- Email: [email protected]
Knowledge and Attitudes of Primary Care Physicians Regarding Prostate Cancer Screening
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Knowledge and Attitudes of Primary Care Physicians Regarding Prostate Cancer Screening John Pendleton, MS; Robert Whit Curry, MD; Ali Kaserian, MD; Myron Chang, PhD; Satoshi Anai, MD; Kogenta Nakamura, MD; Phillip Abdoush, MD; and Charles J. Rosser, MD
Introduction: We report the results of a questionnaire administered to primary care physicians to determine their baseline knowledge of prostate cancer and their attitudes on prostate cancer screening. Materials and Methods: A 27-item questionnaire designed to assess prostate cancer knowledge and screening attitudes was administered to primary care physicians in Duval and Alachua counties. Completed surveys were returned, entered into the master database and analyzed. Results: Mean initial knowledge score was 66%. In multivariate regression analysis, there were no covariates independently associated with knowledge scores. In multivariate regression analysis, there were no covariates independently associated with attitude scores. Lastly, knowledge scores were not associated with attitude scores (p=0.85). Conclusions: Our findings imply that physicians’ knowledge is not an important predictor of their screening behavior. Thus, this study raises the possibility that factors other than educational programs must be assessed as a means to increase screening in specific communities. Key words: prostate cancer n screening n prostatespecific antigen n knowledge, attitudes and beliefs n primary care physician © 2008. From the Division of Urology, The University of Florida, Jacksonville, FL (Pendleton, Anai, Nakamura, Abdoush, Rosser); Departments of Community Health and Family Medicine (Curry), Urology (Kaserian), and Epidemiology and Health Policy Research (Chang), Gainesville, FL. Send correspondence and reprint requests for J Natl Med Assoc. 2008;100:666–670 to: Dr. Charles J. Rosser, Department of Urology, University of Florida College of Medicine, Suite N215, PO Box 100247, Gainesville, FL 32610; phone: (352) 273-7610; fax: (352) 392-8846; e-mail: [email protected]
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arious communities throughout the United States still report a high rate of advanced prostate cancer at initial diagnosis and a high mortality rate from prostate cancer.1,2 Specifically, we reported in a study of inner-city men being screened for prostate cancer that men of African decent presented with higher median serum prostate-specific antigen (PSA), had higher median Gleason scores and were four times 666 JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION
more likely to present with advanced disease than their white counterparts.3 This disparity has been attributed to biologically more aggressive tumors,2 lack of healthcare access,3 cultural factors,4 less-aggressive therapy5 and diagnosis at a higher stage.4 Diagnosis at a higher stage may result from lack of, or ineffective screening. Physician recommendation is perhaps the most powerful factor in promoting screening compliance.5-7 Reasons why physicians do not recommend prostate cancer screening may be due to several factors, ranging from lack of prospective randomized trials demonstrating the benefit of screening, to misconceived notions on prostate cancer screening and treatment, to outdated knowledge of prostate cancer screening and treatment. Adding further confusion is the near-polar stance various agencies have in regards to prostate cancer screening. Both the American Cancer Society and the American Urologic Association recommend considering screening for prostate cancer under appropriate conditions for men aged >50 years.8 On the other hand, the American College of Physicians, American College of Preventive Medicine, Canadian Task Force on Preventive Health Care and U.S. Preventive Services Task Force all have concluded that the evidence is insufficient to recommend for or against routine screening.9 Yet, all of the above-named organizations agree that patients should be counseled about the risks and benefits of screening and the decision to screen should be the individual’s. Previously, we assessed prostate cancer knowledge and screening attitudes in 100 men presenting to our outpatient urology clinic for complaints unrelated to prostate cancer. After obtaining a baseline knowledge score, men were given a brief educational intervention followed by assessment of knowledge and screening attitudes after the intervention. The intervention proved useful in increasing one’s knowledge. Overall screening attitudes did not change. On multivariate regression analysis, only having had a serum PSA within the past 12 months was the only variable associated with higher knowledge level. With regards to screening attitudes, being of Caucasian race, having a higher educational level and having had a serum PSA within the past 12 months were indepenVOL. 100, NO. 6, JUNE 2008
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dently associated with aggressive screening behavior. Lastly, participants who scored poorly (<40%) on the knowledge survey generally had less-favorable attitudes toward prostate cancer screening. We concluded that educational programs may improve men’s overall prostate cancer knowledge and increase screening in communities where prostate cancer continues to be a major healthcare issue.10 However, other factors must be taken into account when addressing prostate cancer screening rates in the inner city. A factor to consider may be the primary care physician’s knowledge and attitude toward prostate cancer screening. Herein, we report the results of a questionnaire administered to primary care physicians to determine their baseline knowledge of prostate cancer and their attitudes on prostate cancer screening. We hypothesize that physicians having less contemporary knowledge on prostate cancer detection and treatment would report lower levels of routine prostate cancer screening in their practice.
Materials and Methods
We surveyed 100 men in Duval County as to their prostate cancer knowledge and prostate cancer screening attitudes. We sought to assess prostate cancer knowledge and screening attitudes in primary care physicians serving the inner city. Due to the anticipated low response rates, primary care physicians in neighboring counties were contacted. Contact information, including e-mail addresses, from 264 random primary care physicians in Duval and Alachua counties in northeast Florida was identified through local medical societies. All physicians were e-mailed an invitation letter describing the nature of the study. The letter had a direct link to the online survey hosted by www.zoomerang.com. Only 20 (8%) physicians responded to the online invitation. Physicians who did not log onto the website were sent another e-mail invitation. Physicians still not responding to the e-mail invitation were personally visited to inquire about their interest in the study. Additional hard copies of the invitation letter and surveys were delivered during these visits. Another 85 physicians completed the survey after the personal visit. Completed surveys were returned, entered into the database and analyzed. A 27-item questionnaire (Appendix A) was administered to these primary care physicians. The questionnaire sought to determine the baseline prostate cancer knowledge as well as the attitudes and practices of primary care physicians in regards to prostate cancer screening. Prior to distribution to the primary care physicians, the questionnaire was tested among a small, diverse group of experienced physicians from family practice, internal medicine, radiation oncology and urology. The questionnaire was subsequently modified before the final version was sent to the study group. Institutional review board approval was obtained prior to contacting primary care physicians. JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION
The first nine items in the questionnaire (four were multiple choice and five were true/false) assessed knowledge regarding risk factors for developing prostate cancer, prevalence and presentation of prostate cancer, and treatment options for prostate cancer. These questions were formulated based on current, accepted literature. Blank responses were coded as wrong responses. The next nine items in the questionnaire (seven were multiple choice and two were true/false) assessed the attitudes and current screening practices for prostate canTable 1. Characteristics of 104 primary care physicians responding to prostate cancer knowledge and screening attitude survey Characteristic(s) Participants Degree MD 91 DO 7 N/A 6 Specialty Internal medicine 36 Family practice 60 General practice 8 Age <30 15 30–45 30 45–60 45 >60 14 Race White 71 Black 4 Other 29 Practice Setting Solo 14 Group/private 18 Group/university 52 Other 7 N/A 13 Office Setting Rural 14 Urban 85 N/A 5 Medicare Patients in Practice (%) <25% 18 25–50% 54 >50% 20 N/A 12 Medicaid Patients in Practice (%) <25% 49 25–50% 37 >50% 6 N/A 12 Minorities Patients in Practice (%) <10 7 11–25% 40 26–50% 24 >50% 24 N/A 9
% 87% 7% 6% 35% 58% 8% 14% 29% 43% 13% 68% 4% 28% 13% 17% 50% 7% 13% 13% 82% 5% 17% 52% 19% 12% 47% 36% 6% 12% 7% 38% 23% 23% 9%
N/A, not answered
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cer among the primary care physicians. Finally, the survey asked about personal demographic and practice characteristics.
Statistical Analysis Average score for nine knowledge questions and average score for first eight attitude questions were computed for each participating primary care physician. The association between the average score and covariates in Table 1 was assessed by univariate and multivariate regression analysis. Backward elimination method was used in multivariate regression analysis. All reported P values were two sided, and those P values <0.05 were considered to be statistically significant. All data were analyzed using SAS® version 9.1.3 software.
Results
Two-hundred-sixty-four physicians were invited to participate in the study. One-hundred-four (39%) returned the questionnaire. Table 1 depicts the demographics of the physicians who completed the questionnaire. Nine knowledge questions were asked of each physician (Table 2). Seventy-five percent correctly reported family history and being of African decent as risk factors for developing prostate cancer. More than 89% of physicians responded correctly to knowing: 1) the incidence of prostate cancer increases with age, 2) prostate cancer is the second most commonly diagnosed cancer in American men age >45 years, 3) men of African decent with prostate cancer have a higher mortality rate than whites, and 4) there are excellent treatment options for localized prostate. However, only 14% of responders knew what these treatment options for localized prostate cancer were. In addition, only 37% of the physicians knew that men <65 years with a serum PSA 2.5–4.0 ng/ ml have approximately a 30% chance of harboring significant prostate cancer on prostate biopsy. Furthermore, 39% noted that serum PSA possesses a high sensitivity and a low specificity in detecting prostate cancer, a very important fact when counseling men about the pros and cons of prostate cancer screening. Even though the majority of prostate cancers seen today are nonpalable
(i.e., T1c) and thus not symptomatic, 55% of physicians believe voiding symptoms are one of the first symptoms of prostate cancer. Together, the overall mean score of the knowledge survey was 66%. Interestingly no demographic factors in Table 1 (age, degree, race, practice type, etc.) could independently predict prostate cancer knowledge in our cohort by multivariate regression analysis. It was found in univariate regression analysis that physicians with an urban office setting had higher knowledge scores than those with a rural office setting (mean score 63 vs. 67, p=0.042), and physicians with more minority patients had higher knowledge scores than those with fewer minority patients (p=0.026). Nine questions were asked of the physicians to elicit their attitude and current prostate cancer screening behavior (Table 3). Though 93% of physicians responded men are more likely to die with prostate cancer than of prostate cancer, 66% believed prostate cancer screening was effective. This was confirmed when the question was reworded to determine if aggressive prostate cancer screening was beneficial to their patients. Sixtyfour percent of responders felt screening was beneficial. Only 53% of physicians offer screening to minorities, whereas 70% offer it to men with a family history of prostate cancer. Forty-six percent of responders stated that they recommend prostate cancer screening to >75% of their patients age >50 years. When asked how they screen for prostate cancer, 79% reported utilizing serum PSA and digital rectal examination (DRE). Thus, 21% either do not screen or do not utilize the screening methods recommended by the American Cancer Society. In the physicians who screen for prostate cancer, 88% screen on an annual basis. Interestingly enough, 46% of physicians report a lack of confidence in interpreting the DRE results of their patients. Lastly, 46% of responders stated their attitudes on prostate cancer screening were based on literature or conferences. No demographic factors in Table 1 (age, degree, race, practice type, etc.) could independently predict prostate cancer attitude in our cohort by multivariate regression analysis. In univariate regression, physicians with an internal medicine specialty had lower attitude sores than family prac-
Table 2. Primary care physicians’ response to nine-item prostate cancer knowledge survey Question Percent with 1. The risk of developing cancer increases with age. 2. Identify the risk factors in the development of prostate cancer. 3. Second most commonly diagnosed cancer in U.S. men >45 years 4. Mortality rate of men of African decent with prostate cancer is higher than the mortality rate of whites with prostate cancer. 5. Nearly a third of men <65 years with serum PSA 2.4–4.0 harbor prostate cancer. 6. Identify treatment options for localized prostate cancer. 7. Excellent treatment options are available for men with prostate cancer. 8. Voiding symptoms are one of the first symptoms of prostate cancer. 9. Serum PSA has a high sensitivity but a low specificity.
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Correct Response 98% 75% 89% 93% 37% 14% 96% 55% 39%
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tice physicians (mean 71 vs. 79, p=0.014). In addition, older physicians had higher attitude scores than younger physicians (p=0.008), physicians with group/university practice setting had lower attitude scores than other practice settings (mean 74 vs. 81, p=0.032), and physicians with urban office setting had higher attitude scores than that with rural office setting (mean 78 vs. 69, p=0.041). Lastly, knowledge scores were not associated with attitude scores (p=0.85).
Discussion
With >30,000 American men succumbing to prostate cancer in 2005, it is the second most common cause of cancer-related deaths in men age >45 years.11 With this said, certain groups may benefit from early prostate cancer detection and treatment. These groups include men who are at high risk of developing prostate cancer. Risk factors clearly linked to the development of prostate cancer are men with a family history of prostate cancer and men of African decent. In a previous study by our group, we reported that inner-city African-American men were four times more likely to present with advance prostate cancer than their white counterparts.3 When these men were queried, they reported scant counseling from their primary care physician regarding prostate cancer screening. It has been previously described that physician recommendation to screen is perhaps the most powerful factor in promoting screening compliance.5-7 Previous researchers have demonstrated that physician knowledge of specific disease process greatly influenced screening behavior.12,13 We surveyed a diverse group of primary care physicians as to their contemporary knowledge and screening attitudes for prostate cancer. The mean correct score on the knowledge questions was 59%. Primary care physicians were less likely to know PSA has a poor specificity, localized prostate cancer generally does not present with any symptoms and to distinguish treatment for localized therapies compared to therapies directed towards advanced disease. Knowl-
edge of prostate cancer was higher on univariate analysis in physicians with offices in urban areas or in physicians whose practice was comprised of >50% minority patients. Interestingly enough, we then demonstrated that there was no correlation between prostate cancer knowledge in primary care physicians and their prostate cancer screening attitude/behavior. Thus, educational programs directed at primary care physicians may not increase prostate cancer screening recommendation and subsequently increase the prevalence of screening in communities at high risk of developing this disease. Previous research has demonstrated that increased prostate cancer knowledge in primary care physicians can polarize their views on prostate cancer screening utility (i.e., some knowledgeable physicians believe PSA screening is overutilized, while others believe in select patients it is a useful tool).14 We believe this may be the case in our study as well. We may benefit from conducting focus group discussions of primary care physicians to assess their concerns with prostate cancer and prostate cancer screening. Realization of their concerns may help us focus our attention on specific areas that, if improved, can result in a more favorable attitude towards prostate cancer screening. Recent research, however, has demonstrated the benefit of early prostate cancer detection and treatment. Since the advent of PSA screening in the late 1980s, prostate cancer mortality in the United States has been steadily decreasing.11,15 Furthermore, in two large European studies, survival improved in men who underwent prostate cancer screening and treatment, but not in men who did not.16,17 Together, these findings clearly suggest that prostate cancer screening programs can significantly increase the detection of treatable cancers and thus decrease mortality. In a companion study, we assessed the knowledge and screening behavior in inner-city men before and after a brief educational intervention. Mean initial knowledge score was 47% compared to 80% after the educational
Table 3. Primary care physicians’ response to nine-item attitude and prostate cancer screening practice survey Question Percent with Correct Response 1. I believe that men are more likely to die with prostate cancer than to die of prostate cancer. 93% 2. I offer prostate cancer screening to minorities. 53% 3. Percentage of your male patients >50 years of age that you screen or recommend screening 45% 4. My method of screening for prostate cancer includes both serum PSA and DRE. 79% 5. I recommend annual screening. 88% 6. Lack confidence level in determining results of DRE 46% 7. I believe prostate cancer screening is effective. 66% 8. I am certain/fairly certain that aggressive prostate cancer screening is beneficial to my patients. 64% 9. My attitude on prostate cancer screening comes from literature or scientific meetings. 46%
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intervention (p<0.0001). In multivariate regression analysis, only having had a serum PSA within the past 12 months was the only variable associated with knowledge (p=0.0062). Prior to the invention, the majority of men (76%) were in favor of early detection. Interestingly, after the brief intervention, the attitudes did not change significantly (76% vs. 84%, p=0.532). Being of Caucasian race, having a higher educational level and having had a serum PSA within the past 12 months were independently associated with aggressive screening behavior (p=0.0189, 0.0300 and 0.0225, respectively). Lastly, responders who scored poorly (<40%) on the knowledge survey generally had more favorable attitudes toward prostate cancer screening (p=0.0028). To date, this is the only study that has assessed a specific community’s primary care physician knowledge and screening patterns for prostate cancer in addition to querying the inner-city inhabitants as to their prostate cancer knowledge and screening behaviors. Unlike the lay public, physicians’ knowledge did not correlate to their screening attitude. The majority of physicians reported the utility in prostate cancer screening in previous reports;17-19 only 52% of physicians in our study report routine screening in minority men. On the other hand, there are primary care physicians who screen men with <10-year life expectancy or who are >80 years.20 This aggressive screening may not be beneficial. Our study has several limitations. First, this was a small pilot study to determine baseline prostate cancer knowledge and attitudes and patterns for prostate cancer screening in inner-city primary care physicians. This small cohort may not represent primary care physicians throughout the country. Furthermore, responders of the questionnaire may have polar views on prostate cancer screening. In addition, the current questionnaire has not been tested for validity and reliability. The main objective of the questionnaire was to report baseline knowledge and attitudes in hopes of formulating a continuing medical education series directed at primary care physicians to update their knowledge of prostate cancer. Thus, the need to test the questionnaire for validity and reliability was not needed. In conclusion, we report the results of a 27-item questionnaire administered to primary care physicians to assess their prostate cancer knowledge and attitudes and pattern for prostate cancer screening. Our findings did not demonstrate that physicians’ knowledge is an important predictor of their prostate cancer screening behavior. Thus, this study raises the possibility that factors other than educational programs must be assessed as a means to increase screening in specific communities.
References
1. Hoffman RM, Gilliland FD, Eley JW, et al. Racial and ethnic differences in advanced-stage prostate cancer: the Prostate Cancer Outcomes Study. J Natl Cancer Inst. 2001;93:388-395.
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2. Powell IJ, Dey J, Dudley A, et al. Disease-free survival difference between African Americans and whites after radical prostatectomy for local prostate cancer: a multivariable analysis. Urology. 2002; 59:907-912. 3. Anai S, Pendleton J, Wludyka P, et al. Prostate cancer screening and detection in inner-city and underserved men. J Natl Med Assoc. 2006; 98:515-519. 4. Shaw M, Elterman L, Rubenstein M, et al. Changes in radical prostatectomy and radiation therapy rates for African Americans and whites. J Natl Med Assoc. 2000;92:281-284. 5. Smith GE, DeHaven MJ, Grundig JP, et al. African-American males and prostate cancer: Assessing knowledge levels in the community. J Natl Med Assoc. 1997; 89:387-391. 6. Nivens AS, Herman J, Weinrich SP, et al. Cues to participation in prostate cancer screening: a theory for practice. Oncol Nursing Forum. 2001; 28:1449-1456. 7. Vernon SW, Laville EA, Jackson GL. Participation in breast screening programs: A review. Soc Sci Med. 1990;30:1107-1118. 8. Bahnson RR, Hanks GE, Huben RP, et al. National Comprehensive Cancer Network. NCCN Practice Guidelines for Prostate Cancer. Oncology. 2000;14:111-135. 9. Chan ECY. Informed Consent and Prostate Specific Antigen Screening: What patients ought to know. In Thompson IM, Resnick MI, Klein EA (eds): Current Clinical Urology: Prostate Cancer Screening. Totowa, NJ: Humana Press Inc.; 2000. 10. Pendleton J, Hopkins C, Anai S, et al. Prostate cancer knowledge and screening attitudes of inner-city men. Present AACR, Science of Cancer Health Disparities. Atlanta, GA: November 20–December 1, 2007. 11. Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2006. CA Cancer J Clin. 2006;56:106-130. 12. Philips GK, Reinier K, Ashikaga T, et al. Attitudes and beliefs of primary care physicians regarding prostate and colorectal cancer screening in a rural state. J Cancer Educ. 2005; 20:167-172. 13. Smith RA, Cokkinides V, Eyre HJ. American Cancer Society guidelines for the early detection of cancer, 2006. CA Cancer J Clin. 2006; 56:11-25. 14. Bell DS, Hays RD, Hoffman JR, et al. A test of knowledge about prostate cancer screening. Online pilot evaluation among Southern California Physicians. J Gen Intern Med. 2006;21:310-314. 15. Robert RO, Bergstralh EJ, Katusic SK, et al. Decline in prostate cancer mortality from 1980 to 1997, and an update on incidence trends in Olmstead County, Minnesota. J Urol. 1999;161:529-533. 16. Bartsch G, Horninger W, Klocker H, et al. Tyrol Prostate Cancer Screening Group. Prostate cancer mortality after introduction of prostate-specific antigen mass screening in the Federal State of Tyrol, Austria. Urology. 2001; 58:417-424. 17. Bill-Axelson A, Holmberg L, Ruutu M, et al. Scandinavian Prostate Cancer Group Study No. 4. Radical prostatectomy versus watchful waiting in early prostate cancer. N Engl J Med. 2005; 352:1977-1984. 18. Curran V, Solberg S, Mathews M, et al. Prostate cancer screening attitudes and continuing education needs of primary care physicians. J Cancer Educ. 2005;20:162-166. 19. Jonler M, Eddy B, Poulsen J. Prostate-specific antigen testing in general practice: a survey among 325 general practitioners in Denmark. Scand J Urol Nephrol. 2005;39:214-218. 20. Fowler FJ Jr, Bin L, Collins MM, et al. Prostate cancer screening and beliefs about treatment efficacy: a national survey of primary care physicians and urologists. Am J Med. 1998;104:526-532. n
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adequate contraception in premenopausal women should be recommended. This possible effect has not been investigated in clinical studies so the frequency of this occurrence is not known. Drug Interactions In vivo drug-drug interaction studies have suggested that pioglitazone may be a weak inducer of CYP 450 isoform 3A4 substrate. An enzyme inhibitor of CYP2C8 (such as gemfibrozil) may significantly increase the AUC of pioglitazone and an enzyme inducer of CYP2C8 (such as rifampin) may significantly decrease the AUC of pioglitazone. Therefore, if an inhibitor or inducer of CYP2C8 is started or stopped during treatment with pioglitazone, changes in diabetes treatment may be needed based on clinical response. Carcinogenesis, Mutagenesis, Impairment of Fertility A two-year carcinogenicity study was conducted in male and female rats at oral doses up to 63 mg/kg (approximately 14 times the maximum recommended human oral dose of 45 mg based on mg/m2). Drug-induced tumors were not observed in any organ except for the urinary bladder. Benign and/or malignant transitional cell neoplasms were observed in male rats at 4 mg/kg/day and above (approximately equal to the maximum recommended human oral dose based on mg/m2). A two-year carcinogenicity study was conducted in male and female mice at oral doses up to 100 mg/kg/day (approximately 11 times the maximum recommended human oral dose based on mg/m2). No drug-induced tumors were observed in any organ. During prospective evaluation of urinary cytology involving more than 1800 patients receiving ACTOS in clinical trials up to one year in duration, no new cases of bladder tumors were identified. In two 3-year studies in which pioglitazone was compared to placebo or glyburide, there were 16/3656 (0.44%) reports of bladder cancer in patients taking pioglitazone compared to 5/3679 (0.14%) in patients not taking pioglitazone. After excluding patients in whom exposure to study drug was less than one year at the time of diagnosis of bladder cancer, there were six (0.16%) cases on pioglitazone and two (0.05%) on placebo. Pioglitazone HCl was not mutagenic in a battery of genetic toxicology studies, including the Ames bacterial assay, a mammalian cell forward gene mutation assay (CHO/HPRT and AS52/XPRT), an in vitro cytogenetics assay using CHL cells, an unscheduled DNA synthesis assay, and an in vivo micronucleus assay. No adverse effects upon fertility were observed in male and female rats at oral doses up to 40 mg/kg pioglitazone HCl daily prior to and throughout mating and gestation (approximately 9 times the maximum recommended human oral dose based on mg/m2). Animal Toxicology Heart enlargement has been observed in mice (100 mg/kg), rats (4 mg/kg and above) and dogs (3 mg/kg) treated orally with pioglitazone HCl (approximately 11, 1, and 2 times the maximum recommended human oral dose for mice, rats, and dogs, respectively, based on mg/m2). In a one-year rat study, drug-related early death due to apparent heart dysfunction occurred at an oral dose of 160 mg/kg/day (approximately 35 times the maximum recommended human oral dose based on mg/m2). Heart enlargement was seen in a 13-week study in monkeys at oral doses of 8.9 mg/kg and above (approximately 4 times the maximum recommended human oral dose based on mg/m2), but not in a 52-week study at oral doses up to 32 mg/kg (approximately 13 times the maximum recommended human oral dose based on mg/m2). Pregnancy Pregnancy Category C. Pioglitazone was not teratogenic in rats at oral doses up to 80 mg/kg or in rabbits given up to 160 mg/kg during organogenesis (approximately 17 and 40 times the maximum recommended human oral dose based on mg/m2, respectively). Delayed parturition and embryotoxicity (as evidenced by increased postimplantation losses, delayed development and reduced fetal weights) were observed in rats at oral doses of 40 mg/kg/day and above (approximately 10 times the maximum recommended human oral dose based on mg/m2). No functional or behavioral toxicity was observed in offspring of rats. In rabbits, embryotoxicity was observed at an oral dose of 160 mg/kg (approximately 40 times the maximum recommended human oral dose based on mg/m2). Delayed postnatal development, attributed to decreased body weight, was observed in offspring of rats at oral doses of 10 mg/kg and above during late gestation and lactation periods (approximately 2 times the maximum recommended human oral dose based on mg/m2). There are no adequate and well-controlled studies in pregnant women. ACTOS should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Because current information strongly suggests that abnormal blood glucose levels during pregnancy are associated with a higher incidence of congenital anomalies, as well as increased neonatal morbidity and mortality, most experts recommend that insulin be used during pregnancy to maintain blood glucose levels as close to normal as possible. Nursing Mothers Pioglitazone is secreted in the milk of lactating rats. It is not known whether ACTOS is secreted in human milk. Because many drugs are excreted in human milk, ACTOS should not be administered to a breastfeeding woman. Pediatric Use Safety and effectiveness of ACTOS in pediatric patients have not been established. Elderly Use Approximately 500 patients in placebo-controlled clinical trials of ACTOS were 65 and over. No significant differences in effectiveness and safety were observed between these patients and younger patients. ADVERSE REACTIONS Over 8500 patients with type 2 diabetes have been treated with ACTOS in randomized, double-blind, controlled clinical trials. This includes 2605 high-risk patients with type 2 diabetes treated with ACTOS from the PROactive clinical trial. Over 6000 patients have been treated for 6 months or longer, and over 4500 patients for one year or longer. Over 3000 patients have received ACTOS for at least 2 years. The overall incidence and types of adverse events reported in placebo-controlled clinical trials of ACTOS monotherapy at doses of 7.5 mg, 15 mg, 30 mg, or 45 mg once daily are shown in Table 2. Table 2
Placebo-Controlled Clinical Studies of ACTOS Monotherapy: Adverse Events Reported at a Frequency s 5% of Patients Treated with ACTOS (% of Patients) Placebo ACTOS N=259 N=606 Upper Respiratory Tract Infection 8.5 13.2 Headache 6.9 9.1 Sinusitis 4.6 6.3 Myalgia 2.7 5.4 Tooth Disorder 2.3 5.3 Diabetes Mellitus Aggravated 8.1 5.1 Pharyngitis 0.8 5.1
Prospective Pioglitazone Clinical Trial In Macrovascular Events (PROactive) In PROactive, 5238 patients with type 2 diabetes and a prior history of macrovascular disease were treated with ACTOS (n=2605), force-titrated up to 45 mg daily or placebo (n=2633) in addition to standard of care. Almost all subjects (95%) were receiving cardiovascular medications (beta blockers, ACE inhibitors, ARBs, calcium channel blockers, nitrates, diuretics, aspirin, statins, fibrates). Patients had a mean age of 61.8 years, mean duration of diabetes 9.5 years, and mean HbA1c 8.1%. Average duration of follow-up was 34.5 months. The primary objective of this trial was to examine the effect of ACTOS on mortality and macrovascular morbidity in patients with type 2 diabetes mellitus who were at high risk for macrovascular events. The primary efficacy variable was the time to the first occurrence of any event in the cardiovascular composite endpoint (see Table 3 below). Although there was no statistically significant difference between ACTOS and placebo for the 3-year incidence of a first event within this composite, there was no increase in mortality or in total macrovascular events with ACTOS. Table 3 Number of First and Total Events for Each Component within the Cardiovascular Composite Endpoint Placebo N=2633 First Events Total Events (N) (N) 900 572 186 122 157 118 119 96 78 63 240 101 28 15 92 57
Cardiovascular Events Any event All-cause mortality Non-fatal MI Stroke ACS Cardiac intervention Major leg amputation Leg revascularization
ACTOS N=2605 First Events Total Events (N) (N) 514 803 110 177 105 131 76 92 42 65 101 195 9 28 71 115
Postmarketing reports of new onset or worsening diabetic macular edema with decreased visual acuity have also been received (see PRECAUTIONS, General, Macular Edema). Laboratory Abnormalities Hematologic: ACTOS may cause decreases in hemoglobin and hematocrit. The fall in hemoglobin and hematocrit with ACTOS appears to be dose related. Across all clinical studies, mean hemoglobin values declined by 2% to 4% in patients treated with ACTOS. These changes generally occurred within the first 4 to 12 weeks of therapy and remained relatively stable thereafter. These changes may be related to increased plasma volume associated with ACTOS therapy and have rarely been associated with any significant hematologic clinical effects. Serum Transaminase Levels: During all clinical studies in the U.S., 14 of 4780 (0.30%) patients treated with ACTOS had ALT values s 3 times the upper limit of normal during treatment. All patients with follow-up values had reversible elevations in ALT. In the population of patients treated with ACTOS, mean values for bilirubin, AST, ALT, alkaline phosphatase, and GGT were decreased at the final visit compared with baseline. Fewer than 0.9% of patients treated with ACTOS were withdrawn from clinical trials in the U.S. due to abnormal liver function tests. In pre-approval clinical trials, there were no cases of idiosyncratic drug reactions leading to hepatic failure (see PRECAUTIONS, General, Hepatic Effects). CPK Levels: During required laboratory testing in clinical trials, sporadic, transient elevations in creatine phosphokinase levels (CPK) were observed. An isolated elevation to greater than 10 times the upper limit of normal was noted in 9 patients (values of 2150 to 11400 IU/L). Six of these patients continued to receive ACTOS, two patients had completed receiving study medication at the time of the elevated value and one patient discontinued study medication due to the elevation. These elevations resolved without any apparent clinical sequelae. The relationship of these events to ACTOS therapy is unknown. OVERDOSAGE During controlled clinical trials, one case of overdose with ACTOS was reported. A male patient took 120 mg per day for four days, then 180 mg per day for seven days. The patient denied any clinical symptoms during this period. In the event of overdosage, appropriate supportive treatment should be initiated according to patient’s clinical signs and symptoms. Rx only Manufactured by: Takeda Pharmaceutical Company Limited Osaka, Japan Marketed by: Takeda Pharmaceuticals America, Inc. One Takeda Parkway Deerfield, IL 60015 ACTOS® is a registered trademark of Takeda Pharmaceutical Company Limited and used under license by Takeda Pharmaceuticals America, Inc. © 1999, 2007 Takeda Pharmaceuticals America, Inc. 05-1141
For most clinical adverse events the incidence was similar for groups treated with ACTOS monotherapy and those treated in combination with sulfonylureas, metformin, and insulin. There was an increase in the occurrence of edema in the patients treated with ACTOS and insulin compared to insulin alone. In a 16-week, placebo-controlled ACTOS plus insulin trial (n=379), 10 patients treated with ACTOS plus insulin developed dyspnea and also, at some point during their therapy, developed either weight change or edema. Seven of these 10 patients received diuretics to treat these symptoms. This was not reported in the insulin plus placebo group. The incidence of withdrawals from placebo-controlled clinical trials due to an adverse event other than hyperglycemia was similar for patients treated with placebo (2.8%) or ACTOS (3.3%). In controlled combination therapy studies with either a sulfonylurea or insulin, mild to moderate hypoglycemia, which appears to be dose related, was reported (see PRECAUTIONS, General, Hypoglycemia). In U.S. double-blind studies, anemia was reported in c 2% of patients treated with ACTOS plus sulfonylurea, metformin or insulin (see PRECAUTIONS, General, Hematologic). In monotherapy studies, edema was reported for 4.8% (with doses from 7.5 mg to 45 mg) of patients treated with ACTOS versus 1.2% of placebo-treated patients. In combination therapy studies, edema was reported for (000#)''/KXb\[XG_XidXZ\lk`ZXcjEfik_8d\i`ZX#@eZ%
7.2% of patients treated with ACTOS and sulfonylureas compared to 2.1% of patients on sulfonylureas alone. In combination therapy studies with metformin, edema was reported in 6.0% of patients on combination therapy compared to 2.5% of patients on metformin alone. In combination therapy studies with insulin, edema was reported in 15.3% of patients on combination therapy compared to 7.0% of patients on insulin alone. Most of these events were considered mild or moderate in intensity (see PRECAUTIONS, General, Edema). In one 16-week clinical trial of insulin plus ACTOS combination therapy, more patients developed congestive heart failure on combination therapy (1.1%) compared to none on insulin alone (see WARNINGS, Cardiac Failure and Other Cardiac Effects).
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Knowledge and Attitudes of Primary Care Physicians Regarding Prostate Cancer Screening John Pendleton, MS; Robert Whit Curry, MD; Ali Kaserian, MD; Myron Chang, PhD; Satoshi Anai, MD; Kogenta Nakamura, MD; Phillip Abdoush, MD; and Charles J. Rosser, MD
Introduction: We report the results of a questionnaire administered to primary care physicians to determine their baseline knowledge of prostate cancer and their attitudes on prostate cancer screening. Materials and Methods: A 27-item questionnaire designed to assess prostate cancer knowledge and screening attitudes was administered to primary care physicians in Duval and Alachua counties. Completed surveys were returned, entered into the master database and analyzed. Results: Mean initial knowledge score was 66%. In multivariate regression analysis, there were no covariates independently associated with knowledge scores. In multivariate regression analysis, there were no covariates independently associated with attitude scores. Lastly, knowledge scores were not associated with attitude scores (p=0.85). Conclusions: Our findings imply that physicians’ knowledge is not an important predictor of their screening behavior. Thus, this study raises the possibility that factors other than educational programs must be assessed as a means to increase screening in specific communities. Key words: prostate cancer n screening n prostatespecific antigen n knowledge, attitudes and beliefs n primary care physician © 2008. From the Division of Urology, The University of Florida, Jacksonville, FL (Pendleton, Anai, Nakamura, Abdoush, Rosser); Departments of Community Health and Family Medicine (Curry), Urology (Kaserian), and Epidemiology and Health Policy Research (Chang), Gainesville, FL. Send correspondence and reprint requests for J Natl Med Assoc. 2008;100:666–670 to: Dr. Charles J. Rosser, Department of Urology, University of Florida College of Medicine, Suite N215, PO Box 100247, Gainesville, FL 32610; phone: (352) 273-7610; fax: (352) 392-8846; e-mail: [email protected]
V
arious communities throughout the United States still report a high rate of advanced prostate cancer at initial diagnosis and a high mortality rate from prostate cancer.1,2 Specifically, we reported in a study of inner-city men being screened for prostate cancer that men of African decent presented with higher median serum prostate-specific antigen (PSA), had higher median Gleason scores and were four times 666 JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION
more likely to present with advanced disease than their white counterparts.3 This disparity has been attributed to biologically more aggressive tumors,2 lack of healthcare access,3 cultural factors,4 less-aggressive therapy5 and diagnosis at a higher stage.4 Diagnosis at a higher stage may result from lack of, or ineffective screening. Physician recommendation is perhaps the most powerful factor in promoting screening compliance.5-7 Reasons why physicians do not recommend prostate cancer screening may be due to several factors, ranging from lack of prospective randomized trials demonstrating the benefit of screening, to misconceived notions on prostate cancer screening and treatment, to outdated knowledge of prostate cancer screening and treatment. Adding further confusion is the near-polar stance various agencies have in regards to prostate cancer screening. Both the American Cancer Society and the American Urologic Association recommend considering screening for prostate cancer under appropriate conditions for men aged >50 years.8 On the other hand, the American College of Physicians, American College of Preventive Medicine, Canadian Task Force on Preventive Health Care and U.S. Preventive Services Task Force all have concluded that the evidence is insufficient to recommend for or against routine screening.9 Yet, all of the above-named organizations agree that patients should be counseled about the risks and benefits of screening and the decision to screen should be the individual’s. Previously, we assessed prostate cancer knowledge and screening attitudes in 100 men presenting to our outpatient urology clinic for complaints unrelated to prostate cancer. After obtaining a baseline knowledge score, men were given a brief educational intervention followed by assessment of knowledge and screening attitudes after the intervention. The intervention proved useful in increasing one’s knowledge. Overall screening attitudes did not change. On multivariate regression analysis, only having had a serum PSA within the past 12 months was the only variable associated with higher knowledge level. With regards to screening attitudes, being of Caucasian race, having a higher educational level and having had a serum PSA within the past 12 months were indepenVOL. 100, NO. 6, JUNE 2008
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dently associated with aggressive screening behavior. Lastly, participants who scored poorly (<40%) on the knowledge survey generally had less-favorable attitudes toward prostate cancer screening. We concluded that educational programs may improve men’s overall prostate cancer knowledge and increase screening in communities where prostate cancer continues to be a major healthcare issue.10 However, other factors must be taken into account when addressing prostate cancer screening rates in the inner city. A factor to consider may be the primary care physician’s knowledge and attitude toward prostate cancer screening. Herein, we report the results of a questionnaire administered to primary care physicians to determine their baseline knowledge of prostate cancer and their attitudes on prostate cancer screening. We hypothesize that physicians having less contemporary knowledge on prostate cancer detection and treatment would report lower levels of routine prostate cancer screening in their practice.
Materials and Methods
We surveyed 100 men in Duval County as to their prostate cancer knowledge and prostate cancer screening attitudes. We sought to assess prostate cancer knowledge and screening attitudes in primary care physicians serving the inner city. Due to the anticipated low response rates, primary care physicians in neighboring counties were contacted. Contact information, including e-mail addresses, from 264 random primary care physicians in Duval and Alachua counties in northeast Florida was identified through local medical societies. All physicians were e-mailed an invitation letter describing the nature of the study. The letter had a direct link to the online survey hosted by www.zoomerang.com. Only 20 (8%) physicians responded to the online invitation. Physicians who did not log onto the website were sent another e-mail invitation. Physicians still not responding to the e-mail invitation were personally visited to inquire about their interest in the study. Additional hard copies of the invitation letter and surveys were delivered during these visits. Another 85 physicians completed the survey after the personal visit. Completed surveys were returned, entered into the database and analyzed. A 27-item questionnaire (Appendix A) was administered to these primary care physicians. The questionnaire sought to determine the baseline prostate cancer knowledge as well as the attitudes and practices of primary care physicians in regards to prostate cancer screening. Prior to distribution to the primary care physicians, the questionnaire was tested among a small, diverse group of experienced physicians from family practice, internal medicine, radiation oncology and urology. The questionnaire was subsequently modified before the final version was sent to the study group. Institutional review board approval was obtained prior to contacting primary care physicians. JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION
The first nine items in the questionnaire (four were multiple choice and five were true/false) assessed knowledge regarding risk factors for developing prostate cancer, prevalence and presentation of prostate cancer, and treatment options for prostate cancer. These questions were formulated based on current, accepted literature. Blank responses were coded as wrong responses. The next nine items in the questionnaire (seven were multiple choice and two were true/false) assessed the attitudes and current screening practices for prostate canTable 1. Characteristics of 104 primary care physicians responding to prostate cancer knowledge and screening attitude survey Characteristic(s) Participants Degree MD 91 DO 7 N/A 6 Specialty Internal medicine 36 Family practice 60 General practice 8 Age <30 15 30–45 30 45–60 45 >60 14 Race White 71 Black 4 Other 29 Practice Setting Solo 14 Group/private 18 Group/university 52 Other 7 N/A 13 Office Setting Rural 14 Urban 85 N/A 5 Medicare Patients in Practice (%) <25% 18 25–50% 54 >50% 20 N/A 12 Medicaid Patients in Practice (%) <25% 49 25–50% 37 >50% 6 N/A 12 Minorities Patients in Practice (%) <10 7 11–25% 40 26–50% 24 >50% 24 N/A 9
% 87% 7% 6% 35% 58% 8% 14% 29% 43% 13% 68% 4% 28% 13% 17% 50% 7% 13% 13% 82% 5% 17% 52% 19% 12% 47% 36% 6% 12% 7% 38% 23% 23% 9%
N/A, not answered
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cer among the primary care physicians. Finally, the survey asked about personal demographic and practice characteristics.
Statistical Analysis Average score for nine knowledge questions and average score for first eight attitude questions were computed for each participating primary care physician. The association between the average score and covariates in Table 1 was assessed by univariate and multivariate regression analysis. Backward elimination method was used in multivariate regression analysis. All reported P values were two sided, and those P values <0.05 were considered to be statistically significant. All data were analyzed using SAS® version 9.1.3 software.
Results
Two-hundred-sixty-four physicians were invited to participate in the study. One-hundred-four (39%) returned the questionnaire. Table 1 depicts the demographics of the physicians who completed the questionnaire. Nine knowledge questions were asked of each physician (Table 2). Seventy-five percent correctly reported family history and being of African decent as risk factors for developing prostate cancer. More than 89% of physicians responded correctly to knowing: 1) the incidence of prostate cancer increases with age, 2) prostate cancer is the second most commonly diagnosed cancer in American men age >45 years, 3) men of African decent with prostate cancer have a higher mortality rate than whites, and 4) there are excellent treatment options for localized prostate. However, only 14% of responders knew what these treatment options for localized prostate cancer were. In addition, only 37% of the physicians knew that men <65 years with a serum PSA 2.5–4.0 ng/ ml have approximately a 30% chance of harboring significant prostate cancer on prostate biopsy. Furthermore, 39% noted that serum PSA possesses a high sensitivity and a low specificity in detecting prostate cancer, a very important fact when counseling men about the pros and cons of prostate cancer screening. Even though the majority of prostate cancers seen today are nonpalable
(i.e., T1c) and thus not symptomatic, 55% of physicians believe voiding symptoms are one of the first symptoms of prostate cancer. Together, the overall mean score of the knowledge survey was 66%. Interestingly no demographic factors in Table 1 (age, degree, race, practice type, etc.) could independently predict prostate cancer knowledge in our cohort by multivariate regression analysis. It was found in univariate regression analysis that physicians with an urban office setting had higher knowledge scores than those with a rural office setting (mean score 63 vs. 67, p=0.042), and physicians with more minority patients had higher knowledge scores than those with fewer minority patients (p=0.026). Nine questions were asked of the physicians to elicit their attitude and current prostate cancer screening behavior (Table 3). Though 93% of physicians responded men are more likely to die with prostate cancer than of prostate cancer, 66% believed prostate cancer screening was effective. This was confirmed when the question was reworded to determine if aggressive prostate cancer screening was beneficial to their patients. Sixtyfour percent of responders felt screening was beneficial. Only 53% of physicians offer screening to minorities, whereas 70% offer it to men with a family history of prostate cancer. Forty-six percent of responders stated that they recommend prostate cancer screening to >75% of their patients age >50 years. When asked how they screen for prostate cancer, 79% reported utilizing serum PSA and digital rectal examination (DRE). Thus, 21% either do not screen or do not utilize the screening methods recommended by the American Cancer Society. In the physicians who screen for prostate cancer, 88% screen on an annual basis. Interestingly enough, 46% of physicians report a lack of confidence in interpreting the DRE results of their patients. Lastly, 46% of responders stated their attitudes on prostate cancer screening were based on literature or conferences. No demographic factors in Table 1 (age, degree, race, practice type, etc.) could independently predict prostate cancer attitude in our cohort by multivariate regression analysis. In univariate regression, physicians with an internal medicine specialty had lower attitude sores than family prac-
Table 2. Primary care physicians’ response to nine-item prostate cancer knowledge survey Question Percent with 1. The risk of developing cancer increases with age. 2. Identify the risk factors in the development of prostate cancer. 3. Second most commonly diagnosed cancer in U.S. men >45 years 4. Mortality rate of men of African decent with prostate cancer is higher than the mortality rate of whites with prostate cancer. 5. Nearly a third of men <65 years with serum PSA 2.4–4.0 harbor prostate cancer. 6. Identify treatment options for localized prostate cancer. 7. Excellent treatment options are available for men with prostate cancer. 8. Voiding symptoms are one of the first symptoms of prostate cancer. 9. Serum PSA has a high sensitivity but a low specificity.
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Correct Response 98% 75% 89% 93% 37% 14% 96% 55% 39%
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tice physicians (mean 71 vs. 79, p=0.014). In addition, older physicians had higher attitude scores than younger physicians (p=0.008), physicians with group/university practice setting had lower attitude scores than other practice settings (mean 74 vs. 81, p=0.032), and physicians with urban office setting had higher attitude scores than that with rural office setting (mean 78 vs. 69, p=0.041). Lastly, knowledge scores were not associated with attitude scores (p=0.85).
Discussion
With >30,000 American men succumbing to prostate cancer in 2005, it is the second most common cause of cancer-related deaths in men age >45 years.11 With this said, certain groups may benefit from early prostate cancer detection and treatment. These groups include men who are at high risk of developing prostate cancer. Risk factors clearly linked to the development of prostate cancer are men with a family history of prostate cancer and men of African decent. In a previous study by our group, we reported that inner-city African-American men were four times more likely to present with advance prostate cancer than their white counterparts.3 When these men were queried, they reported scant counseling from their primary care physician regarding prostate cancer screening. It has been previously described that physician recommendation to screen is perhaps the most powerful factor in promoting screening compliance.5-7 Previous researchers have demonstrated that physician knowledge of specific disease process greatly influenced screening behavior.12,13 We surveyed a diverse group of primary care physicians as to their contemporary knowledge and screening attitudes for prostate cancer. The mean correct score on the knowledge questions was 59%. Primary care physicians were less likely to know PSA has a poor specificity, localized prostate cancer generally does not present with any symptoms and to distinguish treatment for localized therapies compared to therapies directed towards advanced disease. Knowl-
edge of prostate cancer was higher on univariate analysis in physicians with offices in urban areas or in physicians whose practice was comprised of >50% minority patients. Interestingly enough, we then demonstrated that there was no correlation between prostate cancer knowledge in primary care physicians and their prostate cancer screening attitude/behavior. Thus, educational programs directed at primary care physicians may not increase prostate cancer screening recommendation and subsequently increase the prevalence of screening in communities at high risk of developing this disease. Previous research has demonstrated that increased prostate cancer knowledge in primary care physicians can polarize their views on prostate cancer screening utility (i.e., some knowledgeable physicians believe PSA screening is overutilized, while others believe in select patients it is a useful tool).14 We believe this may be the case in our study as well. We may benefit from conducting focus group discussions of primary care physicians to assess their concerns with prostate cancer and prostate cancer screening. Realization of their concerns may help us focus our attention on specific areas that, if improved, can result in a more favorable attitude towards prostate cancer screening. Recent research, however, has demonstrated the benefit of early prostate cancer detection and treatment. Since the advent of PSA screening in the late 1980s, prostate cancer mortality in the United States has been steadily decreasing.11,15 Furthermore, in two large European studies, survival improved in men who underwent prostate cancer screening and treatment, but not in men who did not.16,17 Together, these findings clearly suggest that prostate cancer screening programs can significantly increase the detection of treatable cancers and thus decrease mortality. In a companion study, we assessed the knowledge and screening behavior in inner-city men before and after a brief educational intervention. Mean initial knowledge score was 47% compared to 80% after the educational
Table 3. Primary care physicians’ response to nine-item attitude and prostate cancer screening practice survey Question Percent with Correct Response 1. I believe that men are more likely to die with prostate cancer than to die of prostate cancer. 93% 2. I offer prostate cancer screening to minorities. 53% 3. Percentage of your male patients >50 years of age that you screen or recommend screening 45% 4. My method of screening for prostate cancer includes both serum PSA and DRE. 79% 5. I recommend annual screening. 88% 6. Lack confidence level in determining results of DRE 46% 7. I believe prostate cancer screening is effective. 66% 8. I am certain/fairly certain that aggressive prostate cancer screening is beneficial to my patients. 64% 9. My attitude on prostate cancer screening comes from literature or scientific meetings. 46%
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intervention (p<0.0001). In multivariate regression analysis, only having had a serum PSA within the past 12 months was the only variable associated with knowledge (p=0.0062). Prior to the invention, the majority of men (76%) were in favor of early detection. Interestingly, after the brief intervention, the attitudes did not change significantly (76% vs. 84%, p=0.532). Being of Caucasian race, having a higher educational level and having had a serum PSA within the past 12 months were independently associated with aggressive screening behavior (p=0.0189, 0.0300 and 0.0225, respectively). Lastly, responders who scored poorly (<40%) on the knowledge survey generally had more favorable attitudes toward prostate cancer screening (p=0.0028). To date, this is the only study that has assessed a specific community’s primary care physician knowledge and screening patterns for prostate cancer in addition to querying the inner-city inhabitants as to their prostate cancer knowledge and screening behaviors. Unlike the lay public, physicians’ knowledge did not correlate to their screening attitude. The majority of physicians reported the utility in prostate cancer screening in previous reports;17-19 only 52% of physicians in our study report routine screening in minority men. On the other hand, there are primary care physicians who screen men with <10-year life expectancy or who are >80 years.20 This aggressive screening may not be beneficial. Our study has several limitations. First, this was a small pilot study to determine baseline prostate cancer knowledge and attitudes and patterns for prostate cancer screening in inner-city primary care physicians. This small cohort may not represent primary care physicians throughout the country. Furthermore, responders of the questionnaire may have polar views on prostate cancer screening. In addition, the current questionnaire has not been tested for validity and reliability. The main objective of the questionnaire was to report baseline knowledge and attitudes in hopes of formulating a continuing medical education series directed at primary care physicians to update their knowledge of prostate cancer. Thus, the need to test the questionnaire for validity and reliability was not needed. In conclusion, we report the results of a 27-item questionnaire administered to primary care physicians to assess their prostate cancer knowledge and attitudes and pattern for prostate cancer screening. Our findings did not demonstrate that physicians’ knowledge is an important predictor of their prostate cancer screening behavior. Thus, this study raises the possibility that factors other than educational programs must be assessed as a means to increase screening in specific communities.
References
1. Hoffman RM, Gilliland FD, Eley JW, et al. Racial and ethnic differences in advanced-stage prostate cancer: the Prostate Cancer Outcomes Study. J Natl Cancer Inst. 2001;93:388-395.
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2. Powell IJ, Dey J, Dudley A, et al. Disease-free survival difference between African Americans and whites after radical prostatectomy for local prostate cancer: a multivariable analysis. Urology. 2002; 59:907-912. 3. Anai S, Pendleton J, Wludyka P, et al. Prostate cancer screening and detection in inner-city and underserved men. J Natl Med Assoc. 2006; 98:515-519. 4. Shaw M, Elterman L, Rubenstein M, et al. Changes in radical prostatectomy and radiation therapy rates for African Americans and whites. J Natl Med Assoc. 2000;92:281-284. 5. Smith GE, DeHaven MJ, Grundig JP, et al. African-American males and prostate cancer: Assessing knowledge levels in the community. J Natl Med Assoc. 1997; 89:387-391. 6. Nivens AS, Herman J, Weinrich SP, et al. Cues to participation in prostate cancer screening: a theory for practice. Oncol Nursing Forum. 2001; 28:1449-1456. 7. Vernon SW, Laville EA, Jackson GL. Participation in breast screening programs: A review. Soc Sci Med. 1990;30:1107-1118. 8. Bahnson RR, Hanks GE, Huben RP, et al. National Comprehensive Cancer Network. NCCN Practice Guidelines for Prostate Cancer. Oncology. 2000;14:111-135. 9. Chan ECY. Informed Consent and Prostate Specific Antigen Screening: What patients ought to know. In Thompson IM, Resnick MI, Klein EA (eds): Current Clinical Urology: Prostate Cancer Screening. Totowa, NJ: Humana Press Inc.; 2000. 10. Pendleton J, Hopkins C, Anai S, et al. Prostate cancer knowledge and screening attitudes of inner-city men. Present AACR, Science of Cancer Health Disparities. Atlanta, GA: November 20–December 1, 2007. 11. Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2006. CA Cancer J Clin. 2006;56:106-130. 12. Philips GK, Reinier K, Ashikaga T, et al. Attitudes and beliefs of primary care physicians regarding prostate and colorectal cancer screening in a rural state. J Cancer Educ. 2005; 20:167-172. 13. Smith RA, Cokkinides V, Eyre HJ. American Cancer Society guidelines for the early detection of cancer, 2006. CA Cancer J Clin. 2006; 56:11-25. 14. Bell DS, Hays RD, Hoffman JR, et al. A test of knowledge about prostate cancer screening. Online pilot evaluation among Southern California Physicians. J Gen Intern Med. 2006;21:310-314. 15. Robert RO, Bergstralh EJ, Katusic SK, et al. Decline in prostate cancer mortality from 1980 to 1997, and an update on incidence trends in Olmstead County, Minnesota. J Urol. 1999;161:529-533. 16. Bartsch G, Horninger W, Klocker H, et al. Tyrol Prostate Cancer Screening Group. Prostate cancer mortality after introduction of prostate-specific antigen mass screening in the Federal State of Tyrol, Austria. Urology. 2001; 58:417-424. 17. Bill-Axelson A, Holmberg L, Ruutu M, et al. Scandinavian Prostate Cancer Group Study No. 4. Radical prostatectomy versus watchful waiting in early prostate cancer. N Engl J Med. 2005; 352:1977-1984. 18. Curran V, Solberg S, Mathews M, et al. Prostate cancer screening attitudes and continuing education needs of primary care physicians. J Cancer Educ. 2005;20:162-166. 19. Jonler M, Eddy B, Poulsen J. Prostate-specific antigen testing in general practice: a survey among 325 general practitioners in Denmark. Scand J Urol Nephrol. 2005;39:214-218. 20. Fowler FJ Jr, Bin L, Collins MM, et al. Prostate cancer screening and beliefs about treatment efficacy: a national survey of primary care physicians and urologists. Am J Med. 1998;104:526-532. n
We Welcome Your Comments The Journal of the National Medical Association welcomes your Letters to the Editor about articles that appear in the JNMA or issues relevant to minority healthcare. Address correspondence to [email protected].
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adequate contraception in premenopausal women should be recommended. This possible effect has not been investigated in clinical studies so the frequency of this occurrence is not known. Drug Interactions In vivo drug-drug interaction studies have suggested that pioglitazone may be a weak inducer of CYP 450 isoform 3A4 substrate. An enzyme inhibitor of CYP2C8 (such as gemfibrozil) may significantly increase the AUC of pioglitazone and an enzyme inducer of CYP2C8 (such as rifampin) may significantly decrease the AUC of pioglitazone. Therefore, if an inhibitor or inducer of CYP2C8 is started or stopped during treatment with pioglitazone, changes in diabetes treatment may be needed based on clinical response. Carcinogenesis, Mutagenesis, Impairment of Fertility A two-year carcinogenicity study was conducted in male and female rats at oral doses up to 63 mg/kg (approximately 14 times the maximum recommended human oral dose of 45 mg based on mg/m2). Drug-induced tumors were not observed in any organ except for the urinary bladder. Benign and/or malignant transitional cell neoplasms were observed in male rats at 4 mg/kg/day and above (approximately equal to the maximum recommended human oral dose based on mg/m2). A two-year carcinogenicity study was conducted in male and female mice at oral doses up to 100 mg/kg/day (approximately 11 times the maximum recommended human oral dose based on mg/m2). No drug-induced tumors were observed in any organ. During prospective evaluation of urinary cytology involving more than 1800 patients receiving ACTOS in clinical trials up to one year in duration, no new cases of bladder tumors were identified. In two 3-year studies in which pioglitazone was compared to placebo or glyburide, there were 16/3656 (0.44%) reports of bladder cancer in patients taking pioglitazone compared to 5/3679 (0.14%) in patients not taking pioglitazone. After excluding patients in whom exposure to study drug was less than one year at the time of diagnosis of bladder cancer, there were six (0.16%) cases on pioglitazone and two (0.05%) on placebo. Pioglitazone HCl was not mutagenic in a battery of genetic toxicology studies, including the Ames bacterial assay, a mammalian cell forward gene mutation assay (CHO/HPRT and AS52/XPRT), an in vitro cytogenetics assay using CHL cells, an unscheduled DNA synthesis assay, and an in vivo micronucleus assay. No adverse effects upon fertility were observed in male and female rats at oral doses up to 40 mg/kg pioglitazone HCl daily prior to and throughout mating and gestation (approximately 9 times the maximum recommended human oral dose based on mg/m2). Animal Toxicology Heart enlargement has been observed in mice (100 mg/kg), rats (4 mg/kg and above) and dogs (3 mg/kg) treated orally with pioglitazone HCl (approximately 11, 1, and 2 times the maximum recommended human oral dose for mice, rats, and dogs, respectively, based on mg/m2). In a one-year rat study, drug-related early death due to apparent heart dysfunction occurred at an oral dose of 160 mg/kg/day (approximately 35 times the maximum recommended human oral dose based on mg/m2). Heart enlargement was seen in a 13-week study in monkeys at oral doses of 8.9 mg/kg and above (approximately 4 times the maximum recommended human oral dose based on mg/m2), but not in a 52-week study at oral doses up to 32 mg/kg (approximately 13 times the maximum recommended human oral dose based on mg/m2). Pregnancy Pregnancy Category C. Pioglitazone was not teratogenic in rats at oral doses up to 80 mg/kg or in rabbits given up to 160 mg/kg during organogenesis (approximately 17 and 40 times the maximum recommended human oral dose based on mg/m2, respectively). Delayed parturition and embryotoxicity (as evidenced by increased postimplantation losses, delayed development and reduced fetal weights) were observed in rats at oral doses of 40 mg/kg/day and above (approximately 10 times the maximum recommended human oral dose based on mg/m2). No functional or behavioral toxicity was observed in offspring of rats. In rabbits, embryotoxicity was observed at an oral dose of 160 mg/kg (approximately 40 times the maximum recommended human oral dose based on mg/m2). Delayed postnatal development, attributed to decreased body weight, was observed in offspring of rats at oral doses of 10 mg/kg and above during late gestation and lactation periods (approximately 2 times the maximum recommended human oral dose based on mg/m2). There are no adequate and well-controlled studies in pregnant women. ACTOS should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Because current information strongly suggests that abnormal blood glucose levels during pregnancy are associated with a higher incidence of congenital anomalies, as well as increased neonatal morbidity and mortality, most experts recommend that insulin be used during pregnancy to maintain blood glucose levels as close to normal as possible. Nursing Mothers Pioglitazone is secreted in the milk of lactating rats. It is not known whether ACTOS is secreted in human milk. Because many drugs are excreted in human milk, ACTOS should not be administered to a breastfeeding woman. Pediatric Use Safety and effectiveness of ACTOS in pediatric patients have not been established. Elderly Use Approximately 500 patients in placebo-controlled clinical trials of ACTOS were 65 and over. No significant differences in effectiveness and safety were observed between these patients and younger patients. ADVERSE REACTIONS Over 8500 patients with type 2 diabetes have been treated with ACTOS in randomized, double-blind, controlled clinical trials. This includes 2605 high-risk patients with type 2 diabetes treated with ACTOS from the PROactive clinical trial. Over 6000 patients have been treated for 6 months or longer, and over 4500 patients for one year or longer. Over 3000 patients have received ACTOS for at least 2 years. The overall incidence and types of adverse events reported in placebo-controlled clinical trials of ACTOS monotherapy at doses of 7.5 mg, 15 mg, 30 mg, or 45 mg once daily are shown in Table 2. Table 2
Placebo-Controlled Clinical Studies of ACTOS Monotherapy: Adverse Events Reported at a Frequency s 5% of Patients Treated with ACTOS (% of Patients) Placebo ACTOS N=259 N=606 Upper Respiratory Tract Infection 8.5 13.2 Headache 6.9 9.1 Sinusitis 4.6 6.3 Myalgia 2.7 5.4 Tooth Disorder 2.3 5.3 Diabetes Mellitus Aggravated 8.1 5.1 Pharyngitis 0.8 5.1
Prospective Pioglitazone Clinical Trial In Macrovascular Events (PROactive) In PROactive, 5238 patients with type 2 diabetes and a prior history of macrovascular disease were treated with ACTOS (n=2605), force-titrated up to 45 mg daily or placebo (n=2633) in addition to standard of care. Almost all subjects (95%) were receiving cardiovascular medications (beta blockers, ACE inhibitors, ARBs, calcium channel blockers, nitrates, diuretics, aspirin, statins, fibrates). Patients had a mean age of 61.8 years, mean duration of diabetes 9.5 years, and mean HbA1c 8.1%. Average duration of follow-up was 34.5 months. The primary objective of this trial was to examine the effect of ACTOS on mortality and macrovascular morbidity in patients with type 2 diabetes mellitus who were at high risk for macrovascular events. The primary efficacy variable was the time to the first occurrence of any event in the cardiovascular composite endpoint (see Table 3 below). Although there was no statistically significant difference between ACTOS and placebo for the 3-year incidence of a first event within this composite, there was no increase in mortality or in total macrovascular events with ACTOS. Table 3 Number of First and Total Events for Each Component within the Cardiovascular Composite Endpoint Placebo N=2633 First Events Total Events (N) (N) 900 572 186 122 157 118 119 96 78 63 240 101 28 15 92 57
Cardiovascular Events Any event All-cause mortality Non-fatal MI Stroke ACS Cardiac intervention Major leg amputation Leg revascularization
ACTOS N=2605 First Events Total Events (N) (N) 514 803 110 177 105 131 76 92 42 65 101 195 9 28 71 115
Postmarketing reports of new onset or worsening diabetic macular edema with decreased visual acuity have also been received (see PRECAUTIONS, General, Macular Edema). Laboratory Abnormalities Hematologic: ACTOS may cause decreases in hemoglobin and hematocrit. The fall in hemoglobin and hematocrit with ACTOS appears to be dose related. Across all clinical studies, mean hemoglobin values declined by 2% to 4% in patients treated with ACTOS. These changes generally occurred within the first 4 to 12 weeks of therapy and remained relatively stable thereafter. These changes may be related to increased plasma volume associated with ACTOS therapy and have rarely been associated with any significant hematologic clinical effects. Serum Transaminase Levels: During all clinical studies in the U.S., 14 of 4780 (0.30%) patients treated with ACTOS had ALT values s 3 times the upper limit of normal during treatment. All patients with follow-up values had reversible elevations in ALT. In the population of patients treated with ACTOS, mean values for bilirubin, AST, ALT, alkaline phosphatase, and GGT were decreased at the final visit compared with baseline. Fewer than 0.9% of patients treated with ACTOS were withdrawn from clinical trials in the U.S. due to abnormal liver function tests. In pre-approval clinical trials, there were no cases of idiosyncratic drug reactions leading to hepatic failure (see PRECAUTIONS, General, Hepatic Effects). CPK Levels: During required laboratory testing in clinical trials, sporadic, transient elevations in creatine phosphokinase levels (CPK) were observed. An isolated elevation to greater than 10 times the upper limit of normal was noted in 9 patients (values of 2150 to 11400 IU/L). Six of these patients continued to receive ACTOS, two patients had completed receiving study medication at the time of the elevated value and one patient discontinued study medication due to the elevation. These elevations resolved without any apparent clinical sequelae. The relationship of these events to ACTOS therapy is unknown. OVERDOSAGE During controlled clinical trials, one case of overdose with ACTOS was reported. A male patient took 120 mg per day for four days, then 180 mg per day for seven days. The patient denied any clinical symptoms during this period. In the event of overdosage, appropriate supportive treatment should be initiated according to patient’s clinical signs and symptoms. Rx only Manufactured by: Takeda Pharmaceutical Company Limited Osaka, Japan Marketed by: Takeda Pharmaceuticals America, Inc. One Takeda Parkway Deerfield, IL 60015 ACTOS® is a registered trademark of Takeda Pharmaceutical Company Limited and used under license by Takeda Pharmaceuticals America, Inc. © 1999, 2007 Takeda Pharmaceuticals America, Inc. 05-1141
For most clinical adverse events the incidence was similar for groups treated with ACTOS monotherapy and those treated in combination with sulfonylureas, metformin, and insulin. There was an increase in the occurrence of edema in the patients treated with ACTOS and insulin compared to insulin alone. In a 16-week, placebo-controlled ACTOS plus insulin trial (n=379), 10 patients treated with ACTOS plus insulin developed dyspnea and also, at some point during their therapy, developed either weight change or edema. Seven of these 10 patients received diuretics to treat these symptoms. This was not reported in the insulin plus placebo group. The incidence of withdrawals from placebo-controlled clinical trials due to an adverse event other than hyperglycemia was similar for patients treated with placebo (2.8%) or ACTOS (3.3%). In controlled combination therapy studies with either a sulfonylurea or insulin, mild to moderate hypoglycemia, which appears to be dose related, was reported (see PRECAUTIONS, General, Hypoglycemia). In U.S. double-blind studies, anemia was reported in c 2% of patients treated with ACTOS plus sulfonylurea, metformin or insulin (see PRECAUTIONS, General, Hematologic). In monotherapy studies, edema was reported for 4.8% (with doses from 7.5 mg to 45 mg) of patients treated with ACTOS versus 1.2% of placebo-treated patients. In combination therapy studies, edema was reported for (000#)''/KXb\[XG_XidXZ\lk`ZXcjEfik_8d\i`ZX#@eZ%
7.2% of patients treated with ACTOS and sulfonylureas compared to 2.1% of patients on sulfonylureas alone. In combination therapy studies with metformin, edema was reported in 6.0% of patients on combination therapy compared to 2.5% of patients on metformin alone. In combination therapy studies with insulin, edema was reported in 15.3% of patients on combination therapy compared to 7.0% of patients on insulin alone. Most of these events were considered mild or moderate in intensity (see PRECAUTIONS, General, Edema). In one 16-week clinical trial of insulin plus ACTOS combination therapy, more patients developed congestive heart failure on combination therapy (1.1%) compared to none on insulin alone (see WARNINGS, Cardiac Failure and Other Cardiac Effects).
September 2007
L-PIO-0907-4
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