primary treatment choices for men with clinically localized prostate carcinoma detected by screening

Primary Treatment Choices for Men with ClinicallyLocalized Prostate Carcinoma Detected by Screening

Yan Yan, M.D., Ph.D.

Gustavo F. Carvalhal, M.D.

William J. Catalona, M.D.

James D. Young, M.D.

Division of Urologic Surgery, Department of Sur-gery, Washington University School of Medicine,St. Louis, Missouri.

Supported in part by a grant from Hybritech Inc., asubsidiary of Beckman-Coulter. Hybritech manu-factures prostate specific antigen assays.

The authors thank Dr. Deborah S. Smith for herleadership in the follow-up study when she was inWashington University School of Medicine and Ms.Kay Schneider and Ms. Julie Krygiel for their ef-forts in collecting the data.

Address for reprints: Yan Yan, M.D., Ph.D., Box8242, Division of Urologic Surgery, 4960 Chil-dren’s Place, St. Louis, MO 63110.

Received April 12, 1999; revisions received August2, 1999, and October 28, 1999; accepted October28, 1999.

BACKGROUND. Increasingly, prostate carcinoma is diagnosed through screening.

However, little is known regarding factors that influence a patient’s decision

concerning the treatment choices presented to him.

METHODS. Subjects were prostate carcinoma patients detected through the Wash-

ington University PSA Prostate Cancer Screening Program between September

1989 and June 1998. The sources of data were the prostate specific antigen (PSA)

screening database and follow-up questionnaire.

RESULTS. Among 1809 study subjects, 79.2% chose radical prostatectomy (RP),

12.4% chose radiation therapy, and 8.4% chose watchful waiting (WW) as their

decision regarding primary treatment. In bivariate analyses, education, income,

age, indication for prostate biopsy, comorbidity score, serum PSA level, clinical

stage, and pretreatment urinary and sexual function were associated significantly

with treatment choice, but race, marital status, and Gleason grade were not. In a

multivariate analysis, age, race, clinical stage, PSA level, and pretreatment urinary

and sexual function were found to be associated significantly with treatment

choice. For every 5-year decrease in age, the odds for choosing RP versus WW

increased by 276%; for every 1-ng increase in PSA, the odds for choosing RP versus

WW increased by 12%. Non-African-American patients were greater than four

times more likely to select RP versus WW. Patients with T2 tumors and those with

normal pretreatment urinary function were three times more likely and twice more

likely to choose RP versus WW, respectively.

CONCLUSIONS. In the current study, RP was the most widely used treatment in

patients with screen-detected prostate carcinoma. Age, race, PSA level, clinical

stage, and pretreatment urinary and sexual function were significant factors influ-

encing treatment selection. Cancer 2000;88:1122–30.

© 2000 American Cancer Society.

KEYWORDS: prostate carcinoma, screening program, treatment choices, clinicalstage, prostate specific antigen level.

In recent years, early detection techniques and more public aware-ness have resulted in a dramatic increase in the number of patients

diagnosed with localized prostate carcinoma, and with this increasehas come greater scrutiny of treatment methods. Despite significantadvances in the diagnosis, staging, and treatment of clinically local-ized prostate carcinoma, the optimal management of this diseaseremains controversial. Although radical prostatectomy, radiationtherapy, and watchful waiting are the most frequently selected op-tions for the management of clinically localized prostate cancer, toour knowledge no well designed randomized clinical trial with longterm follow-up systematically comparing these treatments has beenreported. Radical prostatectomy has been the preferred treatmentoption of younger men with localized tumors.1,2 Concerns over sexual

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© 2000 American Cancer Society

potency and urinary continence have limited its ac-ceptance. To our knowledge the excellent results re-ported by centers of excellence3– 6 have not been re-produced in other studies.7–10 Radiation therapy,although not affecting potency and continence to thesame degree as radical prostatectomy, can be compli-cated by bowel and bladder dysfunction, and ques-tions remain regarding tumor control after radiationtherapy.11,12 Watchful waiting is devoid of the treat-ment-related side effects, but permits the progressionof disease and is accompanied by the psychologiceffects of living with untreated cancer.13,14 To ourknowledge the literature does not provide clear evi-dence for the superiority of one form of treatment.The American Urological Association’s (AUA) ProstateCancer Clinical Guidelines Panel recommends thatpatients with newly diagnosed clinically localizedprostate carcinoma be informed of all commonly ac-cepted treatment options.15

It has been demonstrated that decision-makingconcerning the treatment of cancer is a complex pro-cess, being influenced by both clinical and nonclinicalfactors.16 –20 For lung, breast, and other carcinomas,investigators have demonstrated that factors such astumor stage, functional status of the patient, the pres-ence of comorbid conditions, race, marriage, socio-economic status, age, and place of residence are as-sociated with the treatment selected.16 –20 However, toour knowledge, for prostate carcinoma, few studieshave evaluated systematically the interplay of clinicaland nonclinical factors in determining treatmentchoice, especially in screened populations. Somestudies21,22 focused on racial differences in treatmentof prostate carcinoma, and others23 were designed toexamine whether the age of the patient influencedtreatment selection. One study24 assessed the signifi-cance of comorbid and nonclinical factors in the treat-ment choice without consideration of the effect oftumor characteristics. In addition, to our knowledgenone of the studies cited earlier used data fromscreened populations in which earlier cancer detec-tion would offer more treatment options and poten-tially better prospects for favorable outcomes, andnone included prostate specific antigen (PSA) infor-mation. Because PSA testing is widely used for earlydetection, staging, and the monitoring of prostate car-cinoma patients, some authors have raised questionsconcerning limitations of the data derived before thePSA era.25

The current study describes and compares threedifferent treatment choices (radical prostatectomy, ra-diation therapy, and watchful waiting) among menwith different demographic, socioeconomic, and clin-ical characteristics who were diagnosed with prostate

carcinoma through our screening program and iden-tifies important factors associated with the three treat-ment choices. Through this study, we sought to pro-vide a better understanding of factors influencingtreatment selection. We believe this information maybe useful in counseling patients and in obtaining in-formed consent for treatment.

MATERIALS AND METHODSAll study subjects were patients diagnosed with pros-tate carcinoma through a screening program at theWashington University School of Medicine. The infor-mation came from the database collected for thescreening program and follow-up questionnaires.

Since September 1989, . 33,000 male volunteersage $ 50 years have been enrolled in the screeningprogram. These men responded to a press releaseinviting healthy men without a history of prostatecarcinoma or active prostatitis to participate in a studyof PSA measurement as a screening test for prostatecarcinoma. The study protocols have been reportedelsewhere.26 Briefly, these volunteers were screenedfor prostate carcinoma by serum PSA measurementand/or digital rectal examination (DRE) at approxi-mately 6-month intervals. Those who had an elevatedPSA level or suspicious findings on DRE were recom-mended to undergo a minimum of quadrant transrec-tal ultrasound-guided needle biopsies of the prostate(sextant biopsies were performed routinely after May1, 1995). Men with biopsy results not showing carci-noma returned to a regular screening schedule andmen diagnosed with prostate carcinoma were invitedto participate in a follow-up study. The purpose of thefollow-up study is to systematically examine carci-noma recurrence rates, overall and disease specificmortality rates and quality of life among men withscreen-detected prostate carcinoma. After the patientshad selected treatment for prostate carcinoma, theywere sent a baseline questionnaire to collect informa-tion regarding demographics, socioeconomic status,comorbidity, and general and prostate carcinoma spe-cific quality of life. Approximately 1 year later, we sentfollow-up questionnaires to collect similar informa-tion. Posttreatment PSA measurements were obtainedregularly to monitor disease recurrence. We contactedthe Vital Statistics Department of the State of Mis-souri, as well as several other states, and also con-tacted relatives of the patients for information con-cerning the cause of death. All subjects in our studysigned institutional review board-approved informedconsent documents, and all data collection proce-dures also were approved by the Washington Univer-sity Human Studies Committee.

The outcome of interest in this study was the

Treatment Choices in Prostate Carcinoma/Yan et al. 1123

initial treatment selected by the patients for localizedprostate carcinoma. Three treatments (radical prosta-tectomy [perineal or retropubic], radiation therapy[external beam or interstitial seed implantation], andwatchful waiting) were chosen for analyses. Othertreatments rarely were selected by these patients.

Clinical factors of interest were the indication forprostate biopsy (elevated PSA, suspicious DRE, orboth), clinical stage, Gleason grade, serum PSA con-centration, comorbid conditions, and pretreatmenturinary and sexual function. Patients were clinicallystaged according to the TNM System prior to treat-ment.27 T1 tumors were defined as clinically inappar-ent, nonpalpable tumors. T2 tumors were palpabletumors confined to the prostate. Gleason grades (frombiopsy samples) were divided according to the Amer-ican Joint Committee On Cancer into well (GleasonGrade 2– 4), moderately (Gleason Grade 5– 6), moder-ately poorly (Gleason Grade 7), and poorly (GleasonGrade 8 –10) differentiated tumors. Because the ma-jority of our study subjects had Gleason grades , 6,tumor grade was dichotomized into well differentiatedand other. Comorbid conditions were quantified by aCharlson index-like score,28 using the same groupingand scoring criteria as the Charlson index; however,the comorbidity data were not obtained from hospitalrecords but from a self-administered questionnaire.PSA concentration was taken as the last value beforethe diagnosis of carcinoma (usually within 1 month).Pretreatment urinary function was dichotomized asdysfunction, yes or no. No urinary dysfunction wasdefined as total urinary control in the month prior tothe diagnosis, and urinary dysfunction included nocontrol whatsoever, frequent dribbling, or occasionaldribbling. Pretreatment sexual function also was di-chotomized as dysfunction, yes or no. No sexual dys-function was defined as having erections rigid enoughfor intercourse in the month prior to the diagnosis,and sexual dysfunction included having no erectionsat all or having erections not sufficiently rigid for sex-ual activity. The decision for dichotomization of thesetwo variables was made because the majority of thestudy subjects did not have urinary or sexual dysfunc-tion. All other categories were collapsed to enhancethe statistical analyses.

Nonclinical factors included demographic (age,race, and marital status) and socioeconomic charac-teristics (education and income). Because African-Americans have the highest rate of incidence of pros-tate carcinoma and possibly more aggressive tumorbiology,29,30 race was dichotomized as black andother. Other included white, Asian, Hispanic, andother ethnic groups. Due to the small number ofAsian, Hispanic, or patients of other ethnic origin in

the current study, these groups were included withwhites. Education level was grouped into four catego-ries: up to high school, some college, college degree, orgraduate school. Annual household income wasgrouped into three categories: # $30,000, $30,001–50,000, and $ $50,001. These categories represent therelative equal distributions of the data and relativehomogeneity with respect to socioeconomic status.

Statistical analysis included simple descriptivestatistics, bivariate analysis, stratified bivariate analy-sis, and multiple variable analysis. The association ofclinical and nonclinical factors with three treatmentchoices was measured by odds ratios. Pearson chi-square statistics were used to describe the overall as-sociation between categoric variables and the threetreatment choices. Analysis of variance was used tocompare continuous variables among different treat-ment groups, and type I error was adjusted for multi-ple comparison by Tukey’s studentized range (HSD)procedure. In stratified bivariate analysis, we analyzedhighly statistically important factors (P # 0.01) in thebivariate setting, stratifying them by age groups. Wegrouped treatment choice into surgery versus radia-tion therapy and watchful waiting combined to obtainmore reliable estimates. To avoid missing variablesthat might not be statistically significant in bivariateanalysis due to possible confounding, all variableswere considered as candidates for multiple variableanalysis. Polytomous multiple logistic regression wasused to estimate two logit functions simultaneously,which associated the various factors with the threedifferent treatment choices. The effect of an individualfactor on the type of treatment selected was deter-mined by G statistics (22 log likelihood ratio with andwithout the factor in the model) and the correspond-ing degree of freedom. Goodness-of-fit of the finalmodel was tested by comparing the likelihood fromthe unrestricted (saturated) model and the likelihoodfrom the final model. The format of a continuousvariable in the final model was identified by first usingdummy variables at a nominal scale, then using anordinal scale, and finally using a continuous scale, ifappropriate. Product terms among important factorswere entered into the model to test for possible inter-actions. All data analyses were conducted using SASsoftware.31

RESULTSFrom September 1989 to June of 1998, 2582 of thescreening volunteers (8.6%) were found to have pros-tate carcinoma, and 2345 (90.8%) chose 1 of the 3treatments. Among the patients choosing 1 of the 3treatment alternatives, 1809 (77.1%) provided fol-low-up questionnaire information.

1124 CANCER March 1, 2000 / Volume 88 / Number 5

Descriptive statistics comparing the association ofvarious factors with the three treatment choices arepresented in Table 1. Among 1809 prostate carcinomapatients, approximately 79% selected radical prosta-tectomy as their primary treatment and approximately12% and 8%, respectively, selected radiation therapyand watchful waiting as their primary treatment. In-dications for prostate biopsy included 10% due to asuspicious DRE, approximately 60% due to an ele-vated PSA, and approximately 28% for both an ele-vated PSA and an abnormal DRE. The mean age was66.4 years (Standard deviation 5 6.8) and the medianage was 67 years (interquartile range, 71– 62 5 9).Overall, marital status, education, income, indicationfor biopsy, clinical stage, pretreatment urinary andsexual function, comorbidity, age at diagnosis, andPSA concentration were significantly associated withtreatment choice, whereas race and Gleason gradewere not.

Table 2 shows the crude odds ratios and 95%confidence intervals (95% CI) for categoric factors andmean differences and 95% CIs for continuous factors.Table 3 shows the age-adjusted odds ratios and 95% CIfor selected factors associated with radical prostatec-tomy versus radiation therapy and watchful waitingcombined. Effects of the selected factors on the choiceof radical prostatectomy versus other treatments werenot significantly different across age groups. Table 4presents the multivariate-adjusted odds ratios and95% CIs for factors that made independent contribu-tions to the polytomous multiple logistic regressionmodel. Race, clinical stage, pretreatment urinary andsexual function, PSA level, and age at diagnosis ofprostate carcinoma had independent effects on treat-ment choice. Although clinical stage was correlatedpositively with tumor grade, tumor grade did not ap-pear to show any statistically independent effect, evenin the absence of tumor stage in the model. Aftercontrolling for other factors, non-African-Americanpatients were 4.3 times more likely to select radicalprostatectomy and 2.6 times more likely to select ra-diation therapy than watchful waiting compared withAfrican-American patients. Compared with patientswith T1 tumors, patients with T2 tumors were approx-imately three times more likely to select radical pros-tatectomy or radiation therapy than watchful waiting.Patients without urinary dysfunction were approxi-mately 1.7 times more likely to choose radical prosta-tectomy than radiation therapy or watchful waiting.After controlling for other factors, patients withoutsexual dysfunction were approximately twice as likelyto choose watchful waiting and 1.6 times more likelyto choose radical prostatectomy than radiation ther-apy. For every 1-ng/mL increase in the PSA concen-

tration, the odds of electing a definitive therapy (rad-ical prostatectomy or radiation therapy) versuswatchful waiting increased by approximately 13%(odds ratios of 1.12 and 1.15, respectively). For every5-year increase in age at diagnosis, the odds of choos-ing watchful waiting versus radiation therapy in-creased by approximately 104% (odds ratio of 2.04),and the odds of choosing radiation therapy versusradical prostatectomy increased by approximately138% (odds ratio of 2.38).

DISCUSSIONIn our screening population, radical prostatectomywas the most common treatment for clinically local-ized prostate carcinoma, followed by radiation ther-apy and then watchful waiting. Race, clinical stage,pretreatment urinary and sexual function, PSA level,and age at diagnosis were important factors account-ing for differences in the selected treatment. Maritalstatus, education, income, indication for prostate bi-opsy, and comorbidity status were of importance onlywhen ignoring other factors. Gleason grade did notdemonstrate any significant association with the treat-ment choice.

Our results are in agreement with some previousstudies. Age has been demonstrated consistently to bean important factor influencing treatment choice formany tumors.16,17,20 Our study suggests age contrib-utes most significantly to the model and thus is themost important factor influencing treatment choice.Some investigators17 have suggested that older pa-tients might reject potentially effective therapy forreasons such as misinformation, suspicion of physi-cians, or lack of social support. In addition, physiciansmight withhold aggressive therapy or present it unen-thusiastically because of concerns regarding associ-ated morbidity and mortality. The increasing preva-lence of chronic diseases in older patients providedanother explanation for the age-related decline in se-lecting definitive treatments.20 Although we also ob-served an age-related decrease in the use of definitivetreatment, some of these explanations may not applyin the current study. Prostate carcinoma often is aslowly progressing disease, and many prostate carci-noma patients die of other causes.32 Older patientswith a shorter life expectancy are more likely die fromother causes, and thus are less likely to benefit fromdefinitive treatments.

Conflicting data have been published regardingracial differences in selecting definitive therapy forprostate carcinoma.21,22 Schapira et al.21 offered sev-eral suggestions that address the tendency of African-American patients to defer potentially curative ther-apy. These include a possible difference in a


TABLE 1Descriptive Statistics and Overall Associations of Variables with Radical Prostatectomy, Radiation Therapy, andWatchful Waiting for 1809 Patients with Screen-Detected Clinically Localized Prostate Carcinoma

Variables RP RT WW P value

Total 1432 (79.2%) 225 (12.4%) 152 (8.4%) 1809Categoric Age groups (yrs)

, 60 294 (95.2%) 11 (3.6%) 4 (1.3%) 309 (17.1%)60–69 797 (89.2%) 71 (7.9%) 26 (2.9%) 894 (49.4%)70 1 341 (56.3%) 143 (23.6%) 122 (20.2%) 606 (33.5%) 0.001Missing 0 0 0

RaceBlack 63 (78.7%) 9 (11.3%) 8 (10.0%) 80 (4.4%)Other 1362 (79.5%) 211 (12.3%) 141 (8.2%) 1714 (94.7%) 0.833Missing 7 5 3 15 (0.8%)

Currently marriedNo 164 (73.2%) 35 (15.6%) 25 (11.2%) 224 (12.4%)Yes 1262 (80.3%) 186 (11.8%) 124 (7.9%) 1572 (86.9%) 0.048Missing 6 4 3 13 (0.7%)

Education# HS 364 (76.8%) 60 (12.7%) 50 (10.5%) 474 (26.2%)Some college 410 (77.8%) 72 (13.7%) 45 (8.5%) 527 (29.1%)College 303 (79.3%) 47 (12.3%) 32 (8.4%) 382 (21.1%)Graduate 345 (85.2%) 39 (9.6%) 21 (5.2%) 405 (22.4%) 0.041Missing 10 7 4 21 (1.2%)

Income ($)230000 361 (74.3%) 78 (16.1%) 47 (9.7%) 486 (26.9%)30001–50000 412 (79.7%) 57 (11.0%) 48 (9.3%) 517 (28.6%)500011 503 (83.8%) 60 (10.0%) 37 (6.2%) 600 (33.2%) 0.002Missing 156 30 20 206 (11.4%)

Indication for biopsyPSA, elevated only 827 (77.2%) 133 (12.4%) 111 (10.4%) 1071 (59.2%)DRE, suspicious only 153 (85.0%) 15 (8.3%) 12 (6.7%) 180 (10.0%)Both 412 (81.3%) 70 (13.8%) 25 (4.9%) 507 (28.0%) 0.001Off protocol or missinga 40 7 4 51 (2.8%)

Clinical stage:T1 833 (77.1%) 132 (12.2%) 116 (10.7%) 1081 (59.8%)T2 596 (82.2%) 93 (12.8%) 36 (4.9%) 725 (40.1%) 0.000Missing 3 0 0 3 (0.2%)

Gleason gradeWell 435 (80.9%) 60 (11.1%) 43 (8.0%) 538 (29.7%)Other 972 (78.4%) 162 (13.1%) 106 (8.5%) 1240 (68.5%) 0.195Missing 25 3 3 31 (1.7%)

Urinary dysfunctionYes 262 (68.1%) 71 (18.4%) 52 (13.5%) 385 (21.3%)No 1147 (82.9%) 142 (10.3%) 95 (6.9%) 1384 (76.5%) 0.000Missing 23 13 5 41 (2.3%)

Sexual dysfunctionYes 342 (67.1%) 106 (20.8%) 62 (12.2%) 510 (28.2%)No 1046 (85.5%) 103 (8.4%) 74 (6.1%) 1223 (67.6%) 0.000Missing 44 16 16 76 (4.2%)

Charlson index-like score0 709 (82.3%) 86 (9.9%) 67 (7.8%) 862 (47.7%)1 382 (77.2%) 67 (13.5%) 46 (9.3%) 495 (27.4%)2 205 (78.9%) 31 (11.9%) 24 (9.2%) 260 (14.4%)31 136 (70.8%) 41 (21.4%) 15 (7.8%) 192 (10.6%) 0.002Missing 0 0 0

ContinuousAge 64.8 (6.1) 71.0 (5.7) 74.1 (6.4) 0.000PSA 6.3 (6.9) 7.2 (7.8) 5.2 (3.2) 0.001

RP: radical prostatectomy; RT: radiation therapy; WW: watchful waiting; HS: high school; PSA: prostate specific antigen; DRE: digital rectal examination.a 20 prostate carcinoma patients underwent biopsy without suspicious digital rectal examination or elevated prostate specific antigen. These were off-protocol cases.


physician’s recommendations for treatment based onrace and suboptimal interactions between physiciansand African-American patients, leading to a decreasedacceptance of the physician’s recommendations. Wedid not find any association between race and treat-ment choice in bivariate analysis. However, when con-

trolling for age and other factors, non-African-Ameri-can patients were found more often to select radicalprostatectomy or radiation therapy than African-American patients. We believe this discrepancy arisesfrom the fact that African-American patients tend tobe younger than other patients (mean age of 62.8 yearsvs. 66.6 years; P , 0.0001).

To our knowledge few studies have reported anassociation between pretreatment urinary and sexualfunction and treatment choice. We found these vari-ables were associated independently with treatmentchoice. Patients with normal urinary function moreoften chose radical prostatectomy than either radia-tion therapy or watchful waiting. Patients with normalsexual function were more likely to choose watchfulwaiting; however, if they selected definitive treatment,they were more likely to choose radical prostatectomy.Presumably, patients with normal sexual function mayseek to preserve their sexual function by first choosingwatchful waiting. However, if they decide to use de-finitive treatment, their desire for cancer control mayoutweigh the desire for preservation of sexual func-tion, resulting in the selection of more aggressivetreatment.

TABLE 2Crude Estimates of Associations of Variables with RadicalProstatectomy, Radiation Therapy, and Watchful Waiting for 1809Patients with Screen-Detected Clinically Localized ProstateCarcinoma

Variables RP vs. WW RT vs. WW RP vs. RT

Odds ratios and 95% CIsCategoric Age

groups (yrs), 6060–69 0.42 (0.14, 1.21) 0.99 (0.29, 3.40) 0.42 (0.22, 0.80)70 1 0.04 (0.01, 0.10) 0.43 (0.13, 1.37) 0.09 (0.15, 0.17)

Currently marriedNoYes 1.55 (0.98, 2.46) 1.07 (0.61, 1.88) 1.45 (0.97, 2.15)

Education:# HSSome college 1.25 (0.82, 1.92) 1.33 (0.79, 2.26) 0.94 (0.65, 1.36)College 1.30 (0.81, 2.08) 1.22 (0.68, 2.20) 1.06 (0.70, 1.60)Graduate 2.26 (1.33, 3.84) 1.55 (0.81, 2.96) 1.46 (0.95, 2.24)

Income ($):23000030001–50000 1.12 (0.73, 1.71) 0.72 (0.42, 1.21) 1.56 (1.08, 2.26)500011 1.77 (1.13, 2.78) 0.98 (0.57, 1.69) 1.81 (1.26, 2.60)

Indication forbiopsy

PSA, elevated onlyDRE, suspiciousonly 1.71 (0.92, 3.18) 1.04 (0.47, 2.32) 1.64 (0.94, 2.87)

Both 2.21 (1.41, 3.40) 2.34 (1.39, 3.94) 0.95 (0.69, 1.29)Clinical stage

T1T2 2.31 (1.56, 3.40) 2.27 (1.44, 3.59) 1.02 (0.76, 1.35)

Urinary dysfunctionYesNo 2.40 (1.67, 3.45) 1.09 (0.70, 1.70) 2.19 (1.60, 3.00)

Sexual dysfunctionYesNo 2.56 (1.79, 3.67) 0.81 (0.53, 1.26) 3.15 (2.34, 4.24)

Charlson index-likescore

01 0.78 (0.53, 1.17) 1.13 (0.69, 1.86) 0.69 (0.49, 0.97)2 0.81 (0.49, 1.32) 1.01 (0.54, 1.87) 0.80 (0.52, 1.24)31 0.86 (0.48, 1.54) 2.13 (1.09, 4.17) 0.40 (0.27, 0.61)

Mean difference and 95% CIsContinuous

Mean age 29.2 (210.4, 28.0) 23.1 (24.6, 21.6) 26.1 (27.1, 25.1)Mean PSA 1.1 (20.1, 2.4) 2.0 (0.5, 3.6) 20.9 (21.9, 0.2)

RP: radical prostatectomy; WW: watchful waiting; RT: radiation therapy; 95% CI: 95% confidence

interval; HS: high school; PSA: prostate specific antigen; DRE: digital rectal examination.

Odds ratios were calculated using the first category as the reference group.

TABLE 3Age-adjusted Odds Ratios and 95% CI for Selected Factors Associatedwith Radical Prostatectomy versus Radiation Therapy and WatchfulWaiting Combined

Variables Age < 60 yrs Ages 60–69 yrs Age 70 1 yrs

Income ($):23000030001–50000 NA 1.40 (0.81, 2.40) 0.99 (0.65, 1.49)500001 1.86 (0.55, 6.25) 1.25 (0.74, 2.10) 1.20 (0.77, 1.86)

Indication for biopsyPSA, elevated onlyDRE, suspicious orboth 0.84 (0.29–2.50) 1.33 (0.84–2.09) 1.41 (1.00–1.98)

Clinical stageT1T2 0.97 (0.34, 2.80) 1.24 (0.80, 1.92) 1.51 (1.08, 2.11)



Charlson index-like score01 1.21 (0.31, 4.69) 0.69 (0.42, 1.14) 0.77 (0.52, 1.14)2 1 0.75 (0.22, 2.57) 0.61 (0.36, 1.03) 0.92 (0.63, 1.35)

95% CI: 95% confidence interval; NA: no reliable odds ratio available due to a very small sample size;

PSA: prostate specific antigen; DRE: digital rectal examination.

Factors selected were highly statistically significant in bivariate analyses (P # 0.01).

Odds ratios were calculated using the first category as the reference group.


Since the introduction of the serum PSA test as atumor marker, substantial data have accumulateddemonstrating its value in stratifying patients beforetreatment and to assess potential treatment effective-ness.33,34 Previous literature regarding the treatmentof early stage prostate carcinoma evaluated pretreat-ment PSA levels to determine whether PSA facilitatedthe treatment decision.25 Due to a lack of long termfollow-up and standardized definitions of diseasestage and biochemical cure, these investigators failedto reach definitive conclusions. The results of the cur-rent study revealed that a higher PSA level was asso-ciated with the selection of definitive treatments. Thereason for this association may be the positive relationbetween high PSA levels and tumor grade and stage.Thus, for patients with higher PSA levels, physiciansmay be more likely to recommend and patients maymore readily accept definitive treatments. This alsomay explain why the patients with palpable tumors(T2) were more likely to select definitive therapy ver-sus watchful waiting.

Comorbidity status was associated with treatmentchoice in bivariate but not in multiple variable analy-ses in the current study, contradicting some previousfindings. Desch et al.24 reported a significant decreasein the aggressive treatment of prostate carcinoma withincreasing comorbidity score after adjusting for age,income, education, etc. There are some differences inthe study populations and sources for comorbidity

data between these studies. The study population inthe report by Desch et al.24 was comprised of elderlypatients with locoregional disease identified from theVirginia Cancer Registry, whereas the current studypopulation was comprised exclusively of patients withclinically localized prostate carcinoma diagnosedthrough a screening program. The source of comor-bidity data for the study by Desch et al. was the Medi-care Provider Analysis and Review (MEDPAR) file,which recorded hospitalization information, whereasour comorbidity information was collected by fol-low-up questionnaire. We believe the quality of thedata collected from hospital records is better than thatof data collected from patient questionnaires. Never-theless, the results of the current study are in agree-ment with those of Goodwin et al.,19 who found noassociation between comorbidity and treatmentchoices for breast, prostate, and colorectal carcino-mas. The presence and severity of comorbid condi-tions usually is related to advanced age. Consequently,after controlling for age or age-related factors, theeffect of comorbidity status tends to diminish.

Education and income were not found to be in-dependently associated with treatment choice in thecurrent study, in contrast to the findings of Desch etal.24 There is a notable difference between the twostudies with respect to the measurements of educa-tion and income. Desch et al.24 used the age-raceadjusted median income of persons living in the pa-tient’s zip code as the income measurement and therace-adjusted percentage of the population with aninth grade or lower education in the patient’s zipcode as the education measurement. In the currentstudy, the information regarding education and in-come was collected at an individual level. The subjectsin the study by Desch et al.24 had a mean income of$22,011, compared with approximately 70% of sub-jects with an income . $30,000 in our screened pop-ulation. In addition, 74% of patients enrolled in thecurrent study had some college education or higher,representing a highly educated population. Statisti-cally, Desch et al.24 modeled different treatmentchoices by separate logit functions, whereas we simul-taneously modeled the treatment choices by polyto-mous logistic regression.

The current study did not investigate some vari-ables that may have a significant effect on the treat-ment choice, such as distance from the treatmentcenter or insurance status. For lung carcinoma pa-tients, a longer distance from a cancer treatment fa-cility was found to increase the chances of receivingsurgery versus radiation therapy. Moreover, patientswith private insurance were found more often to electsurgery and radiation therapy.18 Our study subjects

TABLE 4Multivariate-Adjusted Odds Ratios and 95% CI of Important FactorsAssociated with Radical Prostatectomy, Radiation Therapy, andWatchful Waiting from Polytomous Multiple Logistic RegressionModel

Variables RP vs. WW RT vs. WW RP vs. RT

RaceBlackOther 4.26 (1.67, 10.86) 2.57 (0.86, 7.67) 1.65 (0.65, 4.19)

Clinical stageT1T2 2.96 (1.84, 4.75) 2.77 (1.65, 4.65) 1.06 (0.67, 1.71)



PSA level 1.12 (1.04, 1.20) 1.15 (1.07, 1.23) 0.97 (0.84, 1.12)Age: (with every 5-

years increase) 0.21 (0.17, 0.27) 0.49 (0.39, 0.63) 0.42 (0.27, 0.67)

95% CI: 95% confidence interval; RP: radical prostatectomy; WW: watchful waiting; RT: radiation

therapy; PSA: prostate specific antigen.

Odds ratios were calculated using the first category for the reference group.


live in the St. Louis metropolitan area and were diag-nosed with carcinoma through our screening pro-gram. Because these patients came for regular screen-ing, there is no reason to suspect the distance to thesame center would affect their treatment choice. Pa-tients age . 65 years have at least partial coverage ofhospital costs through Medicare; therefore, having pri-vate insurance may indicate a higher socioeconomicstatus. In the current study, income and education(surrogate of socioeconomic status) were measured atan individual level and were included in the analyses.Thus, the possible effects of private insurance on thetreatment choice were partially, if not completely,taken into account.

Physician recommendation has been shown to bean important factor influencing treatment decisions.22

Unfortunately, we did not collect information con-cerning the number and specialty of the physiciansindividual patients consulted prior to deciding ontherapeutic alternatives. However, all patients diag-nosed with prostate carcinoma through this screeningprogram were invited to participate in a discussionwith a faculty member from the Division of UrologicSurgery at Washington University. The objective ofthis meeting was to provide information regardingprostate carcinoma and to answer the patient’s andfamily members’ questions regarding the disease andits treatment. A detailed discussion of the risks andbenefits of all accepted treatment alternatives wasconducted.

We are unaware of any studies quantifying theeffect of physician recommendations on an individu-al’s treatment choice with regard to prostate carci-noma. Naturally there would be a bias introduced bythe consulting specialist to recommend a treatmentwith which they are most familiar. Among 2582 pa-tients with prostate carcinoma detected by screening,approximately 70% had surgery, 13% radiation ther-apy, 10% watchful waiting, 2% cryotherapy, and 5%hormonal therapy as their primary treatment. Theyoung age of our patients, early tumor stage, and thehealth care-seeking behavior of the screening programvolunteers may account in part for the high propor-tion of patients undergoing surgery. We believe thewidespread distribution of brochures or pamphletsexplaining the risk factors, diagnosis, and treatment ofprostate carcinoma among the screened patientscombined with their high education (75% had at leastsome college education) decreased the possible biasimparted by the physicians.

Even if a biased recommendation exists, the esti-mated effects of variables on treatment choices shouldbe less biased or even unbiased due to compensationbias mechanisms. In any comparative study, equal

biases among comparison groups tend to compensatefor each other, resulting in less biased or unbiasedestimates of the differences between the groups. Forinstance, if one compares two objects and wants toknow the ratio of their weights if the scale is biased bya factor A (i.e., for an object with true weight w, it givesA*w), because the bias factor A is constant for the twoobjects, the bias factor is canceled out, resulting in anunbiased ratio. For this reason, if a urologist has atendency to recommend surgery for all patients, thenthe estimates of the effects of the various factors ontreatment choice are less biased or even unbiased. Inaddition, our results were similar to many previousstudies. For pretreatment sexual function, which toour knowledge has not been reported by others, wehave a plausible explanation for possible effect ontreatment choice. Therefore, it is unlikely that ourstudy results are distorted.

Another limitation of this study is the generaliz-ability of our findings. Our screening volunteers rep-resent a predominantly affluent, well educated whitepopulation living in metropolitan area. Consequently,the results of our study may not readily be applied toother populations.

In our screening population we found higher tu-mor stage, higher PSA level, non-African Americanrace, and, most important, younger age were stronglyassociated with a patient choosing definitive treat-ments (radical prostatectomy or radiation therapy).We also found normal urinary function was associatedwith definitive treatment choices, but normal sexualfunction was associated with a tendency to choosewatchful waiting. High tumor stage and high PSA levelwere found to be associated with more aggressivetumors, and therefore these patients are more likely toproceed with aggressive therapy. Younger patientsand patients with better health status (normal urinaryfunction) benefit more from definitive treatment.Non-African-American patients tend to have highersocioeconomic status as well as fewer communicationbarriers with their physicians, which may partially ex-plain the different preferences between racial groupsin selecting definitive treatment. Patients are con-cerned with their sexual function when they selecttreatments. Those men with the normal sexual func-tion are more likely to choose watchful waiting topreserve their sexual function. The association ofhigher tumor stage and younger age with definitivetreatment choices reflects a responsible practice asrecommended by the AUA’s Prostate Cancer Guide-line Panel. The association between race, PSA level,and pretreatment urinary and sexual function and thetreatment decision provides further insight for physi-cians when counseling patients. Our findings from a


screening program become increasingly relevant asroutine screening for prostate carcinoma becomes acommon secondary prevention practice.

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primary treatment choices for men with clinically localized prostate carcinoma detected by screening

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