Effects of yoga in men with prostate cancer on quality of life and immune response: a pilot randomized controlled trial

The study addresses whether a perioperative yoga program can improve quality of life (QoL), fatigue, urinary and sexual function, and mindfulness, and modulate immune and inflammatory responses in men newly diagnosed with localized prostate cancer undergoing radical prostatectomy. Prostate cancer diagnosis is associated with substantial psychological distress and reduced QoL, with up to 30% experiencing anxiety and distress and an increased risk of suicide within a year of diagnosis. While yoga has been shown to improve health-related QoL and mental wellbeing in various cancers, evidence in prostate cancer is limited and mechanistic understanding is scarce. This pilot randomized controlled trial aims to evaluate clinical benefits and explore underlying immune and cytokine changes associated with yoga in this population.

Prior research indicates yoga improves QoL, mental health, sleep quality, and reduces fatigue among cancer patients, with most evidence from breast cancer populations. Mindfulness and stress reduction associated with yoga have been linked to decreased oxidative stress and inflammation. A randomized trial in prostate cancer patients receiving radiation therapy (Ben-Josef et al.) showed reduced fatigue and better sexual health scores with yoga. Systematic reviews and meta-analyses across exercise interventions in prostate cancer report significant improvements in fatigue and QoL (FACT scales). However, data specific to perioperative prostatectomy settings and mechanistic immune/cytokine effects are limited, motivating this pilot study to fill these gaps.

Design: Block randomized, open-label, parallel-group pilot randomized controlled trial. Participants: 29 men (aged 30–80) with newly diagnosed, localized prostate cancer scheduled for radical prostatectomy (robotic-assisted or open). Accrual from September 25, 2015, to February 6, 2019. Inclusion required no active synchronous malignancy, not currently practicing yoga/meditation, adequate pain control, no neurological/musculoskeletal limitations preventing exercise, willingness to be randomized and undergo phlebotomy, and ability to consent. Exclusions included absolute contraindications to exercise testing and major psychiatric/addiction/cognitive disorders. Randomization and groups: Yoga group (n=14) underwent a yoga program; control group (n=15) received standard-of-care only. Intervention: Hatha yoga emphasizing physical postures coordinated with gentle breath and awareness, including seated meditation with breathing and pelvic floor engagement. Sessions were 60 minutes, twice weekly, for 6 weeks preoperatively (timing dependent on surgical scheduling) and again for 6 weeks starting 3–6 weeks postoperatively. Certified instructors led sessions at multiple locations in San Antonio, TX, tailoring exercises to participant comfort and monitoring breathing quality. Outcomes and assessments: - Primary: Self-reported QoL at baseline (approximately 6 weeks pre-op), immediately preoperatively, and 6 weeks postoperatively using EPIC (urinary, sexual), FACT-P (total and prostate-specific), FACIT-F, and FACT-G (general). Mindfulness measured with the Five Facets of Mindfulness Questionnaire (FFMQ). Urinary continence via EPIC urinary; erectile function via EPIC sexual. - Secondary: Immune cell status (PBMC phenotyping, functional markers) and plasma cytokine/chemokine levels. Biospecimen and laboratory analyses: - PBMCs: Cryopreserved PBMCs collected at each time point. Thawing, staining with monoclonal antibody panels, viability dyes, and intracellular cytokine staining after stimulation. Flow cytometry (BD LSRII) with gating for CD4+ and CD8+ T-cells, regulatory T-cells (CD3+CD4+CD25+FoxP3+), γδ T-cells, NK cells (CD3−CD56+, CD56bright/dim), myeloid cells including macrophages (M1/M2), MDSCs (monocytic and granulocytic), neutrophils, and dendritic cells. Data visualization included t-SNE mapping. - Cytokines: Plasma analyzed in duplicate using Luminex FlexMap 3D with a 38-plex Milliplex human cytokine/chemokine panel, including G-CSF, MCP-1, Flt-3 ligand, and others. Statistical analysis: Patient-reported outcome scores scaled 0–100 (higher indicates better QoL). Normality assessed via Kolmogorov–Smirnov. Baseline between-group comparisons used Student’s t-test (continuous) or chi-squared/Fisher’s exact (categorical). Intervention effects evaluated as change from baseline to preoperative timepoint, comparing groups via t-test (normal) or Wilcoxon rank-sum (non-normal). Alpha=0.05, two-tailed; no adjustment for multiple comparisons given hypothesis-generating nature. Minimally important difference (MID) defined as one-third SD at baseline. Due to attrition, analyses restricted to baseline and preoperative timepoints (per-protocol). Data analyzed in R. Participant flow: 30 assessed; 29 randomized (14 yoga, 15 control). In yoga, 12 received intervention and were followed pre-op; 2 did not complete (traffic; cardiac issue). In control, 1 lost to follow-up. Complete data for baseline-to-preop analyses available for 26 participants.

- QoL outcomes (change baseline to pre-op): - EPIC-Sexual: Mean difference between groups 8.5 points (yoga +9.1 vs control +0.6; p=0.098); subscale Sexual function significantly improved (MD 9.0; p=0.043). Greater than MID. - FACIT-F (Fatigue): MD 6.3 points (yoga +1.8 vs control −4.5; p=0.098). Greater than MID. - FACT-General: MD 8.2 points (yoga +1.9 vs control −6.3; p=0.065). Greater than MID. - FACT-Prostate: MD 5.9 points (yoga +0.6 vs control −5.3; p=0.086). Greater than MID. - Subscales showing meaningful improvements (≥MID) included FACT-Functional wellbeing (MD 8.6; p=0.113), FACT-Physical wellbeing (MD 5.5; p=0.241), FACT-Social wellbeing (MD 14.6; p=0.103). - Immune cell responses: - Increased IFN-γ production in peripheral cytotoxic CD4+ T-cells (p=0.007) and CD8+ T-cells (p=0.004) in yoga vs control. - Increased NK cell Fc receptor III (CD16) expression (p=0.041) and NK cell IFN-γ expression (p=0.026) in yoga group. - Decreased regulatory T-cells (p=0.029) and myeloid-derived suppressor cells (MDSCs; p=0.002) in yoga group, indicating enhanced antitumor immunity. - Cytokines/chemokines (between-group difference in increase over baseline): - G-CSF: 0.55 (0.05–1.05); p=0.032 (reduced in yoga group). - MCP-1: 0.22 (0.01–0.43); p=0.044 (reduced in yoga group). - Flt-3 ligand: 0.91 (−0.01, 1.82); p=0.053 (trend toward reduction in yoga group). Overall, perioperative yoga was associated with clinically meaningful improvements in several QoL domains, enhanced T and NK cell activation, reductions in immunosuppressive cell populations, and decreased proinflammatory cytokines.

The findings support the hypothesis that a perioperative yoga program can improve patient-reported QoL and positively modulate immune function and inflammatory signaling in men with localized prostate cancer awaiting prostatectomy. Clinically, yoga yielded meaningful gains in sexual function, fatigue, and general/prostate-specific QoL, aligning with prior exercise and yoga literature in cancer populations and a prior prostate cancer yoga trial during radiotherapy. Mechanistically, yoga was associated with increased IFN-γ responses in CD4+ and CD8+ T-cells, enhanced NK cell activation (CD16, IFN-γ), and reduced regulatory T-cells and MDSCs, suggesting a shift toward antitumor immunity. Concurrent reductions in inflammatory cytokines (G-CSF, MCP-1, and a trend in Flt-3 ligand) provide a plausible biological pathway linking stress reduction and improved QoL/fatigue to decreased systemic inflammation. These hypothesis-generating results underscore yoga as a feasible integrative intervention preoperatively and motivate larger, adequately powered trials with comprehensive translational endpoints.

Perioperative yoga improved several QoL domains, enhanced cellular immune responses, and attenuated key inflammatory cytokines in men with newly diagnosed prostate cancer. The intervention was feasible preoperatively but faced high postoperative attrition. Larger randomized studies are needed to confirm efficacy, delineate mechanisms underlying immune and inflammatory changes, optimize timing/adherence (particularly postoperatively), and evaluate effects on oncologic outcomes such as progression and recurrence.

- Small sample size pilot with limited statistical power. - Analyses restricted to baseline and preoperative timepoints due to postoperative attrition (only 2 yoga participants completed the third timepoint); adherence rates not available. - Multiple comparisons were not adjusted (no correction like Bonferroni), increasing risk of type I error; results are hypothesis-generating. - Open-label design may introduce expectation/placebo effects in patient-reported outcomes.