For prostate cancer patients with small, lower-grade tumors, expectant management with delayed surgical intervention (active surveillance) is a rarely used therapeutic option because the opportunity for cure may be lost. We compared outcomes of 38 patients with small, lower-grade prostate cancer in an expectant management program who underwent delayed surgical intervention at a median of 26.5 months (95% confidence interval [CI] = 17 to 32 months; range = 12.0–73.0 months) after diagnosis with 150 similar patients who underwent immediate surgical intervention at a median of 3.0 months (95% CI = 2 to 4 months; range = 1.0–9.0 months) after diagnosis. Noncurable cancer was defined as adverse pathology associated with a less than 75% chance of remaining disease-free for 10 years after surgery. Noncurable cancer was diagnosed in nine (23%) of the 38 patients in the delayed intervention cohort and in 24 (16%) of the 150 men in the immediate intervention group. After adjusting for age and prostate-specific antigen (PSA) density (i.e., PSA value divided by prostate volume) in a Mantel–Haenszel analysis, the risks of noncurable cancer associated with delayed and immediate intervention did not differ statistically significantly (relative risk = 1.08, 95% CI = 0.55 to 2.12; P = .819, two-sided Cochran–Mantel–Haenszel statistic). Age, PSA, and PSA density were all statistically significantly associated with the risk of noncurable cancer (P = .030, .013, and .008, respectively; two-sided chi-square test). Thus, delayed prostate cancer surgery for patients with small, lower-grade prostate cancers does not appear to compromise curability.

Objectives

To determine whether the number of times the prostate-specific antigen (PSA) velocity (PSAV) exceeds a threshold (PSAV risk count) is predictive of high-risk prostate cancer.

Methods

The PSAV was determined in 717 men (606 without prostate cancer; 32 with high-risk prostate cancer defined as death from cancer, PSA level of 20 ng/mL or more, or a Gleason score of 8 or more; and 79 with prostate cancer who were alive or dead of another cause). Multiple PSAVs determined from three repeated measures from each subject during 10 to 20 years were used to determine the risk count by summing the number of times a subject exceeded a PSAV threshold. Cox proportional hazards regression analysis was used to evaluate the associations between the risk count and the probability of high-risk disease. The statistical tests were two-sided.

Results

The probability of high-risk disease increased directly with the risk count. After adjusting for age, PSA level, PSAV, and date of diagnosis, the PSAV risk count was significantly associated with the development of high-risk prostate cancer (relative risk 1.41, 95% confidence interval 1.25 to 1.59 for a PSAV cutpoint 0.2 ng/mL/yr; relative risk 1.49, 95% confidence interval 1.29 to 1.71 for a PSAV cutpoint of 0.4 ng/mL/yr; P <0.001).

Conclusions

The PSAV risk count could be a useful method of interpreting a PSA history to help identify those men who will benefit from a diagnosis of prostate cancer at PSA levels associated with curable disease.

Background

Prostate-specific antigen (PSA) level is typically used as a dichotomous test for prostate cancer, resulting in overdiagnosis for a substantial number of men. The rate at which serum PSA levels change (PSA velocity) may be an important indicator of the presence of life-threatening disease.

Methods

PSA velocity was determined in 980 men (856 without prostate cancer, 104 with prostate cancer who were alive or died of another cause, and 20 who died of prostate cancer) who were participants in the Baltimore Longitudinal Study of Aging for up to 39 years. The relative risks (RRs) of prostate cancer death and prostate cancer–specific survival stratified by PSA velocity were evaluated in the three groups of men by Cox regression and Kaplan–Meier analyses. Statistical tests were two-sided.

Results

PSA velocity measured 10–15 years before diagnosis (when most men had PSA levels below 4.0 ng/mL) was associated with cancer-specific survival 25 years later; survival was 92% (95% confidence interval [CI] = 84% to 96%) among men with PSA velocity of 0.35 ng/mL per year or less and 54% (95% CI = 15% to 82%) among men with PSA velocity above 0.35 ng/mL per year (P<.001). Furthermore, men with PSA velocity above 0.35 ng/mL per year had a higher relative risk of prostate cancer death than men with PSA velocity of 0.35 ng/mL per year or less (RR = 4.7, 95% CI = 1.3 to 16.5; P = .02); the rates per 100 000 person-years were 1240 for men with a PSA velocity above 0.35 ng/mL per year and 140 for men with a PSA velocity of 0.35 ng/mL per year or less.

Conclusions

PSA velocity may help identify men with life-threatening prostate cancer during a period when their PSA levels are associated with the presence of curable disease.

Background

Elevated serum prostate-specific antigen (PSA) levels are predictive of a future diagnosis of prostate cancer. To test the hypothesis that older men with low PSA levels may require less intensive PSA testing because of a reduced prostate cancer detection rate, we evaluated the association between age, baseline PSA level, and prostate cancer detection.

Methods

We conducted a prospective cohort study among participants in a study of aging who had serial PSA measurements taken from age 60 or 65 years until they either were diagnosed with prostate cancer (cancer case subjects) or reached the age of 75 years (subjects without prostate cancer). The time of cancer detection among cancer case subjects was defined as the measurement date on which a PSA level above 4.0 ng/mL was detected (i.e., PSA conversion). Cancer case subjects and subjects without prostate cancer were analyzed according to baseline PSA level and age.

Results

All cancer case subjects in the 60-year-old cohort had baseline PSA levels above 0.5 ng/mL, and 14 of 15 cancer cases that would have been detected by a PSA conversion among the 65-year-old cohort were associated with baseline PSA levels of 1.1 ng/mL or more. If PSA testing were discontinued in men aged 65 years with PSA levels of 0.5 ng/mL or less, 100% (95% confidence interval [CI] = 78%–100%) of the cancers would still be detected by age 75 years; if PSA testing were discontinued in men aged 65 years who had PSA levels of 1.0 ng/mL or less, 94% (95% CI = 70%–100%) of the cancers would still be detected by age 75 years.

Conclusions

These data suggest that a decrease in the intensity of screening among older men with low PSA values may not lead to an increase in undetected prostate cancer.

Purpose

We sought to predict biopsy progression in men on prostate cancer surveillance.

Materials and Methods

A total of 376 men with a median age of 65.5 years (range 45.8 to 79.5) with low risk prostate cancer on surveillance underwent at least 1 followup biopsy after diagnosis. Progression was defined at surveillance biopsy as Gleason pattern 4 or 5, greater than 2 biopsy cores with cancer or greater than 50% involvement of any core with cancer. Proportional hazards analysis was used to evaluate the association between covariates and progression at surveillance biopsy. The Kaplan-Meier method was used to estimate the probability of disease progression.

Results

Of the 376 men 123 (32.7%) had progression a median of 5.6 years (range 0.3 to 8.5) after diagnosis. Percent free PSA and maximum percent core involvement at diagnosis were associated with progression, allowing stratification of the progression risk at initial surveillance biopsy. Cancer presence and PSA density at initial surveillance biopsy were associated with subsequent progression, allowing stratification of the cumulative incidence of progression 3 years after initial surveillance biopsy (cumulative incidence 11.1%, 95% CI 4.7 to 25.2 for negative biopsy and PSAD less than 0.08 ng/ml/cm3 vs 53.6%, 95% CI 38.6 to 70.0 for positive biopsy and PSAD 0.08 ng/ml/cm3 or greater, log rank test p < 0.0001).

Conclusions

Clinical variables at diagnosis and at first surveillance biopsy during followup in an active surveillance program can be used to inform men about the likelihood of an unfavorable prostate biopsy. This information could improve patient and physician acceptance of active surveillance in carefully selected men.

Purpose

The pathological characteristics of stage Tlc cancers in the era of widespread prostate specific antigen (PSA) testing were determined, and the ability of pretreatment parameters to predict tumor significance in men with stage Tlc disease was evaluated.

Materials and Methods

Of 336 men with stage Tlc prostate cancer seen between 1994 and 1996, 240 (71.4%) were treated with radical prostatectomy, 20 (6%) with radiation therapy and 76 (22.6%) expectantly. Recommendations for treatment were based on previously determined criteria predictive of a significant stage Tlc cancer (more than 0.2 cm.3: 1) PSA density 0.15 ng./ml./gm. or more, 2) Gleason score 7 or greater, 3) 3 or more cores involved with cancer, or 4) 50% or more involvement of any core with cancer. Pathological evaluation of prostatectomy specimens allowed classification of tumors as insignificant (confined tumor smaller than 0.2 cm.3 with a Gleason score of less than 7), minimal (confined tumor 0.2 to less than 0.5 cm.3 with a Gleason score of less than 7), moderate (0.5 cm.3 or larger disease, or capsular penetration with a Gleason score of less than 7) and advanced (capsular penetration with a Gleason score of 7 or more, or positive margins, seminal vesicles or lymph nodes). Pathological characteristics of tumors in this series were compared to a previous series of 157 men with stage Tlc cancers who underwent radical prostatectomy between 1988 and 1992.

Results

Of 240 men who underwent radical prostatectomy tumors were insignificant in 40 (17%), minimal in 29 (12%), moderate in 124 (52%) and advanced in 47 (19%). An increase in organ confined cancers (51 to 72%) and a decrease in positive margins (17 to 8%) were noted when comparing stage Tlc series (1988 to 1992 versus 1994 to 1996) but the percentage of insignificant tumors remained stable (16 versus 17%) between series. Ultrasound and sextant biopsies were available for review in 72 cases (current series). If the pretreatment criteria used to recommend therapy suggested significant tumor (64 cases) then insignificant tumor was present in only 10 (16%). If pretreatment criteria suggested insignificant tumor (8 cases), insignificant or minimal tumor was present in 6 (75%) and moderate organ confined disease was present in 2 (25%). The absence of a lesion on ultrasound and measurement of total length of cancer within the biopsy specimen were not predictive of an insignificant tumor.

Conclusions

In a nonscreened population stage Tlc cancers are being discovered earlier with widespread PSA testing. Even with the detection of earlier cancers we demonstrated that it is possible to minimize the number of patients with small tumors who will undergo radical prostatectomy using pretreatment criteria to counsel men regarding appropriate management options.

Objective

To evaluate longitudinal changes in prostate-specific antigen (PSA) levels in men with and without prostate disease.

Design

Case-control study of men with and without prostate disease who were participants in a prospective aging study.

Setting

Gerontology Research Center of the National Institute on Aging; the Baltimore (Md) Longitudinal Study of Aging.

Patients

Sixteen men with no prostate disease (control group), 20 men with a histologic diagnosis of benign prostatic hyperplasia (BPH), and 18 men with a histologic diagnosis of prostate cancer.

Outcome Measures

Multiple PSA and androgen determinations on serum samples obtained from 7 to 25 years prior to histologic diagnosis or exclusion of prostate disease.

Results

Changesin androgen levels with age did not differ between groups. Control subjects did not show a significant change in PSA levels with age. There was a significant difference in the age-adjusted rate of change in PSA levels between groups (prostate cancer>BPH>control; P<.01). At 5 years before diagnosis when PSA levels did not differ between subjects with BPH and prostate cancer, rate of change in PSA levels (0.75 μg/L per year) was significantly greater in subjects with prostate cancer compared with control subjects and subjects with BPH. Also, rate of change in PSA levels distinguished subjects with prostate cancer from subjects with BPH and control subjects with a specificity of 90% and 100%, respectively.

Conclusions

The most significant factor affecting serum PSA levels with age is the development of prostate disease. Rate of change in PSA levels may be a sensitive and specific early clinical marker for the development of prostate cancer.

PURPOSE

We assessed the use of quantitative clinical and pathologic information to predict which patients would eventually require treatment for prostate cancer (CaP) in an expectant management (EM) cohort.

EXPERIMENTAL DESIGN

We identified 75 men having prostate cancer with favorable initial biopsy characteristics; 30 developed an unfavorable biopsy (Gleason grade >6, >2 cores with cancer, >50% of a core with cancer, or a palpable nodule) requiring treatment and 45 maintained favorable biopsies throughout a median follow-up of 2.7years. Demographic, clinical data and quantitative tissue histomorphometry determined by digital image analysis were analyzed.

RESULTS

Logistic regression (LR) modeling generated a quantitative nuclear grade (QNG) signature based on the enrollment biopsy for differentiation of Favorable and Unfavorable groups using a variable LR selection criteria of Pz < 0.05. The QNG signature utilized 12 nuclear morphometric descriptors (NMDs) and had an area under the receiver operator characteristic curve (ROC-AUC) of 87% with a sensitivity of 82%, specificity of 70% and accuracy of 75%. A multivariable LR model combining QNG signature with clinical and pathological variables yielded an AUC-ROC of 88% and a sensitivity of 81%, specificity of 78% and accuracy of 79%. A LR model using prostate volume, PSA density, and number of pre-diagnosis biopsies resulted in an AUC-ROC of 68% and a sensitivity of 85%, specificity of 37% and accuracy of 56%.

CONCLUSIONS

QNG using EM prostate biopsies improves the predictive accuracy of LR models based on traditional clinicopathologic variables in determining which patients will ultimately develop an unfavorable biopsy. Our QNG-based model must be rigorously, prospectively validated prior to use in the clinical arena.

Purpose

The European Randomized Study of Screening for Prostate Cancer (ERSPC) reported a 20% mortality reduction with prostate-specific antigen (PSA) screening. However, they estimated a number needed to screen (NNS) of 1,410 and a number needed to treat (NNT) of 48 to prevent one prostate cancer death at 9 years. Although NNS and NNT are useful statistics to assess the benefits and harms of an intervention, in a survival study setting such as the ERSPC, NNS and NNT are time specific, and reporting values at one time point may lead to misinterpretation of results. Our objective was to re-examine the effect of varying follow-up times on NNS and NNT using data extrapolated from the ERSPC report.

Materials and Methods

On the basis of published ERSPC data, we modeled the cumulative hazard function using a piecewise exponential model, assuming a constant hazard of 0.0002 for the screening and control groups for years 1 to 7 of the trial and different constant rates of 0.00062 and 0.00102 for the screening and control groups, respectively, for years 8 to 12. Annualized cancer detection and drop-out rates were also approximated based on the observed number of individuals at risk in published ERSPC data.

Results

According to our model, the NNS and NNT at 9 years were 1,254 and 43, respectively. Subsequently, NNS decreased from 837 at year 10 to 503 at year 12, and NNT decreased from 29 to 18.

Conclusion

Despite the seemingly simplistic nature of estimating NNT, there is widespread misunderstanding of its pitfalls. With additional follow-up in the ERSPC, if the mortality difference continues to grow, the NNT to save a life with PSA screening will decrease.

Objective

To present an effective approach to the early detection of lethal prostate cancer using longitudinal data on prostate-specific antigen (PSA) and its rate of change, i.e. PSA velocity (PSAV). This longitudinal approach might also be extendible to other biomarkers.

Subjects and methods

PSAV was calculated using five techniques for 634 subjects with at least three PSA measurements in a longitudinal ageing study, censoring PSA levels of > 10 ng/mL. The efficacy for predicting death from prostate cancer was assessed with concordance indices and by using net reclassification improvement (NRI), which indicated the net increase in sensitivity and specificity when adding a biomarker to a base Cox proportional hazards model. The PSAV techniques were compared for the 5–10 years before the clinical diagnosis of prostate cancer. The most effective technique was then applied at the transition point when each man's PSA history curve transformed from linear to exponentially increasing, and its predictive value was compared to that of concurrent PSA level.

Results

A PSA transition point was found in 522 (82%) of the 634 men, including all 11 who died from prostate cancer. At the transition point, the mean PSA level was 1.4 ng/mL, and PSAV but not PSA level was significantly higher among men who died from prostate cancer than among men who did not (P = 0.021 vs P = 0.112; Wilcoxon two-sample test). At the transition point, adding PSAV to a base model consisting of age and date of diagnosis improved the concordance index by 0.05, and significantly improved the overall sensitivity and specificity (NRI, P = 0.028), while adding PSA level to the same base model resulted in little improvement (concordance index increase < 0.01 and NRI P = 0.275).

Conclusion

When the shape of a man's PSA history curve changes from linear to exponential, PSAV might help in the early identification of life-threatening prostate cancer at a time when PSA values are still low in most men.

OBJECTIVE

To evaluate the relationship between testosterone levels and the development of high-risk prostate cancer, by prospectively examining serum androgen concentrations in a well-studied cohort, as the role of testosterone in prostate cancer progression is debated.

PATIENTS AND METHODS

The study comprised 781 men in the Baltimore Longitudinal Study of Aging who had sex steroid measurements before a diagnosis of prostate cancer, or at their last visit for those without cancer (no cancer, 636; cancer, not high risk, 109; cancer, high risk, 36). High-risk cancer was defined as death from prostate cancer, a prostate specific antigen (PSA) level of ≥20 ng/mL at diagnosis, or a Gleason score of ≥8. The hazard ratio (HR) of high-risk disease was determined using a Cox proportional hazards regression model with simple updating, and risk rates were stratified by age and tercile for androgens of interest based on the proportional hazards analyses.

RESULTS

The likelihood of high-risk prostate cancer doubled per unit (0.1) increase in the free testosterone index (FTI) for patients aged >65 years (HR 2.07, 95% confidence interval, CI, 1.01–4.23; P = 0.047); the likelihood for men aged ≤65 years was inversely related to the FTI (HR 0.96, 95% CI 0.35–2.6; P = 0.9). The risk rate per person-years increased from lowest to highest tercile of FTI for the oldest men (age >70 years) but this trend was not apparent among younger men.

CONCLUSION

Higher levels of serum free testosterone are associated with an increased risk of aggressive prostate cancer among older men. These data highlight the importance of prospective trials to insure the safety of testosterone-replacement therapy.

Purpose

We assessed the association of quantitative clinical and pathologic information, including serum and tissue proPSA, with outcomes among men with prostate cancer (PCa) managed expectantly.

Experimental Design

We identified 71 men enrolled in expectant management (EM) with frozen serum and tissue available from diagnosis. 39 subsequently developed unfavorable biopsies (Gleason score>=7, >=3 cores positive for cancer, >50% of any core involved with cancer), while 32 maintained favorable biopsies (median follow-up: 3.93 years). Serum tPSA, fPSA and [−2]proPSA were measured by the Beckman Coulter immunoassay. [−5/−7]proPSA was evaluated in cancer and benign adjacent tissue areas (BAA) by quantitative immunohistochemistry. Cox proportional hazards and Kaplan-Meier analyses were used to identify significant associations with unfavorable biopsy conversion.

Results

The ratio [−2]proPSA/%fPSA in serum was significantly higher at diagnosis (0.87+/−0.44pg/mL vs. 0.65+/−0.36pg/mL, p=0.02) in men developing unfavorable biopsies. [−5/−7]proPSA tissue staining was more intense (4104.09+/−3033.50 vs. 2418.06+/−1606.04, p=0.03) and comprised a greater fractional area (11.58%+/−7.08% vs. 6.88%+/−5.20%, p=0.01) in BAA of these men. Serum [−2]proPSA/%fPSA [HR:2.53(1.18–5.41), p=0.02], BAA [−5/−7]proPSA %area [HR:1.06(1.01–1.12), p=0.02] and BAA [−5/−7]proPSA stain intensity [HR:1.000213(1.000071–1.000354), p=0.003] were significantly associated with unfavorable biopsy in Kaplan-Meier and Cox analyses. Serum [−2]proPSA/%fPSA significantly correlated with BAA [−5/−7]proPSA %area (rho=0.40, p=0.002) and BAA [−5/−7]proPSA stain intensity (rho=0.33, p=0.016).

Conclusions

In a prospective cohort of men enrolled into EM for PCa, serum and tissue levels of proPSA at diagnosis are associated with need for subsequent treatment. The increase in serum proPSA/%fPSA might be driven by increased proPSA production from “pre-malignant” cells in the prostate BAA.

Purpose

Prostate specific antigen testing is common in the elderly despite evidence that older men without aggressive prostate cancer are unlikely to benefit from diagnosis and treatment. We evaluated the relationship between prostate specific antigen and the risk of aggressive prostate cancer developing in men of various ages.

Materials and Methods

This longitudinal cohort study consisted of 849 men (122 with and 727 without prostate cancer) with serial prostate specific antigen measurements participating in the Baltimore Longitudinal Study of Aging. The primary outcome measure was the proportion of men by prostate specific antigen and age who died of prostate cancer or in whom aggressive prostate cancer developed (death from prostate cancer, a prostate specific antigen 20 ng/ml or greater, or Gleason score 8 or greater).

Results

No participants between 75 and 80 years old with a prostate specific antigen less than 3.0 ng/ml died of prostate cancer. In contrast, men of all ages with a prostate specific antigen of 3.0 ng/ml or greater had a continually increasing probability of death from prostate cancer (Fisher’s exact test p <0.001). The time to death or diagnosis of aggressive prostate cancer after age 75 years was not significantly different between the prostate specific antigen categories of 3 to 3.9 and 4 to 9.9 ng/ml (p = 0.634), whereas the time to death or diagnosis of high risk prostate cancer was significantly longer for the prostate specific antigen category of less than 3 vs 3 ng/ml or greater (p = 0.019).

Conclusions

Men 75 to 80 years old with a prostate specific antigen less than 3 ng/ml are unlikely to die of or experience aggressive prostate cancer during their remaining life, suggesting that prostate specific antigen testing might be safely discontinued for these men.

Background

Our group has previously shown that prostate-specific antigen (PSA) velocity (PSAV) is associated with the presence of life-threatening prostate cancer. Less is known about the relative utility of pretreatment PSA doubling time (PSA DT) to predict tumor aggressiveness.

Objective

To compare the utility of PSAV and PSA DT for the prediction of life-threatening prostate cancer.

Design, setting, and participants

From the Baltimore Longitudinal Study of Aging, we identified 681 men with serial PSA measurements.

Measurements

Receiver operating characteristic analysis was used to evaluate the relationship between PSAV, PSA DT, and the presence of high-risk disease.

Results and limitations

Within the period of 5 yr prior to diagnosis, PSAV was significantly higher among men with high-risk or fatal prostate cancer than men without it. By contrast, PSA DT was not significantly associated with high-risk or fatal disease. On multivariate analysis, including age, date of diagnosis, and PSA, the addition of PSAV significantly improved the concordance index from 0.85 to 0.88 (p < 0.001), whereas PSA DT did not.

Conclusions

These data suggest that PSAV is more useful than PSA DT in the pretreatment setting to help identify those men with life-threatening disease.

Background

Some, but not all, published results have shown an association between circulating blood levels of some insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) and the subsequent risk for prostate cancer.

Purpose

To assess the association between levels of IGFs and IGFBPs and the subsequent risk for prostate cancer.

Data Sources

Studies identified in PubMed, Web of Science, and CancerLit.

Study Selection

The principal investigators of all studies that published data on circulating concentrations of sex steroids, IGFs, or IGFBPs and prostate cancer risk using prospectively collected blood samples were invited to collaborate.

Data Extraction

Investigators provided individual participant data on circulating concentrations of IGF-I, IGF-II, IGFBP-II, and IGFBP-III and participant characteristics to a central data set in Oxford, United Kingdom.

Data Synthesis

The study included data on 3700 men with prostate cancer and 5200 control participants. On average, case patients were 61.5 years of age at blood collection and received a diagnosis of prostate cancer 5 years after blood collection. The greater the serum IGF-I concentration, the greater the subsequent risk for prostate cancer (odds ratio [OR] in the highest vs. lowest quintile, 1.38 [95% CI, 1.19 to 1.60]; P < 0.001 for trend). Neither IGF-II nor IGFBP-II concentrations were associated with prostate cancer risk, but statistical power was limited. Insulin-like growth factor I and IGFBP-III were correlated (r = 0.58), and although IGFBP-III concentration seemed to be associated with prostate cancer risk, this was secondary to its association with IGF-I levels. Insulin-like growth factor I concentrations seemed to be more positively associated with low-grade than high-grade disease; otherwise, the association between IGFs and IGFBPs and prostate cancer risk had no statistically significant heterogeneity related to stage or grade of disease, time between blood collection and diagnosis, age and year of diagnosis, prostate-specific antigen level at recruitment, body mass index, smoking, or alcohol intake.

Limitations

Insulin-like growth factor concentrations were measured in only 1 sample for each participant, and the laboratory methods to measure IGFs differed in each study. Not all patients had disease stage or grade information, and the diagnosis of prostate cancer may differ among the studies.

Conclusion

High circulating IGF-I concentrations are associated with a moderately increased risk for prostate cancer.

Purpose

Although prostate specific antigen velocity was proposed to increase the specificity of prostate specific antigen-based screening, there are little published data on the effect of differential prostate growth on prostate specific antigen velocity. If a patient presents with rising prostate specific antigen over a year or more, it would be useful to know whether such a change in prostate specific antigen could be explained by prostate growth. Thus, we investigated the relationship between changes in prostate size and prostate specific antigen changes in a large cohort of men without prostate cancer.

Materials and Methods

We identified 242 men without prostate cancer from the Baltimore Longitudinal Study of Aging who had 2 or greater serial pelvic magnetic resonance imaging studies and contemporaneous prostate specific antigen measurements. In this population we used the t test, correlation coefficients, and regression analysis to examine the relationship between prostate specific antigen changes and prostate volume changes, as assessed by magnetic resonance imaging.

Results

The mean age was 55 years. During 4.2 years of median followup, the median rate of volume change was 0.6 cc per year (range −9.9 to 11.8), and the median prostate specific antigen change was 0.03 ng/ml per year. There was no correlation between prostate specific antigen changes and prostate growth, as measured in cc per year (r = −0.01, p = 0.9) or the percent change per year (r = 0.07, p = 0.3). On multivariate analysis, there was no significant relationship between changes in prostate volume and prostate specific antigen changes.

Conclusions

Our data suggest that volume increases alone do not cause a high prostate specific antigen velocity. Despite growth rates as high as 10 cc per year, prostate specific antigen velocity was less than 0.1 ng/ml per year in most men without prostate cancer. Thus, differential rates of prostatic growth should not confound the use of prostate specific antigen velocity for prostate cancer detection and prognostication.

Context

Benign prostatic hyperplasia poses a significant public health problem, but its etiology remains unclear. Obesity and associated abnormalities in glucose homeostasis may play a role in benign prostatic hyperplasia development by influencing prostate growth.

Objective

The objective of this study was to determine whether obesity, fasting plasma glucose concentration, and diabetes are associated with radiologically determined prostate enlargement, an objective measure of benign prostatic hyperplasia.

Design

This study was a cross-sectional analysis with robust variance estimates to account for multiple measures over time in the same individuals.

Setting

This prospective cohort study was composed of community volunteers.

Patients

Patients studied were 422 adult men enrolled in The Baltimore Longitudinal Study of Aging.

Main Outcome Measurements

Total prostate volume as determined by pelvic magnetic resonance imaging was measured.

Results

Among 422 participants, 91 (21.6%) had prostate enlargement (defined as total prostate volume ≥ 40 cc) at first visit. Compared with men of normal weight [body mass index (BMI) < 25 kg/m2], the age-adjusted odds ratio (OR) for prostate enlargement for overweight men (BMI, 25–29.9 kg/m2) was 1.41 (95% CI, 0.84–2.37), for obese men (BMI, 30–34 kg/m2) was 1.27 (95% CI, 0.68–2.39), and for severely obese men (BMI ≥ 35 kg/m2) was 3.52 (95% CI, 1.45–8.56) (P = 0.01). Men with elevated fasting glucose (> 110 mg/dl) were more likely to have an enlarged prostate than men with normal fasting glucose (≤110 mg/dl) (OR, 2.98; 95% CI, 1.70–5.23), as were men with a diagnosis of diabetes (OR, 2.25; 95% CI, 1.23–4.11).

Conclusions

Obesity, elevated fasting plasma glucose, and diabetes are risk factors for benign prostatic hyperplasia.