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.     

Preoperative p27 status is an independent predictor of prostate specific antigen failure following radical prostatectomy

PURPOSE: p27 is an important cell cycle regulator, and decreased expression in radical prostatectomy specimens is associated with an increased risk of prostate specific antigen (PSA) failure. To our knowledge no prior study has shown that preoperative p27 status independently predicts recurrence after radical prostatectomy. MATERIALS AND METHODS: The prostate needle biopsy specimens of 161 men treated with radical prostatectomy were examined for p27 expression using immunohistochemistry. Various p27 cut points were examined for their ability to separate patients into groups with different risk for time to biochemical recurrence following radical prostatectomy. The best p27 cut point was compared to other clinical variables (PSA, clinical stage, age, biopsy Gleason score and percent of prostate needle biopsy with cancer) on multivariate analysis to determine which variables independently predicted biochemical failure. RESULTS: A p27 cut point of less than 45% positive staining cells resulted in significant preoperative risk stratification for time to PSA failure (HR 2.41, p = 0.010). On multivariate analysis serum PSA (HR 1.04, p = 0.011), biopsy Gleason score (HR 1.51, p = 0.011), percent of biopsy tissue with cancer (HR 10.01, p = 0.001) and less than 45% p27 positive cells (HR 2.44, p = 0.014) were all independent predictors of biochemical recurrence. CONCLUSIONS: Preoperative p27 expression is an independent predictor of time to biochemical recurrence following radical prostatectomy. Patients with less than 45% p27 positive cells in the prostate needle biopsy specimen have almost a 2.5-fold increased risk of biochemical recurrence. To our knowledge this study is the first to show that p27 status of the prostate needle biopsy specimen can be used before radical prostatectomy to predict biochemical failure.     

Biochemical (prostate specific antigen) recurrence probability following radical prostatectomy for clinically localized prostate cancer

PURPOSE: We retrospectively reviewed the clinical followup for a large series of men with clinically localized prostate cancer who underwent radical retropubic prostatectomy to identify clinical and/or pathological indicators of biochemical (prostate specific antigen [PSA]) recurrence. We then used those indicators to develop multivariate models for determination of recurrence probability following radical retropubic prostatectomy. MATERIALS AND METHODS: From 1982 to 1999, 2,091 consecutive men underwent radical retropubic prostatectomy and pelvic lymphadenectomy for clinically localized adenocarcinoma of the prostate (clinical stage T1c or T2 disease with Gleason score 5 or greater). Actuarial analysis was performed comparing freedom from biochemical recurrence after radical retropubic prostatectomy (PSA 0.2 ng./ml. or greater.) using the Kaplan-Meier method. Event time distributions for the time to recurrence were compared using the log rank statistic or the Cox proportional hazards regression model. The first model was developed using preoperative variables only and the second model using all available variables. Observed and predicted recurrence-free survival curves for different models were compared to select a model for calculation of predicted recurrence-free probabilities and confidence intervals. RESULTS: With a median followup of 5.9 years (range 1 to 17) 360 men (17%) had biochemical recurrence. Overall actuarial 5, 10 and 15-year biochemical recurrence-free survival rates were 84%, 72% and 61%, respectively. The relative risk of biochemical recurrence following surgery decreased with time, even after adjusted for other perioperative parameters. Variables identified for the preoperative model were biopsy Gleason score, clinical TNM stage and PSA. Variables identified for the postoperative model were prostatectomy Gleason score, PSA and pathological organ confinement status. Nomograms were generated and corrected for the decreasing relative risk of biochemical recurrence over time. CONCLUSIONS: Using 3 preoperative or postoperative parameters, these nomograms can easily be used to determine the 3, 5, 7 and 10-year biochemical recurrence-free survival probabilities among men who undergo radical retropubic prostatectomy for clinically localized prostate cancer in the modern era.     

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.     

Obesity and biochemical outcome following radical prostatectomy for organ confined disease with negative surgical margins

PURPOSE: We have previously shown that men with a body mass index (BMI) greater than 35 kg/m2 had higher rates of positive surgical margins and significantly higher biochemical recurrence rates following radical prostatectomy (RP). To determine whether the higher prostate specific antigen (PSA) recurrence rates were due solely to the higher positive margin rate, we examined whether obesity was an independent predictor of biochemical failure among men with negative surgical margins. MATERIALS AND METHODS: We examined data from 1,250 men treated with RP between 1988 and 2003 at 5 equal access medical centers, of whom 731 had pathologically organ confined disease and negative surgical margins. Multivariate Cox proportional hazards analysis was used to determine if BMI was a significant independent predictor of biochemical recurrence. RESULTS: Mean BMI significantly increased over time (p = 0.010). Black men were significantly more likely to be obese than white or nonwhite-nonblack men. After controlling for all preoperative characteristics, body mass index was a significant predictor of biochemical failure with moderately and severely obese men (BMI 35 kg/m2 or greater) having greater than a 4-fold increased risk of PSA failure (p = 0.035). After controlling for the higher pathological Gleason grades among obese men, body mass index remained a significant predictor of biochemical failure with moderately and severely obese men (BMI 35 kg/m2 or greater) having nearly a 4-fold increased risk for PSA failure (p = 0.036). CONCLUSIONS: BMI 35 kg/m2 or greater was associated with higher grade tumors and worse outcome following RP in a cohort of men with favorable pathological findings. Thus, surgical technique (margin status) cannot fully explain the worse outcomes among obese men, suggesting that obesity may be associated with a biologically more aggressive form of prostate cancer.     

Obesity adversely affects health related quality of life before and after radical retropubic prostatectomy

PURPOSE: Obesity adversely affects surgical procedures and outcomes. We used a validated health related quality of life measure to examine the effects of obesity on disease specific health related quality of life before and following radical retropubic prostatectomy. MATERIALS AND METHODS: From June 2000 to April 2003, 575 consecutive patients with prostate cancer were approached to participate in a prospective, health related quality of life study. Health related quality of life was assessed before surgery, and 1, 4, 12, 24 and 36 months postoperatively. Repeated measures mixed models were constructed to determine the independent effects of body mass index on health related quality of life. RESULTS: Of 472 consenting subjects 376 (80%) completed a baseline and at least 1 followup survey. Higher body mass index was associated with worse preoperative hormonal/vitality function (p = 0.0009) and bother (p = 0.02), and delayed recovery of bowel function (p = 0.01) and bother (p = 0.01) health related quality of life. There were no measurable differences postoperatively in hormonal/vitality, urinary or sexual health related quality of life associated with higher body mass index. Increased body mass index was associated with prostate specific antigen recurrence (p = 0.05) and adjuvant treatment (p = 0.02). Adjuvant treatment was independently associated with worse bowel function (p = 0.01) and bother (p = 0.01) health related quality of life in obese patients. At 24 months bowel health related quality of life in obese patients no longer significantly differed from that in nonobese patients. CONCLUSIONS: Obesity is associated with worse preoperative hormonal/vitality health related quality of life, slower recovery of bowel function and bother health related quality of life after radical retropubic prostatectomy, and prostate specific antigen recurrence. Impaired health related quality of life recovery in obese patients is influenced by disease recurrence and resultant adjuvant therapies. Despite these findings obese patients should not be dissuaded from considering prostatectomy as definitive treatment for localized prostate cancer.     

Radical prostatectomy nomograms in black American men: accuracy and applicability

PURPOSE: Nomograms have been developed to allow the prediction of disease recurrence based on clinical and pathological parameters in patients with clinically localized prostate cancer. However, they have been constructed using predominantly white American male (CAM) cohorts. We have previously shown that black American males (AAMs) have worse disease-free survival after radical prostatectomy after controlling for known prognostic factors. We tested the accuracy of prognostic nomograms in a population of AAMs with prostate cancer treated with radical prostatectomy. MATERIALS AND METHODS: We tested the performance of published preoperative and postoperative prognostic nomograms in a cohort of patients treated with radical prostatectomy as monotherapy for localized prostate cancer at Wayne State University in the prostate specific antigen era. Predictions made with the nomogram were stratified by race and compared with actual outcomes. The summary statistic used to evaluate the nomogram was the concordance index. A value of 0.5 indicates no predictive discrimination, whereas a value of 1.0 indicates perfect discrimination. RESULTS: A total of 1,043 patients, including 331 AAMs (32%) and 712 CAMs (68%), comprised the study cohort. Treatment failure was defined as increasing prostate specific antigen, which occurred in 193 patients (18.5%). The preoperative concordance index for CAMs and AAMs was 0.78 and 0.74, respectively (p = 0.8). The postoperative index was 0.85 and 0.83, respectively (p = 0.9). CONCLUSIONS: Preoperative and postoperative nomograms can be applied accurately to an individual regardless of race.     

Percent of prostate needle biopsy cores with cancer is significant independent predictor of prostate specific antigen recurrence following radical prostatectomy: results from SEARCH database

PURPOSE: Recent studies have suggested that the percent of positive cores in the prostate needle biopsy is a significant predictor of outcome among men undergoing radical prostatectomy or radiation therapy for prostate cancer. We evaluate whether either percent of cores with cancer or percent of cores positive from the most and least involved side of the prostate needle biopsy was associated with a worse outcome among men treated with radical prostatectomy. MATERIALS AND METHODS: A retrospective survey of 1,094 patients from the SEARCH Database treated with radical prostatectomy at 4 different equal access medical centers in California between 1988 and 2002 was undertaken. We used multivariate analysis to examine whether total percent of prostate needle biopsy cores with cancer, percent of cores positive from each side of the prostate and other clinical variables were significant predictors of adverse pathology and time to prostate specific antigen (PSA) recurrence following radical prostatectomy. RESULTS: On multivariate analysis serum PSA and percent of positive cores were significant predictors of positive surgical margins, nonorgan confined disease and seminal vesicle invasion. Percent of positive cores (p <0.001), serum PSA (p = 0.008) and biopsy Gleason score (p = 0.014) were significant independent predictors of time to biochemical recurrence. On a separate multivariate analysis that included the variables of total percent of positive cores, percent of positive cores from the most involved side of the biopsy, percent of positive cores from the least involved side of the biopsy and whether the biopsy was positive unilaterally or bilaterally, only the percent of positive cores from the most involved side of the biopsy was a significant independent predictor of PSA failure following radical prostatectomy. Percent of positive cores was used to separate patients into a low risk (less than 34%), intermediate risk (34% to 50%) and high risk (greater than 50%) groups, which provided significant preoperative risk stratification for PSA recurrence following radical prostatectomy (p <0.001). Percent of positive cores cut points were able to further risk stratify men who were at low (p = 0.001) or intermediate (p = 0.036) but not high (p = 0.674) risk for biochemical failure based on serum PSA and biopsy Gleason score. CONCLUSIONS: Percent of positive cores in the prostate needle biopsy was a significant predictor of adverse pathology and biochemical failure following radical prostatectomy, and the cut points of less than 34%, 34% to 50% and greater than 50% can be used to risk stratify patients preoperatively. The finding that percent of positive cores from the most involved side of the biopsy was a stronger predictor of PSA failure than the total percent of cores involved suggests that multiple positive biopsies from a single side might be a better predictor of a larger total cancer volume and thus correlate with clinical outcome.     

The relationship between serum prostate specific antigen level and tumor volume persists in the current era

PURPOSE: We compared the relationships of serum prostate specific antigen to tumor volume and to noncancerous prostate tissue volume using multivariate analysis in men undergoing prostatectomy during 2 periods. MATERIALS AND METHODS: From our prostatectomy database we randomly selected 200 men from 1991 to 1994 (early group) and 200 from 2000 to 2003 (recent group) who underwent radical prostatectomy without neoadjuvant therapy. The variables analyzed were patient age, log prostate specific antigen, pathological stage, Gleason score, log total tumor volume and log noncancerous prostate tissue volume. Univariate correlation and multiple regression analyses were performed to assess the linearity of the relationships among the variables. RESULTS: There was a significant difference between the early and recent groups in age (median 64 years, IQR 58-67 vs 59, IQR 53-65; p<0.001), prostate specific antigen (8.3 ng/ml, IQR 5.7-12.5 vs 5.8, IQR 4.4-7.8; p<0.001), total tumor volume (2.0 cc, IQR 1.0-3.6 vs 1.4, IQR 0.6-2.9; p<0.001), Gleason score (7, IQR 7-8 vs 7, IQR 7-7; p<0.001) and the incidence of extraprostatic disease (39% vs 18.5%, p<0.001) but not in noncancerous prostate tissue volume (35.7 cc, IQR 28.6-46.5 vs 37.1, IQR 28.9-50.1). There was a relationship between log prostate specific antigen and log total tumor volume (r=0.486, p<0.001 and r=0.237, p<0.01), and between log prostate specific antigen and log noncancerous prostate tissue volume (r=0.179, p<0.05 and r=0.138, p=0.051) in the early and the recent groups, respectively. Multiple regression analyses revealed that log total tumor volume, log noncancerous prostate tissue volume and Gleason score were significant independent variables for predicting log prostate specific antigen in the 2 groups. In the recent group log noncancerous prostate tissue volume had the most significant association with log prostate specific antigen (p<0.001), whereas in the early group log total tumor volume had the most significant association (p<0.001). CONCLUSIONS: Although the relationship between serum prostate specific antigen and tumor volume decreased from early treatment years to recent years, the association remained at a significant level. In recent years noncancerous prostate tissue volume had the most significant association with prostate specific antigen.     

Prostate cancer stage shift has eliminated the gap in disease-free survival in black and white American men after radical prostatectomy

PURPOSE: The initiation of prostate specific antigen (PSA) testing has led to increased public awareness, early detection and a stage shift in prostate cancer. We have previously reported that black American men have worse disease-free survival independently of pathological or clinical factors. We tested the stage shift effects on disease-free survival in our cohort of patients treated with radical prostatectomy. MATERIALS AND METHODS: A total of 1,042 consecutive patients underwent radical prostatectomy performed by Wayne State University full-time faculty. The cohort was divided by the year of surgery as before (585 men in group 1) or after (457 in group 2) 1996. Clinicopathological and disease-free survival data were obtained from the Karmanos Cancer Institute multidisciplinary prostate cancer database. RESULTS: Improvements in clinical stage, preoperative PSA and biopsy Gleason score were observed in group 2 (p = 0.0001). Pathological organ confined disease increased in group 2 versus 1 in the 2 races, including 89 of 153 (58%) from 66 of 178 (37%) in black men and 189 of 304 (62%) from 194 of 407 (48%) in white men (p = 0.003 and 0.001, respectively). Calculated cancer recurrence-free median probability in group 1 at 42 months was 81% and 68% in white and black men, respectively (log rank test p = 0.001). These differences became insignificant in group 2 patients at 42 months with a median probability of 90% and 88% in white and black men, respectively (log rank test p = 0.39), representing a net increase in disease-free survival of 20% in black men. Specimen Gleason score, PSA and pathological stage were independent predictors of survival in the 2 groups. In contrast, race was an independent predictor only in group 1. CONCLUSIONS: The increased rate of pathological organ confined disease is translating into improved disease-free survival rates. These early data suggest that the survival gap in black and white American men is narrowing and may become statistically insignificant.     

Pretreatment total testosterone level predicts pathological stage in patients with localized prostate cancer treated with radical prostatectomy

PURPOSE: In the last decade numerous groups have shown that low levels of pretreatment serum total testosterone consistently predict more aggressive disease, worse prognosis and worse treatment response in patients with metastatic prostate cancer. Prior studies have not demonstrated this same correlation in patients with known localized disease. We rigorously tested pretreatment total testosterone levels as a potential staging and prognostic marker in a large cohort of 879 patients with localized cancer treated with radical prostatectomy. MATERIALS AND METHODS: We retrospectively reviewed the clinical records of 879 patients treated with radical prostatectomy between January 1, 1986 and June 30, 2002 from 9 hospital sites. Nonparametric tests were used to compare the relationship of pretreatment testosterone to other variables. Multivariate logistic regression analysis was used to assess clinical predictors of extraprostatic disease. Kaplan-Meier survival methods and Cox regression analysis were used to assess predictors of biochemical recurrence. RESULTS: Patients with non-organ confined prostate cancer (pT3-T4) showed significantly lower pretreatment total testosterone levels than those with organ confined cancer (pT1-T2) (nonparametric p = 0.041). In multivariate analysis pretreatment total testosterone emerged as a significant independent predictor of extraprostatic disease (p = 0.046). Total testosterone was not a significant predictor of biochemical (prostate specific antigen) recurrence (p = 0.467). CONCLUSIONS: Pretreatment total testosterone was an independent predictor of extraprostatic disease in patients with localized prostate cancer. As testosterone decreases patients have an increased likelihood of non-organ confined disease. Low testosterone was not predictive of biochemical recurrence, although trends observed dictate study in larger cohorts with mature followup.     

Lymphovascular invasion is a pathological feature of biologically aggressive disease in patients treated with radical prostatectomy

We examined whether invasion of lymphatic and/or vascular vessels (LVI), or perineural spaces (PNI) is associated with prostate cancer features and outcome. MATERIALS AND METHODS: A total of 630 consecutive men underwent radical retropubic prostatectomy for clinically localized disease. LVI and PNI examination was part of the routine specimen evaluation. RESULTS: Foci of LVI were identified in 32 patients (5%) and 381 (60.5%) had PNI. LVI and PNI were associated with clinical stage T2 disease, higher biopsy and final Gleason sum, extraprostatic extension, seminal vesicle involvement, positive surgical margins and a higher percent of positive biopsy cores (p <0.001). LVI was associated with metastases to regional lymph nodes and higher preoperative serum prostate specific antigen (p <0.001 and 0.004, respectively). PNI and LVI were associated with an increased risk of rapid biochemical progression after radical prostatectomy on univariate (p <0.001 and 0.001, respectively) but not on multivariate analysis. LVI was associated with shorter prostate specific antigen doubling time after biochemical progression (p = 0.012) and higher probabilities of failed local salvage radiation therapy (p = 0.0169), distant metastases (p <0.001) and death (p <0.001). CONCLUSIONS: Only LVI is associated with metastases to regional and distant sites, and most importantly with overall survival. LVI and PNI are associated with established markers of biologically aggressive disease and rapid biochemical progression in patients who underwent radical prostatectomy. Our findings support the routine evaluation of LVI status in radical prostatectomy specimens and its inclusion in predictive models for clinical outcomes, since it appears to be a pathological marker of the lethal phenotype of prostate cancer.     

Biochemical recurrence after radical prostatectomy in black and white American men with a positive or negative family history of prostate cancer

PURPOSE: We investigated the impact of a family history of prostate cancer on predicting biochemical recurrence in black and white American men. MATERIAL AND METHODS: Between January 1991 and December 1996, 910 men underwent radical retropubic prostatectomy for clinically localized prostate cancer, of whom 676 had data available on prostate cancer family history. Statistical analysis was performed to identify any correlation among the known predictors of biochemical outcome and family history in each race. RESULTS: Median followup was 34 months (range 2 to 103). We identified 355 (52%) and 321 (48%) white and black American men, respectively, for whom data were available on prostate cancer family history, including 177 (26%) with a positive and 499 (74%) with a negative history. Family history was positive in 94 black (29%) and 83 white (23%) men. No significant difference was noted in the incidence of familial prostate cancer in the 2 races (p = 0.10). In black men the biochemical failure rate was 32% and 26% in those with a positive and negative history (log rank test p = 0.51), while in white men the rate was 17% and 18%, respectively (log rank test p = 0.79). A family history positive for prostate cancer was not associated with biochemical failure in either race. CONCLUSIONS: Biochemical recurrence was not significantly worse in patients with a family history of prostate cancer than in those with nonfamilial disease in either race.     

Long-term outcome following radical prostatectomy in men with clinical stage T3 prostate cancer

PURPOSE: We evaluated patients at our institution who underwent radical prostatectomy for clinical stage T3 prostate cancer to determine their long-term clinical outcomes. MATERIALS AND METHODS: We reviewed our prospective surgical database and identified 176 men who underwent radical retropubic prostatectomy for clinical stage T3 prostate cancer from 1983 to 2003. Clinical and pathological data were reviewed and evaluated in a Cox proportional hazards model to determine preoperative predictors of biochemical recurrence. Clinical progression following biochemical recurrence was evaluated and clinical failure was defined as the development of clinical metastases or progression to hormone refractory prostate cancer. RESULTS: Of the 176 patients with cT3 prostate cancer 64 (36%) received neoadjuvant hormonal therapy. At a mean followup of 6.4 years 84 (48%) patients had disease recurrence with a median time to biochemical recurrence of 4.6 years. The actuarial 10-year probability of freedom from recurrence was 44%. On multivariate analysis biopsy Gleason score, pretreatment serum prostate specific antigen and year of surgery were independent predictors of biochemical recurrence. Neoadjuvant hormonal therapy was not a significant predictor of biochemical recurrence. Following biochemical recurrence clinical failure developed in 30 of 84 (36%) men with a median time of 11 years. Overall the 5, 10 and 15-year probabilities of death from prostate cancer were 6%, 15% and 24%, respectively. CONCLUSIONS: More than half (52%) of our patients remained free of disease recurrence following radical prostatectomy. In our series neoadjuvant hormonal therapy offered no advantage with respect to disease recurrence. Radical prostatectomy remains an integral component in the treatment of select patients with clinical stage T3 prostate cancer.     

Differences between urologists in the United States and Canada in the approach to prostate cancer

PURPOSE: We examine differences in screening, detection, staging and treatment of prostate cancer between urologists in the United States and Canada. MATERIALS AND METHODS: An anonymous questionnaire was developed and mailed to 700 randomly selected American and 350 Canadian urologists. The 7 domains of prostate cancer management comprised screening/case identification, radical prostatectomy indications, staging evaluations, neoadjuvant therapy, nerve sparing techniques, postoperative management and treatment of biochemical recurrence. The Dillman method of questionnaire administration was used. All data were stratified by country and analyzed using the generalized chi-square test. RESULTS: Surveys were adequately completed by 45% and 79% of American and Canadian urologists, respectively. Practice experience and clinical volumes were not significantly different between the 2 cohorts. Overall, there were few differences in prostate cancer screening, staging, postoperative management, biochemical failure and use of neoadjuvant therapy. However, practicing American urologists tended to pursue more aggressive case finding practices, such as a higher age cutoff for prostate specific antigen testing (p = 0.0001) and more frequent use of transition zone biopsies (p = 0.0001). American urologists also displayed a tendency toward more liberal indication for extirpative surgery. They were more likely to perform radical prostatectomy in men older than 70 years, those with higher prostate specific antigen and those with node positive disease. Among both national cohorts there was considerable variation in management patterns for all domains of prostate cancer. Variation was most common among treatment of patients with adverse pathological conditions (positive margins, seminal vesicle involvement) and postoperative biochemical failure. Even when credible evidence exists (biopsy technique, preoperative staging) significant proportions of urologists in both countries continued to practice contrary to existing data. CONCLUSIONS: American and Canadian practice patterns for prostate cancer differ significantly only in the domains of case identification and surgical indications. In addition, considerable intra-national variation in practice patterns exists. These data highlight the necessity to support randomized clinical trials in prostate cancer.     

Is prostate‐specific antigen (PSA) density better than the preoperative PSA level in predicting early biochemical recurrence of prostate cancer after radical prostatectomy?

OBJECTIVE: To investigate the relationship of preoperative prostate-specific antigen (PSA) level and PSA density with several clinical and pathological variables, including biochemical recurrence after radical prostatectomy (RP), and to compare the preoperative PSA level and PSA density as prognostic factors in prostate cancer. PATIENTS AND METHODS: The study included 348 patients who had a RP at one institution, with whole-mount specimens of the prostate examined by one pathologist. Univariate and multivariate analyses were used to assess the relationship of the preoperative PSA level and PSA density with clinical and pathological variables, and by receiver operating characteristic (ROC) analysis to evaluate the relative usefulness of the two factors as predictors for biochemical recurrence. RESULTS: The PSA level before RP was significantly correlated (Spearman's rank correlation) with patient age (P = 0.003), prostate weight (P < 0.001), cancer volume (P < 0.001) and Gleason score (P = 0.033), and with surgical margin status and pathological stage (both P < 0.001) in the RP specimen. In the multivariate analysis controlling for tumour stage, surgical margin status, and Gleason score, both PSA level and PSA density were significant predictors of PSA recurrence (P = 0.027 and 0.01, respectively). ROC analysis showed no statistical difference between the PSA level and PSA density in predicting PSA recurrence after RP (P = 0.40). CONCLUSIONS: These results show a significant correlation of the preoperative PSA level with other established prognostic factors for prostate cancer. In the multivariate analysis, both PSA level and PSA density were independent predictors of PSA recurrence. Because the PSA level is as effective as PSA density in predicting PSA recurrence, the extra effort required to calculate PSA density may not be warranted. We recommend that the PSA level before RP be considered in stratifying patients into different prognostic groups, and in determining the optimum management.     

25-year prostate cancer control and survival outcomes: a 40-year radical prostatectomy single institution series

PURPOSE: We report on 25-year cancer control and survival outcomes after radical prostatectomy in a single center series of patients treated during a 40-year period. MATERIALS AND METHODS: Between 1954 and 1994, 787 consecutive patients underwent radical prostatectomy at Virginia Mason Medical Center in Seattle, Washington. Kaplan-Meier 25-year probabilities of prostate cancer specific, overall, prostate specific antigen progression-free, local and distant progression-free survival were determined. Multivariate Cox regression models addressed prostate cancer specific mortality. RESULTS: Prostate cancer specific survival, overall survival, prostate specific antigen progression-free survival, local and distant progression-free survival ranged from 99.0% to 81.5%, 93.5% to 19.3%, 84.8% to 54.5%, 95.3% to 87.8% and 95.9% to 78.2%, respectively. In univariate analyses pathological stage, surgical margin status, pathological Gleason sum, delivery of hormonal therapy and radiotherapy represented statistically significant predictors of prostate cancer specific mortality (all p < or =0.001). In multivariate analyses only Gleason sum (p = 0.03) and delivery of hormonal therapy (p < 0.001) remained significant. CONCLUSIONS: This is one of the most mature radical prostatectomy series. It demonstrates that long-term biochemical cancer control outcomes after radical prostatectomy might be suboptimal. However, local and distant control outcomes are excellent, and cancer specific mortality is minimal even 25 years after surgery.     

Preoperative prostate needle biopsy p27 correlates with subsequent radical prostatectomy p27, Gleason grade and pathological stage

PURPOSE: Loss of p27 protein expression in radical prostatectomy specimens has been shown to be an adverse prognostic factor in patients with clinically localized prostate cancer. To our knowledge no studies have examined p27 expression in prostate needle biopsies. To test the potential predictive power of p27 in prostate biopsies we compared p27 expression in preoperative biopsies and matched prostatectomy specimens of patients with clinically localized prostate cancer. MATERIALS AND METHODS: Matched biopsies and radical prostatectomy specimens from 44 patients were examined. Mean followup was 22.7 months (range 1 to 46). Tumors expressing less than 30% positive nuclei were classified as low expressors and tumors expressing greater than 30% positive nuclei were classified as high expressors of p27 protein. RESULTS: Expression of p27 in prostate biopsies correlated significantly with subsequent p27 expression in radical prostatectomy specimens (p = 0.002). Sensitivity and specificity of biopsy p27 for predicting subsequent prostatectomy p27 were 87.5% and 88.9%, respectively (p <0.001). Univariate analysis showed that low expression of p27 in the biopsy correlated significantly with biopsy and prostatectomy Gleason score (p = 0.000 and 0.001, respectively), and final pathological stage (p = 0.028). Despite the small sample size and short followup, 36.4% of patients with low p27 expression had a biochemical recurrence compared to only 12.1% with high expression (hazards ratio 3.56). In addition, Kaplan-Meier analysis suggested that low p27 expression in prostate biopsies may be associated with a shorter time to recurrence, although this did not reach statistical significance (p = 0.081). CONCLUSIONS: Expression of p27 in prostate biopsies can be used to predict the degree of expression in radical prostatectomy specimens. As loss of p27 protein expression in prostatectomy specimens has been shown to correlate with biochemical recurrence and shortened prostate specific survival, these results suggest that biopsy p27 may help identify high risk patients preoperatively.