Mindfulness-Based Stress Reduction for Men on Active Surveillance for Prostate Cancer and their Spouses: Design and Methodology of a Randomized Controlled Trial

Abstract

Background

Although active surveillance (AS) is an increasingly adopted treatment paradigm for management of very low risk prostate cancer, many men and their partners face a variety of AS-related psychosocial stressors. Stressors may include anxiety and fear of progression, which may negatively affect short- and long-term psychosocial adjustment and influence early withdrawal from AS in order to seek definitive therapies such as surgery or radiation. Here we describe the protocol for an NCI-funded trial, which seeks to examine the efficacy of mindfulness training compared with a time/attention-matched health promotion control condition in a geographically generalizable sample of men on AS and their spouses.

Methods

Using a randomized, controlled, partially double-blinded study design, this study involves the delivery of 8 weeks of standardized mindfulness training (MBSR; mindfulness-based stress reduction) and patient reported outcomes over a 12-month period (proposed enrollment of 80 men on AS and spouses), compared with a health promotion control (proposed enrollment of 80 men on AS and spouses) that has been matched for time and attention. Baseline (T1) measures (e.g., anxiety, fear of progression, quality of life) are administered just prior to randomization to the two study arms, followed by repeated assessments at 2 months (T2), 6 months (T3) and 12 months (T4).

Conclusion

This study has the potential to offer men and their partners on AS with important educational and self–regulatory skills to better cope and adjust with known stressors related to being placed on this protocol.

Background

Nearly 270,000 new cases of prostate cancer (PC) were diagnosed in 2022.¹ While PC is the second leading cause of cancer-related mortality in American men it also has the highest five-year survival rate (98%) overall, reaching nearly 100% when diagnosed at the local- to regional-stage.² Nevertheless, conventional treatment for PC can significantly diminish a man’s health-related quality of life (HRQOL), affecting physical, functional, social, and emotional wellbeing.^3,4 Spouses of men with PC also report reduced HRQOL⁵ and increased distress.⁶

Almost 90% of initial PC diagnoses occur at the local- to regional-stage and are considered very low-risk,⁷ meaning that they generally do not require definitive treatment (such as surgery or radiation) with the same frequency as higher-risk disease.⁸ In certain cases when specific eligibility criteria are met, men with low-risk PC are encouraged to consider adhering to a supportive disease management approach called active surveillance (AS), which involves the ongoing monitoring and surveillance of disease status indicators through prostate-specific antigen (PSA) tests and biopsies versus other invasive treatments.^8,9 As a recommended healthcare strategy, AS might be considered a reverse adherence paradigm, whereby men are asked to not undergo an active form of therapy with curative intent until medically warranted.¹⁰ The goal of AS is ultimately to prevent unnecessary overtreatment of PC, but this monitoring approach can itself cause anxiety and uncertainty, with negative emotions spiking around the time of follow-up visits.^11,12

Compared to men who receive definitive PC treatment, men on AS report fewer physical symptoms (e.g., incontinence, impotence), but greater psychological sequelae, including anxiety, depression, and worry about disease progression.^13-15 Upwards of 25% of men on AS discontinue prematurely (i.e., opt for definitive treatment), a subset of whom may base this decision on psychological rather than medical factors as reasons for this decision.^16-18 Psychological support is therefore recommended to help men and their support networks to better cope with uncertainties of being on AS for low-risk PC to remain adherent to recommended protocols as long as it is medically justified.

Mindfulness-based stress reduction (MBSR)¹⁹ is a structured, 8-week training program that has been shown to reduce symptoms of stress, anxiety, depression and disease/treatment-related sequelae across multiple medical conditions, including prostate cancer.^20-23 Through intensive training in mindful awareness practices, individuals learn to direct their present moment awareness to thoughts, emotions, and bodily sensations with attitudes of openness, curiosity, non-judgment, self-compassion, and acceptance.²⁴ This practice can highlight and even disrupt ruminative cognitive and affective processes that perpetuate secondary negative elaboration and physiological sequelae.²⁵

Given the growing use of AS and its psychological consequences for men and their spouses, the REASSURE ME study (Reducing the Effects of Active Surveillance Stress, Uncertainty and Rumination thru Engagement in Mindfulness Education) seeks to evaluate the efficacy of couples based MBSR on psychological responses to AS and AS adherence among a geographically dispersed sample of men on AS and their spouses using a randomized control trial (RCT) design. Because mindfulness interventions almost always perform significantly better than doing nothing at all, much more can be learned through the use of a time-and attention-matched control condition.²⁶ This protocol is designed to expand upon the authors’ feasibility and proof of concept pilot trial of delivering MBSR to men diagnosed with PC and their spouses.²⁷

Methods

Objectives and Hypotheses

Objective 1 (Primary Outcome):

Compare the impact of MBSR vs. an attention-matched control condition on improvement of negative psychological responses over a 12-month period during AS for PC.

Hypothesis 1:

MBSR participants will experience significantly fewer negative psychological responses over a 12-month period than control group participants on the following outcomes: fear of progression, prostate cancer anxiety, rumination, uncertainty intolerance, and negative affect.

Objective 2 (Primary Outcome):

Compare the impact of MBSR vs. an attention-matched control condition on improvement of positive psychological responses over a 12-month period during AS for PC.

Hypothesis 2:

MBSR participants will experience significantly more positive psychological responses over a 12-month period than control group participants on the following outcomes: HRQOL, positive affect, posttraumatic growth, self-compassion, and mindfulness.

Objective 3 (Secondary Outcome):

Compare rates of non-disease progression related attrition from AS between MBSR and control group participants.

Hypothesis 3:

Rates of non-disease progression related attrition from AS will be lower among MBSR compared with time and attention matched control group participants.

Objective 4 (Exploratory Outcome):

Examine the association between relationship factors and dyadic congruence on primary and secondary patient reported outcome scores among MBSR and control group participants

Hypothesis 4:

Dyadic congruence will be observed in both MBSR and attention matched control group participants who demonstrate higher relationship satisfaction and responsiveness.

Study Design

Using a multi-site, randomized, placebo-controlled, partially double-blinded design, the REASSURE ME study seeks to advance the understanding and application of MBSR in the context of AS for PC. Goals include enrolling 160 men on AS for PC, as well as their interested/available partners (not required, but encouraged and invited to participate) and randomizing them (couples randomized together) into one of two study groups: MBSR (proposed enrollment = 80 men and spouses) - an intensive in-person, 8-week course that teaches emotional self-regulation skills through the adoption of mindful awareness practices; or HealthPro²⁸ (proposed enrollment = 80 men and spouses) – an in-person, 8-week time and attention matched health promotion control course that focuses on education and goal-setting in healthy lifestyle behaviors beneficial for people with cancer.

Changes due to COVID-19

Prior to 2020, all courses were held in person. Due to COVID-19, course materials were modified to an online format so that 2020 and 2021 courses could be held remotely via Zoom video conference. Randomization methods did not change. However, instructors could be assigned to classes based on availability rather than strictly location. Material previously written on poster boards by instructors can now be presented via screen sharing a power point slide. Online participants are encouraged to share their video and use Zoom’s “gallery view” during discussions and are assigned to breakout rooms when smaller discussions are desirable. During movement practices, participants are encouraged to switch to Zoom’s “speaker view” so that it is easier to see the instructor demonstrating movements during a practice.

Some modifications have been made for certain aspects of in-person classes that did not translate well to an online format. Healthy meals could no longer be provided prior to each class for either group. Also, the half-day retreat for each group has been shortened to two hours to help maintain attention over Zoom.

Participants

Study goals are to approach up to 240 eligible men on AS for PC, with the target of enrolling 160 men (proposed enrollment of 80 men into MBSR and 80 men into the active control group). Spouses or significant others are also invited to participate, but co-enrollment with a spouse or significant other is not required.

Minimizing Attrition

We institute several strategies to prevent or minimize attrition, including: 1) Emphasizing importance of committing to requirements of the intervention; 2) Flexibility with course start date; 3) Maintaining communications with participants at several stages after enrollment (e.g., instructors call participants who miss a class to review that week’s topic and homework); 4) Providing a light healthy meal at the beginning of each in-person class; 5) Offering alternative ways of remaining engaged in class during unforeseen circumstances (e.g., work-related travel, family, or medical complications); 6) Being available to participants after classes to answer individual questions or discuss any difficulties.

A post-intervention satisfaction survey is offered to allow participants to provide feedback on their experience in the study. To incentivize the follow-up assessments, participants receive a $25 gift card following completion of T3 assessment and a $25 gift card following completion of T4 assessment. Participants are also informed that they can receive study-related results and publication information after completion of the overall study.

Plan for loss due to attrition

Analytic models will allow for participant inclusion even if all assessments are incomplete. Over-sampling accounts for participants who may not be able to complete all weekly sessions or the post-intervention assessments. Due to the adherence focus of this study, all participants who attrite are asked to complete a one-page query as to why they left the study.

Eligibility Requirements

Participants are recruited from NorthShore University Health System (Evanston, Illinois), University of Michigan (Ann Arbor, Michigan), Fox Chase Comprehensive Cancer Center (Philadelphia, Pennsylvania), and Northwestern Medicine (Chicago, IL). Eligibility requirements include meeting clinical and pathological criteria for placement onto AS (Table 1).

Table 1.

General and Clinical Participant Eligibility Criteria

General Criteria

Inclusion Criteria for Men on AS for PC

1) ≥ 18 years of age

2) Able to speak, read and understand English

3) Diagnosed with prostate cancer

4) Placed onto AS no longer than three years ago

5) Able to perform basic gentle yoga

6) Cognitively intact/free of severe psychiatric problems (determined by referring medical team)

7) Able to access the internet for PRO assessments

Inclusion Criteria for Spouses

1) Meet criteria 1, 2 and 7 above

2) Have been married or living together for at least 1 year

Exclusion Criteria for Men and Spouses

1) Bedridden or on bed rest

2) Regular use (≥ 3 times a week for the past 2 weeks) of MBSR or a similar meditation

Clinical Criteria

Inclusion Criteria

1) Clinical stage T1c or T2a PC, verified by a participating urologist

2) PC diagnosis made on a 12-core needle biopsy

3) Biopsy Gleason Score </= 6, with no primary or secondary 4 or 5 tumor pattern

4) Biopsy Gleason score 7 (3+4 ONLY), with < 3 cores positive, <50% maximum tumor length/total core length AND total tumor volume of < 5% of biopsy volume.

5) Repeat, confirmatory, 12 core ultrasound-guided prostatic needle biopsy by participating urologist using 3-dimensional MR/TRUS, color Doppler equipment.

6) Pathologist reviewed/reported confirmatory biopsy: a) within 6 months of the patient’s diagnostic biopsy or b) within 1 year from last biopsy prior to enrollment if patient had 2 prior biopsies within a 2-year period with at least 1 of them having been done onsite AND the pathology showed low grade disease (Gleason 3+3), and low volume disease (cancer volume < 5% of biopsy volume) or c) within 1 year from last biopsy prior to enrollment if patient’s diagnostic biopsy was done onsite using the 3D/MRI fusion technique

7) If potential subject was unable to have a confirmation biopsy and/or a 3D MRI fusion biopsy for medical reasons as determined by a study doctor, he may still enroll into the study if he meets the study eligibility criteria

Study participants are referred directly from treatment centers and clinics by a designated physician, nurse, or clinician. Using standard scripts, a trained research assistant (RA) at each site recruits participants (and interested spouses), obtaining informed consent and HIPAA authorization where applicable according to IRB approved procedures.

Randomization

Consented consecutive individuals are assigned to blocks (minimum n=4 per block), creating the group that is randomized to the next intervention course. Intervention courses start seven times each year at every site, with each site running as many courses as they can fill. Intervention courses at each site are assigned to MBSR or HealthPRO based on the random allocation sequence, which is recorded on sequentially numbered, opaque, sealed, and stapled envelopes. See Figure 1. Primary investigators and referring medical team members are blinded to group allocation. Study participants remain blind to specific group differences and content; they are told they are being assigned to one of two different health promotion and wellness groups. All blinded parties remain blinded until a participant’s 12-month assessment has been completed.

Figure 1.

Study Flowchart

The central research coordinator and intervention providers are not blinded to allocation. Each site has a designated MBSR instructor and a separate designated HealthPro instructor to deliver the intervention. Participants receive the MBSR or HealthPro course for free and any parking fees are covered by the study site.

Interventions

Treatment condition: MBSR.

MBSR is a structured 8-week program comprised of a developmentally sequenced curriculum that uses a group format to experientially instruct participants in the practice of mindfulness meditation and mindful Hatha yoga.¹⁹ As a non-religious practice, MBSR facilitates nonjudgmental, moment-to-moment awareness and self-compassion through the practice of mindful meditation. Participants learn through discussion and experiential practices how to incorporate this awareness during stressful emotional and/or physical life situations.²⁹

Prior to beginning the eight (consecutive) week course, MBSR participants engage in a one-hour orientation. MBSR-certified instructors provide an overview of the course, explain participation expectations, and provide each participant with a yoga mat to use during the course. During the course, classes meet once each week for 2.5 hours, and a four-hour retreat occurs between classes six and seven (see Table 2). Each class session includes approximately 1 hour spent in meditation practice, during which instructors guide participants through formal practices such as seated awareness, mindful eating, body awareness, walking meditation, or yoga. Apart from the silent half-day retreat, all sessions also include approximately 1 hour of facilitated group discussion about participants’ experiences with the meditation practices, known as mindful inquiry.

Table 2.

Assessments and Administration Schedule

Form/Measure	Schedule					Description	Purpose of Measure or Outcome
	T1	T2	T3	T4	Post T4
Socio-Demographic Form	x					Date of birth, relationship status & duration, race/ethnicity, occupation, education, smoking and alcohol use.	1,2
Clinical Data	x					Date of diagnosis, height, weight, clinical stage, PSA, PSA doubling time, time to PSA progression, time to clinical progression, Gleason score, psychotropic medications, previous cancer diagnosis, co-morbid medical conditions	1,2
Medical Chart Review					x	Annual review throughout remainder of study funding period of AS attrition status and reasons for leaving protocol	4
Meditation History	x					5-items to determine current and previous experience with any type of meditation.	1,2
Expectancy Scale35	x					6-items based on perceptions and feelings related to the perceived benefit of therapy being offered.	1,2
Intervention Satisfaction		x				11-item scale of participants’ overall satisfaction with program or intervention received	1,2
Blinding Success		x				2 items assessing success of the blinding process.	1,2
Physical Symptoms36	x	x	x	x		8-item PROMIS short forms of Fatigue, Sleep Disturbance, and Pain Interference	1,2
Dispositional Style37	x	x	x	x		17-items assessing Big-5 Inventory subscales Neuroticism and Conscientiousness	1,2
Self-Efficacy	x	x	x	x		6-items assessing health behavior self-efficacy	1,2
Health Behaviors	x	x	x	x		10-items assessing engagement in a variety of different health behaviors	1,2
Prostate Cancer Anxiety65,66	x	x	x	x		18 items representing 3 subscales: Prostate Cancer Anxiety, Fear of Recurrence, and PSA Anxiety.	3
Uncertainty Intolerance38	x	x	x	x		12 items that represent 2 subscales: Prospective Anxiety and Inhibitory Anxiety.	3
Rumination39	x	x	x	x		12-items used to measure state-based ruminative experiences.	3
Negative Affect40	x	x	x	x		8-item PROMIS short forms of Anxiety and Depression	3
Quality of Life41	x	x	x	x		10-item PROMIS Global Health measure	3
Positive Affect42	x	x	x	x		9 items assessing positive emotions and sense of well-being, satisfaction and meaning in life.	3
Mindfulness43	x	x	x	x		23 items from FFMQ sub-scales of awareness, non-reaction, and observe	3
Self-Compassion44	x	x	x	x		10-items assessing self-judgment and self-kindness.	3
Posttraumatic Growth45	x	x	x	x		21-items assessing growth or benefits after a specific traumatic or stressful life event.	3
Couple Satisfaction-446	x	x	x	x		4 items assessing relationship satisfaction.	4
Responsiveness Scale47	x	x	x	x		6 items assessing understanding, valuing and caring about their partner and vice versa.	4

^1:Descriptives

^2:Possible covariate or modeling variable

³⁼Primary Outcome

⁴⁼Exploratory Outcome

Individual practice of meditation and yoga, beginning with guided meditations and progressing to self-directed practice, is assigned as homework each week. Participants record and bring paper copies of their homework practice logs with them to class, which study staff photocopy and retain as data, returning the original copy to the participant. Written homework exercises (e.g., recording pleasant/unpleasant events and stressful communications) are included during some weeks to reinforce education and awareness. Weekly class themes include: 1) An introduction to mindfulness; 2) Dealing with stress, barriers and difficulties; 3) The power of being present; 4) Stress reactivity and the flight, flight or freeze response; 5) Responding vs. reacting; 6) Interpersonal and relational mindfulness; 7) Integrating mindfulness into daily life; 8) Mindfulness in the rest of your life.

Time-and attention-matched control condition: HealthPro.

The structure of the HealthPro course mirrors that of MBSR. Rooted in Social Cognitive Theory³⁰ and the Transtheoretical Model of Change,³¹ the HealthPro curriculum is based on our review of evidence-based health promotion programs³² as well as preference data from our national survey of 200 men with PC,³³ which indicated interest in physical activity, diet/nutrition, and weight management. Although the course is interspersed with occasional prostate cancer-specific examples, content focuses more broadly on health promotion and wellness. This approach was chosen to match the broad nature of MBSR and for applicability to diverse populations, including spouse participants.

Prior to beginning the eight (consecutive) week course, HealthPro participants engage in a one-hour orientation. Instructors provide an overview of the course, explain participation expectations, and provide each participant with a Fitbit to use during the course. During the course, classes meet once for 2.5 hours, and a four-hour retreat occurs between classes six and seven. Each of the 8 weekly HealthPro classes includes a 30–45-minute presentation of evidence-based information related to the respective week’s topic and up to 20 minutes of low-intensity stretching exercises. These exercises were selected to mirror the mindful movement component of MBSR without being yoga. To mirror the experiential/applied learning of MBSR inquiries, participants also engage in didactic activities designed to increase their awareness of factors shaping health behaviors. Each week participants make a personalized goal relevant to the current week’s topic. Time is spent at the end of each class reviewing participants’ new goals and identifying resources and strategies for overcoming any anticipated barriers. Progress toward these goals is reviewed in group discussion at the beginning of class the following week.

Like meditations assigned as homework in MBSR, HealthPro participants are asked to record number of daily steps (via Fitbit) and monitor progress toward weekly health promotion goals. Participants record and bring paper copies of their homework practice logs with them to class, which study staff photocopy and retain as data, returning the original copy to the participant. Weekly class themes include: 1) Healthy Behaviors and Goal Setting, 2) Physical Activity, 3) Nutrition, 4) Emotional Wellness and Coping with Difficult Situations, 5) Relationships and Health, 6) Weight Management, 7) Retreat, 8) Symptom Management, and 9) Health Behavior Maintenance.

Intervention Protocol Fidelity

Intervention protocol fidelity is assured through established methods outlined by the NIH Treatment Fidelity Workgroup of the NIH Behavior Change Consortium ³⁴ on consistency in dose, providers, delivery, and receipt of the intervention.

Communications.

Conference calls and in-person meetings have occurred quarterly with all data collectors and interventionists (i.e., MBSR and HealthPro instructors) to review procedures. During delivery of courses, the Principal Investigator and/or intervention director receive performance and protocol fidelity updates from site instructors through weekly supervision calls. Research operations members meet weekly to review study progress and troubleshoot problems.

Consistency.

All MBSR and HealthPro participants are involved in an 8-week instructor-facilitated course in which attendance and course homework is tracked and recorded. All groups are incentivized to complete all patient reported outcomes (PRO) measures. A standard script guides recruitment and RA interactions with patients.

Instructors.

MBSR and HealthPro instructors are all sufficiently trained and participate in weekly fidelity calls during courses with an MBSR or HealthPro intervention director, respectively. Certified MBSR instructors who have vast teaching experience and education in MBSR deliver this intervention. This intervention director oversees all protocol training with MBSR and HealthPro instructors. All HealthPro instructors have teaching experience and education in a health-related field and participate in an online training to learn about the course content, patient population and tips for leading HealthPro group sessions.

Assessments and Measures

PROs are administered just prior to randomization (T1) and immediately following completion of the 8-week intervention (T2) as well as at 6 months (T3) and 12 months post-randomization (T4) (see Table 2). Administration occurs via the Research Electronic Data Capture (REDCap), a HIPPA compliant web application for building and managing research studies’ online surveys and databases, either remotely or in person using portable touchscreen tablet devices provided by study staff. See Table 2 for demographic, clinical, primary, and secondary outcomes at each assessment timepoint.

Statistical Power and Planned Analyses

This study implements a series of multivariate mixed effects models to evaluate PRO scores over time. Separate models are fit for each outcome measure of interest in men on AS for PC and their spouses. Contrasts are used to test the primary hypotheses comparing the longitudinal trends of MBSR and HealthPro participants. Assuming 80 PC patients per group, a conservative estimated correlation of rho=0.55 between consecutive measurements, and a two-sided alpha = 0.05, we estimate having 80% power to detect a moderate effect size of 0.36 for differences between groups on the primary hypotheses.

An intent-to-treat approach to standard statistical methods will be used in initial calculation of frequency distributions, measures of central tendency, and variability for all variables of interest. Missing data will not be imputed for primary analyses, but multiple imputation may be examined in sensitivity analyses to ensure that final conclusions are consistent across different assumptions for the missing data mechanism. Given the eligibility criteria of this study does not include having a partner or spouse, it is possible there are various differences between men who enroll and either do or do not have a partner/spouse. Therefore, since randomization was not stratified on this variable, we will confirm whether groups differ on this variable and will adjust as necessary. Additional covariates differing across treatment groups will also be considered for inclusion in adjusted regression models based on the literature and their effects on outcome measurements. The Statistical Analysis System (SAS) software suite, version 3 will be used in all data analyses.

Primary and Secondary Outcomes.

Mixed-effects multivariate models to estimate and test treatment group differences at each timepoint as well as the rate of change across timepoints will be implemented.⁴⁸ The basic model will include fixed effects (treatment, time, and the treatment*time interaction term) and random effects (patient, patient*time). A quadratic (time²) or higher order effect may be included to evaluate the possibility of nonlinear change over time, and the best fitting model will be selected. The basic model will then be re-run to adjust for relevant covariates. Contrasts will be used to test the primary hypotheses comparing the longitudinal trends of MBSR and HealthPRO. Separate models will be fit for each outcome measure of interest and for men and spouses.

Exploratory Outcome: AS Attrition by Intervention Arm.

AS adherence will be analyzed two ways: as a binary adherent versus non-adherent variable and as a time-to event variable. Logistic regression models will be used to evaluate predicators of adherence as a binary variable. Independent variables in the model will include baseline clinical and disease characteristics, intervention group, baseline anxiety and fear of progression, uncertainty intolerance, rumination, posttraumatic growth, and HRQOL. Spouses’ baseline characteristics will also be investigated. Cox proportional hazard regression models will be used for the time-to-event analysis. Patients will be classified as non-adherence “events” at the time that they withdraw from AS for any reason other than disease progression. Patients who withdraw from AS due to disease progression will be censored at the date of progression. Patients who do not withdraw from AS (i.e., remain on study, withdraw from the study for unrelated reasons, death) will be censored at the last date that they were known to be adhering to AS. The same independent variables described above will be investigated here with the additional inclusion of time-dependent covariates for those variables that are assessed repeatedly.

Exploratory Outcome: Dyadic Congruence.

Similar to Ezer et.al (2011),⁴⁹ when evaluating dyadic congruence and its association to PROs and AS adherence, we will calculate a difference score between patients’ and their spouses’ scores for all common measures to estimate the degree of incongruence. The longitudinal pattern for incongruence using the mixed modelling techniques described in the primary aim, with a particular focus on the differences between intervention arms, will be explored.

Ethics and Data Safety and Monitoring

This study has been approved by the IRB at Northwestern University. A Data Safety and Monitoring plan was developed to ensure participant safety and confidentiality, ensure validity of study data, and ensure the appropriate termination of a participant’s involvement or the entire study if significant risks are uncovered. Participant confidentiality is maintained according to Health and Human Services (HHS) Office for Human Research Protections (OHRP) regulations (45 CFR 46.111(a)(7)). Data are maintained on an secured server and a random sample reviewed for reliability at regular intervals. Adverse effects are monitored by MBSR and HealthPRO instructors as well as RAs who interact with patients regularly.

Conclusion

Men diagnosed with very low risk prostate cancer who select AS need supportive interventions to help manage negative emotions associated with this treatment approach. Ultimately, this could not only improve psychosocial wellbeing but may decrease negative physiological consequences of stress and improve medical outcomes such as adherence to treatment recommendations. The REASSURE ME study therefore aims to examine a psychosocial and behavioral intervention (MBSR) that could help support men and their spouses during AS and prevent unjustified attrition and unnecessary medical intervention.

MBSR was selected for this multi-site, RCT because mindfulness helps bring awareness to stressors while cultivating new skills to better tolerate them.^50-53 Instead of worrisome thoughts mindlessly escalating into uncontrollable ruminative cycles, mindfulness grounds one’s thoughts in the present moment, which creates space for more purposeful cognitive engagement.^54,55 In this way, thoughts may remain more neutral and evoke less emotional distress when they appear.^51,54 By developing a new relationship with these attentional processes, mindfulness-based interventions provide benefits that cannot be attributed solely to relaxation effects alone.⁵⁶ Thus, mindfulness may provide an effective tool for dealing with high levels of uncertainty associated with AS, interrupting ruminative and worrisome thought cycles and decreasing anxiety. By establishing a more constructive cognitive and emotional environment, positive psychological responses such as posttraumatic growth may also emerge.

Unlike most clinical trials for men with PC, which focus solely on individual men, REASSURE ME engages spouses in the intervention. In light of the negative effects of PC on spouses ^57,58 and the bidirectional influences between men’s wellbeing and that of their spouse,^59-61 spousal participation in the study may benefit both partners. In our 2009 survey, men with clinically localized PC indicated that including their spouses in health promotion research would make their participation easier and more enjoyable, facilitating increased attendance and adherence to homework.³³ This is consistent with the prevailing PC literature that posits that spouses often serve as the “healthcare broker” and primary support provider to men and that including them in supportive care interventions can be beneficial not only to support the man’s involvement, but also to support their own psychosocial distress and coping.^49,62-64

A particular strength of REASSURE ME is the use of a time- and attention-matched control group. With the growth in mindfulness-based research, waitlist control groups are no longer sufficient.⁶⁵ Participants assigned to the mindfulness condition almost always report better outcomes than those who receive no intervention.²⁶ Based on a scoping review of lifestyle interventions, we designed the HealthPro control group³² to match key structural elements of MBSR (i.e., length, frequency and duration; group format; combination of instruction and experiential exercises; weekly homework assignments) while delivering unique content focused on improving lifestyle behaviors known to improve a wide variety of health outcomes. Although other researchers have suggested that blinding participants is impossible in trials of mindfulness-based interventions,⁶⁶ we maintain participant blinding by presenting both groups as a “health promotion and lifestyle wellness course,” further increasing the rigor of our study.

REASSURE ME is the first multi-site RCT of MBSR to help men on AS and their spouses tolerate the uncertainties associated with AS and to investigate whether it can improve AS adherence. While the study period may not allow sufficient time to detect all possible attritions that were not medically necessary, it will enable a critical examination of initial patterns within this behavioral adherence paradigm. Future studies may need to follow men with PC for a longer period of their AS trajectory to further determine whether MBSR promotes long-term adherence to AS and other biomedical and psychosocial outcomes.