Associations of Postdiagnosis Physical Activity and Change from Prediagnosis Physical Activity with Quality of Life in Prostate Cancer Survivors

This article is featured in Highlights of This Issue, p. 153

Prostate cancer is the second most common cancer in men worldwide (1, 2). Early detection and improved treatment options have increased prevalence and decreased the mortality rate associated with prostate cancer (3). Because of the increase in 5-year survival rates, currently approximately 81% in Canada (4), men diagnosed with low-grade (stage I–II) prostate cancer, more likely than not, die from other causes, particularly after age 75 (5). In addition, PSA screening programs often overdetect low-grade cancers, which, for the most part, are indolent for long periods of time (6). In turn, overtreatment of potentially non–life threatening disease has burdened prostate cancer survivors and the health care system (7, 8). Consequently, priorities in prostate cancer control involve reducing the burdens of living beyond cancer diagnosis, improving health, overall functioning, care, quality of life (QoL; ref. 9), and addressing the specific needs of prostate cancer survivors (10).

Prostate cancer survivors who undergo surgery (11, 12) and receive treatments such as androgen deprivation therapy (13, 14) or radiotherapy (11, 15, 16) often experience worse QoL. Physical activity is an inexpensive, modifiable behavior that has been shown to improve QoL after diagnosis and may be associated with survival (17–20). Observational epidemiologic research (21–32) and randomized controlled exercise intervention trials (33–40) have shown that physical activity can improve QoL in prostate cancer survivors. No study to date, however, has examined the associations between changes in physical activity across the diagnostic period and QoL in prostate cancer survivors. Furthermore, only one study (27) explicitly examined different types of physical activity, including household and occupational physical activity and QoL. Moreover, previous observational research has had methodologic limitations associated with inadequate control for confounding and an inability to examine effect modification because of the small sample sizes.

The parent study was primarily designed to examine the associations of physical activity and survival in prostate cancer survivors (17). In this current analysis, we examined the role of both total postdiagnosis physical activity and each type of activity, including recreational, occupational, and household activity, and changes in physical activity over the diagnostic period on physical and mental QoL in prostate cancer survivors. In addition, this study had a large sample size that can explore multiple subgroup analyses.

A prospective cohort of prostate cancer survivors that originated from a population-based case–control study in Alberta, Canada, was conducted between November 1997 and December 2000 (41). All cases from the original case–control study were recontacted and followed up for postdiagnosis measurements and mortality outcomes to 2014. Details regarding this study have been published previously (17). Briefly, prostate cancer cases were histologically confirmed, invasive cases of stage II or greater prostate cancer and identified from the Alberta Cancer Registry, a population-based cancer registry. The prostate cancer survivors were <80 years of age, English speaking with no previous cancer diagnosis except for nonmelanoma skin cancer. Permission to contact prostate cancer cases for in-person interviews was obtained through the referring urologist. All surviving cases from the case–control study were recontacted by telephone for voluntary recruitment and provided written informed consent for the prostate cancer cohort follow-up study (2% rate of refusal). The cohort study began in 2000 when additional funding was obtained, to permit follow-up and further data collection from the cases. In addition, referring urologists were recontacted for additional missing medical data. This study received ethics approval from the Alberta Cancer Research Ethics Board and the Conjoint Health Research Ethics Board at the University of Calgary (Alberta, Canada).

Through in-person interviews, conducted in the original case–control study, participants reported on their personal health history, prostate cancer screening history, prostate conditions, surgery history, family history of cancer, lifetime physical activity patterns prior to diagnosis, dietary intake during the reference year (year prior to cancer diagnosis), lifetime alcohol consumption history, smoking habits, current social support and motivation for lifestyle change, demographic characteristics, and adult height and weight at each decade from age 20 to 60 years. Anthropometric measurements were measured directly at the interview. In addition, as a part of the cohort follow-up study, survivors were interviewed to assess their physical activity behavior within the first two years after diagnosis. At the cohort follow-up interview, self-reported questionnaires on current QoL were completed by participants. At a second and third follow-up time points, approximately 2 years apart, self-administered questionnaires asking participants about their past 2 years of physical activity behavior as well as their current QoL were mailed to participants to complete. Furthermore, medical chart abstractions and vital status assessments were completed throughout the follow-up to capture updated medical information, treatments, and outcomes.

Physical activity was assessed using the Lifetime Total Physical Activity Questionnaire (LTPAQ) and the Past Year Total Physical Activity Questionnaire (PYTPAQ) previously tested for reliability and validity (42, 43). Both the LTPAQ and the PYTPAQ record all types of physical activity (occupational, household, and recreational) as well as all parameters of activity (frequency, duration, and intensity) from childhood to the time of diagnosis. The LTPAQ was interview administered as part of the baseline case–control study, and the results from that study have been published (41). The participants were reinterviewed between 2000 and 2002 using the LTPAQ restricted to their activity done since the first interview, which had occurred between 1997 and 2000. Two additional assessments of physical activity were obtained through the self-administered PYTPAQ between 2002 and 2004 and 2004 and 2007. Hence, continuous levels of physical activity throughout the participant's life up until 2007 (when active data collection ceased) were obtained.

All physical activities (pre- and postdiagnosis) were assigned a metabolic equivalent (MET) value defined as a ratio of the associated metabolic rate for a specific activity as compared with the resting metabolic rate. These MET values were based on the Compendium of Physical Activities (44) and used with the reported frequency and duration of activity to derive the MET-hours/week/year for each type of activity. Moderate-to-vigorous recreational activity was defined as any activity >3 METs according to the Compendium of Physical Activities categorization (44). Moderate-to-vigorous total and recreational physical activity (hour/week/year) were derived to examine activity duration similar to general cancer survivorship physical activity guidelines (45, 46).

To assess the change in physical activity over the diagnosis period, a change score was derived using the difference between prediagnosis lifetime and average postdiagnosis physical activity. The average postdiagnosis physical activity variables contained up to three postdiagnosis time points. For those with missing assessments, because of nonresponse or death, the average physical activity levels were derived from available complete assessments. In addition, adherence to physical activity guidelines for cancer prevention and survivorship (150 minutes of moderate or 75 minutes of vigorous recreational physical activity; refs. 45, 46) over the diagnosis period was assessed, and behaviors were categorized as follows: consistently not meeting pre- and postdiagnosis (nonexercisers); not meeting prediagnosis to meeting guidelines postdiagnosis (adopters); meeting prediagnosis to not meeting guidelines postdiagnosis (relapsers); or consistently meeting guidelines pre- and postdiagnosis (maintainers). Active data collection ended in 2007; therefore, we utilized the physical activity cancer prevention and survivorship guidelines specific to aerobic physical activity.

QoL assessments at up to three follow-ups were obtained through a single questionnaire, the RAND 36-Item Short Form Health Survey (SF-36) version 1.0. The SF-36 has been used in several settings, is one of the most widely used QoL questionnaires (47), and has been validated in colorectal cancer survivors (48). The SF-36 addresses eight domains of health status that have been summarized into a physical component summary (PCS) score and a mental component summary (MCS) score. Both scores range from 0 to 100; higher scores indicate better QoL. Accordingly, clinically meaningful QoL score differences reflect >5 point changes (49).

Descriptive statistics were performed on all variables to report study characteristics. Next, multivariable least squares linear regression was used in all analyses (all statistical linear regression assumptions, including distributional, homogeneity of variances, were verified). A priori variables deemed to be predictors of QoL were forced into the models: prostatectomy surgery (yes, no), postdiagnosis Charlson comorbidity score (0, 1, 2, ≥3; ref. 50), aggressive or nonaggressive disease (Gleason score >8 or stage >II cancer; ref. 51), type of treatment (none, hormone, radiotherapy, both hormone and radiotherapy), and age at diagnosis (years). The aforementioned variables were first tested for interaction. Furthermore, we tested the following covariates for potential confounding first, with univariate analyses (P < 0.2) and secondly through backward elimination: prediagnosis lifetime physical activity (MET-hour/week/year) to adjust for baseline differences, nonlinearity of age at diagnosis, family history of cancer (yes, no), PSA score at diagnosis (≤4, >4 and ≤10, >10 and ≤20, >20), smoking status at diagnosis (never, former, current), total alcohol consumption at diagnosis (grams/year), region of residence (urban, rural), ethnicity (Caucasian, other), education (less than high school, high school, trade school, other non-university degree, university degree), marital status (married, other), weight at diagnosis (kg), body mass index (kg/m²), daily caloric intake at diagnosis (kcal/day), lifestyle change postdiagnosis (yes, no), family support (yes, no), friend support (yes, no), and ever joined a support group (yes, no). In addition, recreational, occupational, and household physical activity types and other physical activity intensities were mutually adjusted to control for the effects of one type/intensity on another. All quantitative variables were centered at the median for ease of interpretation.

To investigate the associations between postdiagnosis physical activity and QoL, the first follow-up data (collected 2000–2002) for both physical activity and QoL were used. To determine changes in pre- and postdiagnosis physical activity and the influence on QoL, lifetime prediagnosis physical activity and average (over all available time points) postdiagnosis physical activity data were used to derive change scores and adherence groups. In addition, average (over all available time points) postdiagnosis QoL scores were derived for these analyses.

Sensitivity analyses were performed by removing survivors diagnosed with stage III/IV and IV metastatic cancer to account for disease severity differences. In addition, cases who died prior to completing all three postdiagnosis follow-ups were excluded in the physical activity change over the diagnostic period analysis to determine the impact of these data potentially missing not at random. Estimated rates of change of QoL scores, per unit of physical activity values and their corresponding 95% confidence intervals (CI) were reported in multivariable adjusted models. A priori hypotheses were assessed with a significance level of P < 0.05, using the statistical package Stata v.13.

There were initially 830 men who survived up until the first follow-up time point (2000–2002); 8 of those participants were missing first follow-up QoL data and 5 participants were missing first follow-up lifetime physical activity data, and therefore, the analytic sample was 817 for these analyses. The majority of the study participants were diagnosed with stage II cancer, married, and had at least one comorbidity postdiagnosis (Table 1). The mean age of the participants at the start of follow-up was 67.3 years. The sample had a postdiagnosis first follow-up total physical activity median of 78.7 MET-hour/week/year; however, the recreational physical activity median was only 11.1 MET-hour/week/year. Furthermore, their first follow-up mean PCS score was 40.8 (SD = 12.4) and MCS score was 50.8 (SD = 11.8), which were approximately symmetrically distributed.

Final multivariable adjusted models found statistically significant associations between three postdiagnosis types of physical activity in relation to first follow-up PCS score (Table 2). Only one type of physical activity was significantly associated with MCS score. Recreational physical activity revealed the strongest associations (relative to the other types) with an estimated increase of 0.16 (95% CI, 0.12–0.20; P < 0.001) in PCS score and 0.05 (95% CI, 0.01–0.09; P = 0.024) for MCS score per MET-hour/week/year increase in physical activity volume. Although other physical activity types were not significantly associated with MCS score, associations appeared to be consistent in direction with estimated PCS score, except household physical activity, which was slightly negative. Furthermore, sensitivity analyses excluding stage III/IV and IV cancers (n = 130) did not appear to substantially influence these results.

Analyses restricted to duration (hour/week/year) of moderate-to-vigorous total and recreational physical activity are presented in Table 2. Recreational moderate-to-vigorous activity was positively associated with both PCS and MCS scores with estimated increases of 0.68 (95% CI, 0.50–0.85; P < 0.001) and 0.22 (95% CI, 0.03–0.40; P = 0.021) per hour of recreational activity, respectively. Total moderate-to-vigorous physical activity was also positively associated with PCS score with an estimated increase of 0.09 (95% CI, 0.05–0.13; P < 0.001) but not with MCS score (β = −0.01 [95% CI, −0.05–0.04; P = 0.76]). Interestingly, the sensitivity analysis excluding stage III/IV and IV cancers increased the recreational moderate-to-vigorous physical activity associations, but not those for total activity.

The analysis evaluating changes of physical activity volume (MET-hour/week/year) between lifetime (prediagnosis) and postdiagnosis activity on average postdiagnosis QoL for up to three follow-ups revealed similar results to the postdiagnosis physical activity analysis (Table 3). Although recreational physical activity change was consistently associated with PCS score (β = 0.15; 95% CI, 0.11–0.19; P < 0.001 and MCS score β = 0.06; 95% CI, 0.02–0.11; P = 0.006), total and occupational activity change were only associated with PCS score. Similarly, household activity did not impact the PCS or MCS scores significantly. Excluding stage III/IV and IV cancers or those who died before completing all three follow-ups did not materially change results.

Table 3 also presents physical activity change focused on moderate-to-vigorous total and recreational activity, which indicated associations with recreational activity and both PCS and MCS QoL scores with estimated increases of 0.72 (95% CI, 0.54–0.90; P < 0.001) and 0.35 (95% CI, 0.15–0.55; P = 0.001) per hour of activity performed. Total physical activity was once again statistically significantly associated with PCS score (β = 0.11; 95% CI, 0.07–0.16; P < 0.001) but not MCS score (β = 0.04; 95% CI, −0.01–0.09; P = 0.15). Nonetheless, in the sensitivity analysis excluding participants diagnosed with stage III/IV and IV cancers, recreational activity associations were slightly heightened; however, this finding was not seen in the total activity analysis, nor in the analysis excluding those who did not complete all three follow-ups.

Finally, the change in behavior over the diagnostic period according to the physical activity cancer survivorship guidelines (46) relative to PCS and MCS scores is presented. This analysis provides more definitive physical activity change according to existing cancer survivorship guidelines. First, the median prediagnosis and postdiagnosis physical activity levels for each cancer survivorship guideline adherence group were produced (Fig. 1). Maintainers and adopters increased physical activity levels, whereas relapsers and nonexercisers reduced physical activity levels from prediagnosis to postdiagnosis. In multivariable analyses (Table 4), prostate cancer survivors who were characterized as adopters experienced an increase of PCS score by 4.80 (95% CI, 2.82–6.78; P < 0.001) and MCS score by 2.26 (95% CI, 0.09–4.43; P = 0.041) relative to nonexercisers. Furthermore, maintainers showed the strongest results with increased PCS score of 6.01 (95% CI, 4.15–7.86; P < 0.001) and MCS score of 2.32 (95% CI, 0.29–4.34; P = 0.025) relative to nonexercisers. Interestingly, relapsers had nonstatistically significant worse scores. Slight attenuations were shown in the analysis excluding stage III/IV and IV cancers and participants that did not complete all follow-ups due to death, specifically in MCS scores for adopters and maintainers; however, point estimates and CIs remained fairly unchanged. Evidence of statistical interactions were not present in these analyses; therefore, estimated PCS and MCS scores for the entire study population were reported.

This study found that postdiagnosis physical activity was associated with PCS scores in prostate cancer survivors. Specifically, the positive association between recreational physical activity and PCS score was consistent across analyses; however, the magnitude of the association of physical activity on PCS score was relatively small (49). Total, occupational and household activities were not associated with QoL at the first follow-up. It is also interesting to note that mean first follow-up PCS scores were 10 points lower than MCS scores. Adherence to cancer survivorship physical activity guidelines resulted in 5- and 6-point increases in average PCS scores for prostate cancer survivors who were adopters and maintainers relative to nonexercisers. These results were clinically relevant. Both relapsers and nonexercisers had reduced physical activity levels postdiagnosis (Fig. 1). Future interventions should consider strategies to improve adherence to current exercise and cancer guidelines prior to and after prostate cancer diagnosis.

Our results illustrated a positive association between physical activity and QoL in prostate cancer survivors, similar to other cohort studies (26, 27). However, the studies differed in their methods for physical activity and QoL assessment; therefore, comparisons between studies are somewhat difficult. For example, in the Health Professionals Follow-up Study (24), prostate cancer–specific QoL was measured, and physical activity was significantly associated with vitality/hormonal functioning scores. On the other hand, four exercise intervention studies (52–55) measured generic QoL using PCS and MCS scores. One of these interventions (55) found statistically significant and clinically relevant effects with PCS score (similar to our study); however, three studies (52, 53, 55) found significant associations with MCS score. However, to our knowledge, our study is the first to measure change in lifetime physical activity prior to and after prostate cancer diagnosis in relation to QoL.

The lack of association in total activity may be attributed to the increased duration of occupational and household physical activities in the average day for those who were employed postdiagnosis. Retired men who had an occupational score of zero (Tables 2 and 3) would not have contributed to these associations and therefore, may have spent more time performing recreational activities. We also considered the possibility that cancer survivors with progressing disease or diminishing health would experience a decrease in their QoL and in turn, exercise less. To minimize this bias, we performed sensitivity analyses excluding men with stage III/IV and IV cancer at diagnosis, as well as those who died before completing all three postdiagnosis assessments. Regardless, we continued to observe positive associations between recreational physical activity and PCS scores.

Reverse causation was of less concern with the change in physical activity analysis. Men who were maintainers and adopters had the highest QoL scores. Furthermore, slightly stronger effects were observed for analyses restricted to moderate-to-vigorous recreational physical activity. Nonetheless, given that a majority of our sample had stage II prostate cancer at diagnosis and only a small portion of the sample was confirmed to be stage IV (n = 55), we cannot be certain whether disease severity did not have an impact on the physical activity and QoL relationship.

There are multiple proposed mechanisms by which physical activity has been linked to physical and mental QoL. First, in prostate cancer exercise intervention studies, fatigue (56, 57), cardiorespiratory fitness (57), walking speed (56), upper body strength (56), and lower body functional performance (58) has been identified as possible mediators between exercise intervention and different aspects of QoL. Furthermore, marital status, time since diagnosis, and use of bisphosphonates (58) have been described as moderators. In epidemiologic studies, physical activity has been shown to reduce adiposity (27, 59) and inflammation (60), which can account for increased physical functioning. Furthermore, physical activity decreases secretion of insulin (61), enhances sex hormone regulation (59), and in turn, increases insulin resistance and QoL (62). Specifically, improved sex hormone regulation may lead to decreased erectile dysfunction and improved marital relations (62–64). Therefore, modifiable behaviors like physical activity can reduce these burdens. With respect to mental QoL, physical activity has been associated with increased regulation of neurotransmitters associated with mood (65), improved self-esteem, self-efficacy, and reduced anxiety (66), all aspects of psychological functioning. More work is needed to confirm these mechanisms specific to changes in recreational physical activity over the course of the diagnostic period in prostate cancer survivors.

There are some inherent limitations that need to be considered when interpreting these results. First, this was an observational study and, therefore, subject to bias. Measurement bias in physical activity assessment may exist, which could attenuate the results. However, these data were collected first, by in-person interviews and additionally by self-reported questionnaires; therefore, measurement bias was minimized. Also, measurement and adjustment for sedentary behavior in all analyses would strengthen these results by further isolating physical activity levels. Furthermore, in the physical activity change analysis, we used a change score and are limited in our generalizability of interpretations to individual participants. Change scores are not related to individual baseline values; although we did adjust for prediagnosis physical activity, in general, we cannot differentiate between participant-specific changes in their physical activity levels. However, the analysis examining adherence to physical activity cancer survivorship guidelines addresses these concerns by evaluating physical activity against a standard. Another limitation arises from missing data due to mortality. However, sensitivity analyses excluding those who died before the third follow-up did not materially change the results. Finally, we restricted our study sample to patients with ≥stage II cancers aged <80 years of age; therefore, we can only generalize our results to these cancer populations.

There are implicit strengths that should also be noted. First, this study included a large population-based sample of prostate cancer survivors with a follow-up of 10 years for QoL outcomes. The assessment of physical activity was comprehensive as all parameters of physical activity (i.e., frequency, duration, and intensity) of three separate physical activity types (i.e., recreational, occupational, and household) were captured. Furthermore, using the PCS and MCS scores, rather than individual QoL domains, reduced the issue of multiple testing while providing summary scores of physical and mental QoL. Moreover, the pre- and postdiagnosis physical activity measurements enabled us to examine associations with change in physical activity over the diagnostic period in prostate cancer survivors. Finally, several potential effect modifiers and confounding variables were considered for this analysis to reduce the chance of spurious results and to identify potential subgroups within the population.

This study provided insights regarding the types of physical activity that impact QoL in prostate cancer survivors. Objective measurements of physical activity by accelerometry or fitness trackers are warranted in this population to reduce any suspicions of measurement error and further confirm the benefits of recreational physical activity on QoL. Health professionals should emphasize the importance of recreational physical activity to their patients as a modifiable and a possible behavioral change for most prostate cancer survivors. Interpretations may need to be tailored to prediagnosis physical activity level to ensure prostate cancer survivors can achieve recommended physical activity thresholds. Future research should focus on sedentary behavior to determine efficacy of increased physical activity postdiagnosis in a phase III trial or health promotion program.

No potential conflicts of interest were disclosed.

Conception and design: K.S. Courneya, S.E. McGregor, C.M. Friedenreich

Development of methodology: M.S. Farris, K.S. Courneya, C.M. Friedenreich

Acquisition of data (provided animals, acquired and managed patients, provided facilities, etc.): K.A. Kopciuk, C.M. Friedenreich

Analysis and interpretation of data (e.g., statistical analysis, biostatistics, computational analysis): M.S. Farris, K.A. Kopciuk, K.S. Courneya, Q. Wang, C.M. Friedenreich

Writing, review, and/or revision of the manuscript: M.S. Farris, K.A. Kopciuk, K.S. Courneya, S.E. McGregor, Q. Wang, C.M. Friedenreich

Administrative, technical, or material support (i.e., reporting or organizing data, constructing databases): C.M. Friedenreich

Study supervision: C.M. Friedenreich

Other (co-investigator on the grants that obtained the follow-up information, including the timing of the data collection as well as the information to be collected, and a member of the thesis committee of M.S. Farris and worked closely with her on these analyses): K.A. Kopciuk

Study coordination was done by Aleata Ryhorchuk and Sana Fakih. Interviewers for this study were Jodi Parrotta, Linda Davison, Pearl Cooke, Nicole Slot, Carol-Anne Zawalykut, and Catherine Munro. Data entry was done by Carla Quesnel and chart abstraction by Yvonne LeBlanc and Sarah MacLaughlin. Steven J. Angyalfi provided clinical expertise regarding prostate cancer treatment and care.

C.M. Friedenreich held career awards from Alberta Innovates: Health Solutions and Alberta Cancer Foundation. K.S. Courneya was supported by the Canada Research Chairs Program and S.E. McGregor by the Alberta Heritage Foundation for Medical Research.

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