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.     

Retropubic versus perineal radical prostatectomy in early prostate cancer: eight-year experience

BACKGROUND: Prostate cancer is the most common malignancy in men and the second leading cause of cancer death. A randomized study was performed on patients with localized prostate cancer and treated with radical prostatectomy using the perineal or the retropubic approach comparing oncological outcomes, cancer control, and functional results. STUDY DESIGN: Between 1997 and 2004, in a randomized study 200 patients underwent a radical prostatectomy performed by retropubic (100 patients) or perineal (100 patients) approach. RESULTS: Differences between hospital stay, duration of catheter drainage, intraoperative blood loss, and transfusion requirements were statistically significant in favor of perineal prostatectomy. Differences between positive surgical margins and urinary continence in the two groups were not statistically significant at 6 and 24 months. Differences between erectile function at 24 months were statistically significant in favor of retropubic prostatectomy. CONCLUSIONS: Radical perineal prostatectomy is an excellent alternative approach for radical surgery in the treatment of early prostate cancer.     

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.     

Correlation of margin status and extraprostatic extension with progression of prostate carcinoma.

BACKGROUND: The correlation of surgical margins and extraprostatic extension (EPE) with progression is uncertain with regard to prostate carcinoma patients treated by radical prostatectomy. The objective of this study was to define factors predictive of cancer progression; emphasis was placed on surgical margins and their relation to extraprostatic extension. METHODS: The study group consisted of 377 patients who were treated by radical retropubic prostatectomy and bilateral pelvic lymphadenectomy at the Mayo Clinic between 1986 and 1993. All specimens were totally embedded and whole-mounted. Patients ranged in age from 41 to 79 years (mean, 65 years). Those with seminal vesicle invasion or lymph node metastasis and those treated preoperatively with radiation or androgen deprivation were excluded. Final pathologic T classifications were pT2a (41 patients), pT2b (237), and pT3a (99). Progression was defined as biochemical failure (prostate specific antigen [PSA] >0.2 ng/mL), clinical or biopsy-proven local recurrence, or distant metastasis. The mean follow-up was 5.8 years (range, 0.2-11.4 years). Seventy-nine patients who received adjuvant treatment within 3 months after surgery were excluded from survival analysis. RESULTS: The overall margin positivity rate was 29%. Seventy-two patients (19%) had only positive surgical margins without evidence of EPE ("surgical incision"), 53 (14%) had only EPE, 37 (10%) had both, and 215 (57%) had neither. Positive margins were correlated with the finding of EPE (P = 0.003). Progression free survival rates at 5 and 10 years were 88% and 67%, respectively. In univariate analysis, preoperative PSA concentration, positive surgical margins, Gleason grade, cancer volume, and DNA ploidy were significant in predicting progression (P values, <0.001, <0.001, 0.01, 0.007, and <0.001, respectively). In multivariate analysis, margin status and DNA ploidy were independent predictors of progression (relative risk for margin status, 1.9; 95% confidence interval [CI], 1.1-3.4; P = 0.03; relative risk for DNA ploidy, 5.1; 95% CI, 2.4-10.9; P<0.001). Among patients with positive margins, 5-year progression free survival was 78% for those with negative EPE and 55% for those with positive EPE. CONCLUSIONS: Surgical margin status and DNA ploidy were independent predictors of progression after radical prostatectomy. To improve cancer control, adjuvant therapy may be considered for patients with positive surgical margins or nondiploid cancer.     

Surgical pathology examination of radical prostatectomy specimens. Updated protocol based on the Italian TAP study

Between January 1996 and June 2000, 192 men with prostate cancer underwent radical retropubic prostatectomy (RP) and bilateral pelvic node dissection in 26 centers participating in the Italian randomized prospective TAP study. The reviewing pathologist evaluated 145 RP specimens. Seventy-five cases had not been treated with total androgen ablation before RP was performed, whereas 70 had been treated for three months. Whole-mount sectioning of the complete radical prostatectomy specimens was adopted in each center for accurately evaluating the pathological stage of prostate cancer and resection limit status. The results of this study suggest that total androgen ablation before RP is beneficial in men with clinical stage T2 because of the significant pathological down-staging and decrease in the number of positive margins in the RP specimens. On the basis of the experience acquired through the Italian TAP study and recent publications on prognostic factors in prostate cancer, the original practice protocol for examination of RP specimens removed from patients with carcinoma of the prostate glands was updated.     

Impact of obesity on biochemical control after radical prostatectomy for clinically localized prostate cancer: a report by the Shared Equal Access Regional Cancer Hospital database study group.

PURPOSE: Given the limited information regarding the impact of obesity on treatment outcomes for prostate cancer, we sought to examine the relationship between body mass index (BMI) and cancer control after radical prostatectomy (RP). PATIENTS AND METHODS: We compared clinicopathologic and biochemical outcome information across BMI groups from 1,106 men treated with RP between 1988 and 2002. Multivariate analysis was used to determine if BMI significantly predicted adverse pathology or biochemical recurrence. RESULTS: Obesity was related to year of surgery (P <.001) and race (P <.001), with black men having the highest obesity rates. Obese patients had higher biopsy and pathologic grade tumors (P <.001). On multivariate analysis, BMI > or = 35 kg/m(2) was associated with a trend for higher rates of positive surgical margins (P =.008). Overweight patients (BMI, 25 to 30 kg/m(2)) had a significantly decreased risk of seminal vesicle invasion (P =.039). After controlling for all preoperative clinical variables including year of surgery, BMI > or = 35 kg/m(2) significantly predicted biochemical failure after RP (P =.002). After controlling for surgical margin status, BMI > or = 35 kg/m(2) remained a significant predictor of biochemical failure (P =.012). There was a trend for BMI > or = 35 kg/m(2) to be associated with higher failure rates than BMI between 30 and 35 kg/m(2) (P =.053). CONCLUSION: The percentage of obese men undergoing RP in our data set doubled in the last 10 years. Obesity was associated with higher-grade tumors, a trend toward increased risk of positive surgical margins, and higher biochemical failure rates among men treated with RP. A BMI > or = 35 kg/m(2) was associated with a higher risk of failure than a BMI between 30 and 35 kg/m(2).     

Does the Presence of Primary Circulating Prostate Cells Imply the Presence of Agressive Prostate Cancer with Early Biochemical Failure: a Comparison with the Walz Nomogram

Background: To determine the utility of primary circulating prostate cells (CPC) for predicting early biochemical failure after radical prostatectomy for prostate cancer and compare the results with the Walz nomogram. Materials and Methods: A single centre prospective study of men with prostate cancer treated with radical prostatectomy was conducted between 2004 and 2014. Clinicalpathological details were registered, along with total serum PSA presurgery, Gleason score, extracapsular extension, positive surgical margins, infiltration of lymph nodes, seminal vesicles and pathological stage. Primary circulating prostate cells were obtained using differential gel centrifugation and detected using standard immunocytochemistry with antiPSA. Biochemical failure was defined as a PSA >0.2ng/ml, predictive values were calculated using the Walz nomagram and CPC detection. Results: A total of 285 men participated, of whom 103/285 (36.1%) suffered biochemcial failure; 32/103 (31.1%) within two years of radical prostatectomy. Men with higher Gleason scores, higher pathological stage, infiltration of the surgical margin or prostate capsule and infiltration of seminal vesicles were more likely to undergo biochemical failure. There was a significant increase in the frequency of biochemical failure with increasing number of CPCs detected (p     

Continence after radical prostatectomy with bladder neck preservation.

PURPOSE: Bladder neck preservation during radical prostatectomy has been advocated for improving urinary continence. We evaluate bladder neck preservation looking at continence rates, surgical cancer control and bladder neck contracture. MATERIALS AND METHODS: A total of 40 patients underwent retropubic radical prostatectomy for clinically localized carcinoma of the prostate. The prostatic urethra was dissected in continuity with the bladder away from the lumen of the prostate, which allows for a true urethra-to-urethra anastomosis. RESULTS: Continence was noted immediately in 26 patients, within 2 weeks in 9 and within 6 weeks in 3. Only 2 patients required pads 3 months postoperatively. Microscopic positive surgical margins were noted in 2 of 40 patients. In 1 patient the urethral margins were not involved with carcinoma. In the other patient the urethra was not the sole positive margin and microscopic positive margins were noted elsewhere. Early results of cancer control were good. CONCLUSIONS: Early follow-up of this technique of radical retropubic prostatectomy suggest that preservation of the continence mechanism at the level of the bladder neck and prostatic urethra results in significantly improved postoperative urinary continence without adversely affecting cancer control.     

Association between biomarkers of obesity and risk of high-grade prostatic intraepithelial neoplasia and prostate cancer – Evidence of effect modification by prostate size

Prostate enlargement is common with aging and obesity. We investigated the association between obesity and prostate cancer controlling for differential detection related to prostate enlargement. In an analysis of 500 men, we found body mass index, waist–hip ratio, and blood leptin levels were significantly associated with high-grade PC, but only among men without prostate enlargement. Leptin was also significantly associated with high-grade prostatic intraepithelial neoplasia (HGPIN) in the absence of prostate enlargement. Our results suggest obesity advances prostate carcinogenesis, and that detection biases at prostate biopsy may explain past inconsistencies in the association between obesity and PC.     

Comparison of the Walz Nomogram and Presence of Secondary Circulating Prostate Cells for Predicting Early Biochemical Failure after Radical Prostatectomy for Prostate Cancer in Chilean Men

Purpose: To determine the utility of secondary circulating prostate cells for predicting early biochemicalfailure after radical prostatectomy for prostate cancer and compare the results with the Walz nomagram.Materials and Methods: A single centre, prospective study of men with prostate cancer treated with radicalprostatectomy between 2004 and 2014 was conducted, with registration of clinical-pathological details, total serumPSA pre-surgery, Gleason score, extracapsular extension, positive surgical margins, infiltration of lymph nodes,seminal vesicles and pathological stage. Secondary circulating prostate cells were obtained using differentialgel centrifugation and assessed using standard immunocytochemistry with anti-PSA. Biochemical failure wasdefined as a PSA >0.2ng/ml, predictive values werecalculated using the Walz nomagram and CPC detection.Results: A total of 326 men participated, with a median follow up of 5 years; 64 had biochemical failure withintwo years. Extracapsular extension, positive surgical margins, pathological stage, Gleason score ≥ 8, infiltration ofseminal vesicles and lymph nodes were all associated with higher risk of biochemical failure. The discriminativevalue for the nomogram and circulating prostate cells was high (AUC >0.80), predictive values were higher forcirculating prostate cell detection, with a negative predictive value of 99%, sensitivity of 96% and specificity of75%. Conclusions: The nomagram had good predictive power to identify men with a high risk of biochemicalfailure within two years. The presence of circulating prostate cells had the same predictive power, with a highersensitivity and negative predictive value. The presence of secondary circulating prostate cells identifies a groupof men with a high risk of early biochemical failure. Those negative for secondary CPCs have a very low risk ofearly biochemical failure.     

Association between tumor-associated macrophage infiltration,high grade prostate cancer,and biochemical recurrence after radical prostatectomy

Background: Tumor-associated macrophages (TAMs) are a key component of the inflammatory microenvironment. Their role in prostate cancer development and progression remains unclear. We examined whether the amount of TAMs in prostate cancer is: 1) higher than prostatic intraepithelial neoplasia (PIN) and benign tissue 2) associated with poorly differentiated disease, and 3) predictive of biochemical recurrence among surgically treated men. Methods: A tissue microarray (TMA) of prostatectomy specimens from 332 patients was stained for CD68, a TAM marker. A separate TMA was used for validation. Associations between mean TAMs in cancer cores and PSA recurrence were determined by Cox proportional hazards models after adjusting for age, preoperative PSA, race, body mass index, pathologic Gleason sum, seminal vesicle invasion, extracapsular extension, and margin status. Results: Mean TAM number was higher in cancer versus PIN and benign tissue (p<0.0001). Mean TAM number was higher in Gleason grade 4 cores vs. Gleason grade 3 cores (p=0.003). On multivariable analysis, no association was observed between mean TAM number per cancer core and biochemical recurrence in either cohort. Conclusion: Mean TAM number was higher in cancer cores vs. PIN and benign tissue, and higher in high grade prostate cancer supporting the potential role of TAMs in prostate cancer development. However, TAMs were not associated with biochemical recurrence after radical prostatectomy suggesting TAM counts do not provide independent prognostic value among surgically treated men. Further studies are required to elucidate the functional significance of TAMs in the prostate cancer microenvironment.     

Obesity and survival after radical prostatectomy: A 10-year prospective cohort study

BACKGROUND: Obesity and prostate cancer are among the most common health problems affecting American men today. The authors' goal was to assess the impact of obesity on clinical and pathologic features of prostate cancer and long-term outcomes. METHODS: The authors performed a prospective cohort study on 5313 men who underwent radical prostatectomy between 1990 and 1999. Patient height and weight were measured at the time of surgery to calculate the body mass index (BMI). The patients were separated into 3 BMI groups: BMI <25, 25-29.9, and > or =30 kg/m2. The associations between BMI and age, prostate-specific antigen (PSA) level, and Gleason score were assessed with the Spearman rank correlation test. The associations between BMI and pathologic features were assessed with the Mantel-Haenszel chi 2 test. Fifteen-year biochemical progression-free survival, systemic progression-free survival, cancer-specific survival, and overall survival were estimated using the Kaplan-Meier method and evaluated using Cox models. RESULTS.: The median length of follow-up for the entire cohort was 10.1 years. Clinical and pathologic features appear worse in patients with a higher BMI. On univariate and multivariate analyses, it was found that BMI had no impact on biochemical progression, systemic progression, prostate cancer survival, or overall survival. CONCLUSIONS: Obese patients appear to have worse pathologic features at the time of prostatectomy. Despite these features, long-term oncologic outcomes, including cancer-specific survival, remain the same regardless of BMI. BMI appears to influence prostate cancer outcomes at the time of prostatectomy, as evidenced by more aggressive pathologic features. However, after prostatectomy, BMI does not appear to be an independent predictor of recurrence or survival.     

Antegrade radical retropubic prostatectomy with preliminary ligation of vascular pedicles in 614 consecutive patients

BACKGROUND: We present our procedure of antegrade radical retropubic prostatectomy with preliminary ligation of vascular pedicles and assess the time trends of patient characteristics, surgical and oncological outcome in 614 consecutive patients in a single institution over a 12-year period. METHODS: From April 1994 to December 2005, 614 consecutive Japanese patients with cT1-3N0M0 prostate cancer underwent antegrade radical prostatectomy with preliminary ligation of vascular pedicles (dorsal vein complex and prostatic pedicles) prior to the tumor manipulation. Biochemical progression is defined as prostate-specific antigen value over 0.2 ng/ml or the initiation of therapy after surgery. Biochemical progression-free, cancer-specific and overall survival curves were calculated by the Kaplan-Meier method. RESULTS: During the study period pre-operative PSA, clinical T stage, duration of surgery, amount of estimated blood loss have decreased. Pathological stage showed a significant downward migration and the rate of positive surgical margin has also decreased. At a mean follow-up of 48 months, 21 men were dead including eight who died of prostate cancer. Overall and cancer-specific survival rates were 97/99% at 5 years and 89/95% at 10 years, respectively. Neoadjuvant hormonal treatment had no beneficial impact on oncological outcome of patients regardless of clinical stage. In 370 patients treated surgically alone, cancer-specific and biochemical progression-free survival rates were 99.6/80.5% at 5 years and 97.9/73.3% at 10 years for patients with clinical T1/2 disease and 95.5/41.9% at 5 years and 87.5/41.9% at 10 years for those with T3 disease, respectively. In the 370 patients biochemical progression-free survival has been significantly improved over the 12-year period (P < 0.0001). CONCLUSIONS: Antegrade radical prostatectomy with preliminary ligation of vascular pedicles can be performed with excellent oncological outcome.     

The combined percentage of Gleason patterns 4 and 5 is the best predictor of cancer progression after radical prostatectomy.

PURPOSE: Clinical outcome is variable in prostate cancer patients treated with radical prostatectomy. The Gleason histologic grade of prostatic adenocarcinoma is one of the strongest predictors of biologic aggressiveness of prostate cancer. We evaluated the significance of the relative proportion of high-grade cancer (Gleason patterns 4 and/or 5) in predicting cancer progression in prostate cancer patients treated with radical prostatectomy. PATIENTS AND METHODS: Radical prostatectomy specimens from 364 consecutive prostate cancer patients were totally embedded and whole mounted. Various clinical and pathologic characteristics were analyzed. All pathologic data, including Gleason grading variables, were collected prospectively. RESULTS: A multiple-factor analysis was performed that included the combined percentage of Gleason patterns 4 and 5, Gleason score, tumor stage, surgical margin status, preoperative prostate-specific antigen (PSA), extraprostatic extension, and total tumor volume. Using Cox regression analysis with bootstrap resampling for predictor selection, we identified the combined percentage of Gleason patterns 4 and 5 (P < .0001) and total tumor volume (P = .009) as significant predictors of PSA recurrence. CONCLUSION: The combined percentage of Gleason patterns 4 and 5 is one of the most powerful predictors of patient outcome, and appears superior to conventional Gleason score in identifying patients at increased risk of disease progression. On the basis of our results, we recommend that the combined percentage of Gleason patterns 4 and 5 be evaluated in radical prostatectomy specimens. The amount of high-grade cancer in a prostatectomy specimen should be taken into account in therapeutic decision making and assessment of patient prognosis.     

Risk of positive margins and biochemical recurrence in relation to nerve-sparing radical prostatectomy.

PURPOSE: To assess the effect of nerve-sparing (NS) radical retropubic prostatectomy (RRP) on surgical margins and biochemical recurrence. PATIENTS AND METHODS: Location and incidence of positive surgical margins, recurrence, and time to recurrence were assessed in a consecutive series of 734 men who underwent RRP for localized prostate cancer from 1992 through February 2000. NS procedures were used in 33% (n = 240) of 734 patients studied. RESULTS: Surgical margins were positive for 24% (n = 58) and 31% (n = 152) of NS and non-NS patients, respectively (P =.06). No significant difference between the groups was found in location of positive margins (P =.92). Prostate-specific antigen level greater than 10 ng/mL, extraprostatic extension, tumor volume more than 20%, capsular penetration, Gleason score > or = 7, positive margins, and seminal vesicle invasion were associated with significantly increased risk of recurrence. However, NS patients were not at increased risk of recurrence compared with non-NS patients (hazard ratio, 0.96; 95% confidence interval, 0.53 to 1.72). The cumulative risk of recurrence within 3 and 5 years of surgery in NS patients was 9.7% and 14.4%, respectively, as compared with 17.1% and 21.1% for non-NS patients. CONCLUSION: In patients with localized prostate cancer, neither margin status nor biochemical-free survival within 5 years of surgery were altered by the nerve preservation technique. Given our experience, we recommend preservation of neurovascular bundles in these patients whenever the procedure is technically feasible.     

Body mass index is weakly associated with, and not a helpful predictor of, disease progression in men with clinically localized prostate carcinoma treated with radical prostatectomy

BACKGROUND: Several studies have recently suggested an association between body mass index (BMI) and disease progression after radical prostatectomy. In the current study, the authors examined this association and that between the reciprocal of BMI (INVBMI, 1/BMI) and progression-free probability in men treated with radical retropubic prostatectomy (RRP) for clinically localized prostate carcinoma. METHODS: The authors retrospectively studied 2210 patients who underwent RRP at Memorial Sloan-Kettering Cancer Center between September 1986 and May 2003. Clinicopathologic variables analyzed included BMI (kg/m2), preoperative serum prostate-specific antigen level (ng/mL), clinical T classification, year of surgery, race, biopsy-derived primary and secondary Gleason grades, and INVBMI, known to better correlate with percent body fat than BMI. Cox regression analysis was used to examine the possible association between BMI or its reciprocal with disease progression after controlling for the effects of common prognostic factors. The areas under the receiver operating curve (AUC) for models with and without INVBMI were calculated. RESULTS: Of the 2210 patients analyzed, 251 experienced disease progression in a median follow-up time of 25.9 months (range, 0-143 months). After adjusting for all clinical variables, both BMI (P = 0.071; hazards ratio [HR] = 1.027) and INVBMI (P = 0.041; HR < 0.001) were associated with disease progression. However, the areas under AUC for models with and without INVBMI were similar (range, 0.794-0.798). CONCLUSIONS: Although conflicting evidence has been reported regarding the link between obesity and an increased risk of developing prostate carcinoma, as well as an increased risk of developing aggressive disease and prostate carcinoma-related mortality, the authors found weak associations with disease progression for both BMI and INVBMI. These variables were of negligible prognostic value in men who received surgery. Studies with longer follow-up, that examine alternative end points, and that follow treatment(s) besides surgery are needed.     

Influence of obesity on biochemical and clinical failure after external-beam radiotherapy for localized prostate cancer

BACKGROUND: Several reports have shown that obesity is associated with increased risk of biochemical failure after radical prostatectomy. However, limited information is available regarding the impact of obesity on prostate cancer progression after radiotherapy. The current study sought to determine whether obesity was an independent predictor of biochemical failure (BF) and clinical recurrence (CF) among patients treated with external-beam radiotherapy (EBRT). METHODS: A retrospective analysis was performed on 873 patients receiving EBRT as the sole treatment for localized prostate cancer between 1988 and 2001. The Kaplan-Meier method, log-rank test, and Cox proportional hazards analyses were performed. RESULTS: Of the 873 patients, 18% were mildly obese and 5% were moderately to severely obese. Obesity was related to younger age at diagnosis (P < .001), more recent year of diagnosis (P = .03), and race (P = .03), with African-American men having the highest obesity rates. During a mean follow-up of 96 months, 295 patients experienced BF and 127 had CF. On multivariate analysis, controlling for clinical and treatment characteristics, increased body mass index (BMI) significantly predicted BF (hazards ratio [HR] = 1.04; 95% confidence interval [95% CI], 1.02-1.07) with a positive trend by BMI category (P = .001). Similar results were found when the outcome was CF; BMI remained an independent predictor of progression (HR = 1.05; 95% CI, 1.01-1.09), with a statistically significant trend by increased BMI category (P = .03). CONCLUSIONS: The current findings validate the important role of obesity, not only on BF but also on CF, and suggest a link to the biologic basis of tumor progression that can be therapeutically exploited.     

Weight change,obesity and risk of prostate cancer progression among men with clinically localized prostate cancer

Obesity is associated with an increased risk of fatal prostate cancer. We aimed to elucidate the importance and relevant timing of obesity and weight change for prostate cancer progression. We identified 5,158 men diagnosed with localized prostate cancer (clinical stage T1/T2) from 1986 to 2012 in the Health Professionals Follow‐up Study. Men were followed for biochemical recurrence and lethal prostate cancer (development of distant metastasis or prostate cancer‐specific mortality) until 2012. Cox regression estimated hazard ratios (HRs) for body mass index (BMI) at age 21, BMI at diagnosis, “long‐term” weight change from age 21 to diagnosis and “short‐term” weight change over spans of 4 and 8 years preceding diagnosis. Because weight, weight change and mortality are strongly associated with smoking, we repeated analyses among never smokers only (N = 2,559). Among all patients, neither weight change nor BMI (at age 21 or at diagnosis) was associated with lethal prostate cancer. Among never smokers, long‐term weight gain was associated with an increased risk of lethal disease (HR for gaining >30 pounds vs. stable weight [±10 pounds] 1.59, 95% CI, 1.01‐2.50, p‐trend = 0.06). Associations between weight change, BMI and lethal prostate cancer were stronger for men with BMI ≥ 25 at age 21 compared to those with BMI < 25. Weight change and obesity were not associated with an increased risk of biochemical recurrence. Our findings among never smoker men diagnosed with localized prostate cancer suggest a positive association between long‐term weight gain and risk of lethal prostate cancer. Metabolic changes associated with weight gain may promote prostate cancer progression.     

Preoperative plasma endoglin levels predict biochemical progression after radical prostatectomy.

PURPOSE: Endoglin (CD105) is a transmembrane glycoprotein expressed by human vascular endothelial cells thought to play a pivotal role in endothelial cell proliferation. The aim of this study was to evaluate the association of preoperative plasma endoglin levels with established clinical and pathologic features of prostate cancer and disease progression after radical prostatectomy. EXPERIMENTAL DESIGN: Preoperative plasma endoglin levels were measured in 425 patients who underwent radical prostatectomy for clinically localized prostate cancer using a commercially available ELISA assay. Multivariate logistic regression was used to test the association of plasma endoglin levels with biochemical progression after radical prostatectomy. RESULTS: Median follow-up for patients alive at the time of analysis was 36.8 months (interquartile range, 44.1). Of 425 patients, 77 patients (18.1%) experienced biochemical progression after radical prostatectomy. Preoperative plasma endoglin levels were significantly elevated in patients with higher preoperative total serum prostate-specific antigen (P < 0.001) and adverse pathologic features. Preoperative plasma endoglin was an independent predictor of biochemical progression after surgery after adjusting for the effects of standard preoperative and postoperative features (P < 0.001 and P = 0.026, respectively). CONCLUSIONS: Preoperative plasma endoglin levels are associated with established features of advanced prostate cancer. More importantly, higher preoperative plasma endoglin levels are independent predictors of an increased risk of biochemical progression in patients treated with radical prostatectomy and bilateral pelvic lymphadenectomy.     

Biochemical outcome after radical prostatectomy among men with normal preoperative serum prostate-specific antigen levels

BACKGROUND: Recent studies have shown that a significant number of men with normal prostate-specific antigen (PSA) levels have prostate carcinoma. Whether malignancies in such men are associated with better outcomes is unclear. The authors compared the risk of biochemical failure after radical prostatectomy (RP) between men with normal PSA levels and men with elevated PSA levels. METHODS: Data were examined from 1582 men who underwent RP between 1988 and 2002 at 1 of 5 equal-access medical centers. Patients were segregated into groups based on serum PSA levels (with stratification according to age-specific reference ranges). Clinical and pathologic characteristics and biochemical outcome data were compared across groups using analyses of variance, log-rank tests, and Cox proportional hazards analysis. RESULTS: Men who had normal PSA levels had significantly fewer high-grade tumors compared with men who had higher PSA levels (P < 0.001). The former group had a significantly decreased incidence of positive surgical margins, extracapsular disease, seminal vesicle invasion, and lymph node involvement (P < 0.001). On multivariate analysis, only serum PSA level (P < 0.001) and biopsy Gleason score (P < 0.001) predicted the time to disease recurrence. When only men with serum PSA levels < 10 ng/mL were examined, PSA level treated as a continuous variable remained a significant predictor of time to biochemical failure (P = 0.02). CONCLUSIONS: Men who had normal PSA levels had significantly fewer high-grade tumors and significantly better biochemical outcomes after undergoing RP compared with men who had elevated PSA levels. Overall, men with normal PSA levels who undergo RP represent a favorable risk group.