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Biomedical subjects

Stephen J Freedland

Publications and source records attributed to Stephen J Freedland.

At least 19 recordsLinked to original sources

Changing nature of high risk patients undergoing radical prostatectomy.

PURPOSE: We examined the outcomes of radical prostatectomy alone in high risk patients with prostate cancer and evaluated changes in high risk prostate cancer outcomes with time. MATERIALS AND METHODS: From 1988 to 2003, 251 men with high risk prostate cancer (prostate specific antigen more than 20 ng/ml and/or biopsy Gleason greater than 7) were identified in a cohort of 1,796 (14%) enrolled in the Shared Equal Access Regional Cancer Hospital Database. Temporal changes in clinicopathological characteristics and prostate specific antigen recurrence rates were examined stratified by 4, 4-year periods. RESULTS: With time significantly more men were considered at high risk due to a high biopsy Gleason score relative to prior years, when the most common reason for being considered at high risk was increased PSA (p <0.001). Only 3% of high risk men from 2000 to 2003 had increased prostate specific antigen and high biopsy Gleason score compared to 23% from 1988 to 1991. With time there were no differences in biochemical recurrence rates (p = 0.147). Men with a high biopsy Gleason score and increased prostate specific antigen had worse outcomes than men with only a high Gleason score or men with only high prostate specific antigen (p = 0.046 and 0.081, respectively). On multivariate analysis that only included preoperative clinical characteristics only prostate specific antigen was an independent predictor of prostate specific antigen failure following radical prostatectomy (p = 0.014). There was a trend, which did not attain statistical significance, for higher biopsy Gleason scores and higher clinical stage to be associated with higher failure rates (p = 0.060 and 0.081, respectively). CONCLUSIONS: Patients are designated as high risk by Gleason grade more commonly now than early in the prostate specific antigen era. Outcomes in high risk patients undergoing radical prostatectomy alone have not significantly improved with time. New treatment strategies, such as multimodality therapy, are needed to improve outcomes in high risk patients with prostate cancer.

Aged↗

Body mass index, weight change, and risk of prostate cancer in the Cancer Prevention Study II Nutrition Cohort.

BACKGROUND: Obesity has been associated with aggressive prostate cancer. The extent of this association, which varies by stage and grade, remains unclear. The role of recent weight change had not been previously examined. METHODS: We examined body mass index (BMI) and weight change in relation to incident prostate cancer by disease stage and grade at diagnosis among 69,991 men in the Cancer Prevention Study II Nutrition Cohort. Participants provided information on height and weight in 1982, and again at enrollment in 1992. During follow-up through June 30, 2003 (excluding the first 2 years of follow-up), we documented 5,252 incident prostate cancers. Cox proportional hazards models were used to estimate rate ratios (RR) and 95% confidence intervals (95% CI). RESULTS: The association between BMI in 1992 and risk of prostate cancer differed by stage and grade at diagnosis. BMI was inversely associated with risk of nonmetastatic low-grade prostate cancer (RR, 0.84; 95% CI, 0.66-1.06), but BMI was positively associated with risk of nonmetastatic high-grade prostate cancer (RR, 1.22; 95% CI, 0.96-1.55) and risk of metastatic or fatal prostate cancer (RR, 1.54; 95% CI, 1.06-2.23). Compared with weight maintenance, men who lost >11 pounds between 1982 and 1992 were at a decreased risk of nonmetastatic high-grade prostate cancer (RR, 0.58; 95% CI, 0.42-0.79). CONCLUSION: Obesity increases the risk of more aggressive prostate cancer and may decrease either the occurrence or the likelihood of diagnosis of less-aggressive tumors. Men who lose weight may reduce their risk of prostate cancer.

Aged↗

Multiinstitutional validation of the UCSF cancer of the prostate risk assessment for prediction of recurrence after radical prostatectomy.

BACKGROUND: The University of California, San Francisco (UCSF) Cancer of the Prostate Risk Assessment (CAPRA) is a novel preoperative index which predicts the risk of biochemical recurrence after radical prostatectomy. The performance of the index is at least as good as the best available instruments based on clinical variables, and the 0 to 10 score is simple to calculate for both clinical and research purposes. This study used a large external dataset to validate CAPRA. METHODS: Data were abstracted from the Shared Equal Access Regional Cancer Hospital (SEARCH) database, a registry of men who underwent radical prostatectomy at 4 Veterans Affairs and 1 active military medical center. Of 2096 men in the database, 1346 (64%) had full data available to calculate the CAPRA score. Performance of the CAPRA score was assessed with proportional hazards regression, survival analysis, and the concordance (c) index. RESULTS: Of the studied patients, 41% were non-Caucasian, and their mean age was 62 years. Twenty-six percent suffered recurrence; median follow-up among patients who did not recur was 34 months. The hazard ratio (HR) for each 1-point increase in CAPRA was 1.39 (95% CI [confidence interval], 1.31-1.46). The 5-year recurrence-free survival rate ranged from 86% for CAPRA 0-1 patients to 21% for CAPRA 7-10 patients. Increasing CAPRA scores were significantly associated with increasing risk of adverse pathologic outcomes. The c-index for CAPRA for the validation set was 0.68, compared with 0.66 for the original development set. CONCLUSIONS: The UCSF-CAPRA accurately predicted both biochemical and pathologic outcomes after radical prostatectomy among a large, diverse, cohort of men. These results validated the effectiveness of this powerful and straightforward instrument.

Adult↗

Clinical and pathologic outcome after radical prostatectomy for prostate cancer patients with a preoperative Gleason sum of 8 to 10.

BACKGROUND: Men with a biopsy Gleason sum of 8 to 10 are considered high-risk. The current study sought to identify whether there was a subset of men with high biopsy Gleason sums who would have a good pathologic and biochemical outcome with surgical monotherapy. To increase the generalizability of the findings, data were used from patients treated at 2 very different practice settings: a tertiary care referral center (Johns Hopkins Hospital) and multiple equal-access medical centers (Shared Equal Access Regional Cancer Hospital [SEARCH] Database). METHODS: The data were retrospectively reviewed from men with biopsy Gleason sums 8 to 10 treated by radical prostatectomy at the Johns Hopkins Hospital (n = 220, 3.8% of total cohort) and within the SEARCH Database (n = 149, 7.7% of total cohort). The preoperative clinical characteristics predicting unfavorable pathologic disease (nonorgan-confined and/or positive surgical margins) and time to biochemical recurrence were determined using logistic regression and Cox proportional hazards analysis, respectively. RESULTS: Favorable pathologic outcome (organ-confined and negative surgical margins) was observed in 21% of the men in the Johns Hopkins cohort and 41% from the SEARCH cohort. On multivariate analysis, higher serum prostate-specific antigen (PSA) was the only variable that significantly predicted an unfavorable pathologic outcome from both the Johns Hopkins (P = .047) and SEARCH cohorts (P = .002). The 5-year and 10-year estimated biochemical-free survival rates in the Johns Hopkins cohort were 40% (95% confidence interval [CI], 33-48%) and 27% (95% CI, 18-36%), respectively, and 32% (95% CI, 22-42%) and 28% (95% CI, 18-38%) in the SEARCH cohort, respectively. Among men with favorable pathologic findings, the 5- and 10-year estimated biochemical-free survival rates in the Johns Hopkins cohort were 79% (95% CI, 62-89%) and 50% (95% CI, 25-71%), respectively, and 49% (95% CI, 32-65%) and 49% (95% CI, 32-65%) in the SEARCH cohort, respectively. No single preoperative variable significantly predicted the risk of biochemical progression in both the SEARCH or Johns Hopkins cohorts. CONCLUSIONS: The majority of men with a biopsy Gleason sum of >or=8, regardless of where the patient is treated, had unfavorable pathologic disease and experienced a biochemical progression after radical prostatectomy. Even among men with organ-confined disease and negative surgical margins or pathologic Gleason sum <8, at least half of the men experienced a PSA recurrence. Patients with biopsy Gleason sum 8 to 10 cancers are good candidates for multimodal therapy. Whereas multimodal therapy has often meant radiation plus hormonal therapy, newer possibilities for multimodal therapy exist such as surgery with neoadjuvant or adjuvant chemohormonal therapy or surgery with adjuvant radiation.

Aged↗

Effect of altering dietary omega-6/omega-3 fatty acid ratios on prostate cancer membrane composition, cyclooxygenase-2, and prostaglandin E2.

PURPOSE: To determine whether altering the dietary content of omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids affects the growth of androgen-sensitive prostate cancer xenografts, tumor membrane fatty acid composition, and tumor cyclooxygenase-2 and prostaglandin E(2) (PGE(2)) levels. EXPERIMENTAL DESIGN: Individually caged male severe combined immunodeficiency mice were fed isocaloric 20% kcal fat diets with the fat derived either primarily from n-6 fatty acids (n-6 group) or with the fat consisting of n-6 and n-3 fatty acids in a ratio of 1:1 (n-3 group), and injected s.c. with Los Angeles Prostate Cancer 4 (LAPC-4) cells. Tumor volumes and mouse weights were measured weekly, caloric intake was measured 3 days per week, and tumors and serum were harvested at 8 weeks postinjection. RESULTS: Tumor growth rates, final tumor volumes, and serum prostate-specific antigen levels were reduced in the n-3 group relative to the n-6 group. The n-3 group tumors had decreased proliferation (Ki67 staining) and increased apoptosis (terminal nucleotidyl transferase-mediated nick end labeling staining). In vitro proliferation of LAPC-4 cells in medium containing n-3 group serum was reduced by 22% relative to LAPC-4 cells cultured in medium containing serum from the n-6 group. The n-6/n-3 fatty acid ratios in serum and tumor membranes were lower in the n-3 group relative to the n-6 group. In addition, n-3 group tumors had decreased cyclooxygenase-2 protein and mRNA levels, an 83% reduction in PGE(2) levels, and decreased vascular endothelial growth factor expression. CONCLUSION: These results provide a sound basis for clinical trials evaluating the effect of dietary n-3 fatty acids from fish oil on tumor PGE(2) and membrane fatty acid composition, and serum and tumor biomarkers of progression in men with prostate cancer.

Administration, Oral↗

Are findings from studies of obesity and prostate cancer really in conflict?

Recent studies on the association between obesity and prostate cancer appear to be in conflict. A recent prospective cohort study reported that the incidence of prostate cancer was lower among obese men under the age of 60 years and among those men with a family history of prostate cancer. Similarly, a case-control study found obesity was inversely associated with prostate cancer risk in men aged 40-64 years. However, several prospective cohort studies found that obese men are more likely to die from prostate cancer than non-obese men. Finally, two recent studies found that among men with prostate cancer, obese men were more likely to have a biochemical progression after surgery. We postulate that by closely examining the comparison groups used in these studies, these findings may, in fact, be in agreement. Specifically, this paradox within the literature may result from the possibility that obesity influences the development of aggressive (i.e., higher stage, higher grade, recurrence, death) and non-aggressive disease differently. We suggest that obesity may reduce the risk of non-aggressive disease but simultaneously increase the risk of aggressive disease. Finally, additional methodological issues are discussed that investigators need to be aware of to be able to draw inferences across studies of obesity and prostate cancer outcomes.

Disease Progression↗

Pathological outcomes and biochemical progression in men with T1c prostate cancer undergoing radical prostatectomy with prostate specific antigen 2.6 to 4.0 vs 4.1 to 6.0 ng/ml.

PURPOSE: Recent studies have suggested that the cut point for recommending prostate biopsy among men with a normal digital rectal examination should be greater than 2.5 ng/ml as opposed to the more traditional greater than 4.0 ng/ml. We compared outcomes between men with clinical stage T1c disease undergoing radical prostatectomy who had a low vs slightly increased prostate specific antigen. MATERIALS AND METHODS: The study population consisted of 2,896 men treated with radical prostatectomy between 1985 and 2004 at a tertiary care referral center with clinical stage T1c disease and a pre-biopsy prostate specific antigen between 2.6 and 6.0 ng/ml. Using multivariate analysis we evaluated the association between pre-biopsy prostate specific antigen 2.6 to 4.0 ng/ml (784) vs 4.1 to 6.0 ng/ml (2,112), and pathological outcomes and biochemical progression. RESULTS: After adjusting for multiple clinical and pathological characteristics, lower preoperative serum prostate specific antigen values were associated with decreased odds of Gleason score 7 or greater in the surgical specimen (p = 0.004), positive surgical margins (p = 0.02) and extraprostatic extension (p = 0.001). There was no significant association between these preoperative prostate specific antigen groups and odds of seminal vesicle invasion (p = 0.47) or lymph node metastasis (p = 0.90). Among the 1,534 men with followup information available there was a trend for increased risk of biochemical progression associated with a higher preoperative prostate specific antigen, although this trend did not reach statistical significance (relative risk 1.48, 95% CI 0.69-3.19, p = 0.31). CONCLUSIONS: In the current study of men with clinical stage T1c treated with radical prostatectomy a lower preoperative prostate specific antigen was associated with significantly more favorable pathological findings. Whether this degree of improved outcomes justifies the limitations associated with decreasing the prostate specific antigen cut point (eg increased biopsies performed and diagnosis of insignificant cancers) remains to be determined.

Disease Progression↗

Black race does not independently predict adverse outcome following radical retropubic prostatectomy at a tertiary referral center.

PURPOSE: There is controversy in the literature as to whether black race is associated with poorer oncological outcomes among men undergoing radical prostatectomy for clinically localized prostate cancer. To address this issue we examined the outcomes of a cohort of black and white men treated by multiple surgeons at our institution. MATERIALS AND METHODS: The study population consisted of 4,962 white and 326 black men treated with anatomical radical retropubic prostatectomy between 1988 and 2004 by 10 different surgeons at the Johns Hopkins Hospital, a tertiary care referral center. We evaluated the association between race and adverse pathological features, and biochemical progression. RESULTS: Black men had significantly higher preoperative serum prostate specific antigen (mean 7.2 vs 6.0 ng/ml, p <0.001), body mass index (median 27.4 vs 26.3 kg/m, p <0.001) and incidence of higher grade disease (Gleason sum 4 + 3 or greater) on prostate biopsy (17% vs 14%, p = 0.011). After adjustment for multiple clinical variables there was no statistically significant association between race and the adverse pathological characteristics of high grade disease, positive surgical margins, extraprostatic extension or seminal vesicle invasion. Black race was associated with a significantly increased risk of biochemical progression on univariate analysis (HR 1.52, 95% CI 1.16-2.00, p = 0.002). However, after adjusting for clinical and pathological characteristics, black race was not an independent predictor of biochemical progression (HR 1.09, 95% CI 0.81-1.45, p = 0.578). CONCLUSIONS: Black men were more likely to be obese and present with adverse preoperative clinical features at a younger age, and have a higher rate of biochemical progression. However, on multivariate analysis black race was not an independent predictor of adverse pathological outcome or biochemical recurrence. Further efforts are needed to detect prostate cancer earlier among black men.

Adenocarcinoma↗

Time to prostate specific antigen recurrence after radical prostatectomy and risk of prostate cancer specific mortality.

PURPOSE: In patients treated with radical prostatectomy who have biochemical recurrence we have previously reported that time from surgery to biochemical recurrence and postoperative prostate specific antigen doubling time are significantly related to the risk of prostate cancer death. We performed a more thorough examination of the association of time from surgery to biochemical recurrence and the risk of prostate cancer death. MATERIALS AND METHODS: We retrospectively studied the records of 379 patients treated with radical prostatectomy between 1982 and 2000 who had had biochemical recurrence. We examined the association of time from surgery to prostate specific antigen recurrence and prostate specific antigen doubling time, and the risk of prostate cancer death using the Spearman correlation and Cox proportional hazards regression, respectively. RESULTS: Longer time from surgery to prostate specific antigen recurrence was associated with a slower prostate specific antigen doubling time (Spearman r = 0.36, p < 0.001) and a decreased risk of prostate cancer death (RR 0.76, 95% CI 0.66 to 0.88, p < 0.001). The 15-year actuarial prostate cancer specific survival rate after biochemical recurrence in patients with recurrence at 3 years or less was 41% (95% CI 29 to 53) compared to 87% (95% CI 75 to 93) in patients with recurrence more than 3 years after radical prostatectomy. On multivariate analysis a shorter time from surgery to prostate specific antigen recurrence was associated with an increased risk of prostate cancer death (3 or less vs more than 3 years, RR 2.70, 95% CI 1.37 to 5.31, p = 0.004). CONCLUSIONS: Earlier prostate specific antigen recurrence is associated with an increased risk of prostate cancer death. These data suggest that perhaps time to prostate specific antigen recurrence may be a reasonable intermediate end point in patients treated with radical prostatectomy, although this must be validated in other studies.

Aged↗

Is biopsy Gleason score independently associated with biochemical progression following radical prostatectomy after adjusting for pathological Gleason score?

PURPOSE: Biopsy Gleason score is known to be associated with prostate specific antigen failure following radical prostatectomy. However, it is unclear whether it remains associated with outcome after surgery when the pathological Gleason score is known. MATERIALS AND METHODS: We determined the association between biopsy Gleason score and biochemical progression after correcting for preoperative and postoperative characteristics, including pathological Gleason score, in 1,931 men treated with radical prostatectomy between 1988 and 2005 in the Shared Equal Access Regional Cancer Hospital Database Study Group database. Gleason score was examined as a categorical variable of 2 to 6, 3 + 4 and 4 + 3 or greater. RESULTS: Higher biopsy Gleason scores were positively associated with extracapsular extension (p <0.001), positive surgical margins (p <0.001), seminal vesicle invasion (p <0.001), positive lymph nodes (p <0.001) and biochemical progression (log rank p <0.001). After adjusting for only preoperative characteristics biopsy Gleason 3 + 4 and 4 + 3 or greater were associated with increased risk of biochemical progression compared to biopsy Gleason 6 or less (p = 0.001 and <0.001, respectively). After further adjusting for multiple pathological characteristics, including pathological Gleason score, the association between higher biopsy Gleason score and progression was little changed, in that men with biopsy Gleason 3 + 4 and 4 + 3 or greater were significantly more likely to experience progression (p = 0.001 and <0.001, respectively). Furthermore, when stratified by pathological Gleason score, higher biopsy Gleason scores were associated with an increased risk of biochemical progression in each pathological Gleason score category (log rank p </=0.007). CONCLUSIONS: Biopsy Gleason score remained strongly associated with progression even when the pathological Gleason score was known and controlled for. If confirmed at other centers, incorporation of biopsy Gleason score into postoperative nomograms designed to estimate the progression risk might improve model precision.

Aged↗

Insight on pathogenesis of varicoceles: relationship of varicocele and body mass index.

OBJECTIVES: Varicoceles, present in 15% to 20% of men, are the most common abnormal finding among men presenting with infertility, yet controversy exists regarding their etiology. Anecdotal experience suggests that varicoceles are more prevalent in lean men, supporting the "nutcracker" effect of the superior mesenteric artery compressing the left renal vein over the aorta. We examined this hypothesis in a large adult population. METHODS: A total of 2106 men were evaluated for infertility or erectile dysfunction from 1990 to 1996. The men were examined for the presence and severity of a varicocele. The association between age, height, body mass index, year of evaluation, and reason for consultation and the presence and severity of a varicocele was examined using logistic regression analysis. RESULTS: The mean age was 47 years (range 18 to 85), and the median body mass index was 26.4 kg/m2 (range 15.4 to 53.3). A varicocele was present in 398 men (18.9%). Stratified by grade, 59 (14.8%) were grade III, 155 (38.9%) were grade II, and 184 (46.2%) were grade I. The prevalence of varicoceles in the erectile dysfunction group (12.7%) was significantly less (P <0.001) than in the infertile group (32.2%). Multivariate logistic regression analysis revealed a statistically significant inverse relationship between body mass index and the presence of a varicocele. CONCLUSIONS: Varicoceles were less likely to be diagnosed among obese men. Although this suggests that the "nutcracker" phenomenon or other biophysical effects of increased adiposity may play a role in the pathogenesis, other factors could not be excluded as contributing to our findings.

Adolescent↗

Obesity, serum prostate specific antigen and prostate size: implications for prostate cancer detection.

PURPOSE: Obesity has been associated with lower serum testosterone, theoretically resulting in decreased PSA production. Obesity has also been associated with prostatic enlargement, making the detection of existent cancer more difficult. Together these findings would result in an apparent protective effect of obesity on prostate cancer risk due to technical detection issues unrelated to cancer biology. We examined the association between BMI, and PSA and prostate weight in a cohort of men undergoing RP. MATERIALS AND METHODS: We evaluated the association of BMI with prostate weight and PSA using linear regression, adjusting for patient age at RP, year of RP, race, and pathological stage and grade in 1,414 men treated with RP between 1988 and 2004 at the 5 equal access medical centers that comprise the Shared Equal Access Regional Cancer Hospital Database. RESULTS: On multivariate analysis increasing BMI was associated with increasing prostate weight but only in men younger than 63 years and not in men 63 years or older (p-trend <0.001 and 0.44, respectively). In men younger than 63 years mean multivariate adjusted prostate weight +/- SE in those with a BMI of less than 25 vs 30 to 34.9 kg/m was 33.8 +/- 1.4 vs 41.4 +/- 1.6 gm. There was no significant association between BMI and preoperative PSA (p-trend = 0.70). CONCLUSIONS: In a cohort of men undergoing RP obesity was associated with larger prostate size but only in younger men. There was no association between BMI and PSA. Assuming equal PSA, the degree of prostatic enlargement observed in younger obese men in this study would be expected to result in a modest decrease in the odds of detecting prostate cancer in a contemporary series of PSA screened men due to the decreased sensitivity of cancer detection related to larger prostate size. Obesity may appear protective for prostate cancer in younger men due to technical issues unrelated to cancer biology.

Humans↗

Delay of radical prostatectomy and risk of biochemical progression in men with low risk prostate cancer.

PURPOSE: Men newly diagnosed with prostate cancer are faced with multiple treatment options. Understanding these options and their associated side effects, and making a decision often requires time, resulting in a delay before receiving treatment. This is particularly pertinent in men with low risk disease who may be considered candidates for watchful waiting and, thus, may not experience strong pressure to undergo treatment promptly. Whether delays and especially prolonged delays, eg greater than 180 days, before RP negatively impact the disease outcome is unclear. MATERIALS AND METHODS: We examined the association between time from diagnosis to surgery, and pathological features of the RP specimen and risk of biochemical progression in 895 men with low risk prostate cancer (prostate specific antigen less than 10 ng/ml and biopsy Gleason sum 6 or less) treated with RP between 1988 and 2004 in the Shared-Equal Access Regional Cancer Hospital Database using logistic regression and Cox proportional hazards, respectively. RESULTS: Time from biopsy to surgery was not significantly related to high grade disease in the RP specimen, positive surgical margins or extraprostatic extension (all p-trend >0.05). After adjustment for multiple clinical covariates a longer time from biopsy to surgery was significantly associated with an increased risk of biochemical progression (p-trend = 0.002). However, this increased risk of progression was only apparent in men with delays greater than 180 days (median 263, vs 90 or fewer days RR 2.73, 95% CI 1.51 to 4.94). CONCLUSIONS: Our data suggest that patients with low risk prostate cancer can be reassured that immediate treatment is not necessary. Whether long delays (greater than 180 days) decrease the likelihood of curability in some patients requires further study.

Disease Progression↗

Update on outcomes research databases in prostate cancer 2006.

PURPOSE OF REVIEW: The purpose of this review is to summarize single-institution prostate-cancer-outcomes databases (which are most commonly derived from large academic medical centers, Veterans Affairs medical centers, and military hospitals) to summarize the design and development of three well characterized outcomes databases that combine data from multiple sites (Carcinoma of the Prostate Strategic Urological Research Endeavor, Center for Prostate Disease Research, and the Shared Equal Access Regional Cancer Hospital database) and to use the examples of obesity and prostate-specific antigen changes over time to highlight the importance of these databases in prostate-cancer outcomes. RECENT FINDINGS: Multiple databases have demonstrated that obese men are at greater risk of biochemical progression following radical prostatectomy. In addition, objective data have shown that it is more difficult to operate on obese men leading to greater risk of positive surgical margins, which may contribute to poorer outcomes. Several databases have shown that a rapidly increasing prostate-specific antigen, measured either before diagnosis or after failed primary therapy, is associated with increased risk of prostate-cancer-specific mortality. SUMMARY: Outcomes databases are extremely useful tools. They have lead to dramatic improvements of our understanding of prostate cancer. The challenge is to use this information from past patients to help us better manage our current and future patients.

Databases, Factual↗

Racial differences in prognostic value of adult height for biochemical progression following radical prostatectomy.

PURPOSE: Adult height, as a surrogate of childhood and adolescent hormone activity and diet, has been associated with the risk for development and death from prostate cancer in predominantly White populations. However, hormonal activity and diets vary between races. We examined whether height was significantly associated with biochemical progression following radical prostatectomy and whether there was an interaction between height and race. EXPERIMENTAL DESIGN: Multivariate Cox proportional hazards analysis was used to determine if height significantly predicted biochemical progression among 1,503 men (450 Black and 1,053 White) treated with radical prostatectomy between 1988 and 2003. We examined for possible interactions between height and race. RESULTS: Taller men (>175.3 cm) were significantly younger (P = 0.001), treated in more recent years (P = 0.02), had more clinical stage T(1) disease (P = 0.001), and were less likely to have extraprostatic extension (P = 0.02) than shorter men (< or =175.3 cm). Height was not significantly related to race, preoperative serum prostate-specific antigen concentrations, biopsy or pathologic Gleason sum, positive surgical margins, seminal vesicle invasion, or lymph node metastasis. Height was significantly associated with progression among Black men [relative risk (RR), 1.67; 95% confidence interval (95% CI), 1.00-2.79] but not among White men (RR, 1.03; 95% CI, 0.77-1.38). The interaction between race and height for predicting biochemical progression was statistically significant (P(interaction) = 0.05). CONCLUSIONS: There was an interaction between height and race in that height predicted progression for Black men but not for White men. The explanation for these findings is unclear, although lower insulin-like growth factor-binding protein-3 concentrations among Black men may be involved.

Aged↗

Prostate size and risk of high-grade, advanced prostate cancer and biochemical progression after radical prostatectomy: a search database study.

PURPOSE: Prostate growth and differentiation are under androgenic control, and prior studies suggested that tumors that develop in hypogonadal men are more aggressive. We examined whether prostate weight was associated with tumor grade, advanced disease, or risk of biochemical progression after radical prostatectomy (RP). PATIENTS AND METHODS: We evaluated the association of prostate weight with pathologic tumor grade, positive surgical margins, extracapsular disease, and seminal vesicle invasion using logistic regression and with biochemical progression using Cox proportional hazards regression among 1,602 men treated with RP between 1988 and 2003 at five equal-access medical centers, which composed the Shared Equal Access Regional Cancer Hospital (SEARCH) Database. RESULTS: In outcome prediction models including multiple predictor variables, it was found that the predictor variable of prostate weight was significantly inversely associated with the outcomes of high-grade disease, positive surgical margins, extracapsular extension (all P < or = .004), and biochemical progression (comparing prostate weight < 20 v > or = 100 g: relative risk = 8.43; 95% CI, 2.9 to 24.0; P < .001). Similar associations were seen between preoperative transrectal ultrasound-measured prostate volume and high-grade disease, positive surgical margins, extracapsular extension (all P < or = .005), seminal vesicle invasion (P = .07), and biochemical progression (P = .06). CONCLUSION: Men with smaller prostates had more high-grade cancers and more advanced disease and were at greater risk of progression after RP. These results suggest that prostate size may be an important prognostic variable that should be evaluated for use pre- and postoperatively to predict biochemical progression.

Humans↗