Secondary Logo

Journal Logo

Transitions in Symptom Cluster Subgroups Among Men Undergoing Prostate Cancer Radiation Therapy

Dirksen, Shannon Ruff PhD, RN, FAAN; Belyea, Michael J. PhD; Wong, William MD; Epstein, Dana R. PhD, RN

doi: 10.1097/NCC.0000000000000236
ARTICLES
Free

Background: Prostate cancer is a common type of cancer worldwide and in the United States. However, little information has been reported on the symptoms of men over time who receive radiation therapy.

Objective: The objectives of this study were to identify subgroups of men at pre– and post–radiation therapy on general and treatment-related symptoms and to determine transitions in subgroup membership over time.

Methods: Men (n = 84) receiving radiation therapy completed questionnaires on fatigue, insomnia, pain, depression, anxiety, and sexual, urinary, and bowel problems at pretreatment and posttreatment. Latent class analysis identified subgroups. One-way analyses of variance determined subgroups differed on symptoms, participant characteristics, and quality of life. Latent transition analysis examined subgroup transitions over time.

Results: At pretreatment, 4 subgroups were identified: resilient group, with little to no symptom reporting; adjusted group, with moderately high treatment-related symptoms, low insomnia, depression, and anxiety; distressed group, consistently high on most symptoms; and emerging group, with moderately high fatigue, depression, and anxiety with few treatment-related symptoms. At posttreatment, similar results were seen in groups to those at pretreatment: resilient, adjusted. and distressed groups with an impacted group having high pain, insomnia, depression, and urinary and bowel symptoms. Quality of life and participant characteristics further distinguished groups at pretreatment and posttreatment. Income level predicted a transition in group membership.

Conclusions: Men can be classified into distinctly different subgroups over time.

Implications for Practice: Assessment and intervention with men in subgroups such as distressed and emerging before and during treatment may lessen potential for remaining distressed or moving into impacted group where symptom severity is high at posttreatment. Interventions to reduce multiple symptoms are vitally needed.

Author Affiliations: College of Nursing and Health Innovation, Arizona State University, Phoenix (Drs Dirksen and Belyea); Mayo Clinic, Scottsdale (Dr Wong); Phoenix Veterans Affairs Health Care System, Phoenix, Arizona (Dr Epstein).

This research study was supported by the National Institutes of Health/National Cancer Institute (R21 CA139079).

The contents of this article do not represent the views of the Department of Veterans Affairs or the US Government.

The authors have no conflicts of interest to disclose.

Correspondence: Shannon Ruff Dirksen, PhD, RN, FAAN, College of Nursing and Health Innovation, Arizona State University, 500 N 3rd St, Phoenix, AZ 85004-0698 (shannon.dirksen@asu.edu).

More than 1 million men worldwide are diagnosed annually with prostate cancer.1 Prostate cancer is the most common cancer among American men with an estimated 233 000 new cases in 2014.2 Despite the growing number of patients with prostate cancer, the symptoms of these individuals who subsequently undergo treatment have not been extensively studied in comparison to other cancer types. Treatment options may include watchful waiting (active surveillance), surgery (radical prostatectomy), cryotherapy, radiation therapy (RT) (external beam and brachytherapy), hormone therapy, and/or chemotherapy. In the United States, about 40% of all men receive RT for prostate cancer.3

General symptoms frequently associated with cancer treatment are fatigue, pain, insomnia, depression, and anxiety. These symptoms have been described in a limited number of studies among men before and after RT. In addition, to our knowledge, there are no prostate cancer studies that have examined over time these general symptoms, with the symptoms commonly reported with RT including sexual, urinary, and bowel problems. The presence of concurrent multiple symptoms may negatively impact quality of life (QOL) in persons undergoing cancer treatment.

Men undergoing RT for prostate cancer frequently report baseline fatigue (41%), with levels of fatigue further increasing (66%) for up to 5 years after treatment.4 A recent systematic review that examined fatigue in prostate cancer patients revealed the common occurrence of fatigue across all treatment modalities.5 This review, which included men undergoing RT, concluded that fatigue severity differed across studies, with findings reporting decreased fatigue for many men from baseline to end of treatment, whereas other studies suggested fatigue more commonly increases from baseline to end of treatment. Insomnia has also been noted to occur during prostate cancer treatment with up to 39% of men indicating sleep difficulties before treatment begins.6 A majority of men receiving outpatient prostate cancer treatment indicated sleep difficulties, with 36% reporting clinically significant levels of insomnia.7 Further analysis revealed half of these men also had significant depression.

Anxiety may be commonly experienced in patients undergoing RT. In a longitudinal study of patients receiving RT including men with prostate cancer, anxiety was measured over a 6-month period.8 Distinct trajectories of anxiety symptoms were noted in 3 patient subgroups during and following RT, including 1 group with clinically significant anxiety levels at baseline, which lessened over time. It is interesting to note this group with greater anxiety scores also had the highest depressive symptoms, with researchers emphasizing the importance of examining clusters of symptoms over time to gain insight into the interrelationships among single symptoms. Almost 18% of all patients with cancer including prostate cancer, who were scheduled to receive RT, have reported clinically significant levels of depression and anxiety.9 Patients with these high levels of mood disturbance also had the lowest sleep quality. In a study tracking singular symptoms in patients with prostate cancer over the duration of RT, results indicated many men reported decreases in pain, difficulties sleeping, and a lack of energy over time.10 At RT baseline, researchers noted the somewhat unexpected finding of a moderately high prevalence (50%) of pain with etiology of the pain not known. Pretreatment pain was also found to be a significant predictor for a lack of energy.

Sexual, urinary, and bowel symptoms are often reported by men receiving prostate cancer treatment, with sexual difficulties being the most frequently cited concern.11 Prostatectomy, radiotherapy, and brachytherapy were found to worsen urinary and sexual bother and sexual functioning over time when compared with pretreatment measures of these symptoms.12 Radiotherapy in particular resulted in a worsening of bowel function and bother among men after treatment.

Three or more symptoms that commonly occur together can be referred to as a symptom cluster.13 Symptom cluster research has often focused on determining the existence of symptom clusters related to the multiple symptoms observed in patients during cancer treatment. Seminal findings in patients undergoing treatment with varying cancer diagnoses revealed the existence of 4 symptom subgroups based on a predefined symptom cluster of fatigue, pain, depression, and sleep disturbance.14 The 4 groups included patients with highest severity in sleep disturbance and depression (all high), patients having the lowest scores in fatigue and sleep disturbance (all low), and patients with high fatigue and low pain, or low fatigue and high pain. Group membership was not predicted by cancer type, stage, or treatment received. Further research has validated the subgrouping of patients into specific clusters based on similar symptom experiences, including patients with various types of cancer receiving biotherapy, chemotherapy, radiotherapy, and/or hormonal therapy.13,15,16

In the limited number of studies on symptom clusters in prostate cancer patients during RT, 1 study revealed most men could be grouped into a cluster characterized by low levels of pain, fatigue, sleep disturbance, and depression.17 In a second study, 5 distinct symptom clusters were identified in men 6 to 8 months following prostate cancer treatment.18 These clusters were further distinguished by levels of pain, fatigue, emotional distress, and urinary, sexual, and bowel dysfunction. Four clusters had symptom scores in the moderate range indicating men continue to experience multiple symptoms for many months following treatment.

Symptom cluster subgroups in patients undergoing cancer treatment are an understudied area of inquiry. A recent systematic review found that many cancer patients have multiple symptoms that are associated with greater levels of distress.19 This review concluded that there is a need to more fully explore not only the occurrence of cancer-related multiple symptoms over time, but also their relationship to participant characteristics and QOL. It was also recommended that this research be conducted with participants having the same cancer diagnosis and treatment for effective interventions to be developed and implemented.

The Theory of Unpleasant Symptoms (TOUS) characterizes symptoms according to their severity (intensity), quality, distress, and duration.20 Central to the TOUS is the premise that multiple disease-related symptoms often occur concurrently and have interactive and adverse synergy. In cancer patients, this premise is supported by findings indicating the worst fatigue and sleep quality were related to the most severe pain.21 Patient factors influencing the symptom experience include participant age, marital status, disease stage, and comorbidity. The outcome of the symptom experience is performance that is conceptualized as functional health status, cognitive functioning, and/or QOL. In summary, the TOUS helps guide the current study by providing a framework that postulates (1) symptoms are multidimensional and interrelated; (2) patient factors influence the experience of symptoms and symptom clusters; and (3) QOL is an outcome of the symptom experience.

A second theoretical perspective underpinning this study is transitions. Transitions are multidimensional, complex, and often unexpected individual experiences that result because of changes in life, health, relationships, and the environment.22 Men receiving treatment for prostate cancer who report changes in symptom prevalence and severity from pretreatment to posttreatment may be experiencing transitions in their health status and QOL.

Currently, there are no published findings in men receiving prostate cancer RT related to symptom cluster subgroups at treatment baseline and how these identified subgroups may transition or change at posttreatment. Identifying and tracking subgroups over time would result in a better understanding of treatment impact on the symptom experience and ultimately assist patient care through the development of interventions that would target the management of multiple symptoms. The purpose of this study was to (1) identify and describe symptom cluster subgroups before and after RT in men with prostate cancer, (2) determine if the subgroups could be further distinguished by participant characteristics and QOL, and (3) examine transitions in subgroup membership from pretreatment to posttreatment. Both general and treatment-related symptoms were chosen for examination in this study as they appear to occur commonly and concurrently, and thus, these symptoms may be related to each other.

Back to Top | Article Outline

Methods

In a descriptive, longitudinal design, participants were recruited from outpatient RT sites prior to beginning treatment. Men who were at least 21 years of age; able to read, speak, and understand English; diagnosed with stage I, II, or III prostate cancer; and receiving RT for the first time were eligible for participation. Radiation therapy included external beam radiation and brachytherapy. Men with stage IV disease were not included in the study because a cure is rarely possible, and hormonal manipulation is often the main treatment given.

All study participants were verified by their radiation oncologist as having nonmetastatic disease. Institutional review board approval was received prior to obtaining informed consent from each participant. Questionnaires were completed by participants within 2 weeks before the start of RT and again at 8 weeks (end of therapy). Men receiving brachytherapy were also measured at this second time point with the expectation they would be experiencing acute symptoms after 8 weeks of treatment.

Back to Top | Article Outline

Measures

Participants provided information on age, ethnicity, marital status, education, and income on a form developed by the investigator. Clinical information obtained from the medical record included cancer stage, time since diagnosis, Gleason score, prostate-specific antigen (PSA) level, and prior prostatectomy. Participants indicated on a Comorbidity Index from an established listing of 26 health problems if a healthcare provider had diagnosed them as having the condition (yes or no).23

Fatigue was measured by the 7-item Profile of Mood States Fatigue/Inertia Subscale.24 Responses are on a 5-point scale ranging from 0 (not at all) to 4 (extremely). Higher scores indicate increased fatigue. Test-retest reliability, internal consistency, concurrent, and construct validity have been demonstrated.25 The Profile of Mood States has been used in studies of men undergoing prostate cancer treatment.7 In this study, Cronbach’s α was .95.

Insomnia was measured by the 7-item Insomnia Severity Index.26 Responses range from 1 (not at all) to 5 (very much) with a total cutoff score of 15 indicating clinically significant insomnia. The Insomnia Severity Index has been used in prostate cancer studies with support for reliability and convergent and construct validity.27 In this study, Cronbach’s α was .90.

Pain was measured by the 2-item Pain Numeric Rating Scale, which rates pain severity (0 = no pain to 10 = pain as intense as you can imagine) and impairment due to pain (0 = does not interfere to 10 = completely interferes). Responses to the 2 items were summed. A higher score indicates greater pain severity and impairment. Single-item pain intensity rating scales are a valid, reliable measure of cancer pain.28

Depression was measured by the 20-item Center for Epidemiologic Studies–Depression Scale with responses ranging from 0 (rarely or none of the time) to 3 (most or all of the time).29 A score of 16 or greater indicates depression. The Center for Epidemiologic Studies–Depression Scale has evidence of reliability in clinical populations.30 In this study, Cronbach’s α was .84.

Anxiety was measured by 20-item State Anxiety Subscale of the State-Trait Anxiety Inventory with scale responses ranging from 1 (rarely) to 4 (all the time).31 Higher scores indicate greater anxiety. The State-Trait Anxiety Inventory demonstrates concurrent, convergent, divergent, and construct validity.31 In this study, Cronbach’s α was .91.

Treatment-related symptoms were measured by the 26-item Expanded Prostate Cancer Index Composite (EPIC-26), which evaluates patient functioning and bother after prostate cancer treatment.32 The EPIC-26 contains domain scores for sexual, urinary irritative and obstructive, and bowel symptoms. A higher score suggests better health status for the symptom. The EPIC has shown construct validity.32 In this study, Cronbach’s α’s for the subscales ranged from .57 (urinary irritative) to .92 (sexual).

Quality of life was measured by the 39-item Functional Assessment of Cancer Therapy–Prostate (FACT-P), which measures prostate cancer QOL.33 Items are rated from 0 (not at all) to 4 (very much), with higher scores indicating better QOL. The FACT-P demonstrates internal consistency, concurrent validity, and sensitivity to change.34 In this study, Cronbach’s α was .86.

Back to Top | Article Outline

Statistical Analysis

Descriptive statistics were used to examine participant characteristics and scale scores. Changes in symptom scores for the sample were calculated as the posttreatment score minus the pretreatment score. Latent class analysis was used to identify symptom cluster subgroups based on reported symptoms. A sequence of latent class analysis models, from 1 to 5 classes, was run with fatigue, insomnia, pain, depression, anxiety, sexual, urinary irritative and obstructive, and bowel symptoms. The Akaike Information Criterion (AIC) and Bayesian Information Criterion (BIC) were computed to compare the 4 models, and a model was selected based on minimizing either the AIC or BIC.35 In addition, the quality of the resulting classification was evaluated in terms of the separation of the subgroups using the entropy index. Entropy denotes how possible it is to predict group membership given the observed indicators. Values range from 0 to 1, with high values (>0.90) indicating the groups are highly discriminative. All models were fit using MPlus software, version 5.36 After subgroups were created, 1-way analyses of variance were examined to determine whether the groups differed on symptoms, participant characteristics, and QOL.

Latent transition analysis was used to examine transitions in membership among the symptom cluster subgroups over time. Latent transition analysis estimates the probability of moving from 1 subgroup at pretreatment into another group at posttreatment. Logistic regression was used to determine if participant characteristics and QOL predicted who changed groups from pretreatment to posttreatment.

Back to Top | Article Outline

Results

One hundred forty men were approached, with 84 giving written informed consent. Most common reasons for refusal were too busy (n = 14) and not interested (n = 31). Most men were white and married and had a mean age of 69 years (Table 1). Mean education level was 15 years, with an annual household income of $50 000 to 60 000. Mean number of comorbidities was 3.4, with a mean time since diagnosis of 20.6 months (1.7 years). Mean Gleason score was 7.2 (median, 7.0), with a mean PSA level of 8.7 ng/mL.

Among the participants at pretreatment, QOL was reported as moderately high with a mean FACT-P score of 129.0 (SD, 16.8 [range, 75–154]). At posttreatment the mean QOL score was 120.4 (SD, 19.8 [range, 73–153]), indicating a slight decrease in QOL from pretreatment to posttreatment.

Table 1

Table 1

Back to Top | Article Outline

Symptom Cluster Subgroups

Sample means and SDs for the symptoms at pretreatment and posttreatment are presented in Table 2. Fatigue, pain, insomnia, and sexual, urinary (irritative and incontinence), and bowel symptoms significantly worsened for the participants from pretreatment to posttreatment. Anxiety and depression did not significantly change.

Table 2

Table 2

Based on the lowest Akaike (AIC) value of 5249.08, lowest BIC value of 5365.76, and entropy value of 0.92, 4 groups were identified at pretreatment with different symptom patterns. Table 3 presents symptom means and SDs for the 4 symptom cluster subgroups identified. At pretreatment, group 1 (n = 39), who reported little to no symptoms, was labeled as “resilient.” This group had less symptom reporting related to the other 3 subgroups except for urinary irritative symptoms. Group 2 (n = 34) was characterized by moderately high sexual, urinary, and bowel symptoms with lower levels of insomnia, depression, and anxiety. This group was labeled “adjusted” as they were further distinguished by moderately high QOL scores. Group 3 (n = 3), which was labeled “distressed,” was composed of men who were consistently high on all symptoms except urinary incontinence. Depression and insomnia were above the scale cutoff levels for clinical significance. Group 4 (n = 14), which was moderately high on anxiety, depression, and fatigue with few treatment-related symptoms, was labeled “emerging.” With a combination of high and low symptoms, it was not apparent if group 4 members at posttreatment would remain relatively constant with this profile or experience an overall worsening or improvement in symptoms.

Table 3

Table 3

Based on the F statistic value, the largest contributor to the identification of the subgroups at pretreatment was depression, with the distressed group being the most depressed followed by the emerging group. The second largest contributor to identifying subgroup membership was anxiety, with the distressed and emerging groups having the highest and second highest levels of anxiety. These subgroups were also highest and second highest on insomnia and fatigue. Pain and urinary incontinence did not contribute to overall identification of the symptom cluster subgroups at pretreatment

At posttreatment, based on the lowest Akaike (AIC) value of 5520.23, lowest BIC value of 5636.33, and entropy value of 0.91, 4 groups were identified with different symptom patterns. Table 4 presents symptom means and SDs for the 4 subgroups. All symptoms contributed to the identification of the subgroups. Similar to the groups found at pretreatment, the resilient, adjusted, and distressed subgroups remained at posttreatment. Once again, the resilient group reported the best symptom scores (less symptoms) compared with the other groups, the adjusted group had the second best scores and continued to report moderately high QOL, whereas the distressed group had the worst scores on fatigue, insomnia, depression, anxiety, and sexual. A newly identified fourth group at posttreatment had the worst scores on pain, urinary irritative and incontinence, and bowel, and the second worse scores on insomnia and depression in relation to the other 3 groups. This fourth group was labeled “impacted” as it appeared these men may have experienced a stronger reaction to RT compared with the other 3 groups, as demonstrated by their higher levels of symptoms commonly associated with this treatment.

Table 4

Table 4

Back to Top | Article Outline

Differences in Sample Characteristics and QOL Among Subgroups

At pretreatment, there were significant subgroup differences for participant age, with men in the adjusted and resilient groups being older than those in the distressed group (Table 5). Gleason scores differed by group, with the resilient group having lower scores than the adjusted and distressed groups. Prostate-specific antigen levels also differed by group, with the distressed group having significantly higher levels than the other 3 groups. There were significant group differences in QOL. The resilient group had higher QOL compared with the other 3 groups.

Table 5

Table 5

At posttreatment, there were also significant differences among the groups in participant characteristics and QOL (Table 5). Differences in participant age persisted among the subgroups, with those in the adjusted group being older than those in the distressed group. Significant differences in income level that were not present at pretreatment were now found between the adjusted and distressed groups. Significant differences in Gleason scores revealed the distressed group had higher scores than did the resilient group. Significant differences in PSA level were also noted between the distressed group who had higher scores when compared with the resilient and adjusted groups. Significant differences in QOL persisted, with the resilient group reporting greater QOL than the other 3 groups. There were no additional significant differences in participant or clinical characteristics at pretreatment or posttreatment related to the subgroups including months since diagnosed, prior prostatectomy, or comorbidities.

Back to Top | Article Outline

Transitions in Subgroup Membership

Because of the similar structure (ie, 4 subgroups) observed for the symptoms at pretreatment and posttreatment, we were able to estimate transition probabilities. The latent transition analysis model specifying a 4-group solution had satisfactory fit to the data (AIC value of 10741.11, lowest BIC value of 10996.35, and entropy value of 0.93). Table 6 presents the transition probabilities of moving from 1 subgroup at pretreatment to another group at posttreatment. Membership in the resilient, adjusted, and distressed groups remained relatively stable over time, with 73%, 90%, and 100%, of the men, respectively, staying within their group. In contrast, all of the men in the emerging group identified at pretreatment moved to another group; 66% moved to the distressed group, 21% to the adjusted group, and 13% to the resilient group. Among all subgroups in which an individual moved to another group, there was a greater probability of transitioning from a pretreatment group of lower symptom reporting to a posttreatment group with higher level of symptom reporting. Logistic regression revealed the only significant predictor of a transition in group membership from pretreatment to posttreatment was income level (Table 7). Men with higher incomes were less likely to move to another group compared with men with lower incomes.

Table 6

Table 6

Table 7

Table 7

Back to Top | Article Outline

Discussion

Participants reported a significant increase at posttreatment in severity for many of the symptoms measured. Significantly higher levels of fatigue, pain, and insomnia following RT as found in this study have also been reported in patients undergoing RT for uterine and breast cancer.37,38 Consistent with earlier prostate cancer findings, results in the current study also indicated that men experienced a significant worsening in urinary, bowel, and sexual symptoms following RT.39,40

Anxiety and depression did not significantly change for the sample from pretreatment to posttreatment. Anxiety was moderately high at pretreatment, which supported statements expressed by many men that making a decision regarding treatment (prostatectomy vs RT) was stressful, with the decision often reached close to the start of RT. Why anxiety remained moderately high at posttreatment is not known. Perhaps anxiety following treatment is now related to concerns of a different nature (eg, treatment adverse effects) than those experienced at pretreatment. Depression and anxiety were the largest contributors to the identification of pretreatment subgroups, even though sample mean values for these symptoms did not significantly change over time. This finding supports the importance of using symptom data to classify patients into subgroups to gain a more accurate representation of symptom patterns before RT begins. When reporting symptom results over time only as sample means rather than stratifying patients into subgroups, valuable information may be lost that would more clearly define the impact of prostate cancer on patient functioning and distress.41

Four subgroups were identified at pretreatment according to distinctly different symptom cluster patterns. The presence of a distressed group who were high on most symptoms has been documented in several investigations of patients undergoing cancer treatment. Among patients receiving biotherapy, 7% of the sample clustered into a group characterized by significantly high levels of fatigue, pain, sleep disturbance, and depression.42 Breast cancer patients receiving chemotherapy and RT could also be characterized into all-high subgroup with consistently elevated depression, fatigue, pain, and insomnia.43 The current study demonstrates the value at pretreatment in measuring not only general symptoms but also those symptoms associated with RT (ie, sexual, urinary, bowel problems), which help to further define the symptoms of the distressed group as “all high.”

Men in the distressed group were younger in age, with higher Gleason scores and PSA levels. It was not surprising younger men with professional and personal roles to meet who had greater disease severity and were starting RT that may affect sexual, urinary, and bowel functioning would report higher symptom levels. Quality of life was also lower in the distressed subgroup than that in the other 3 subgroups, indicating that as the number of symptoms rated as high increased, QOL also was adversely affected.

Similar to prior investigations that revealed the existence of a group high on all symptoms, this study supported earlier findings that identified a second distinct subgroup at pretreatment that reported the lowest symptoms and the highest QOL.14,43 Specifically, the resilient group had the lowest levels of fatigue, pain, insomnia, depression, anxiety, and sexual, urinary, and bowel problems. This subgroup, which constituted almost half of the participants (46%), had the lowest Gleason scores, which may relate to lower symptom reporting and higher QOL. Another explanation may involve resilience or the ability of an individual to quickly recover from stressful life circumstances. Individuals who are resilient have a greater capacity in challenging situations to rapidly regain a sense of self, physiologically and psychologically.44 Future research into variables, which may influence an individual’s response to a cancer diagnosis and treatment such as coping styles and skills, social relationships, and learned resourcefulness, is warranted to gain a better understanding into the defining characteristics of this subgroup.

Identification of an adjusted subgroup consisting of older men (mean age, 71 years) with moderately high sexual, urinary, and bowel symptoms and QOL was not unexpected. Although reasons for an elevation in physiological symptoms are not known, it appears accommodation to these symptoms may have occurred as evidenced by low mood scores and high QOL. Accommodation may relate to findings that report that some men experience age-associated declines in erectile, urinary, and bowel functioning.45–47 In addition, research has found older men undergoing prostate cancer treatment have better mental well-being than do younger men, despite indicating poorer sexual and urinary functioning.48

An emerging subgroup with a significantly different symptom pattern has been verified elsewhere with cancer patients including Kim et al,43 who identified subgroups of patients with high pain and low fatigue, and high fatigue and low pain. Groups with somewhat counterintuitive symptom levels were also revealed by Dodd et al,42 who reported 1 subgroup with mild pain and sleep disturbance, moderate fatigue, and depression and a second subgroup characterized by mild pain and fatigue, sleep disturbance, and no depression. Once again as with other identified subgroups in this study, participant characteristics, traits, or other attributes that would further define the emerging group are lacking. Continued research into underlying physiological makers (ie, neuroendocrine, genetic) looks promising as one explanation for level of symptom distress. In a subsample of participants from this study, our prior reported findings suggested the lack of a strong association at both pretreatment and posttreatment between cytokine levels and symptoms.49

The 3 subgroups identified at posttreatment labeled as resilient, adjusted, and distressed were similar in symptom profile and participant characteristics to those found at pretreatment. A majority of men in the emerging group with its pretreatment profile of low sexual, urinary, and bowel symptoms had moved to an impacted group, with scores indicating a worsening in pain, urinary, and bowel symptoms. In addition, the already moderately high mood and fatigue levels reported at pretreatment for the emerging group did not lessen from these levels for those moving into the impacted group. Identification of a distressed group at pretreatment (n = 3) and posttreatment (n = 10) suggests high levels on most symptoms may not dissipate over time. Furthermore, some men who were not all high before the start of treatment now reported being high on most symptoms. When taken together, the symptoms of the impacted and distressed groups contained the worst scores on all symptoms. Similarities in the symptom profiles of these 2 groups suggest they may be related. Future research is needed to identify which men prior to RT may be at increased risk for these high symptom levels at posttreatment, which comprised 16% of the sample. As evident in this study, a more in-depth description of the subgroups was limited by the number of participant characteristics examined.

Income level at posttreatment significantly differentiated the subgroups between the lowest (distressed) and highest (adapted) income levels. Lower income levels have been linked to higher depression and somatic symptoms across different cancer types and treatments.50 Lower income levels at posttreatment were also related to increased symptoms in women with breast cancer, with income proposed as a major factor in whether posttreatment care was accessed.51

The large number of men (83%) in the resilience and adapted subgroups indicates many men had high QOL and were experiencing few to no symptoms following RT. Whether this profile is found many months following prostate cancer treatment was addressed by Maliski et al,18 who reported that at 8 months after treatment, the largest number of men (48%) clustered into a group characterized by minimally low symptom scores. These men were further described as “doing well.” One reason for why symptom reporting may be lower than expected at posttreatment may be found in research, which indicates men with prostate cancer who were aware of their diagnosis and treatment plan experienced less distress than did persons with other cancer types (eg, breast, digestive, lung, gynecologic, head/neck).52 It was surmised that prostate cancer treatment (surgery or RT) may have been perceived by men as a less intense type of treatment with fewer residual effects compared with other cancer diagnoses and treatments.

Research is needed to determine the relationships among income level, symptom reporting, and transitions in subgroup membership. Having financial resources may assist individuals in pursuing options to mitigate distressful symptoms. For example, findings revealed Hispanic women with higher income levels receiving breast cancer treatment had greater use of complementary and alternative medicine, with results suggesting a significant relationship between depression and prayer.53 Income may also be an important factor in decreasing patient symptoms at the end of life, with greater symptom burden strongly linked to lower levels of wealth.54

Study limitations include that the participants who were mostly white, married, and well educated with high income levels, restricts generalizability of the findings to men with a similar demographic profile. The small sample size and low number of men in some of the subgroups warrant the replication of these results in larger studies of men undergoing RT. Evaluating prevalence and severity of multiple symptoms in a more ethnically and economically diverse sample is recommended because symptom experiences may be significantly different. An examination of symptoms, symptom patterns, and transitions in subgroup membership for more than the 2 time points of pretreatment and posttreatment may result in a more accurate depiction of how symptoms change during and after RT. Study strengths include the use of multi-item validated measures to assess each symptom that may have contributed to a better understanding of the components that determine a symptom’s prevalence and severity. Study findings provided new insight into an understudied population who may be experiencing symptoms at baseline that are not apparent until their severity reaches recognizable levels at posttreatment. Future study to examine which subgroups respond to an intervention that targets multiple symptoms would be of value.

Men diagnosed with prostate cancer report concurrent multiple symptoms, which may worsen with treatment. Our preliminary findings suggest it may be important to intervene early at baseline when patients with a cluster of moderate to high symptoms have been identified and in doing so proactively lessen symptom burden before its severity can increase with RT. By assessing and intervening with men in subgroups such as distressed and emerging before and during treatment, the potential for remaining distressed or moving into the impacted group may lessen. Our current ability to address multiple symptoms has been restricted by a dearth of evidence-based practice interventions that effectively target more than 1 symptom. Lessening the impact of concurrent symptoms before and after treatment through a greater focus on the development and testing of interventions is imperative if we are to make the cancer experience more manageable and improve QOL.

Back to Top | Article Outline

References

1. Cancer Research United Kingdom. Worldwide cancer incidence statistics Web site. http://www.cancerresearchuk.org/cancer-info/cancerstats/world/incidence/#Common. Accessed October 13, 2014.
2. Seigel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin. 2014; 64( 1): 9–29.
3. Brooks D. Choosing the best prostate cancer treatment for you. American Cancer Society Web site. http://www.cancer.org/cancer/news/expertvoices/post/2013/06/13/choosing-the-best-prostate-cancer-treatment-for-you.aspx. Accessed October 13, 2014.
4. Fransson P. Fatigue in prostate cancer patients treated with external beam radiotherapy: a prospective 5-year long-term patient-reported evaluation. J Cancer Res Ther. 2010; 6( 4): 516.
5. Langston B, Armes J, Levy A, Tidey E, Ream E. The prevalence and severity of fatigue in men with prostate cancer: a systematic review of the literature. Support Care Cancer. 2013; 21( 6): 1761–1771.
6. Savard J, Ivers H, Villa J, Caplette-Gingras A, Morin CM. Natural course of insomnia comorbid with cancer: an 18-month longitudinal study. J Clin Oncol. 2011; 29( 26): 3580–3586.
7. Dirksen SR, Epstein D, Hoyt M. Insomnia, depression, and distress among outpatients with prostate cancer. Appl Nurs Res. 2009; 22( 3): 154–158.
8. Dunn LB, Aouizerat BE, Cooper BA, et al. Trajectories of anxiety in oncology patients and family caregivers during and after radiation therapy. Eur J Oncol Nurs. 2012; 16( 1): 1–9.
9. van Onselen C, Dunn LB, Lee K, et al. Relationship between mood disturbance and sleep quality in oncology outpatients at the initiation of radiation therapy. Eur J Oncol Nurs. 2010; 14( 5): 373–379.
10. Knapp K, Cooper B, Koetters T, et al. Trajectories and predictors of symptom occurrence, severity, and distress in prostate cancer patients undergoing radiation therapy. J Pain Symptom Manage. 2012; 44( 4): 486–507.
11. Sonn GA, Sadetsky N, Presti JC, Litwin MS. Differing perceptions of quality of life in patients with prostate cancer and their doctors. J Urol. 2013; 189( 1): S59–S65.
12. Huang GJ, Sadetsky N, Penson DF. Health related quality of life for men treated for localized prostate cancer with long-term followup. J Urol. 2010; 183( 6): 2206–2212.
13. Dodd MJ, Miaskowski C, Paul SM. Symptom clusters and their effect on the functional status of patients with cancer. Oncol Nurs Forum. 2001; 28( 3): 465–470.
14. Miaskowski C, Cooper BA, Paul SM, et al. Subgroups of patients with cancer with different symptom experiences and quality-of-life outcomes: a cluster analysis. Oncol Nurs Forum. 2006; 33( 5): E79–E89.
15. Liu L, Fiorentino L, Natarajan L, et al. Pre-treatment symptom cluster in breast cancer patients is associated with worse sleep, fatigue and depression during chemotherapy. Psychooncology. 2009; 18( 2): 187–194.
16. Dodd MJ, Cho MH, Cooper BA, Miaskowski C. The effect of symptom clusters on functional status and quality of life in women with breast cancer. Eur J Oncol Nurs. 2010; 14( 2): 101–110.
17. Illi J, Miaskowski C, Cooper B, et al. Association between pro- and anti-inflammatory cytokine genes and a symptom cluster of pain, fatigue, sleep disturbance, and depression. Cytokine. 2012; 58( 3): 437–447.
18. Maliski SL, Kwan L, Elashoff D, Litwin MS. Symptom clusters related to treatment for prostate cancer. Oncol Nurs Forum. 2008; 35( 5): 786–793.
19. Kim JE, Dodd MJ, Aouizerat BE, Jahan T, Miaskowski C. A review of the prevalence and impact of multiple symptoms in oncology patients. J Pain Symptom Manage. 2009; 37( 4): 715–736.
20. Lenz ER, Suppe F, Gift AG, Pugh LC, Milligan RA. Collaborative development of middle-range nursing theories: toward a theory of unpleasant symptoms. ANS Adv Nurs Sci. 1995; 17( 3): 1–13.
21. Lenz ER, Pugh LC, Milligan RA, Gift A, Suppe F. The middle-range theory of unpleasant symptoms: an update. ANS Adv Nurs Sci. 1997; 19( 3): 14–27.
22. Meleis A, Sawyer L, Im E, Messias D, Schumacher K. Experiencing transitions: an emerging middle-range theory. ANS Adv Nurs Sci. 2000; 23( 1): 12–28.
23. Satariano WA, Ragheb NE, Dupuis MH. Comorbidity in older women with breast cancer: an epidemiologic approach. In Yancik R, Yates J, eds. Cancer in the Elderly: Approaches to Early Detection and Treatment. New York, NY: Springer Publishing Company; 1989: 71–107.
24. McNair DM, Lorr M, Droppleman LF. Manual for the Profile of Mood States. San Diego, CA: Educational and Industrial Testing Service; 1971.
25. McNair DM, Lorr M, Droppleman LF. EdITS Manual for the Profile of Mood States. San Diego, CA: Educational and Industrial Testing Service; 1992.
26. Morin CM, Colecchi C, Stone J, Sood R, Brink D. Behavioral and pharmacological therapies for late-life insomnia: a randomized controlled trial. JAMA. 1999; 281( 11): 991–999.
27. Bastien CH, Vallieres A, Morin CM. Validation of the insomnia severity index as an outcome measure for insomnia research. Sleep Med. 2001; 2( 4): 297–307.
28. Jensen MP. The validity and reliability of pain measures in adults with cancer. J Pain. 2003; 4( 1): 2–21.
29. Radloff L. The CES-D scale: a self-report depression scale for research in the general population. Appl Psychol Meas. 1977; 1( 3): 385–401.
30. Sheehan TJ, Fifield J, Reisine S, Tennen H. The measurement structure of the Center for Epidemiologic Studies Depression Scale. J Pers Assess. 1995; 64( 3): 507–521.
31. Spielberger CD. State-Trait Anxiety Inventory: A Comprehensive Bibliography. Palo Alto, CA: Consulting Psychologists Press; 1984.
32. Wei JT, Dunn RL, Litwin MS, Sandler HM, Sanda MG. Development and validation of the expanded prostate cancer index composite (EPIC) for comprehensive assessment of health-related quality of life in men with prostate cancer. Urology. 2000; 56( 6): 899–905.
33. Cella DF, Tulsky DS, Gray G, et al. The functional assessment of cancer therapy scale: development and validation of the general measure. J Clin Oncol. 1993; 11( 3): 570–579.
34. Esper P, Mo F, Chodak G, Sinner M, Cella D, Pienta KJ. Measuring quality of life in men with prostate cancer using the functional assessment of cancer therapy-prostate instrument. Urology. 1997; 50( 6): 920–928.
35. Burnham KP, Anderson DR. Model Selection and Multimodel Inference: A Practical Information-Theoretic Approach. 2nd ed. New York: Springer; 2002.
36. Muthen LK, Muthen BO. MPlus User’s Guide, 5th ed, Los Angeles, CA: Muthen & Muthen; 2007.
37. Ahlberg K, Ekman T, Gaston-Johansson F. Fatigue, psychological distress, coping resources, and functional status during radiotherapy for uterine cancer. Oncol Nurs Forum. 2005; 32( 3): 633–640.
38. Hofsø K, Rustøen T, Cooper BA, Bjordal K, Miaskowski C. Changes over time in occurrence, severity, and distress of common symptoms during and after radiation therapy for breast cancer. J Pain Symptom Manage. 2013; 45( 6): 980–1005.
39. Cameron S, Springer C, Fox-Wasylyshyn S, El-Masri MM. A descriptive study of functions, symptoms, and perceived health state after radiotherapy for prostate cancer. Eur J Oncol Nurs. 2012; 16( 3): 310–314.
40. Dandapani S, Sanda M. Measuring health-related quality of life consequences from primary treatment for early-stage prostate cancer. Semin Radiat Oncol. 2008; 18( 1): 67–72.
41. Chen R, Clark J, Talcott J. Individualizing quality-of-life outcomes reporting: how localized prostate cancer treatments affect patients with different levels of baseline urinary, bowel, and sexual function. J Clin Oncol. 2009; 27( 4): 3916–3922.
42. Dodd MJ, Cho MH, Cooper BA, et al. Identification of latent classes in patients who are receiving biotherapy based on symptom experience and its effect on functional status and quality of life. Oncol Nurs Forum. 2011; 38( 1): 33–42.
43. Kim HJ, Barsevick AM, Beck SL, Dudley W. Clinical subgroups of a psychonuerologic symptom cluster in women receiving treatment for breast cancer: a secondary analysis. Oncol Nurs Forum. 2012; 39( 1): E20–E30.
44. Zautra A. Resilience: one part recovery, two parts sustainability. J Pers. 2009; 77( 6): 1935–1943.
45. Blanker M, Bohmen A, Groeneveld F, et al. Correlates for erectile and ejaculatory dysfunction in older Dutch men: a community-based study. J Am Geriatr Soc. 2001; 49( 4): 436–442.
46. Kwong PW, Cumming R, Chan L, et al. Urinary incontinence and quality of life among older community-dwelling Australian men: the CHAMP study. Age Ageing. 2010; 39( 3): 349–354.
47. Markland AD, Goode PS, Burgio KL, et al. Incidence and risk factors for fecal incontinence in black and white older adults: a population-based study. J Am Ger Soc. 2010; 58( 7): 1341–1346.
48. Eton DT, Lepore SJ, Helgeson VS. Early quality of life in patients with localized prostate carcinoma: an examination of treatment-related, demographic, and psychosocial factors. Cancer. 2001; 92( 6): 1451–1459.
49. Dirksen SR, Kirschner K, Belyea M. Association of symptoms and cytokines in men with prostate cancer undergoing radiation treatment. Biol Res Nurs. 2014; 16( 3): 250–257.
50. Cohen M. (2014). Depression, anxiety, and somatic symptoms in older cancer patients: a comparison across age groups. Psychooncology. 2014; 23( 2): 151–157.
51. Eversley R, Estrin D, Dibble S, Wardlaw L, Pedrosa M, Favila-Penney W. Post-treatment symptoms among ethnic minority breast cancer survivors. Oncol Nurs Forum. 2005; 32( 2): 250–256.
52. Admiraal J, Reyners A, Hoekstra-Weebers J. Do cancer and treatment type affect distress?Psycho-Oncology. 2013; 22( 8): 1766–1773.
53. Owens B, Jackson M, Berndt A. Complementary therapy used by Hispanic women during treatment for breast cancer. J Holist Nurs. 2009; 27( 3): 167–176.
54. Silveira M, Kabeto M, Langa K. Net worth predicts symptom burden at the end of life. J Palliat Med. 2005; 8( 4): 827–837.
Keywords:

Prostate cancer; Quality of life; Radiation therapy; Symptom clusters

Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved