinical findings are compelling, clinical translation is still evolving.

Attenuation of Chronic Inflammation: Chronic inflammation fosters a pro-tumorigenic environment, a condition that physical activity may effectively counteract through its anti-inflammatory properties. Preclinical validation is provided by studies such as one employing a murine model of breast cancer, where regular endurance exercise training significantly mitigated the elevated systemic levels of key inflammatory mediators MCP-1 and IL-6 observed during tumor development. Importantly, this dampening of systemic inflammation coincided with significantly reduced tumor growth, indicating that the attenuation of these inflammatory pathways likely contributes to the anti-cancer benefits of exercise (14).

Metabolic Reprogramming and Hormonal Regulation: Exercise exerts profound effects on host metabolism, potentially creating a systemic and local environment less permissive for cancer growth. A key mechanism involves enhanced systemic metabolic control; regular physical activity improves insulin sensitivity and can decrease circulating levels of insulin and Insulin-like Growth Factor 1 (IGF-1). This improved metabolic profile subsequently dampens the activation of critical pro-proliferative signaling cascades, such as the PI3K/Akt/mTOR pathway (15). Concurrently, exercise modulates the TME itself. By promoting normalization of tumor vasculature, physical activity can improve perfusion, thereby potentially enhancing crucial energy substrate availability while reducing the accumulation of metabolic byproducts like lactate within the TME (16). Furthermore, exercise influences hormonal balance, a factor particularly relevant for hormone-sensitive malignancies. While long-term training is often associated with reduced basal concentrations of circulating sex hormones (15), the interaction appears complex. For instance, in a chemically-induced rat model of hormone-receptor-positive breast cancer, exercise training inhibited metastasis despite causing an increase in circulating estrogen levels, suggesting that exercise can also exert protective, hormone-independent effects (17). Clinical trials in cancer survivors have largely corroborated these metabolic benefits, demonstrating that structured exercise can improve insulin sensitivity and reduce circulating IGF-1 levels (18). However, data specifically from frail or very old patient cohorts remain limited, representing a key knowledge gap.

Prehabilitation, defined as interventions implemented between cancer diagnosis and the commencement of acute treatment such as surgery, aims to optimize physiological reserve and potentially enhance surgical outcomes (19). While evidence supporting its efficacy is growing, particularly for multimodal approaches, its impact across all postoperative endpoints requires further elucidation. A recent systematic review and meta-analysis focusing on abdominal cancer surgery indicated that multimodal prehabilitation, typically combining exercise, nutritional optimization, and psychological support, significantly improved preoperative functional capacity, evidenced by increased 6-minute walk distance, and reduced hospital length of stay (19). However, this analysis did not find a statistically significant reduction in overall postoperative complications associated with prehabilitation interventions compared to standard care.

Postoperatively, early mobilization is emphasized as a critical component of contemporary recovery strategies, such as Enhanced Recovery After Surgery (ERAS) protocols (20). The prompt initiation of physical activity, particularly ambulation, is advocated based on established physiological benefits: stimulating intestinal peristalsis to reduce the risk of ileus, promoting effective lung ventilation thereby preventing respiratory complications, and enhancing systemic blood flow, which serves to mitigate the risk of venous thromboembolism (20).

Prolonged sedentary time—characterized by minimal energy expenditure (≤1.5 Metabolic Equivalents [METs]) during waking hours while sitting, reclining, or lying—constitutes a distinct health risk factor, independent of overall physical activity levels (21). Robust evidence synthesized through meta-analyses and systematic reviews demonstrates that extensive sedentary behavior is associated with an increased incidence of several cancers, including endometrial, colorectal, and breast cancer, as well as elevated overall cancer mortality (21, 22).

Conversely, integrating even light-intensity physical activity (1.6-2.9 METs) (23) into daily routines may hold potential benefits. Emerging research exploring routine activities, such as household chores, suggests a possible association between preoperative housework participation and improved survival outcomes among male patients following urologic cancer surgery (24). To mitigate risks, guidelines recommend strategies for reducing and interrupting sedentary time. Emerging evidence suggests that regularly interrupting prolonged sitting bouts with brief periods of standing or light ambulation is an evidence-based strategy that may improve metabolic health and is a particularly achievable goal for older adults with functional limitations (25). Key recommendations include consciously incorporating incidental activity via household tasks, regularly interrupting periods of extended sitting with brief standing or ambulation, utilizing stairs instead of elevators when practical, and prioritizing active rather than passive leisure-time pursuits (26).

A substantial body of evidence indicates that engaging in physical activity following a cancer diagnosis significantly influences patient prognosis (27, 28). Comprehensive systematic reviews and meta-analyses consistently demonstrate that cancer survivors achieving higher levels of post-diagnosis physical activity experience markedly lower mortality rates compared to their less active counterparts. Specifically, pooled analyses reveal statistically significant risk reductions of approximately 37-39% for all-cause mortality and 37% for cancer-specific mortality across various cancer types when comparing the most active survivors to the least active (28). Reduced risk of cancer recurrence has also been strongly associated with higher physical activity levels (27).

Beyond impacting survival, physical activity confers significant benefits for the health-related quality of life (HRQoL) among cancer survivors. Systematic reviews, including a comprehensive Cochrane analysis, indicate that structured exercise interventions can yield positive effects on overall HRQoL and various domains such as emotional well-being, sleep disturbance, social functioning, anxiety, and pain (29). Specific modalities like yoga have also demonstrated improvements in overall quality of life and psychosocial well-being (30). Furthermore, physical activity is recognized as an effective strategy for managing cancer-related fatigue (CRF)—a persistent exhaustion not adequately alleviated by rest. Network meta-analyses comparing non-pharmacological approaches confirm that various forms of exercise (aerobic, resistance, or combined), alongside interventions like relaxation and yoga, represent key evidence-based strategies for mitigating CRF during and after cancer treatment (31).

Regarding psychological health, exercise interventions can positively impact mood and alleviate distress. A meta-analysis focused on depressive symptoms established that exercise yields modest yet significant reductions among cancer survivors (32, 33). Potential benefits for reducing anxiety have also been reported in systematic reviews evaluating exercise and yoga interventions (29, 30). Particularly for older cancer survivors, improvements in these psychosocial dimensions can substantially enhance overall quality of life. Beyond mood, physical activity may bolster neurocognitive function (34). There is growing evidence that exercise can improve domains like executive function in cancer survivors, which is critical for maintaining independence.

The profound benefits of physical activity in older cancer patients can be framed through the lens of geroscience, which posits that targeting the fundamental biological processes of aging can prevent or mitigate age-related diseases like cancer. Exercise directly counteracts several “hallmarks of aging” (37). For instance, it enhances mitochondrial function, reduces the burden of senescent cells, improves nutrient-sensing pathways (e.g., dampening mTOR signaling), and attenuates chronic inflammation—all of which are implicated in both aging and cancer progression. By intervening in these core pathways, physical activity may not only manage cancer-related outcomes but also improve an older individual’s overall physiological resilience and “intrinsic capacity” as defined by the WHO (8).

Despite strong evidence, implementation challenges persist, particularly for older adults. Significant barriers at the patient level include the high prevalence of geriatric syndromes such as sarcopenia, frailty, cognitive decline, polypharmacy, and severe comorbidities, which can make conventional exercise difficult. Psychosocial barriers are also common, including fear of injury, pain, fatigue, low self-efficacy, and lack of social support. At the healthcare system level, structural barriers are a major impediment. These include a lack of provider education on exercise prescription, insufficient time during clinical encounters for counseling, and a lack of standardized, reimbursed referral pathways to qualified professionals such as physiotherapists or certified cancer exercise trainers.

Older adults are not a monolith; their functional status ranges from robust to frail. A “one-size-fits-all” approach is inadequate. Precision exercise prescription is needed, tailored to tumor type, treatment phase, comorbidities, and frailty phenotype. Clinical assessment tools can guide this process. For example, the Short Physical Performance Battery (SPPB) (38) can objectively measure physical function and help stratify patients to determine a safe and effective starting intensity. Geriatric assessment tools like the Cancer and Aging Research Group (CARG) score (39) can identify vulnerabilities that may require modifications to an exercise plan. For frail individuals, the initial focus may be on low-intensity functional exercises to build a foundation and prevent falls, before progressing to moderate-intensity aerobic or resistance training.

Key future research priorities must address these challenges. These include:

Healthcare professionals should incorporate physical activity assessment and counseling as standard components of geriatric oncology care. In conclusion, current evidence strongly supports physical activity as an integral component of comprehensive cancer care for older adults, offering a non-pharmacological intervention that enhances physiological outcomes and quality of life.

This schematic illustrates the beneficial effects of physical activity at each stage of the cancer care continuum. Physical activity provides multiple benefits during prevention (reducing cancer risk through immune enhancement and metabolic regulation), perioperative period (optimizing physiological reserve and facilitating recovery), and survivorship (improving both quantity and quality of life). Recommended activity modalities for older cancer patients include aerobic exercise, resistance training, mind-body practices, and daily activities, all of which should be tailored to individual functional capacity and medical conditions.