Preoperative Serum Prostate-specific Antigen Level Research Articles

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

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. 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. 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). 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.

Prognostic significance of neuroendocrine expression in lymph node-positive prostate cancer

Objectives To evaluate the expression of chromogranin A, a marker for neuroendocrine (NE) differentiation, in patients with lymph node-positive prostate cancer to determine its prognostic significance. NE cells are involved in cellular growth and differentiation in both normal and pathologic conditions of the prostate. Methods We reviewed the data of 140 patients with lymph node-positive prostate adenocarcinoma treated with radical prostatectomy and pelvic lymphadenectomy. The median follow-up was 10.9 years (range 0.8 to 19.7). Immunohistochemical staining for chromogranin A was evaluated in areas of benign epithelium, primary prostate cancer, and lymph node metastasis. The association between chromogranin A expression and the clinical and pathologic factors (preoperative serum prostate-specific antigen and prostatectomy Gleason score and stage) and clinical outcomes, including overall and recurrence-free survival, was evaluated. Results Staining was positive in 86% of benign areas, 61% of primary cancer specimens, and 12% of lymph node deposits. The preoperative serum prostate-specific antigen level and pathologic stage and grade of the primary tumor did not show any statistically significant correlation with NE staining in any of the areas. Only NE expression in the primary tumor was associated with clinical recurrence, with a 10-year recurrence-free survival rate for those with less than 5% staining of 67% compared with 35% for those with 5% staining or greater ( P = 0.03). Furthermore, after adjusting for age, greater NE expression in the primary tumor (relative risk 2.15, P = 0.02) and lymph node deposit (relative risk 2.03, P = 0.03) was associated with poorer overall survival. Conclusions NE expression in the primary tumor and lymph node metastasis of patients with node-positive prostate cancer may provide additional prognostic stratification.

The Anatomic Distribution and Pathological Characteristics of Prostate Cancer: A Mapping Analysis

Purpose: We mapped the location of prostate cancer in Korean men, and investigated the volume and tumor distribution in relation to clinicopathological variables. Materials and Methods: The volume of cancer and the anatomic location of each tumor foci were determined from 186 radical prostatectomy specimens, which were digitized to fit into a prototype prostate model. Using the computer-based digital images, the zonal cancer volume and distributional frequency were analyzed with respect to the clinical and pathological parameters, which were demonstrated in gray scales. Results: The preoperative serum prostate-specific antigen (PSA) level ranged from 2.0 to 38.9ng/ml. The mean cancer volume of the 186 specimens was 4.5ml (median 1.9ml, range 0.01-37.7). The impalpable cancers were located more anteriorly and in the transition zone, and were also were smaller in volume (2.7ml vs. 5.5ml, p=0.004) than the palpable cancers. Cancers with seminal vesicle invasion were located more medially in the peripheral zone, and were larger in volume than organ-confined cancers or cancers with extracapsular extension (13.2ml vs. 3.0ml, p<0.001). For Gleason scores of 2-6, 7, and 8-10, the mean cancer volumes were 2.2, 3.7 and 8.2ml, respectively (p<0.001). High grade cancers were located more medially in the peripheral zone, especially when approaching the apex. Conclusions: T1c cancers are located more anteriorly and in the transition zone; therefore, inclusion of these areas for targeted biopsy may help to improve the detection of cancer in patients with elevated PSA levels and impalpable prostate cancer. A medial location of seminal vesicle invasive cancers may imply an ejaculatory ducts route of invasion rather than a direct extracapsular extension. (Korean J Urol 2006;47:578-585) ꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏ

Is preoperative serum prostate‐specific antigen level significantly related to clinical recurrence after radical retropubic prostatectomy for localized prostate cancer?

To evaluate the influence of preoperative serum prostate-specific antigen (PSA) level and other clinicopathological variables on the probability of biochemical failure and clinical recurrence after radical prostatectomy (RP) for localized prostate cancer. The study was a retrospective survival analysis in 211 patients undergoing retropubic RP for clinically localized prostate cancer in the period 1988-2000. Survival was estimated using the Kaplan-Meier method; survival endpoints were biochemical failure, defined as a PSA level of > or = 0.5 ng/mL or clinical recurrence consisting of palpable tumours in the prostatic fossa or distant metastases. In 58 patients with biochemical failure after surgery, we assessed the impact of the doubling time of serum PSA level (PSADT) on the risk of developing skeletal metastases or local recurrence. The median (range) observation period was 66 (9-160) months. Biochemical failure occurred in 92 patients (44%) of whom 39 (42%) had local recurrence or skeletal metastases. There was a highly significant association (P < 0.001) between clinical T stage, histological grade, capsular penetration, surgical margin status, seminal vesicle invasion, preoperative serum PSA level and the probability of biochemical failure-free survival. By contrast there was no statistically significant association between preoperative serum PSA level, clinical T stage, surgical margin status, and clinical recurrence. There was a significant relationship between age (P = 0.021), histological grade (P = 0.025), capsular penetration (P = 0.018), seminal vesicle invasion (P = 0014), and clinical recurrence. Cox regression analysis showed that only histological grade and seminal vesicle invasion were independent predictors of clinical recurrence. In a subgroup of 58 patients with a rising serum PSA level after RP, a PSADT of < or = 12.8 months conferred a significantly higher risk (P = 0.015) of developing skeletal metastases than a PSADT of >12.8 months. In the present patients undergoing RP the preoperative serum PSA level was not associated with the clinical outcome, whereas it was significantly related to biochemical failure rate. The probability of skeletal metastases was significantly associated with the PSADT after biochemical failure.

Visual estimation of tumour extent is not an independent predictor of prostate specific antigen recurrence

To analyse tumour extent as a predictor of cancer progression after radical prostatectomy (RP), using a multivariate Cox regression model, as several variables (e.g. Gleason grade and tumour stage) are well-established prognostic factors in prostate cancer but it is uncertain if the visual estimation of tumour extent (percentage of carcinoma) is an independent predictor for prostate cancer recurrence. Tumour extent was estimated in the RP specimens from 504 men with clinically localized prostate cancer; clinical follow-up data were available for 459 men. The mean (range) follow-up was 44.3 (1.5-144) months. Cancer progression was defined by the development of biochemical recurrence, local recurrence, or distant metastasis. Multivariate analysis was used to assess tumour extent as a predictor of cancer progression. Of the 459 patients, 157 had cancer progression; the mean tumour extent was 36% and 24% in those with and without cancer progression, respectively (P < 0.001). Univariate analysis showed a significant association between the visual estimation of tumour extent and tumour stage, Gleason grade, surgical margins, extraprostatic extension, seminal vesicle invasion, lymph node metastasis, and preoperative serum prostate-specific antigen level (all P < 0.001). However, in a multivariate Cox regression model controlling for pathological stage, Gleason score, and surgical margin status, the visual estimation of tumour extent was no longer a significant predictor of cancer progression (P = 0.84). The visual estimation of tumour extent was associated with various established prognostic factors for prostate cancer, and with cancer progression in a univariate analysis, but it was not a significant predictor of cancer progression in the multivariate analysis controlling for pathological stage, Gleason score, and surgical margin status.

The percentage of positive biopsy cores as a predictor of disease recurrence in patients with prostate cancer treated with radical prostatectomy

To analyse the prognostic value of the percentage of positive biopsy cores (PPBC) in determining the pathological features and biochemical outcome of patients with prostate cancer treated by radical prostatectomy, as published data evaluating the prognostic value of PPBC in such patients have limitations. A group of 534 patients with clinically localized prostate cancer was selected. The PPBC was defined as the number of positive biopsy cores/total number of biopsy cores x 100, and grouped into categories of <25%, 25.1-50%, 50.1-75% and 75.1-100%. Patients were divided in low-, intermediate- and high-risk groups according to the usual variables. The mean follow-up was 60.5 months. PPBC was associated with the preoperative serum prostate-specific antigen (PSA) level, biopsy Gleason score and clinical stage. On multivariate analysis, PPBC was a significant predictor of extraprostatic disease and seminal vesicle involvement. Of patients in the four PPBC categories, 16%, 27%, 33% and 60%, respectively, had biochemical recurrence (P < 0.001), and on Cox regression analysis, PPBC was an independent predictor of disease recurrence. After segregating patients into risk groups the PPBC further stratified patients using thresholds of 75% (P = 0.006), 25% (P = 0.026) and 50% (P = 0.011) for low-, intermediate- and high-risk groups, respectively. We confirmed, with a longer follow-up, the clinical utility of the PPBC in determining the pathological features and biochemical outcome of patients with prostate cancer treated with radical prostatectomy, and established thresholds for use in patients in the three risk groups.

N-cadherin switching occurs in high Gleason grade prostate cancer

The inappropriate expression of non-epithelial N-(neural) cadherin by epithelial cells, called cadherin switching, has been suggested to play a role in prostate cancer (PC) progression. We explored the role of N-cadherin as a biomarker in PC by correlating the expression with clinical parameters. Two pathologists blinded to patients' history independently reviewed and scored the intensity and extent of staining of N-cadherin expression in 44 randomly selected radical prostatectomy specimens. The expression was correlated with total Gleason grade, individual Gleason patterns, tumor stage, and preoperative serum prostate specific antigen (PSA) levels and P-values < 0.05 were considered statistically significant. Of the 44 PC specimens, 14 (32%), 23 (52%), 7 (16%) consisted of Gleason grade 5-6, 7, and 8-10, respectively and 20/44 (45%) demonstrated N-cadherin expression. N-cadherin was expressed in 1/14 (7%) of Gleason 5-6 compared to 15/23 (65%) of Gleason grade 7, and 4/7 (57%) of Gleason grade 8-10, demonstrating a significant correlation between N-cadherin switching and higher Gleason grade (P = 0.001). While only about a third of primary or secondary Gleason pattern 3 demonstrated N-cadherin expression, a majority of Gleason patterns of > or = 4 expressed N-cadherin (P > 0.05), further suggesting that N-cadherin switching occurs with higher Gleason pattern. However, N-cadherin expression did not significantly correlate with preoperative serum PSA levels or tumor stage in our study cohort. We have demonstrated for the first time that N-cadherin switching occurs in higher grade PC and correlates significantly with increasing Gleason patterns. N-cadherin may be as a useful biomarker of aggressive PC.

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

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. 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. 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). 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.

Correlation of Gleason Scores Between Needle-Core Biopsy and Radical Prostatectomy Specimens in Patients with Prostate Cancer

The histologic grade of a prostate needle-core biopsy specimen can determine whether a patient with prostate cancer is a candidate for radical prostatectomy or other treatment. Incorrect histologic grading can result in inappropriate treatment and possible liability. Thus, we conducted this study to determine the histologic-grading accuracy of prostate cancer needle-core biopsy specimens. Fifty-two patients with localized prostate cancer treated with radical prostatectomy were included in the study. The overall correlation between Gleason scores for needle-biopsy and prostatectomy specimens was evaluated by analyzing the following parameters: biopsy-core number; accurate biopsy-core length; prostate volume; and preoperative, serum prostate-specific antigen (PSA) level. A "downgrade" was defined as the Gleason score for the prostatectomy specimen being greater than that for the biopsy specimen, whereas an "upgrade" was defined as the converse. No difference in Gleason scores was noted for 31% of specimens, whereas a downgrade was noted for 40%, and an upgrade for 29%. The accuracy of Gleason scores for biopsy specimens taken by the sextant systemic-biopsy method increased when specimens were >15 mm in length. No correlation was noted between difference in Gleason scores and biopsy-core number, prostate volume, and preoperative serum PSA level. The accuracy of Gleason scores determined by needle biopsy in patients with prostate cancer seems to be unreliable. Therefore, further evaluation of patients is necessary. No correlations were noted between biopsy-measured errors in Gleason score and biopsy number, prostate volume, or preoperative serum PSA level.

Long-term oncologic results of salvage radical prostatectomy for locally recurrent prostate cancer after radiotherapy

Salvage radical prostatectomy (RP) may potentially cure patients who have isolated local prostate cancer recurrence after radiotherapy (RT). We report the long-term cancer control associated with salvage RP in a consecutive cohort of patients and identify the variables associated with disease progression and cancer survival. A total of 100 consecutive patients underwent salvage RP with curative intent for biopsy-confirmed, locally recurrent, prostate cancer after RT. Disease progression after salvage RP was defined as a prostate-specific antigen (PSA) level of > or =0.2 ng/mL or by initiation of androgen deprivation therapy. Cancer-specific mortality was defined as active clinical disease progression despite castration. Cox regression analysis was used to evaluate these endpoints. The median follow-up from RT was 10 years (range, 3-27 years) and from salvage RP was 5 years (range, 1-20 years). Overall, the 5-year progression-free probability was 55% (95% confidence interval, 46-64%), and the median progression-free interval was 6.4 years. The preoperative PSA level was the only significant pretreatment predictor of disease progression in the multivariate analysis (p = 0.01). The 5-year progression-free probability for patients with a preoperative PSA level of <4, 4-10, and >10 ng/mL was 86%, 55%, and 37%, respectively. The 10-year and 15-year cancer-specific mortality after salvage RP was 27% and 40%, respectively. The median time from disease progression to cancer-specific death was 10.3 years (95% confidence interval, 7.6-12.9). After multivariate analysis, the preoperative serum PSA level and seminal vesicle or lymph node status correlated independently with disease progression. Greater preoperative PSA levels are associated with disease progression and cancer-specific death. Long-term control of locally recurrent prostate cancer after definitive RT is possible when salvage RP is performed early in the course of recurrent disease.

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

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. 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. 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). 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.

Continuing trends in pathological stage migration in radical prostatectomy specimens

Prostate-specific antigen (PSA) screening has resulted in a profound clinical stage migration. Extracapsular extension (ECE) presents a poor prognosis after radical prostatectomy (RP). In this study the trends in rate of ECE for cancers detected by PSA screening between 1987, when PSA screening became routine in the United States, and 2001, were examined. The clinical outcome of patients (total 1505; 888 clinical Tlc, 614 clinical T2, and 3 clinical T3) with prostate cancer diagnosed by PSA screening and treated with RP without neoadjuvant hormonal therapy was analyzed. The primary outcome variable was ECE rate with respect to year of treatment for a given tumor stage, preoperative PSA level, biopsy Gleason score, and surgical Gleason score. Logistic regression analysis was used to identify predictors of ECE. Biochemical relapse-free survival (bRFS) by year of treatment was analyzed by Kaplan-Meier Curve. Rate of ECE decreased from 65.8 to 25.2% during the 15-year study duration. Multivariate analysis of clinical tumor stage, age, preoperative serum PSA level, and Gleason score confirmed that year of treatment was an independent predictor of ECE. Six-year bRFS rates (by years of treatment) were 75.1% for 1987 to 1994 and 82.6% for 1995 to 2001 ( P-value = 0.0022). PSA screening has resulted in a downward pathological stage migration. These observations demonstrate improved biochemical failure rates in more recently treated patients.

Biopsy indication—a predictor of pathologic stage among men with preoperative serum PSA levels of 4.0 ng/mL or less and T1c disease

Objectives To determine the indications for biopsy among men with a prostate-specific antigen (PSA) level of 4 ng/mL or less and T1c disease and whether the reason for biopsy correlated with the final pathologic stage. It is not uncommon for men to undergo radical prostatectomy (RP) with a prostate-specific antigen (PSA) level of 4 ng/mL or less and T1c disease. Methods We examined the percentage of men with T1c disease and PSA level of 4.0 ng/mL or less undergoing RP over time. We identified 874 men with T1c prostate adenocarcinoma and PSA levels of 4 ng/mL or less who were treated with RP between 1994 and 2003. We excluded 72 patients who had received preoperative hormonal therapy and 86 patients for whom the reason for biopsy was unclear. The pathologic outcomes were compared between the various biopsy indication groups using analysis of variance. Results The percentage of men with T1c disease and a PSA level of 4.0 ng/mL or less has steadily increased from 0% before 1990 to 19% in 2003. Among men treated between 1994 and 2003, the most common indication for biopsy was a spike in the PSA level to greater than their reference level before biopsy (n = 471, 66%), although in all patients, the PSA level returned to 4 ng/mL or less before surgery. In 163 patients (35%), the PSA level remained elevated above the reference range and in the remaining 308 patients (65%), the PSA declined to a value below the reference range before surgery. The second most common indication for biopsy was an abnormal digital rectal examination by the referring/primary physician that, when repeated by the attending surgeon, was believed to be normal (n = 155, 22%). Abnormal PSA velocity accounted for biopsy in 68 patients (10%). Among patients with the three most common indications for biopsy, no statistically significant differences in the pathologic tumor characteristics between the groups were noted on the basis of the biopsy indication. Conclusions One in five men undergoing RP at our institution today has T1c disease and a PSA value of 4.0 ng/mL or less. The most common indication for biopsy was an elevated PSA level above their reference range, although in most, the PSA had returned to a normal value before surgery. Regardless of the indication for biopsy, these men had favorable findings at RP. That 22% of patients underwent biopsy because of what was perceived to be an abnormal digital rectal examination underscores the need to continue to perform digital rectal examination along with PSA determination as a part of routine prostate cancer screening.

Important preoperative prognostic factors for extracapsular extension, seminal vesicle invasion and lymph node involvement in cases with radical retropubic prostatectomy

Initial diagnostic evaluation may provide information about the extent of disease after radical retropubic prostatectomy (RRP). The aim of this study was to investigate the predictive value of preoperative serum prostate specific antigen (PSA) level, local disease extension identified by transrectal ultrasound (TRUS), total number of positive biopsies and percentage of positive cores for cancer, as well as TRUS Biopsy Gleason score in determining the extent of disease in radical retropubic prostatectomy specimens. A retrospective analysis was performed on 171 patients who underwent RRP from March 1993 to February 2003 for organ confined prostate cancer and whose follow-up data was accessible. The correlation of preoperative serum PSA level, local disease extension in TRUS, the total number of positive sextant biopsies and the percent of cores positive for cancer and Gleason score at TRUS biopsy specimen with the extent of disease at final pathology (Extra-capsular extension (ECE), seminal vesicle invasion (SVI), lymph node involvement (LNI) and surgical margin (SM) status on RRP specimens) were analyzed. The median age of the patients was 65 years. The mean preoperative serum PSA level of all patients was 11.6+/-1.2 (median 8.6) ng/ml. Histopathological evaluation of RRP specimens revealed 60 (35%) patients with ECE, 38 (22.2%) with SVI, 7 (0.04%) with LNI, and 58 (33.9%) had positive SM. Comparing the preoperative TRUS findings and postoperative evaluation of RRP specimens, the sensitivity of TRUS in predicting the ECE was 11.8% and specificity was 96%. Sensitivity of TRUS in predicting SVI was 9.8% and its specificity was 99%. With univariate analysis (sample t-test), Gleason score, percent of cores positive for cancer, and DRE were found to be predictive factors for extra-prostatic disease in RRP specimens. But with multivariate analysis (logistic regression test) Gleason score appears to be the most important and independent predictive factor for extra-prostatic disease in RRP specimens. Serum PSA levels and percentages of cores positive for cancer were also significant predictors of non organ-confined disease found at final pathology. Gleason score is the most important and independent predictive factor for extra-prostatic disease. Serum PSA levels and percentages of cores positive for cancer are the other important but non-independent predictive factors.

Characterisation of biomolecular profiles in primary high-grade prostate cancer treated by radical prostatectomy

The aim of this study was to compare the biomolecular profile of high-grade (HG) with low-grade (LG) prostate cancers matched by preoperative serum prostate-specific antigen (PSA) levels. From 2,560 patients undergoing radical prostatectomy for localised disease, 24 men with HG cancer (Gleason score > or =9) were eligible. Their clinical data were compared with those of 24 LG tumours (Gleason score < or =6), matched by PSA values. The expression of Ki-67, p53, Bcl-2, chromogranin A, alpha-catenin, and PSA were analysed and compared between both groups. The expression of Ki-67 (P=0.031), p53 (P=0.008), Bcl-2 (P=0.002), and chromogranin A (P=0.042) were expressed significantly higher, and alpha-catenin (P=0.020) and PSA (P<0.001) significantly lower in HG tumours. Cancer volumes of HG and LG differed significantly (10.6 cm3 vs 5.3 cm3; P=0.006). Overall, cancer volume correlated with increased expression of p53 (r=0.52; P<0.001) and chromogranin A (r=0.46; P<0.001), and with decreased expression of PSA (r=0.41; P<0.004). According to our data, tumour grade is clearly associated with a change in the biomolecular profile, even between patients with similar serum PSA levels. As the prognosis of HG prostate cancer is poor, these tumours should be analysed by immunohistochemical staining to identify specific tumour features for an appropriate selection of adjuvant therapy.

Pathologic comparison of laparoscopic versus open radical retropubic prostatectomy specimens

ObjectivesTo compare the pathologic evaluation of 60 sequential laparoscopic radical prostatectomy (LRP) specimens with 60 sequential and 60 stage and grade-matched open radical retropubic prostatectomy (RRP) cohort specimens. MethodsOf 68 patients undergoing LRP, 3 requiring open conversion and 5 receiving neoadjuvant hormonal therapy were excluded, leaving 60 for analysis. Among 72 sequential open RRP specimens, 60 from patients not receiving neoadjuvant hormonal therapy and without nodal metastases were analyzed. A third cohort of 60 RRP specimens matched with the LRP specimens for clinical stage and biopsy grade was also evaluated. ResultsThe specimen weight and preoperative serum prostate-specific antigen level were similar for each cohort, and approximately 75% of patients from each cohort were clinical Stage T1c. Forty-six LRP and matched open RRP (76.7%) and 39 sequential open RRP (65%) specimens were biopsy Gleason sum 6, and the remainder were primarily Gleason sum 7. The pathologic grade and stage distribution were similar for each cohort. Ten LRP (16.9%) and 12 open RRP (20%) specimens from each cohort had positive inked margins (P > 0.10). Positive apex margins were noted in 3, 7, and 7 and multiple positive margin sites in 0, 5, and 6 of the LRP, matched open RRP, and sequential open RRP specimens (P < 0.05), respectively. ConclusionsPathologic evaluation of the LRP and open RRP specimens from patients not receiving neoadjuvant hormonal therapy demonstrated similar overall positive margin rates, but LRP had a lower rate of apex and multiple-site positive margins.

Prediction of outcome after radical prostatectomy in men with organ-confined Gleason score 8 to 10 adenocarcinoma

Objectives Most adenocarcinomas of the prostate with a Gleason score greater than 8 at radical prostatectomy have extraprostatic extension and a high risk of progression. With prostate-specific antigen screening, we have seen some cases of earlier detected, organ-confined, high-grade adenocarcinoma. Few data are available as to the likelihood of cure in these cases. Methods We reviewed 27 cases of pathologically organ-confined adenocarcinoma with a prostatectomy Gleason score of 8 to 10. To exclude cases with a significant proportion of Gleason pattern 3, we excluded cases of Gleason score 3+5=8 and Gleason score 5+3=8. All cases of Gleason score 8 at radical prostatectomy were Gleason score 4+4. The prognostic value of the clinical parameters (clinical stage, serum prostate-specific antigen level, age) and pathologic factors (biopsy Gleason score, radical prostatectomy Gleason score, prostatectomy tumor volume) were tested to predict postoperative progression. Results The mean age at diagnosis was 59.7 years (range 46 to 69) with preoperative serum prostate-specific antigen levels ranging from 1.4 to 28 ng/mL (mean 7.8). All tumors were classified as pathologic Stage T2N0Mx. Fifteen patients (55.6%) had a Gleason score of 8, 11 patients (40.7%) had a Gleason score of 9, and 1 had a Gleason score of 10 (3.7%). Tumor volumes ranged from 0.02 to 1.44 cm 3 (mean 0.56). Follow-up information was available for all men. The mean follow-up for those without progression was 30.6 months (range 7 to 73) and for those with progression was 23.6 months (range 9 to 44). The 33-month actuarial risk of progression was 32%, with 10 men developing progression during the study. None of the preoperative or postoperative variables predicted progression. Conclusions Even when high-grade tumor is organ confined, it is associated with a relatively unfavorable short-term outcome that is not predictable on the basis of either preoperative clinicopathologic data or postoperative pathologic information obtained from the radical prostatectomy specimen.

Disease-free survival difference between African Americans and whites after radical prostatectomy for local prostate cancer: a multivariable analysis

Objectives. Age-adjusted mortality rates (per 100,000) for men with prostate cancer from 1991 through 1997 reported by the Surveillance, Epidemiology, and End Results national registry have consistently demonstrated that African-American men (AAM) have twice the death rate of white men (WM). However, there has been considerable controversy as to how this relates to progression-free survival among these men. In an attempt to address this controversy of localized prostate cancer, we report on a multivariable analysis of survival data of a large number of AAM and WM who underwent radical prostatectomy. Methods. The study cohort was composed of 791 men whose only prostate cancer treatment was radical prostatectomy performed between July 1990 and December 1999. The variables analyzed were age, preoperative prostate-specific antigen level, pathologic grade and stage, and race/ethnicity. Pathologic examination of all specimens was performed in a uniform manner according to an established protocol. Multivariable analysis based on Cox’s proportional hazards regression model was performed to assess whether a significant difference in progression-free survival time between AAM and WM persisted after controlling for the main effects of other prognostic factors. Results. The study cohort consisted of 229 AAM and 562 WM. Our results indicated that all variables, except age, had highly significant effects on progression-free survival, even in the presence of other predictors. Conclusions. The effects of age, preoperative serum prostate-specific antigen level, and pathologic grade and stage did not account for the racial disparity in progression-free survival among men diagnosed with clinically localized prostate cancer and treated with radical prostatectomy.

PREOPERATIVE SERUM PROSTATE SPECIFIC ANTIGEN LEVELS BETWEEN 2 AND 22 NG./ML. CORRELATE POORLY WITH POST-RADICAL PROSTATECTOMY CANCER MORPHOLOGY: PROSTATE SPECIFIC ANTIGEN CURE RATES APPEAR CONSTANT BETWEEN 2 AND 9 NG./ML.

Serum prostate specific antigen (PSA) is widely used as a guide to initiate prostatic biopsies and to follow men older than 50 years old with and without prostate cancer. However, benign prostatic hyperplasia (BPH) is a common cause of serum PSA values between 2 and 10 ng./ml. A better understanding of the relationships among serum PSA, prostate cancer and BPH is important. A total of 875 men underwent radical prostatectomy at our institution between December 1984 and January 1997. Of these men 784 had a serum PSA of 2 to 22 ng./ml., including 579 with the largest cancer located in the peripheral zone of the prostate. Of the 579 men 406 had serum PSA followups for greater than 3 years after radical prostatectomy. We examined Pearson correlations (R2) between preoperative serum PSA, and the volume of Gleason grades 4/5 and 3 to 1 cancer in 784 men, separating peripheral zone from transition zone cancers. We used broken line regression with break points of 7 and 9 ng./ml. preoperative PSA to summarize the relationship of each PSA doubling to 5 different morphological variables in 579 men with peripheral zone cancer. A 9 ng./ml. break point was used for prostate weight. Trend summaries with a local regression line for the relationships between 6 morphological variables and PSA were superimposed on full scatterplots of the 579 men with PSA less than 22 ng./ml. Cox proportional hazard models were used to examine 5-year PSA failure-free probabilities based on 406 men with minimal PSA followups greater than 3 years at break points of 7 to 9 ng./ml. PSA. Pearson correlation between cancer volume and preoperative serum PSA in 875 men was weak (r2 = 0.27) and driven by large cancers with serum PSA greater than 22 ng./ml. For peripheral zone cancer the overall R2 x 100 for 641 men with low and high grade cancer was 10% and only 3% for low grade cancer, that is almost no PSA produced by these peripheral zone cancers enters the serum. All morphological variables changed at rates of doubtful medical significance below a PSA of 7 to 9 ng./ml. but at rates that were significantly worse above 9 ng./ml. R2 for these relationships was never greater than 15%. Large individual morphological variations at all levels of PSA emphasize the serious limitation of PSA as a predictor of prostate cancer morphology. Below 9 ng./ml. prostate weight increased by 21% for each doubling of PSA but above 9 ng./ml. the increase was only 4.8%. Preoperative serum PSA has a clinically useless relationship with cancer volume and grade in radical prostatectomy specimens, and a limited relationship with PSA cure rates at preoperative serum PSA levels of 2 to 9 ng./ml. Trend summaries for prostate weight on broken line regression showed that below 9 ng./ml. BPH is a strong contender for the cause of PSA elevation, constituting the primary cause of the over diagnosis of prostate cancer.

Advanced prostatic carcinoma with low levels of serum prostate-specific antigen

The serum levels of prostate-specific antigen (PSA) represent a significant diagnostic and monitoring parameter of prostatic carcinoma (PC). The aim of the study was to establish correlation of serum PSA level in addition to grade, histological type, and clinical stage of PC in patients with normal or intermediary PSA serum level. In 37 untreated PC patients with preoperative serum PSA levels ranging between 0.1 and 9.6 ng/ml, paraffin-embedded tissue and serum samples were immunohistologically studied and immunoassay for PSA was done. The most representative was poorly differentiated PC with D stage. In serum samples from PC patients 27 (73.7%) normal (< or = 4.0 ng/ml), and 10 (27.3%) intermediate (4.1-10 ng/ml) PSA levels were found. Immunohistochemistry, in 36 PC (97.3%) had demonstrated the expression of PSA. Our study results had shown low serum PSA levels in some patients with advanced poorly differentiated PC.