Danielle A. Stackhouse

Men Older Than 70 Years Have Higher Risk Prostate Cancer and Poorer Survival in the Early and Late Prostate Specific Antigen Eras

PURPOSE We clarified whether men older than 70 years have a higher risk of prostate cancer and poorer survival in the early and late prostate specific antigen eras. MATERIALS AND METHODS A cohort of 4,561 men who underwent radical prostatectomy were stratified into 3 age groups (younger than 60, 60 to 70 and older than 70 years), and early and late prostate specific antigen eras based on the year of surgery (before 2000 and 2000 or later). Race, body mass index, prostate specific antigen, prostate weight, tumor volume, pathological Gleason sum, pathological tumor stage, extracapsular extension, seminal vesicle invasion and surgical margin status were submitted for univariate and multivariable analyses against the previously mentioned groups. Survivals (prostate specific antigen recurrence, distant metastasis and disease specific death) were compared among the 3 age groups using univariate and multivariable methods. RESULTS Compared with younger age groups (younger than 60, 60 to 70 years) men older than 70 years had a higher proportion of pathological tumor stage 3/4 (33.0 vs 44.3 vs 52.1%, p <0.001), pathological Gleason sum greater than 7 (9.5% vs 13.4% vs 17.2%, p <0.001) and larger tumor volume (3.7 vs 4.7 vs 5.2 cc, p <0.001). Pathological Gleason sum in men older than 70 years did not differ between the early and late prostate specific antigen eras (p = 0.071). Men older than 70 years had a higher risk of prostate specific antigen recurrence, distant metastasis and disease specific death on univariate (p <0.05) but not multivariable analysis. CONCLUSIONS Men older than 70 years had higher risk disease and poorer survival in the early and late prostate specific antigen eras. Pathological Gleason sums did not change between the 2 eras. Patient age was an important variable in prostate specific antigen screening, biopsy, treatment and prognosis.

Tumor Volume, Tumor Percentage Involvement, or Prostate Volume: Which Is Predictive of Prostate-specific Antigen Recurrence?

OBJECTIVES To compare the effects of tumor volume (TV), tumor percentage involvement (TPI), and prostate volume (PV) on prostate-specific antigen (PSA) recurrence (PSAR) after radical prostatectomy (RP). METHODS A cohort of 3528 patients receiving RP between 1988 and 2008 was retrieved from the Duke Prostate Center. Patients were stratified by TV (< 3, 3-6, > 6 cm(3)), TPI (< 10%, 10%-20%, > 20%), and PV (< 35, 35-45, > 45 cm(3)) and their effects on PSAR evaluated using Kaplan-Meier analysis. Clinicopathologic variables included in univariate analysis were age at surgery, race, year of surgery, PSA, pathologic Gleason score, pathologic tumor stage, margin status, extracapsular extension, and seminal vesicle invasion. The effects of TV, TPI, and PV (as continuous and categorical variables) on PSAR were compared using Cox analysis. RESULTS TPI, TV, and PV were predictive of PSAR (P <.05) in Kaplan-Meier analysis. In multivariate analysis as continuous variables, TPI and PV were predictive of PSAR (hazard ratio [HR] = 1.16 and HR = 0.65, P <.05). As categorical variables, TPI > 20% and PV 10-35 cm(3) were predictive of PSAR (HR = 1.45 and OR = 1.25, P <.05). TV was not predictive of PSAR in either analysis. Pathologic Gleason score > or = 7, PSA, positive margins, seminal vesicle invasion, and tumor stage T3/T4 were found to be predictors of PSAR (P <.05). CONCLUSIONS TV, TPI, and PV were predictive of PSAR in univariate analysis, but in multivariate analysis, only TPI and PV were predictive of PSAR. TPI and PV should be considered when evaluating, assessing, and counseling patients regarding PSAR risk.

Delayed Prostate-specific Antigen Recurrence After Radical Prostatectomy: How to Identify and What Are Their Clinical Outcomes?

OBJECTIVES To identify factors that predict delayed (> 5 years) prostate-specific antigen recurrence (PSAR) after radical prostatectomy (RP) and to analyze the associated clinical outcomes. METHODS A cohort of 4561 men who underwent RP between 1988 and 2008 was retrieved from the Duke University Prostate Center database. Among them, 1207 (26.5%) had PSAR and were included in this study. The cohort was then divided into 2 groups; PSAR before 5 years (early PSAR) and PSAR after 5 years (delayed PSAR), and Kaplan Meier analysis was performed. Univariate and logistic regression analysis was carried out to determine significant predictors of delayed PSAR, using factors such as race, age, body mass index, PSA, surgical margin status, pathologic Gleason sum, pathologic tumor stage, and prostate weight. RESULTS There was a marginal difference between the early and delayed PSAR groups with regard to metastasis-free survival (P = .062). A significant difference in disease-specific survival was found between the 2 groups (P = .025). Patients with pathologic Gleason sums < 7 were more likely to have delayed PSAR as compared to those with pathologic Gleason sums > 7 (OR = 2.38). Patients with a PSA < 10 ng/mL were more likely to have delayed PSAR in comparison to those with PSA > 20 ng/mL (OR = 2.38). CONCLUSIONS Approximately 90% of PSAR occurred within 5 years after RP. Lower pathologic Gleason sums and lower PSA at diagnosis were associated with delayed PSAR. Patients with delayed PSAR have a disease-specific survival advantage as compared to men with early PSAR.

Factors Predicting Prostatic Biopsy Gleason Sum Under Grading

PURPOSE We determined clinical factors affecting the under grading of biopsy Gleason sum compared with prostatectomy pathology and developed a model predicting the probability of under grading. MATERIALS AND METHODS We analyzed a cohort of 1,701 patients treated for prostate cancer at our institution between 1988 and 2007 with complete biopsy and pathological data available. Patients with a biopsy Gleason sum of 7 or less were included in our analysis. Cases were categorized as under graded or not under graded by comparing biopsy and radical prostatectomy Gleason sums. Logistic regression was used to determine the predictors of under grading based on clinical variables (race, age at diagnosis, body mass index, prostate weight, diagnostic prostate specific antigen, biopsy positive-to-total core ratio, maximal cancer percent in positive cores and time from diagnosis to surgery). A nomogram was developed to calculate the probability of under grading. Results were validated using bootstrapping. RESULTS Under grading occurred in 46.6% of our cohort. Significant variables predicting under grading were age at diagnosis, biopsy Gleason sum, diagnostic prostate specific antigen, prostate weight, biopsy positive-to-total core ratio and maximal percent of cancer in cores (p <0.05). Nomogram predictive accuracy was 72.4%. CONCLUSIONS The risk of Gleason sum under grading can be predicted to a satisfactory level using our nomogram. Predicting under grading would improve patient consulting and identify those who should consider repeat biopsy, ultimately enhancing the accuracy of prostate cancer diagnosis.

Tumor Percent Involvement Predicts Prostate Specific Antigen Recurrence After Radical Prostatectomy Only in Men With Smaller Prostate

PURPOSE We determined the predictive power of tumor percent involvement on prostate specific antigen recurrence in patients when stratified by prostate weight. MATERIALS AND METHODS Data on 3,057 patients who underwent radical prostatectomy between 1988 and 2008 was retrieved from our institutional prostate cancer database. Patients with data on tumor percent involvement, prostate volume and prostate specific antigen recurrence were included in analysis. Patients were divided into 3 groups based on prostate volume less than 35, 35 to 45 and greater than 45 cc. The variables tumor percent involvement, age at surgery, race, prostate specific antigen, pathological Gleason score, positive surgical margins, extraprostatic extension, seminal vesicle invasion and surgery year were analyzed using the chi-square and Mann-Whitney tests to determine individual effects on prostate specific antigen recurrence. Tumor percent involvement and prostate specific antigen were evaluated as continuous variables. Significant variables on univariate analysis were included in multivariate Cox regression analysis to compare their effects on prostate specific antigen recurrence. RESULTS Tumor percent involvement significantly predicted prostate specific antigen recurrence in men with a small prostate (p = 0.006) but not in those with a prostate of greater than 35 cc. Black race was a marginally significant predictor of prostate specific antigen recurrence in men with a medium prostate (p = 0.055). Age at surgery was a predictor of prostate specific antigen recurrence in men with a larger prostate (p = 0.003). Prostate specific antigen, positive surgical margins, seminal vesicle invasion and pathological Gleason score 7 or greater predicted prostate specific antigen recurrence in men with all prostate sizes. CONCLUSIONS In men with a prostate of less than 35 cc tumor percent involvement is an important variable when assessing the risk of prostate specific antigen recurrence. Tumor percent involvement and prostate volume should be considered when counseling patients and determining who may benefit from heightened surveillance after radical prostatectomy.

Effect of age and pathologic Gleason score on PSA recurrence: analysis of 2911 patients undergoing radical prostatectomy.

OBJECTIVES To clarify the relationship between age and pathologic Gleason score and their effect on prostate-specific antigen recurrence (PSAR). METHODS The data from a cohort of 2911 men who had undergone radical prostatectomy from 1988 to 2006 were retrieved from the Duke Prostate Center database. Patient age was divided into 3 groups: <60, 60-64, and >or=65 years. The pathologic Gleason score was divided into 5 groups: <or=5, 6, 3 + 4, 4 + 3, and >7. PSAR was defined as the prostate-specific antigen level increasing to >0.2 ng/mL >30 days after radical prostatectomy. The associations between age and pathologic Gleason score on PSAR and the time to PSAR were analyzed using parametric, nonparametric, Kaplan-Meier, and Cox regression techniques. RESULTS Patient age and interval to PSAR had no significant association (P > .05). Kaplan-Meier analysis demonstrated a significant difference in PSAR among age groups. The pathologic Gleason scores of 3 + 3, 3 + 4, 4 + 3, and >7 were significant in determining the incidence of PSAR. Age was not significant for PSAR in patients with a pathologic Gleason score of <or=7. In patients with a pathologic Gleason score of >7, a statistically significant difference was observed among the age groups. Men <60 years old with a pathologic Gleason score >7 had a lower incidence of PSAR than did older men with a similar pathologic Gleason score. A pathologic Gleason score of >or=6 was significant in predicting PSAR. CONCLUSIONS Age alone was an independent factor in predicting PSAR, but not in predicting the interval to PSAR. The pathologic Gleason score remained a predictor of PSAR, and patient age should be considered in patients with a pathologic Gleason score >7.

Predicting non-organ-confined prostate cancer in men diagnosed after 2000

The objective of this study was to preoperatively predict non-organ-confined disease in patients considering radical prostatectomy. To account for the stage migration seen in prostate cancer, we included only those patients who underwent prostatectomy after the year 2000. Information on a cohort of 1895 patients who underwent radical prostatectomy from 2000 to 2008 was retrieved from the Duke Prostate Center database. Race (African American, non-African American), body mass index, age at surgery, PSA, biopsy Gleason sum (<7, 7 and >7) and clinical tumor stage (cT1, cT2/3) were analyzed by univariate analysis followed by logistic regression analysis. The Duke Interactive Clinical Equation for staging (DICE-S score) was calculated from the logistic regression model. The model was then internally validated using a bootstrapping technique. Biopsy Gleason sums 7 and >7 were more likely to have non-organ-confined disease compared with <7 (OR=2.97, Gleason sum=7; OR=3.25, Gleason sum>7). Clinical tumor stage, cT2/3, predicted non-organ-confined disease (OR=1.58). Older age was associated with non-organ-confined disease (OR=1.02), as was greater PSA (OR=1.12). DICE-S equation x=ln (p/1−p)=−3.627+0.019 (age)+0.109 (PSA)+1.087 (bGleason=7)+1.180 (bGleason >7)+0.459 (clinical T stage >T1), where p=(ex)/(1+ex). A concordance index (prediction accuracy) of 0.73 was reached on internal validation. Using the DICE-S score, age, PSA, biopsy Gleason sum and clinical tumor stage, we can predict non-organ-confined disease in radical prostatectomy at an acceptable accuracy. Preoperative information on disease stage may aid in treatment decisions and surgical approach.

Risk stratification in the hormonal treatment of patients with prostate cancer

Prostate cancer (PCa) is the most common type of cancer found in American men, other than skin cancer. The American Cancer Society estimates that there will be 186,320 new cases of prostate cancer in the United States in 2008. About 28,660 men will die of this disease this year and PCa remains the second-leading cause of cancer death in men. One in six men will get PCa during his lifetime and one in 35 will die of the disease. Today, more than 2 million men in the United States who have had PCa are still alive. The death rate for PCa continues to decline, chiefly due to early detection and treatment, and improved salvage therapy such as hormone therapy (HT). HT continues to be a mainstay for primary-recurrent PCa and locally-advanced PCa. However, HT is associated with many undesirable side effects including sexual dysfunction, osteoporosis and hot flashes, all of which can lead to decreased quality of life (QOL). These risks are seen in both long- and short-term HT regimens. Additionally, research in recent years has revealed trends related to clinico pathological variables and their predictive ability in HT outcomes. Awareness of the potential adverse effects, the risks associated with HT and the prognostic ability of clinical and pathological variables is important in determining optimal therapy for individual patients. A rigorous evaluation of the current scientific literature associated with HT was conducted with the goal of identifying the most favorable balance of benefits and risks associated with HT.

TUMOR VOLUME, TUMOR PERCENTAGE INVOLVEMENT OR PROSTATE VOLUME: WHICH IS PREDICTIVE OF PSA RECURRENCE?

Objective To compare the effects of tumor volume (TV), tumor percentage involvement (TPI) and prostate volume (PV) on PSA recurrence (PSAR) following radical prostatectomy (RP).