- Email: [email protected]
Fear of Recurrence, Symptom Burden, and Health-Related Quality of Life in Men With Prostate Cancer
Outcomes Fear of Recurrence, Symptom Burden, and Health-Related Quality of Life in Men With Prostate Cancer Keith M. Bellizzi, David M. Latini, Janet E. Cowan, Janeen DuChane, and Peter R. Carroll OBJECTIVES
METHODS
RESULTS
CONCLUSION
To examine the contributions of fear of recurrence and the more commonly examined treatment-related symptoms to the health-related quality of life (HRQOL) of men treated for localized prostate cancer. A total of 730 men with localized disease were identified from the Cancer of the Prostate Strategic Urologic Research Endeavor, a national, prospective study of men with prostate cancer. Pre- to post-treatment changes in fear of recurrence, treatment-specific symptoms and burden, comorbidities at diagnosis, number of new symptoms, and post-treatment HRQOL data were analyzed. Linear regression, adjusted for clinical and demographic characteristics, showed that improved fear of recurrence (P ⬍0.01), higher number of post-treatment symptoms (P ⬍0.01), and improved bowel function (P ⬍0.01) significantly predicted better mental health scores. For physical health, improved urinary bother (P ⬍0.01) and lower number of post-treatment symptoms (P ⬍0.01) were associated with better physical health. Understanding men’s fears about cancer recurrence and how these fears influence physical and mental health are important components of providing care to this growing population. UROLOGY 72: 1269 –1273, 2008. © 2008 Elsevier Inc.
A
dvances in early detection and treatment modalities for prostate cancer have resulted in an increase in the 5-year relative survival rate from 67% to 99% over the past 20 years.1 Despite the improvement in survival, many survivors are at risk for posttreatment psychosocial and physical sequelae. One of the major psychosocial concerns that prostate cancer survivors report is fear of cancer recurrence (FOR).2–7 Although FOR may vary in intensity as time progresses, prior studies have found FOR to be an important issue in both newly treated prostate cancer survivors as well as in longer-term prostate cancer survivors.2,5,7 Studies have shown fear of recurrence to be linked to increased distress and poorer psychological adaptation in survivors of breast cancer8 and in bone-marrow transplant survivors.9 However, few studies exist regarding the impact of FOR on CaPSURE is sponsored by TAP Pharmaceutical Products, Lake Forest, Illinois, and is managed by the Urology Outcomes Research Group at the University of California-San Francisco. Funding was provided by a CaPSURE Scholars Grant from the University of California, San Francisco. From the Office of Cancer Survivorship, Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda Maryland; Scott Department of Urology and Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas; Department of Urology, University of California-San Francisco, San Francisco, California; and TAP Pharmaceutical Products, Lake Forest, Illinois Reprint requests: Keith Bellizzi, Office of Cancer Survivorship, National Cancer Institute, 6116 Executive Blvd., Suite 404, MSC 8336, Bethesda, MD 20892. E-mail: [email protected] Submitted: August 24, 2007, accepted (with revisions): December 17, 2007
© 2008 Elsevier Inc. All Rights Reserved
prostate cancer survivors’ health-related quality of life (HRQOL).4,6 Moreover, studies identified in the literature fail to account for important confounders, specifically treatment-specific symptoms. Because of the long natural history of most prostate cancer and the often anxiety-producing subtle fluctuations in prostate-specific antigen (PSA) surveillance,10 it is important to understand the association between fear of recurrence and men’s HRQOL to help prostate cancer survivors manage this persistent issue. The literature has characterized treatment-specific symptoms associated with treatment for prostate cancer.11–15 In general, these studies have demonstrated an array of treatment-related effects, including urinary and bowel incontinence and sexual dysfunction. Other studies have examined more general post-treatment symptoms, including fatigue, well-being, cognitive changes, weight gain, arthritis, muscle pain, and insomnia.16,17 Although studies have examined the association between treatment-related effects and HRQOL,18,19 there is no information about the comparative influence of FOR versus treatment-specific and more general post-treatment symptoms on prostate cancer survivors’ HRQOL. The medical management of treatment-related symptoms (urinary and bowel incontinence and sexual dysfunction) is different from providing supportive psychological care for the management of fears of recurrence. 0090-4295/08/$34.00 doi:10.1016/j.urology.2007.12.084
1269
This study examined the contributions of fear of recurrence and the more commonly examined treatmentrelated symptoms to the HRQOL of men treated for localized prostate cancer. Its primary aim was to examine the associations between pre- to post-treatment changes in fear of recurrence and treatment-specific symptoms, number of new post-treatment general symptoms, and mental and physical HRQOL. We hypothesized, on the basis of related empirical work, that (1) men with an improvement in FOR and treatment-specific symptoms and lower post-treatment general symptoms will have better mental and physical HRQOL; and (2) fear of recurrence, treatment-specific symptoms, and number of new post-treatment general symptoms will contribute differentially to the variance explained in mental and physical HRQOL.
MATERIAL AND METHODS Source of Data Designed to measure disease, treatment, and HRQOL outcomes, CaPSURE (Cancer of the Prostate Strategic Urologic Research Endeavor) is a prospective, observational registry of more than 12,000 men with biopsy-proven prostate cancer. Patients are recruited from more than 30 community- and academic-based urology practices across the United States and followed over time until death or withdrawal from the study. Participating urologists report complete clinical data and follow-up information on diagnostic tests and treatments. Data collection relies on validated, self-report instruments that patients complete by mail questionnaire every 6 months that include both general and treatment-specific HRQOL data.20
Participants Data were analyzed from CaPSURE patients diagnosed between 1999 and 2002 (n ⫽ 5071) with localized disease (n ⫽ 4597) who underwent either radical prostatectomy monotherapy (RP), brachytherapy monotherapy (BT), or external-beam radiation monotherapy (EBRT) (n ⫽ 2480) as primary treatment. Of those, 730 cases had HRQOL and FOR data (the Fear of Recurrence scale was only administered between 1999 and 2002) for the 9 months before treatment and within 1 year after treatment (mean [standard deviation] ⫽ 135 [69.7] days); this group represents the final sample.
Measures Health-related quality of life was measured with the wellvalidated Medical Outcomes Survey Short-Form-36 (SF-36).21 Construction of the physical component summary (PCS) and mental component summary (MCS) scores was based on U.S. population norms, so that scores above or below 50 are above or below the average in the general adult population.22 The 20item University of California-Los Angeles Prostate Cancer Index (PCI) 23 was used to measure treatment-specific function and bother (bowel, urinary, sexual). It has demonstrated good psychometric properties in men treated for prostate cancer.23 Higher scores represent better function for both the SF-36 and the PCI. We used Kornblith’s 5-item Fear of Recurrence Scale.24 Questions include, “I am afraid of my cancer getting worse,” and “I will probably have a relapse within the next 5 years.” Items 1270
are rated on a 5-point Likert scale, with response choices ranging from “not at all” to “very much.” For this analysis, FOR scores were rescaled to 0 to 100, with higher scores representing more fear. The reliability and validity of this scale have been previously established.24 Using checklists created for CaPSURE, patients and/or their physicians reported the number of comorbid conditions at diagnosis (ie, arthritis, blood disease, diabetes, hypertension, heart disease, lung disease, kidney problem, other cancer, other urinary condition, stomach problem, and stroke) and number of new general physical symptoms (eg, weight change, fatigue, abdominal, bowel, chest, lung, muscle, joint, bone, nervous system, cognitive, hormonal, skin, urinary, and genitourinary).
Analytic Methods Mean change in fear of recurrence and PCI scores from before to after treatment were computed for regression models. We used linear regression to examine the association between changes in FOR and treatment-specific symptoms and number of new symptoms on post-treatment mental and physical HRQOL. Model predictors were changes in PCI, change in FOR, number of new post-treatment general symptoms, and pre-treatment MCS and PCS scores, as well as sample characteristics and clinical risk category. Independent variables were entered in blocks, with clinical predictors in block one, demographic predictors in block two, treatment-specific symptoms in block three, FOR in block four, and comorbidities at diagnosis and general post-treatment symptoms in block five. Bonferroni correction was used to adjust for multiple-comparison tests of significance.
RESULTS Characteristics of Sample Chi-square tests revealed no significant differences in education, income, health insurance, PSA level, or Gleason score between the 730 men in the final sample and the 1750 patients not in the sample. However, those who were in the final sample reported more new post-treatment symptoms than those who were not in the sample (mean ⫽ 5.1 [3.2] and 4.2 [4.7], respectively; P ⬍0.01). Demographic and clinical characteristics of the sample are summarized in Table 1. Table 2 shows pre- to posttreatment mean change scores in treatment-specific symptoms, number of new symptoms, FOR, and MCS and PCS. At baseline, the average FOR score was 36.1 (18.3), with a significant improvement at the 12-month post-treatment follow-up: 23.5 (18.6). Treatment-related symptom scores (eg, sexual, urinary, bowel function) were significantly worse from baseline to 12-month posttreatment follow-up, with mean change scores ranging from ⫺3.4 (16.4) for bowel function to ⫺32.2 (26.8) for sexual function. With the exception of a nominal pre- to post-treatment improvement in mental health, men treated (RP, BT, EBRT) for localized prostate cancer reported worse physical HRQOL and an average of 5.1 (3.2) new symptoms after treatment. UROLOGY 72 (6), 2008
Table 1. Demographic and clinical characteristics (N ⫽ 730) Characteristic Age (yr), mean ⫾ standard deviation Ethnicity (missing ⫽ 1) White Other Education (missing ⫽ 4) ⬍High school High school graduate Some college College graduate Primary treatment (missing ⫽ 0) RP monotherapy EBRT monotherapy BT monotherapy PSA (ng/mL) (missing ⫽ 17) 0–4.0 4.1–10.0 10.1–20.0 ⬎20 Risk category* (missing ⫽ 18) Low Medium High Comorbidities (missing ⫽ 6) None 1 to 2 3⫹ BMI category (kg/m2) (missing ⫽ 9) Normal (⬍25.0) Overweight (25.0–29.9) Obese (30.0)
n (%) 63.2 ⫾ 7.72 669 (92.0) 60 (8.0) 77 (11.0) 181 (25.0) 139 (19.0) 329 (45.0) 562 (77.0) 33 (5.0) 135 (18.0) 122 (17.0) 501 (70.0) 78 (11.0) 12 (2.0) 381 (54.0) 256 (36.0) 75 (11.0) 129 (18.0) 399 (55.0) 196 (27.0) 171 (24.0) 403 (56.0) 147 (20.0)
RP ⫽ radical prostatectomy monotherapy; EBRT ⫽ external-beam radiation monotherapy; BT ⫽ brachytherapy monotherapy; PSA ⫽ prostate-specific antigen; BMI ⫽ body mass index. * Clinical risk groups defined based on D’Amico et al., JAMA 1998.30
Psychosocial and Physical Correlates of Mental and Physical Health The overall regression models for mental and physical HRQOL were significant: R2 ⫽ 0.439, F(24, 552) ⫽ 18.00, P ⬍0.01, and R2 ⫽ 0.445, F(24, 552) ⫽ 18.46, P ⬍0.01, respectively. After adjusting for clinical and demographic characteristics, improved FOR (P ⬍0.01) and improved bowel function (P ⬍0.01) significantly predicted better mental health scores, whereas higher number of posttreatment symptoms (P ⬍0.01) was correlated with worse mental health (Table 3). For physical health, improved urinary bother (P ⬍0.01) and fewer number of post-treatment general symptoms (P ⬍0.01) were associated with better physical health. As for FOR, there seems to be a marginally significant trend, such that improved FOR was related to better physical health (P ⫽ 0.06). As for the differential impact of fear of recurrence versus treatment-related symptoms on physical and mental HRQOL, treatment-specific symptoms (R2 ⫽ 0.101 and 0.044, respectively) and number of new symptoms (R2 ⫽ 0.122 and 0.145, respectively) explained more of the variance in PCS and MCS than FOR (R2 ⫽ 0.010 and 0.015, respectively). UROLOGY 72 (6), 2008
COMMENT This study used one of the largest observational studies of prostate cancer survivors to examine the association between fear of recurrence and mental and physical HRQOL of prostate cancer survivors. We hypothesized that (1) men with an improvement in fear of recurrence and treatment-specific symptoms and fewer post-treatment general symptoms would report better mental and physical HRQOL; and (2) fear of recurrence, treatmentspecific symptoms, and post-treatment general symptoms would contribute differentially to the explanatory power of mental and physical HRQOL. Our findings support both hypotheses in that they show that better mental and physical health were associated with an improvement in fear of recurrence (only significantly associated with mental health), improvement in treatment-specific symptoms, and fewer symptoms following treatment. Treatment-specific symptoms and new symptoms after treatment explained more variance in physical and mental HRQOL than fear of recurrence. Some limitations of the study include our inability to generalize these findings to men not treated with RP, BT, or EBRT (eg, luteinizing hormone-releasing hormone agonist, anti-androgen, cryosurgery, watchful waiting) and those with more advanced disease. However, most men with localized prostate cancer select one of those three treatment alternatives. Furthermore, men diagnosed with advanced-stage prostate cancer represent a relatively small percentage of the population of prostate cancer survivors (⬍10%).25 Men in CaPSURE may not be representative of the broader population of men with localized prostate cancer because participants are more likely to be white and of higher socioeconomic status than the typical man with localized prostate cancer in the United States. Last, HRQOL and FOR data were analyzed only up to 1 year after treatment. Although FOR data were available up to 3 years after treatment (mean FOR scores show a leveling off after treatment [data not known]), the reduction in sample size (n ⫽ 127) severely reduces our power; thus, analyses were restricted to within 1 year from treatment. Despite these limitations, this study has several strengths, including the large sample size, the community-based nature of CaPSURE, and the use of standardized measures of HRQOL, FOR, and treatment-specific symptoms. On average, men treated for localized prostate cancer in our sample reported worse physical HRQOL and treatment-related symptoms and improvement in fear of recurrence from before to after treatment. However, no significant change was seen in mental HRQOL scores from baseline to follow-up. Levels of mental HRQOL at both assessment points were comparable to U.S. population-based norms for healthy adults.22 This finding is similar to recently published studies of quality of life in prostate cancer.2,4 Because our sample primarily consisted of men with early-stage prostate cancer, we might not have captured men who were more affected by ad1271
Table 2. Mean change scores in independent variables and mental and physical HRQOL Variable Fear of recurrence* Number of new symptoms† Comorbidities‡ Sexual function Sexual bother Urinary function Urinary bother Bowel function Bowel bother Mental HRQOL Physical HRQOL
Pretreatment
Post-treatment
Mean Change
P Value
36.1 (18.3) — 1.8 (1.4) 57.2 (27.6) 62.8 (37.0) 92.7 (12.5) 86.7 (22.1) 87.8 (13.8) 89.8 (20.3) 51.3 (9.5) 51.7 (8.7)
23.5 (18.6) 5.1 (3.2) — 25.1 (23.7) 33.4 (35.7) 69.6 (25.8) 68.7 (30.1) 84.4 (17.6) 83.5 (25.3) 51.9 (9.6) 48.9 (10.0)
⫺12.53 (17.5) — — ⫺32.2 (26.8) ⫺29.7 (41.1) ⫺22.9 (25.9) ⫺17.9 (32.6) ⫺3.4 (16.4) ⫺6.6 (25.0) 0.6 (9.0) ⫺2.8 (8.5)
⬍0.01 ⬍0.01 ⬍0.01 ⬍0.01 ⬍0.01 ⬍0.01 ⬍0.01 ⬍0.08 ⬍0.01
Values are mean (standard deviation). HRQOL ⫽ health-related quality of life. * Fear of recurrence scores can range from 0 to 100, with higher scores representing worse fear. † Number of new symptoms reported after treatment. ‡ Represented by total number of comorbid conditions at diagnosis.
Table 3. Regression analyses of outcome variables by predictors of interest* (N ⫽ 730) Parameter Sexual function change Sexual bother change Urinary function change Urinary bother change Bowel function change Bowel bother change Fear-of-recurrence change Comorbidities at diagnosis Post-treatment symptom onset
Mental HRQOL Estimate (SE) t 0.01 (.02) ⫺0.01 (.01) 0.02 (.02) 0.02 (.01) 0.07 (.03) ⫺0.02 (.02) ⫺0.07 (.02) 0.08 (.25) ⫺0.73 (.10)
0.87 ⫺0.95 1.10 1.36 2.59 ⫺0.98 ⫺3.74 0.31 ⫺7.17
P 0.39 0.34 0.27 0.17 ⬍0.01 0.33 ⬍0.01 0.76 ⬍0.01
Physical HRQOL Estimate (SE) t ⫺0.01 (.02) ⫺0.01 (.01) 0.02 (.02) 0.03 (.01) 0.03 (.03) 0.03 (.02) ⫺0.03 (.02) ⫺0.17 (.27) ⫺0.46 (.10)
⫺0.76 ⫺0.54 1.23 2.50 1.02 1.54 ⫺1.86 ⫺0.63 ⫺4.49
P 0.45 0.59 0.22 0.01 0.31 0.12 0.06 0.53 ⬍0.01
HRQOL ⫽ health-related quality of life; SE ⫽ standard error. * Adjusted for age at diagnosis, education, race, income, relationship status, insurance, clinical risk group at diagnosis, and body mass index at diagnosis.
vanced disease. This problem is endemic in many studies that examine quality of life issues in survivors of prostate cancer.2,5,16 Another explanation could be that many men treated for localized prostate cancer simply move on from their experience and spend little time thinking about cancer.16 Findings from this study suggest that treatment-specific symptoms, FOR, and the number of new symptoms are significantly associated with physical and mental HRQOL. However, the treatment-related and general post-treatment symptoms explained more of the variance in physical and mental health compared with FOR. Treatment for localized prostate cancer involves modalities that often have significant physical consequences for men. It is, conceivably, a difficult task for men to adapt to urinary, bowel, and sexual dysfunction. As a result, their HRQOL is likely more negatively affected to a higher degree by these post-treatment physical symptoms. As for the smaller effect of FOR on physical and mental health, perhaps men with localized prostate cancer are better able to assimilate and adapt to fears of recurrence compared with the physical symptoms. Alternatively, some studies suggest that FORs are maladaptive to one’s HRQOL,9,26 whereas others suggest that FOR could be adaptive to one’s HRQOL,27,28 Perhaps our findings are reflective of a combination of these two opposing trajec1272
tories. Future research examining the potential adaptive and maladaptive role of FOR on HRQOL may be fruitful. Although fears about disease recurrence seem to decline after treatment, as seen in other research,2 even at lower post-treatment levels, FOR remains associated with a decrease in HRQOL. Understanding how these fears influence physical and mental health is an important component of providing care to this growing population. Management of men’s fears of recurrence requires educational and psychotherapeutic approaches that address emotional and cognitive responses to prostate cancer.29 Allowing men with prostate cancer to discuss their fears may help reduce threats to their quality of life.29 Physicians and nurses are in a position to provide appropriate counsel about recurrence rates, if appropriate, and how to interpret them, which can also help reduce anxiety producing fears. Fear of recurrence is prevalent in survivors of localized prostate cancer, and despite the decrease in scores from before to after treatment, FOR significantly predicts worse mental HRQOL. This association exists above and beyond the contribution of treatment-related and more general physical symptoms. Because this is the first study, to our knowledge, to examine the concurrent contributions of FOR and the more commonly examined treatment-related symptoms to the HRQOL of men treated UROLOGY 72 (6), 2008
for localized prostate cancer, replication is encouraged. Future studies should focus on men with more advanced disease because they may report higher fears of recurrence and perhaps worse mental and physical HRQOL. Implications for clinicians include appropriate counsel and referral to mental health professionals, particularly for men who seem to be struggling with recurrence concerns, as managing HRQOL is becoming an important part of optimal care to the growing number of prostate cancer survivors. Acknowledgment. To Sonora Hudson for editorial services. References 1. American Cancer Society: Cancer Facts and Figures. Atlanta, Georgia, American Cancer Society, 2006. 2. Mehta SS, Lubeck DP, Pasta DJ, et al: Fear of recurrence in patients undergoing definitive treatment for prostate cancer: results from CaPSURE. J Urol 170: 1931-1933, 2003. 3. Baker F, Denniston M, Smith T, et al: Adult cancer survivors: how are they faring? Cancer 104: 2565-2576, 2005. 4. Hart SL, Latini DM, Cowan JE, et al: Fear of recurrence, treatment satisfaction, and quality of life after radical prostatectomy for prostate cancer. Support Care Cancer 16: 161-169, 2008. 5. Deimling G, Bowman K, Sterns S, et al: Cancer-related health worries and psychological distress among older adult, long-term cancer survivors. Psychooncology 15: 306-320, 2006. 6. Germino BB, Mishel MH, Belyea M, et al: Uncertainty in prostate cancer: ethnic and family patterns. Cancer Pract 6: 107-113, 1998. 7. Ullrich P, Carson M, Lutgendorf S, et al: Cancer fear and mood disturbance after radical prostatectomy: consequences of biochemical evidence of recurrence. J Urol 169: 1449-1452, 2003. 8. Stanton AL, Danoff-Burg S, and Huggins ME: The first year after breast cancer diagnosis: hope and coping strategies as predictors of adjustment. Psychooncology 11: 93-102, 2002. 9. Saleh US, and Brockopp DY: Quality of life one year following bone marrow transplantation: psychometric evaluation of the quality of life in bone marrow transplant survivors tool. Oncol Nurs Forum 28: 1457-1464, 2001. 10. Balmer L, and Greco K: Prostate cancer recurrence fear: the prostate-specific antigen bounce. Clin J Oncol Nurs 8: 361-366, 2004. 11. Eton D, Lepore S, and Helgeson V: Early quality of life in patients with localized prostate carcinoma. Cancer 92: 1451-1459, 2001. 12. Hu J, Elkin E, Pasta D, et al: Predicting quality of life after radical prostatectomy: results from CaPSURE. J Urol 171: 703-708, 2004. 13. Penson D, Litwin M, and Aronson N: Health related quality of life in men with prostate cancer. J Urol 169: 1653-1661, 2003. 14. Litwin MS, Sadetsky N, Pasta DJ, et al: Bowel function and bother after treatment for early stage prostate cancer: a longitudinal quality of life analysis from CaPSURE. J Urol 172: 515-519, 2004.
UROLOGY 72 (6), 2008
15. Hoffman R, Gilliland F, Penson D, et al: Cross-sectional and longitudinal comparisons of health-related quality of life between patients with prostate carcinoma and matched controls. Cancer 101: 2011-2019, 2004. 16. Blank T, and Bellizzi K: After prostate cancer: predictors of wellbeing among long-term prostate cancer survivors. Cancer 106: 2128-2135, 2006. 17. Latini D, Miaskowski C, Cowan J, et al: Symptom patterns and quality of life reported by men with prostate cancer receiving androgen deprivation monotherapy: data from CaPSURE. J Urol 173: 52-61, 2005. 18. Bacon C, Giovannucci E, Testa M, et al: The association of treatment-related symptoms with quality-of-life outcomes for localized prostate carcinoma patients. Cancer 94: 862-871, 2002. 19. Litwin M, Lubeck D, Spitalny G, et al: Mental health in men treated for early stage prostate carcinoma. Cancer 95: 54-60, 2002. 20. Lubeck D, Litwin M, Henning J, et al: The CaPSURE database: a methodology for clinical practice and research in prostate cancer. CaPSURE Research Panel. Cancer of the Prostate Strategic Urologic Research Endeavor. Urology 48: 773-777, 1996. 21. Ware J, and Sherbourne C: The MOS 36-item short form health survey (SF-36). I. Conceptual framework and item selection. Med Care 36: 473-483, 1992. 22. Ware J, Kosinski M, and Dewey J: How to Score Version 2 of the SF-36 Health Survey. Lincoln, Rhode Island, QualityMetric Incorporated, 2000. 23. Litwin M, Hays R, Fink A, et al: The UCLA Prostate Cancer Index: development, reliability, and validity of a health-related quality of life measure. Med Care 30: 1002-1012, 1998. 24. Greenberg D, Kornblith A, and Herndon J: Quality of life of adult leukemia survivors treated on clinical trials of cancer and leukemia group B during the period of 1971–1988: predictors for later psychologic distress. Cancer 80: 1936-1944, 1997. 25. American Cancer Society: Detailed Guide: Prostate Cancer: What Are the Key Statistics About Prostate Cancer? Atlanta, Georgia, American Cancer Society, 2006. 26. Kuehn T, Klauss W, Darsow M, et al: Long-term morbidity following axillary dissection in breast cancer patients— clinical assessment, significance for life quality and the impact of demographic, oncologic and therapeutic factors. Breast Cancer Res Treat 64: 275-286, 2000. 27. Eysenck M: Anxiety: The Cognitive Perspective. Hove, United Kingdom, Lawrence Erlbaum, 1992. 28. Brennan J: Adjustment to cancer— coping or personal transition. Psychooncology 10: 1-18, 2001. 29. Lee-Jones C, Humphris G, Dixon R, et al: Fear of cancer recurrence—a literature review and proposed cognitive formulation to explain exacerbation of recurrence fears. Psychooncology 6: 95105, 1997. 30. D’Amico AV, Whittington R, Malkowicz SB, et al: Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer. JAMA 280: 969-974, 1998.
1273
METHODS
RESULTS
CONCLUSION
To examine the contributions of fear of recurrence and the more commonly examined treatment-related symptoms to the health-related quality of life (HRQOL) of men treated for localized prostate cancer. A total of 730 men with localized disease were identified from the Cancer of the Prostate Strategic Urologic Research Endeavor, a national, prospective study of men with prostate cancer. Pre- to post-treatment changes in fear of recurrence, treatment-specific symptoms and burden, comorbidities at diagnosis, number of new symptoms, and post-treatment HRQOL data were analyzed. Linear regression, adjusted for clinical and demographic characteristics, showed that improved fear of recurrence (P ⬍0.01), higher number of post-treatment symptoms (P ⬍0.01), and improved bowel function (P ⬍0.01) significantly predicted better mental health scores. For physical health, improved urinary bother (P ⬍0.01) and lower number of post-treatment symptoms (P ⬍0.01) were associated with better physical health. Understanding men’s fears about cancer recurrence and how these fears influence physical and mental health are important components of providing care to this growing population. UROLOGY 72: 1269 –1273, 2008. © 2008 Elsevier Inc.
A
dvances in early detection and treatment modalities for prostate cancer have resulted in an increase in the 5-year relative survival rate from 67% to 99% over the past 20 years.1 Despite the improvement in survival, many survivors are at risk for posttreatment psychosocial and physical sequelae. One of the major psychosocial concerns that prostate cancer survivors report is fear of cancer recurrence (FOR).2–7 Although FOR may vary in intensity as time progresses, prior studies have found FOR to be an important issue in both newly treated prostate cancer survivors as well as in longer-term prostate cancer survivors.2,5,7 Studies have shown fear of recurrence to be linked to increased distress and poorer psychological adaptation in survivors of breast cancer8 and in bone-marrow transplant survivors.9 However, few studies exist regarding the impact of FOR on CaPSURE is sponsored by TAP Pharmaceutical Products, Lake Forest, Illinois, and is managed by the Urology Outcomes Research Group at the University of California-San Francisco. Funding was provided by a CaPSURE Scholars Grant from the University of California, San Francisco. From the Office of Cancer Survivorship, Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda Maryland; Scott Department of Urology and Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas; Department of Urology, University of California-San Francisco, San Francisco, California; and TAP Pharmaceutical Products, Lake Forest, Illinois Reprint requests: Keith Bellizzi, Office of Cancer Survivorship, National Cancer Institute, 6116 Executive Blvd., Suite 404, MSC 8336, Bethesda, MD 20892. E-mail: [email protected] Submitted: August 24, 2007, accepted (with revisions): December 17, 2007
© 2008 Elsevier Inc. All Rights Reserved
prostate cancer survivors’ health-related quality of life (HRQOL).4,6 Moreover, studies identified in the literature fail to account for important confounders, specifically treatment-specific symptoms. Because of the long natural history of most prostate cancer and the often anxiety-producing subtle fluctuations in prostate-specific antigen (PSA) surveillance,10 it is important to understand the association between fear of recurrence and men’s HRQOL to help prostate cancer survivors manage this persistent issue. The literature has characterized treatment-specific symptoms associated with treatment for prostate cancer.11–15 In general, these studies have demonstrated an array of treatment-related effects, including urinary and bowel incontinence and sexual dysfunction. Other studies have examined more general post-treatment symptoms, including fatigue, well-being, cognitive changes, weight gain, arthritis, muscle pain, and insomnia.16,17 Although studies have examined the association between treatment-related effects and HRQOL,18,19 there is no information about the comparative influence of FOR versus treatment-specific and more general post-treatment symptoms on prostate cancer survivors’ HRQOL. The medical management of treatment-related symptoms (urinary and bowel incontinence and sexual dysfunction) is different from providing supportive psychological care for the management of fears of recurrence. 0090-4295/08/$34.00 doi:10.1016/j.urology.2007.12.084
1269
This study examined the contributions of fear of recurrence and the more commonly examined treatmentrelated symptoms to the HRQOL of men treated for localized prostate cancer. Its primary aim was to examine the associations between pre- to post-treatment changes in fear of recurrence and treatment-specific symptoms, number of new post-treatment general symptoms, and mental and physical HRQOL. We hypothesized, on the basis of related empirical work, that (1) men with an improvement in FOR and treatment-specific symptoms and lower post-treatment general symptoms will have better mental and physical HRQOL; and (2) fear of recurrence, treatment-specific symptoms, and number of new post-treatment general symptoms will contribute differentially to the variance explained in mental and physical HRQOL.
MATERIAL AND METHODS Source of Data Designed to measure disease, treatment, and HRQOL outcomes, CaPSURE (Cancer of the Prostate Strategic Urologic Research Endeavor) is a prospective, observational registry of more than 12,000 men with biopsy-proven prostate cancer. Patients are recruited from more than 30 community- and academic-based urology practices across the United States and followed over time until death or withdrawal from the study. Participating urologists report complete clinical data and follow-up information on diagnostic tests and treatments. Data collection relies on validated, self-report instruments that patients complete by mail questionnaire every 6 months that include both general and treatment-specific HRQOL data.20
Participants Data were analyzed from CaPSURE patients diagnosed between 1999 and 2002 (n ⫽ 5071) with localized disease (n ⫽ 4597) who underwent either radical prostatectomy monotherapy (RP), brachytherapy monotherapy (BT), or external-beam radiation monotherapy (EBRT) (n ⫽ 2480) as primary treatment. Of those, 730 cases had HRQOL and FOR data (the Fear of Recurrence scale was only administered between 1999 and 2002) for the 9 months before treatment and within 1 year after treatment (mean [standard deviation] ⫽ 135 [69.7] days); this group represents the final sample.
Measures Health-related quality of life was measured with the wellvalidated Medical Outcomes Survey Short-Form-36 (SF-36).21 Construction of the physical component summary (PCS) and mental component summary (MCS) scores was based on U.S. population norms, so that scores above or below 50 are above or below the average in the general adult population.22 The 20item University of California-Los Angeles Prostate Cancer Index (PCI) 23 was used to measure treatment-specific function and bother (bowel, urinary, sexual). It has demonstrated good psychometric properties in men treated for prostate cancer.23 Higher scores represent better function for both the SF-36 and the PCI. We used Kornblith’s 5-item Fear of Recurrence Scale.24 Questions include, “I am afraid of my cancer getting worse,” and “I will probably have a relapse within the next 5 years.” Items 1270
are rated on a 5-point Likert scale, with response choices ranging from “not at all” to “very much.” For this analysis, FOR scores were rescaled to 0 to 100, with higher scores representing more fear. The reliability and validity of this scale have been previously established.24 Using checklists created for CaPSURE, patients and/or their physicians reported the number of comorbid conditions at diagnosis (ie, arthritis, blood disease, diabetes, hypertension, heart disease, lung disease, kidney problem, other cancer, other urinary condition, stomach problem, and stroke) and number of new general physical symptoms (eg, weight change, fatigue, abdominal, bowel, chest, lung, muscle, joint, bone, nervous system, cognitive, hormonal, skin, urinary, and genitourinary).
Analytic Methods Mean change in fear of recurrence and PCI scores from before to after treatment were computed for regression models. We used linear regression to examine the association between changes in FOR and treatment-specific symptoms and number of new symptoms on post-treatment mental and physical HRQOL. Model predictors were changes in PCI, change in FOR, number of new post-treatment general symptoms, and pre-treatment MCS and PCS scores, as well as sample characteristics and clinical risk category. Independent variables were entered in blocks, with clinical predictors in block one, demographic predictors in block two, treatment-specific symptoms in block three, FOR in block four, and comorbidities at diagnosis and general post-treatment symptoms in block five. Bonferroni correction was used to adjust for multiple-comparison tests of significance.
RESULTS Characteristics of Sample Chi-square tests revealed no significant differences in education, income, health insurance, PSA level, or Gleason score between the 730 men in the final sample and the 1750 patients not in the sample. However, those who were in the final sample reported more new post-treatment symptoms than those who were not in the sample (mean ⫽ 5.1 [3.2] and 4.2 [4.7], respectively; P ⬍0.01). Demographic and clinical characteristics of the sample are summarized in Table 1. Table 2 shows pre- to posttreatment mean change scores in treatment-specific symptoms, number of new symptoms, FOR, and MCS and PCS. At baseline, the average FOR score was 36.1 (18.3), with a significant improvement at the 12-month post-treatment follow-up: 23.5 (18.6). Treatment-related symptom scores (eg, sexual, urinary, bowel function) were significantly worse from baseline to 12-month posttreatment follow-up, with mean change scores ranging from ⫺3.4 (16.4) for bowel function to ⫺32.2 (26.8) for sexual function. With the exception of a nominal pre- to post-treatment improvement in mental health, men treated (RP, BT, EBRT) for localized prostate cancer reported worse physical HRQOL and an average of 5.1 (3.2) new symptoms after treatment. UROLOGY 72 (6), 2008
Table 1. Demographic and clinical characteristics (N ⫽ 730) Characteristic Age (yr), mean ⫾ standard deviation Ethnicity (missing ⫽ 1) White Other Education (missing ⫽ 4) ⬍High school High school graduate Some college College graduate Primary treatment (missing ⫽ 0) RP monotherapy EBRT monotherapy BT monotherapy PSA (ng/mL) (missing ⫽ 17) 0–4.0 4.1–10.0 10.1–20.0 ⬎20 Risk category* (missing ⫽ 18) Low Medium High Comorbidities (missing ⫽ 6) None 1 to 2 3⫹ BMI category (kg/m2) (missing ⫽ 9) Normal (⬍25.0) Overweight (25.0–29.9) Obese (30.0)
n (%) 63.2 ⫾ 7.72 669 (92.0) 60 (8.0) 77 (11.0) 181 (25.0) 139 (19.0) 329 (45.0) 562 (77.0) 33 (5.0) 135 (18.0) 122 (17.0) 501 (70.0) 78 (11.0) 12 (2.0) 381 (54.0) 256 (36.0) 75 (11.0) 129 (18.0) 399 (55.0) 196 (27.0) 171 (24.0) 403 (56.0) 147 (20.0)
RP ⫽ radical prostatectomy monotherapy; EBRT ⫽ external-beam radiation monotherapy; BT ⫽ brachytherapy monotherapy; PSA ⫽ prostate-specific antigen; BMI ⫽ body mass index. * Clinical risk groups defined based on D’Amico et al., JAMA 1998.30
Psychosocial and Physical Correlates of Mental and Physical Health The overall regression models for mental and physical HRQOL were significant: R2 ⫽ 0.439, F(24, 552) ⫽ 18.00, P ⬍0.01, and R2 ⫽ 0.445, F(24, 552) ⫽ 18.46, P ⬍0.01, respectively. After adjusting for clinical and demographic characteristics, improved FOR (P ⬍0.01) and improved bowel function (P ⬍0.01) significantly predicted better mental health scores, whereas higher number of posttreatment symptoms (P ⬍0.01) was correlated with worse mental health (Table 3). For physical health, improved urinary bother (P ⬍0.01) and fewer number of post-treatment general symptoms (P ⬍0.01) were associated with better physical health. As for FOR, there seems to be a marginally significant trend, such that improved FOR was related to better physical health (P ⫽ 0.06). As for the differential impact of fear of recurrence versus treatment-related symptoms on physical and mental HRQOL, treatment-specific symptoms (R2 ⫽ 0.101 and 0.044, respectively) and number of new symptoms (R2 ⫽ 0.122 and 0.145, respectively) explained more of the variance in PCS and MCS than FOR (R2 ⫽ 0.010 and 0.015, respectively). UROLOGY 72 (6), 2008
COMMENT This study used one of the largest observational studies of prostate cancer survivors to examine the association between fear of recurrence and mental and physical HRQOL of prostate cancer survivors. We hypothesized that (1) men with an improvement in fear of recurrence and treatment-specific symptoms and fewer post-treatment general symptoms would report better mental and physical HRQOL; and (2) fear of recurrence, treatmentspecific symptoms, and post-treatment general symptoms would contribute differentially to the explanatory power of mental and physical HRQOL. Our findings support both hypotheses in that they show that better mental and physical health were associated with an improvement in fear of recurrence (only significantly associated with mental health), improvement in treatment-specific symptoms, and fewer symptoms following treatment. Treatment-specific symptoms and new symptoms after treatment explained more variance in physical and mental HRQOL than fear of recurrence. Some limitations of the study include our inability to generalize these findings to men not treated with RP, BT, or EBRT (eg, luteinizing hormone-releasing hormone agonist, anti-androgen, cryosurgery, watchful waiting) and those with more advanced disease. However, most men with localized prostate cancer select one of those three treatment alternatives. Furthermore, men diagnosed with advanced-stage prostate cancer represent a relatively small percentage of the population of prostate cancer survivors (⬍10%).25 Men in CaPSURE may not be representative of the broader population of men with localized prostate cancer because participants are more likely to be white and of higher socioeconomic status than the typical man with localized prostate cancer in the United States. Last, HRQOL and FOR data were analyzed only up to 1 year after treatment. Although FOR data were available up to 3 years after treatment (mean FOR scores show a leveling off after treatment [data not known]), the reduction in sample size (n ⫽ 127) severely reduces our power; thus, analyses were restricted to within 1 year from treatment. Despite these limitations, this study has several strengths, including the large sample size, the community-based nature of CaPSURE, and the use of standardized measures of HRQOL, FOR, and treatment-specific symptoms. On average, men treated for localized prostate cancer in our sample reported worse physical HRQOL and treatment-related symptoms and improvement in fear of recurrence from before to after treatment. However, no significant change was seen in mental HRQOL scores from baseline to follow-up. Levels of mental HRQOL at both assessment points were comparable to U.S. population-based norms for healthy adults.22 This finding is similar to recently published studies of quality of life in prostate cancer.2,4 Because our sample primarily consisted of men with early-stage prostate cancer, we might not have captured men who were more affected by ad1271
Table 2. Mean change scores in independent variables and mental and physical HRQOL Variable Fear of recurrence* Number of new symptoms† Comorbidities‡ Sexual function Sexual bother Urinary function Urinary bother Bowel function Bowel bother Mental HRQOL Physical HRQOL
Pretreatment
Post-treatment
Mean Change
P Value
36.1 (18.3) — 1.8 (1.4) 57.2 (27.6) 62.8 (37.0) 92.7 (12.5) 86.7 (22.1) 87.8 (13.8) 89.8 (20.3) 51.3 (9.5) 51.7 (8.7)
23.5 (18.6) 5.1 (3.2) — 25.1 (23.7) 33.4 (35.7) 69.6 (25.8) 68.7 (30.1) 84.4 (17.6) 83.5 (25.3) 51.9 (9.6) 48.9 (10.0)
⫺12.53 (17.5) — — ⫺32.2 (26.8) ⫺29.7 (41.1) ⫺22.9 (25.9) ⫺17.9 (32.6) ⫺3.4 (16.4) ⫺6.6 (25.0) 0.6 (9.0) ⫺2.8 (8.5)
⬍0.01 ⬍0.01 ⬍0.01 ⬍0.01 ⬍0.01 ⬍0.01 ⬍0.01 ⬍0.08 ⬍0.01
Values are mean (standard deviation). HRQOL ⫽ health-related quality of life. * Fear of recurrence scores can range from 0 to 100, with higher scores representing worse fear. † Number of new symptoms reported after treatment. ‡ Represented by total number of comorbid conditions at diagnosis.
Table 3. Regression analyses of outcome variables by predictors of interest* (N ⫽ 730) Parameter Sexual function change Sexual bother change Urinary function change Urinary bother change Bowel function change Bowel bother change Fear-of-recurrence change Comorbidities at diagnosis Post-treatment symptom onset
Mental HRQOL Estimate (SE) t 0.01 (.02) ⫺0.01 (.01) 0.02 (.02) 0.02 (.01) 0.07 (.03) ⫺0.02 (.02) ⫺0.07 (.02) 0.08 (.25) ⫺0.73 (.10)
0.87 ⫺0.95 1.10 1.36 2.59 ⫺0.98 ⫺3.74 0.31 ⫺7.17
P 0.39 0.34 0.27 0.17 ⬍0.01 0.33 ⬍0.01 0.76 ⬍0.01
Physical HRQOL Estimate (SE) t ⫺0.01 (.02) ⫺0.01 (.01) 0.02 (.02) 0.03 (.01) 0.03 (.03) 0.03 (.02) ⫺0.03 (.02) ⫺0.17 (.27) ⫺0.46 (.10)
⫺0.76 ⫺0.54 1.23 2.50 1.02 1.54 ⫺1.86 ⫺0.63 ⫺4.49
P 0.45 0.59 0.22 0.01 0.31 0.12 0.06 0.53 ⬍0.01
HRQOL ⫽ health-related quality of life; SE ⫽ standard error. * Adjusted for age at diagnosis, education, race, income, relationship status, insurance, clinical risk group at diagnosis, and body mass index at diagnosis.
vanced disease. This problem is endemic in many studies that examine quality of life issues in survivors of prostate cancer.2,5,16 Another explanation could be that many men treated for localized prostate cancer simply move on from their experience and spend little time thinking about cancer.16 Findings from this study suggest that treatment-specific symptoms, FOR, and the number of new symptoms are significantly associated with physical and mental HRQOL. However, the treatment-related and general post-treatment symptoms explained more of the variance in physical and mental health compared with FOR. Treatment for localized prostate cancer involves modalities that often have significant physical consequences for men. It is, conceivably, a difficult task for men to adapt to urinary, bowel, and sexual dysfunction. As a result, their HRQOL is likely more negatively affected to a higher degree by these post-treatment physical symptoms. As for the smaller effect of FOR on physical and mental health, perhaps men with localized prostate cancer are better able to assimilate and adapt to fears of recurrence compared with the physical symptoms. Alternatively, some studies suggest that FORs are maladaptive to one’s HRQOL,9,26 whereas others suggest that FOR could be adaptive to one’s HRQOL,27,28 Perhaps our findings are reflective of a combination of these two opposing trajec1272
tories. Future research examining the potential adaptive and maladaptive role of FOR on HRQOL may be fruitful. Although fears about disease recurrence seem to decline after treatment, as seen in other research,2 even at lower post-treatment levels, FOR remains associated with a decrease in HRQOL. Understanding how these fears influence physical and mental health is an important component of providing care to this growing population. Management of men’s fears of recurrence requires educational and psychotherapeutic approaches that address emotional and cognitive responses to prostate cancer.29 Allowing men with prostate cancer to discuss their fears may help reduce threats to their quality of life.29 Physicians and nurses are in a position to provide appropriate counsel about recurrence rates, if appropriate, and how to interpret them, which can also help reduce anxiety producing fears. Fear of recurrence is prevalent in survivors of localized prostate cancer, and despite the decrease in scores from before to after treatment, FOR significantly predicts worse mental HRQOL. This association exists above and beyond the contribution of treatment-related and more general physical symptoms. Because this is the first study, to our knowledge, to examine the concurrent contributions of FOR and the more commonly examined treatment-related symptoms to the HRQOL of men treated UROLOGY 72 (6), 2008
for localized prostate cancer, replication is encouraged. Future studies should focus on men with more advanced disease because they may report higher fears of recurrence and perhaps worse mental and physical HRQOL. Implications for clinicians include appropriate counsel and referral to mental health professionals, particularly for men who seem to be struggling with recurrence concerns, as managing HRQOL is becoming an important part of optimal care to the growing number of prostate cancer survivors. Acknowledgment. To Sonora Hudson for editorial services. References 1. American Cancer Society: Cancer Facts and Figures. Atlanta, Georgia, American Cancer Society, 2006. 2. Mehta SS, Lubeck DP, Pasta DJ, et al: Fear of recurrence in patients undergoing definitive treatment for prostate cancer: results from CaPSURE. J Urol 170: 1931-1933, 2003. 3. Baker F, Denniston M, Smith T, et al: Adult cancer survivors: how are they faring? Cancer 104: 2565-2576, 2005. 4. Hart SL, Latini DM, Cowan JE, et al: Fear of recurrence, treatment satisfaction, and quality of life after radical prostatectomy for prostate cancer. Support Care Cancer 16: 161-169, 2008. 5. Deimling G, Bowman K, Sterns S, et al: Cancer-related health worries and psychological distress among older adult, long-term cancer survivors. Psychooncology 15: 306-320, 2006. 6. Germino BB, Mishel MH, Belyea M, et al: Uncertainty in prostate cancer: ethnic and family patterns. Cancer Pract 6: 107-113, 1998. 7. Ullrich P, Carson M, Lutgendorf S, et al: Cancer fear and mood disturbance after radical prostatectomy: consequences of biochemical evidence of recurrence. J Urol 169: 1449-1452, 2003. 8. Stanton AL, Danoff-Burg S, and Huggins ME: The first year after breast cancer diagnosis: hope and coping strategies as predictors of adjustment. Psychooncology 11: 93-102, 2002. 9. Saleh US, and Brockopp DY: Quality of life one year following bone marrow transplantation: psychometric evaluation of the quality of life in bone marrow transplant survivors tool. Oncol Nurs Forum 28: 1457-1464, 2001. 10. Balmer L, and Greco K: Prostate cancer recurrence fear: the prostate-specific antigen bounce. Clin J Oncol Nurs 8: 361-366, 2004. 11. Eton D, Lepore S, and Helgeson V: Early quality of life in patients with localized prostate carcinoma. Cancer 92: 1451-1459, 2001. 12. Hu J, Elkin E, Pasta D, et al: Predicting quality of life after radical prostatectomy: results from CaPSURE. J Urol 171: 703-708, 2004. 13. Penson D, Litwin M, and Aronson N: Health related quality of life in men with prostate cancer. J Urol 169: 1653-1661, 2003. 14. Litwin MS, Sadetsky N, Pasta DJ, et al: Bowel function and bother after treatment for early stage prostate cancer: a longitudinal quality of life analysis from CaPSURE. J Urol 172: 515-519, 2004.
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