DNA ploidy and prostate-specific antigen as prognostic factors in clinically resectable prostate cancer.

Prostate-specific antigen (PSA) and DNA ploidy as measured by flow cytometry were compared with conventional prognostic indicators in 112 patients who underwent radical prostatectomy for clinically resectable prostate cancer. The variables examined included age, race, prostatic acid phosphatase (PAP), Gleason score of the radical prostatectomy specimen, and pathologic stage. No significant relationships were found between DNA ploidy and age, mean PAP value, and absolute PAP value. Of the 112 patients, 65 (58.0%) had disease limited to the prostate (pathologic Stages A and B); 47 (42.0%) had extraprostatic disease (pathologic Stages C and D1). The stage was related to the Gleason score (P less than 0.0001) where extraprostatic disease was associated with a Gleason score of 6 to 10. Nineteen (17.0%) patients had aneuploid tumors, and 93 (83.0%) had diploid tumors. DNA ploidy significantly correlated with pathologic stage (P = 0.04); aneuploidy was identified more frequently in patients with Stages C and D1 tumors. Aneuploid tumors occurred more frequently than diploid tumors in patients with a Gleason score of 6 to 10 (P = 0.034). Mean PSA values were higher in patients with aneuploid tumors (P = 0.078), extraprostatic neoplasms (P = 0.00001), and cancers with a Gleason score of 6 to 10 (P = 0.0004). Furthermore, PSA values greater than 10.0 ng/ml were associated with extraprostatic disease and a Gleason score of 6 to 10 (P less than 0.05 and P less than 0.001, respectively). Significant racial differences were found with respect to DNA ploidy, mean DNA indices, and mean PSA values. The 18 black patients had more DNA aneuploid tumors (P = 0.043), a higher mean DNA index (P = 0.017), and a higher mean PSA value (P = 0.043) than the 94 white patients. Both PSA and DNA ploidy analysis by flow cytometry appear to be valuable indicators in the evaluation of patients with prostatic carcinoma.     

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

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

Prognostic significance of positive surgical margins in patients with extraprostatic carcinoma after radical prostatectomy

BACKGROUND: A significant number of prostate adenocarcinoma patients undergoing radical prostatectomy are found to have microscopic extraprostatic disease extension. A majority of these patients have focal extraprostatic extension limited to one or both sides of the prostate. In addition, positive surgical margins are a common pathologic finding in this patient subgroup. In the current study, the authors evaluated the impact of positive surgical margins as an independent predictive factor for prostate specific antigen (PSA) progression in patients with pT3a/b N0M0 carcinoma. METHODS: The Mayo Clinic prostate cancer registry list provided 1202 patients with pT3a/b NO prostate carcinoma (no seminal vesicle or regional lymph node involvement) who underwent a radical prostatectomy between 1987-1995. To reduce confounding variables, patients who received preoperative therapy or adjuvant therapy were excluded, resulting in 842 patients who were eligible for analysis. RESULTS: A total of 354 patients (42%) had > or = 1 positive surgical margins whereas 488 patients (58%) demonstrated no margin involvement. The sites of margin positivity were as follows: apex (n = 163), base (n = 47), posterior prostate (n = 227), and anterior prostate (n = 11). A total of 111 patients had > or = 2 positive surgical margins. The 5-year survival free of clinical recurrence and/or biochemical failure (postoperative PSA level > 0.2 ng/mL) for patients with no positive surgical margins was 76% and was 65% for patients with 1 positive surgical margin (P = 0.0001). There was no significant difference in biochemical disease progression between patients with 1 versus those with > or = 2 surgical margins (65% vs. 62%). Multivariate analysis revealed that positive surgical margins were a significant predictor (P = 0.0017) of clinical disease recurrence and biochemical failure (relative risk, 1.55; 95% confidence interval, 1.18-2.04) after controlling for preoperative PSA, Gleason score, and DNA ploidy. CONCLUSIONS: In the current study, positive surgical margins were found to be a significant predictor of disease recurrence in patients with pT3a/b NO prostate carcinoma, a finding that is independent of PSA, Gleason score, and DNA ploidy. The benefit of adjuvant therapy in optimizing recurrence-free survival remains to be tested.     

A prospective study of the serum prostate specific antigen concentrations and Gleason histologic scores of black and white men with prostate carcinoma.

BACKGROUND: The stage specific survival rates of black American men with prostate carcinoma are less favorable than those of white American men. The authors conducted a prospective study of the serum prostate specific antigen (PSA) concentrations and Gleason histologic scores of black and white men with newly diagnosed prostate carcinoma to determine whether there were racial differences in these prognostic variables. METHODS: At a Veterans Affairs Medical Center between January 1, 1992, and December 31, 1997, clinical stage, Gleason histologic score, serum PSA concentration, prostate volume, and PSA density were determined for 796 consecutive men (465 black and 331 white) who had biopsy-detected prostate carcinoma. RESULTS: The percentages, respectively, of black and white men with local, regional, and metastatic carcinoma were 58 and 72; 22 and 17; and 20 and 11 (P < 0.0001). Of 271 black and 329 white men with local stage cancer, 20% and 12%, respectively, had Gleason 8-10 tumors (P = 0.02), and the age-adjusted risk of Gleason 8-10 cancer was 1.39 times greater for black men (95% confidence interval [CI] = 1.09-2.93). Gleason 8-10 cancer was found in 12 of 68 black (18%) and 5 of 87 white (6%) men with local cancer who were age 65 years or younger (P = 0.02). Among black and white men with local stage cancer, the mean PSA was 12.9 (95% CI = 11.5-14.4) and 8.5 (95% CI = 7.6-9.4) ng/mL, respectively (P < 0.0001), and among black and white men with regional stage cancer the mean PSA was 53.3 (95% CI = 42.7-63.9) and 35.0 (95% CI = 27.3-42.6) ng/mL, respectively (P = 0.02). The mean PSA of black and white men with local cancer who were age 65 years or younger was 11.6 (95% CI = 8.8-14.4) and 6.9 (95% CI = 5.9-8.0) ng/mL, respectively (P = 0.0009). CONCLUSIONS: Disparities in the risk of Gleason score 8-10 cancer for black and white men with local stage disease and in the serum PSA concentrations of black and white men with local and regional stage disease help to explain racial differences in cancer survival. Racial differences in the risk of Gleason 8-10 cancer and in the serum PSA concentrations of men age 65 years or younger have implications regarding the potential benefits of screening for prostate carcinoma in the African American community.     

Preoperative prediction of extracapsular tumor extension at radical retropubic prostatectomy in Taiwanese patients with T1c prostate cancer

BACKGROUND: To find a predictor for extracapsular tumor extension at radical retropubic prostatectomy (RRP) in Taiwanese patients with stage T1c prostate cancer (PC), preoperative transrectal sonoguiding prostate biopsy outcomes and clinicopathological data obtained from these patients were reviewed. METHODS: Fifty-five consecutive men who underwent radical retropubic prostatectomy for stage T1c PC were included. Preoperative sextant needle biopsies of the prostate were performed and whole-mount prostatectomy specimens were processed. The pathological end point was tumor capsular perforation extending entirely through the prostate capsule. Preoperative prostate-specific antigen (PSA), free-to-total PSA ratio, prostate volume, PSA density, Gleason score, number of positive biopsy cores, percentage cancer of sextant biopsies, percentage cancer of one lobe and percentage cancer of one core were analyzed for their ability to predict extracapsular tumor extension at RRP. RESULTS: Eighteen of the 55 specimens showed evidence of tumor capsular perforation. Those with extracapsular tumor extension (ECE) had higher PSA than organ-confined disease (OCD) (18.4 vs 8.3 ng/ml, P < 0.01). The ECE had a higher PSA density than OCD (0.556 vs 0.226, P < 0.01). The percentage of cancer in biopsies, percentage cancer of one lobe and percentage cancer of one core were all higher in ECE than OCD (P < 0.05). The ECE had a higher biopsy Gleason score than OCD (5.6 vs 4.5, P < 0.01). CONCLUSIONS: The four strongest predictors for extracapsular tumor extension of patients with T1c PC were PSA density >or=0.35, biopsy Gleason score >or=6, >or=20% cancer in biopsies and PSA >or=10 ng/ml.     

The radial distance of extraprostatic extension of prostate carcinoma: implications for prostate brachytherapy.

BACKGROUND: Extraprostatic extension (EPE) is an unfavorable prognostic factor in patients with prostate carcinoma. Prior studies have reported the linear extent of EPE measured circumferentially along the edge of the prostate. In this study, the authors defined and evaluated a novel measure of EPE in a large series of radical prostatectomy specimens. These results have important clinical implications in the management of localized prostate carcinoma by brachytherapy and other modalities. METHODS: The authors reviewed the preoperative records and biopsy findings from 376 patients who underwent radical retropubic prostatectomy between September 1991 and June 1993. Whole mount radical prostatectomy specimens were examined, and the location of EPE for each specimen was recorded. The radial EPE distance was measured perpendicular to the edge of the prostate. For specimens with multiple EPE sites, the maximum radial EPE distance was recorded. Established eligibility criteria for prostate brachytherapy were evaluated using these results, with emphasis placed on achieving adequate radiation dose coverage 3-5 mm beyond the capsule or the edge of the prostate. RESULTS: EPE was identified in 105 of 376 specimens (28%) at 248 sites. The radial EPE distance in these specimens had a mean of 0.8 mm (range, 0.04-4.4 mm) and a median of 0.5 mm. Of these 105 patients, the median and mean preoperative prostate specific antigen (PSA) concentrations were 11.8 ng/mL and 17.9 ng/mL, respectively. The mean and range of the Gleason score and prostate volume for all specimens were 6.3 (range, 3-9) and 39 cc (range, 8-294 cc), respectively. In 107 patients who met the selection criteria for prostate brachytherapy eligibility of a PSA level < 10 ng/mL, Gleason score < 7, and gland volume < 60 cc, the maximum and mean radial EPE distances were 0.6 mm and 0.03 mm, respectively. CONCLUSIONS: The radial distance of EPE is an important measure that influences treatment strategies for patients with localized prostate carcinoma. Currently described criteria for the treatment of early stage prostate carcinoma by brachytherapy alone appear satisfactory to ensure effective radiation dose coverage of EPE of prostate tumors. Treating the prostate with a 3-5 mm margin by brachytherapy would encompass all known tumor in approximately 99% of the specimens examined in this study.     

The percentage of prostate needle biopsy cores with carcinoma from the more involved side of the biopsy as a predictor of prostate specific antigen recurrence after radical prostatectomy: results from the Shared Equal Access Regional Cancer Hospital (SEARCH) database

BACKGROUND: The authors previously found that, although the total percentage of prostate needle biopsy cores with carcinoma was a significant predictor of prostate specific antigen (PSA) failure among men undergoing radical prostatectomy (RP), there was a trend toward a lower risk of recurrence in patients with positive bilateral biopsies, suggesting that high-volume, unilateral disease was a worse predictor of outcome than an equivalent number of positive cores distributed over two lobes. In the current study, the authors sought to compare the total percentage of cores with carcinoma directly with the percentage of cores from the more involved or dominant side of the prostate with carcinoma for their ability to predict outcome among men who underwent RP. METHODS: A retrospective survey of 535 patients from the Shared Equal Access Regional Cancer Hospital database who underwent RP at 4 different equal-access medical centers between 1988 and 2002 was undertaken. The total percentage of cores positive was compared with the percentage of cores positive from the dominant and nondominant sides for their ability to predict biochemical recurrence after RP. The best predictor then was compared with the standard clinical variables PSA, biopsy Gleason score, and clinical stage in terms of ability to predict time to PSA recurrence after RP using multivariate analysis. RESULTS: The adverse pathologic features of positive surgical margins and extracapsular extension were significantly more likely to be ipsilateral to the dominant side on the prostate biopsy. The percentage of cores positive from the dominant side provided slightly better prediction (concordance index [C] = 0.636) for PSA failure than the total percentage of cores positive (C = 0.596) and markedly better than the percentage of cores from the nondominant side (C = 0.509). Cutoff points for percentage of cores positive from the dominant side were identified (< 34%, 34-67%, and > 67%) that provided significant risk stratification for PSA failure (P < 0.001). On multivariate analysis, the percentage of cores positive from the dominant side was the strongest independent predictor of PSA recurrence (P < 0.001). Biopsy Gleason score (P = 0.017) also was a significant, independent predictor of recurrence. There was a trend, which did not reach statistical significance, toward an association between greater PSA values and biochemical failure (P = 0.052). Combining the PSA level, biopsy Gleason score, and percentage of cores positive from the dominant side of the prostate resulted in a model that provided a high degree of prediction for PSA failure (C = 0.671). CONCLUSIONS: The percentage of cores positive from the dominant side of the prostate was a slightly better predictor of PSA recurrence than was the total percentage of cores positive. Using the percentage of cores from the dominant side along with the PSA level and the biopsy Gleason score provided significant risk stratification for PSA failure.     

Predicting prostate specific antigen failure after radical retropubic prostatectomy for T1c prostate cancer

PURPOSE: Clinicopathological data were reviewed to find a predictor of prostate specific antigen (PSA) failure in Taiwanese patients who had received radical retropubic prostatectomy (RRP) for stage T1c prostate cancer (PC). METHODS: Fifty-five consecutive men who underwent RRP for stage T1c PC were included. The clinical end point was PSA failure (PSA >0.2 ng/ml). Preoperative PSA, free-to-total PSA ratio, prostate volume, PSA density, transrectal sextant biopsy and whole mount of RRP parameters were analyzed for their ability to predict postoperative PSA failure. RESULTS: Fifteen of the 55 patients developed PSA failure during the follow-up period. Those with PSA failure had higher PSA, higher percentage of cancer in biopsies and higher biopsy Gleason score than the freedom from PSA failure group (all P < 0.05). The PSA failure group had higher pathology Gleason score and a higher incidence of extracapsular tumor extension than the freedom from PSA failure group (all P < 0.05). The PSA failure group had a larger tumor volume and higher incidence of combined peripheral lobe with transitional lobe involvement than the freedom from PSA failure group (all P < 0.05). Multivariate analysis revealed that the predictors for PSA failure after RRP were biopsy Gleason score > or =6, tumor volume > or =2.5 ml and PSA > or =10 ng/ml. CONCLUSION: The single most significant predictor for PSA failure in T1c PC patients after RRP was tumor volume > or =2.5 ml.     

The relevance of prostatectomy findings for brachytherapy selection in patients with localized prostate carcinoma

BACKGROUND: The efficacy of brachytherapy for patients with localized prostate carcinoma depends on adequate radiotherapeutic coverage of the primary tumor and its subclinical extraprostatic extensions. Predictive models based on pretherapy factors may be useful to estimate the likelihood for clinically relevant extraprostatic disease and may be incorporated into selection criteria for this procedure. METHODS: Multivariate logistic regression model building was performed using pretherapy factors in 2905 surgically staged patients with localized prostate carcinoma to estimate the probability of seminal vesicle and/or lymph node involvement. Bootstrap methods were employed to assess the stability of the final model parameters and to determine the sensitivity and specificity of the final model. RESULTS: Clinical tumor classification, biopsy Gleason score groupings, and serum prostate specific antigen (PSA) levels were associated with seminal vesicle and/or pelvic lymph node involvement. These factors were incorporated into a multivariate model that predicted for these adverse histopathologic features. Allowing for up to a 10% likelihood for seminal vesicle and/or pelvic lymph node involvement, patients with tumors classified as T1c-T2a, Gleason scores of 2-6, and PSA < or = 16 ng/mL; or with tumors classified as T1c-T2a, Gleason scores of 7-10, and PSA < or = 4 ng/mL; or with tumors classified as T2b-T2c, Gleason scores of 2-6, and PSA < or = 6 ng/mL would be potential candidates for brachytherapy alone. CONCLUSIONS: The predictive model presented may provide criteria whereby an adequately performed prostate brachytherapy procedure is expected to encompass the intraprostatic and adjacent extraprostatic disease. Prostate brachytherapy alone may be considered in these circumstances, whereas the addition of external beam radiotherapy may be reserved for patients with disease that is apt to extend beyond the brachytherapy target volume.     

Prostate specific antigen outcome based on the extent of extracapsular extension and margin status in patients with seminal vesicle negative prostate carcinoma of Gleason score < or = 7

BACKGROUND: Early (< or = 2 years) prostate specific antigen (PSA) failure after radical prostatectomy (RP) has been shown to predict for distant failure. After excluding patients with the pathologic predictors of early PSA failure, an analysis of PSA failure free (bNED) survival was performed to identify patients who may benefit from the use of postprostatectomy radiation therapy (RT). METHODS: Of 1,028 patients treated with RP for clinically localized prostate carcinoma between 1989 and 1999, 862 (84%) had either organ confined (OC), specimen confined (SC), or margin positive disease with negative seminal vesicles (SV) and a prostatectomy Gleason score < or = 7. A Cox regression multivariate analysis was performed in these patients evaluating the ability of the extent of extracapsular extension (ECE) (into but not through the capsule, SC focal ECE, SC established ECE, margin positive) and prostatectomy Gleason score (2-6 vs. 7) to predict time to postoperative PSA failure. RESULTS: SC focal ECE (P = 0.0017), SC established ECE (P < 0.0001), and margin positive disease (P < 0.0001) were significant predictors of time to postoperative PSA failure, whereas prostatectomy Gleason score and disease extending into but not through the capsule were not. Five-year bNED rates were 90%, 88%, 69%, 45%, and 33% for patients with OC, into but not through capsule, SC focal ECE, SC established ECE, and margin positive prostate carcinoma, respectively. CONCLUSIONS: Patients with SC ECE or margin positive prostate carcinoma and a prostatectomy Gleason score < or = 7 with no evidence of SV invasion may benefit from adjuvant postoperative RT.     

Prognostic value of DNA analysis of prostate adenocarcinoma: correlation to clinicopathologic predictors

The ability to accurately predict tumor behavior and patient survival is a problem in managing patients with prostate cancer. DNA ploidy provides important information for the evaluation of the prognosis of prostate cancer. The aim of this study was to investigate the DNA ploidy in imprints from prostate adenocarcinomas in a group of 70 patients in relation to Gleason score, tumor differentiation, stage and PSA serum levels. The DNA content was studied in Feulgen-stained imprint smears through the image analysis technique using a SAMBA 2005 Image analyzer. According to our measurements, a strong correlation was observed between DNA ploidy status and tumor differentiation (p<0.001). A statistically significant difference was found between DNA aneuploidy and increased pretreatment PSA serum levels (>4 ng/ml) (p<0.001), as well as between ploidy pattern and stage of the disease (p<0.001). Our results conclude that DNA ploidy status appears to be an additional marker in the field of prognosis of prostatic adenocarcinoma and could provide useful information on the potential behavior of prostate cancer.     

Predictors of delayed therapy after expectant management for localized prostate cancer in the era of prostate-specific antigen

OBJECTIVE: To identify risk factors for delayed cancer-directed intervention in modern era prostate cancer patients who initially elect expectant management. MATERIALS AND METHODS: An observational, cohort study of expectantly managed patients, diagnosed with clinical T(1-4)NxM0 prostate cancer between 1993 and 2000 was carried out. Data including TNM stage, age, serum prostate-specific antigen (PSA), prostate gland volume by transrectal ultrasound, Gleason score, percent biopsies positive for cancer, imaging results, initial treatment selection, and outcome data were collected on all patients. RESULTS: 192 of 561 patients (34.3%) elected expectant management, and follow-up data were available for 187 (97.4%) patients. With a median follow-up of 3.6 years, 90 (48.1%) patients had a cancer-directed intervention. Gleason score (p = 0.0097) and percent of positive biopsy cores (p = 0.03) were independent predictors of time to intervention. As expected, PSA doubling time became the most significant predictor of intervention (p = 0.0057) when added to the model. These independent covariates are able to characterize low-, intermediate- and high-risk groups for cancer-directed intervention. CONCLUSIONS: Cancer-directed intervention is common in patients who choose expectant management in the PSA era. Gleason score and percent of positive biopsy cores predict cancer-directed interventions, thus, these patients may be least suitable for expectant management.     

Relationship between prostate volume, prostate-specific antigen nadir, and biochemical control

PURPOSE: In patients treated with definitive three-dimensional conformal radiotherapy (3D-CRT) for localized prostatic adenocarcinoma, we sought to evaluate the relationship between pretreatment prostate gland volume and posttreatment prostate-specific antigen (PSA) nadir, as well as the relationship of prostate volume and PSA nadir with biochemical control (bNED). Two subgroups were studied: favorable (PSA <10 ng/mL, Gleason score 2-6, and T1-T2A) and unfavorable (one or more: PSA >/=10 ng/mL, Gleason score 7-10, T2B-T3). MATERIALS AND METHODS: A total of 655 men (n = 271 favorable and 384 unfavorable) were treated with 3D-CRT alone between May 1989 and November 1997. All patients had information on prostate volume and a minimum follow-up of 24 months (median 56, range 24-126). Of the 655 men, 481 (n = 230 favorable and 251 unfavorable) remained bNED at time of analysis, with biochemical failure defined in accordance with the American Society for Therapeutic Radiology and Oncology consensus definition. Factors analyzed for predictors of bNED included pretreatment prostate volume, posttreatment PSA nadir, pretreatment PSA, palpation T stage, Gleason score, center of the prostate dose, and perineural invasion (PNI). We also analyzed pretreatment prostate volume and its correlation to prognostic factors. For bNED patients, the relationship between PSA nadir and prostate volume was evaluated. RESULTS: On multivariate analysis, prostate volume (p = 0.04) and palpation T stage (p = 0.02) were the only predictors of biochemical failure in the favorable group. On multivariate analysis of the unfavorable group, pretreatment PSA (p <0.0001), Gleason score (p = 0.02), palpation T stage (p = 0.009), and radiation dose (p <0.0001) correlated with biochemical failure, and prostate volume and PNI did not. For all 481 bNED patients, a positive correlation between pretreatment volume and PSA nadir was demonstrated (p <0.0001). Subgroup analysis of the favorable and unfavorable patients also demonstrated a positive correlation between prostate volume and PSA nadir (p = 0.003 and p = 0.0002, respectively). Using multiple regression analysis, the following were found to be predictive of PSA nadir in all bNED patients: prostate volume (p <0.0001), pretreatment PSA (p <0.0001), palpation T stage (p = 0.0002), and radiation dose (p = 0.0034). Gleason score and PNI were not predictive. For the favorable group, palpation T stage (p = 0.0006), pretreatment PSA (p = 0.0083), prostate volume (p = 0.0186), and Gleason score (p = 0.0592) were predictive of PSA nadir, and PNI and radiation dose were not predictive. In the unfavorable group, prostate volume (p = 0.0024), radiation dose (p = 0.0039), pretreatment PSA (p = 0.0182), and palpation T stage (p = 0.0296) were predictive of PSA nadir, and Gleason score and PNI were not predictive. CONCLUSION: This report is the first demonstration that prostate volume is predictive of PSA nadir for patients who are bNED in both favorable and unfavorable subgroups. PSA nadir did not correlate with bNED status in the favorable patients, but it was strongly predictive in the unfavorable patients. Prostate gland volume was also predictive of bNED failure in the favorable but not the unfavorable group.     

Prospective study of cancer detection in black and white men with normal digital rectal examination but prostate specific antigen equal or greater than 4.0 ng/mL

BACKGROUND: The serum prostate specific antigen (PSA) concentration with no clinical evidence of prostate carcinoma is higher and more variable in black than in white American men. The influence of this phenomenon on relations between race, PSA, and cancer detection in men with a PSA greater than or equal to 4.0 ng/mL has not been investigated. METHODS: Between January 1992 and December 2000, 451 black and 480 white men with a normal digital rectal examination and a PSA greater than or equal to 4.0 ng/mL had an initial prostate biopsy at one medical center. The histology of the biopsy specimens and the Gleason score of malignant specimens was determined by one uropathologist. RESULTS: Cancer was detected in 207 (46%) black and 167 (35%) white men (P = 0.0006). When adjusted for PSA, cancer detection was also greater in the black than the white men, but the difference did not achieve statistical significance (relative risk, 1.30; 95% confidence interval [CI], 0.99-1.71; P = 0.06). Gleason score 7-10 cancer was detected in 88 (20%) black and 45 (9%) white men (P = 0.0001), and the difference remained significant when adjusted for PSA (relative risk, 1.73; 95% CI, 1.16-2.61; P = 0.0008). In the intermediate PSA range of 4.0-9.9 ng/mL, cancer detection and Gleason score 7-10 cancer detection was greater in black than in white men younger than 60, 60-69, and 70 years of age or older, but the difference was significant only for Gleason score 7-10 cancer detection among men 60-69 years of age (P = 0.006). CONCLUSIONS: There is a direct correlation between Gleason score and cause specific survival with local stage prostate carcinoma. The authors' study indicates that prostate carcinomas with established malignant potential are more likely to be identified in black than in white men with PSA elevation as the only indication of malignancy and raises the possibility that a PSA threshold less than 4.0 ng/mL in black men younger than 70 years of age may reduce racial disparities in prostate carcinoma morbidity and mortality.     

超声引导下前列腺10点加定点穿刺活检术诊断前列腺癌

目的 探讨经直肠彩色多普勒超声引导下前列腺穿刺活组织检查在前列腺癌诊断中的应用.方法 181例疑诊前列腺癌的患者进行血清总前列腺特异性抗原(T-PSA)检测,采用10点加前列腺癌可疑灶定点穿刺活检术.结果 181例中检出前列腺癌80例(44.2%),前列腺增生63例(34.8%).前列腺炎36例(19.9%),前列腺结核1例(0.6%),前列腺平滑肌瘤1例(0.6%).T-PSA水平＞20μg/L组的前列腺癌发生率高于其他各组.随着T-PSA水平的升高,Gleason评分增加(P＜0.001).结论 超声引导下10点加定点穿刺活检术诊断前列腺癌的阳性率高,对T-PSA＞20μg/L的疑诊前列腺癌患者活检意义较大.     

Biochemical outcome after radical prostatectomy or external beam radiation therapy for patients with clinically localized prostate carcinoma in the prostate specific antigen era

BACKGROUND: To the authors' knowledge, consensus is lacking regarding the relative long-term efficacy of radical prostatectomy (RP) versus conventional-dose external beam radiation therapy (RT) in the treatment of patients with clinically localized prostate carcinoma. METHODS: A retrospective cohort study of 2635 men treated with RP (n = 2254) or conventional-dose RT (n = 381) between 1988-2000 was performed. The primary endpoint was prostate specific antigen (PSA) survival stratified by treatment received and high-risk, intermediate-risk, or low-risk group based on the serum PSA level, biopsy Gleason score, 1992 American Joint Commission on Cancer clinical tumor category, and percent positive prostate biopsies. RESULTS: Estimates of 8-year PSA survival (95% confidence interval [95% CI]) for low-risk patients (T1c,T2a, a PSA level < or = 10 ng/mL, and a Gleason score < or = 6) were 88% (95% CI, 85, 90) versus 78% (95% CI, 72, 83) for RP versus patients treated with RT, respectively. Eight-year estimates of PSA survival also favored RP for intermediate-risk patients (T2b or Gleason score 7 or a PSA level > 10 and < or = 20 ng/mL) with < 34% positive prostate biopsies, being 79% (95% CI, 73, 85) versus 65% (95% CI, 58, 72), respectively. Estimates of PSA survival in high-risk (T2c or PSA level > 20 ng/mL or Gleason score > or = 8) and intermediate-risk patients with at least 34% positive prostate biopsies initially favored RT, but were not significantly different after 8 years. CONCLUSIONS: Intermediate-risk and low-risk patients with a low biopsy tumor volume who were treated with RP appeared to fare significantly better compared with patients who were treated using conventional-dose RT. Intermediate-risk and high-risk patients with a high biopsy tumor volume who were treated with RP or RT had long-term estimates of PSA survival that were not found to be significantly different.     

前列腺特异性膜抗原和前列腺特异性抗原表达强度与前列腺癌Gleason评分之间的相关性研究

目的研究前列腺特异性膜抗原(PSMA)和前列腺特异性抗原(PSA)的表达强度与前列腺癌Gleason评分之间的相关性。方法制备抗PSMA膜外段表位的单克隆抗体,应用免疫组织化学方法检测前列腺癌中PSMA的表达,统计分析其与Gleason评分之间的相关性,并和PSA与Gleason评分之间的相关性进行对比。结果制备出8株分泌抗PSMA膜外段表位的单抗的杂交瘤细胞株。免疫组化结果表明,PSMA的表达强度与前列腺癌的Gleason评分之间存在相关性。在分化差的前列腺癌中,PSMA水平高于分化中等和分化良好的前列腺癌(P<0.01),而PSA在前列腺癌中的表达无明显差异(P>0.05)。结论PSMA表达水平在分化差的前列腺癌中明显升高,与Gleason评分存在相关性,可以作为前列腺癌的Gleason分级的标记物,提示PSMA可以作为对激素疗法效果不敏感的低分化前列腺癌抗体介导的免疫治疗靶点。     

Prediction of pelvic lymph node metastasis by the ratio of cathepsin B to stefin A in patients with prostate carcinoma

BACKGROUND: Pathologic grade and/or histologic score, extraprostatic extension indicated by invasion of the prostatic capsule, margin, and/or seminal vesicles by prostate cancer cells, serum total prostate-specific antigen (PSA), free PSA, complexed PSA levels and/or their ratios, regional pelvic lymph node metastases, and clinical staging have been used to diagnose and monitor the treatment of prostate carcinoma (PC) patients. The Gleason grading system is also used to grade/score a patient's stage of disease, with lower to higher scores indicating progression of PC. However, Gleason's system cannot be used to distinguish biologically aggressive PCs within a single Gleason score. Our objective was to identify subpopulations (or clones) of aggressive prostate cancers within an individual Gleason score by utilizing biological molecule(s) that also facilitate cancer cell invasion to prostatic stroma and metastasis to the lymph nodes. MATERIALS AND METHODS: Specimens were collected from 97 patients with PC and from 8 patients with benign prostatic hyperplasia. These patients had not been treated with hormonal and/or chemotherapeutic agents before undergoing a prostatectomy at the Minneapolis Veterans Affairs Medical Center. Formalin-fixed, paraffin or paraplast-embedded prostate tissue sections were stained with hematoxylin and eosin for pathologic diagnosis and adjacent sections were stained for for immunohistochemical study. We also collected data on age, race, extraprostatic extension, margin status, seminal vesicle, and lymph node invasion by cancer cells, clinical stage at prostatectomy, and mortality/survival data, including the available presurgery and postsurgery serum total PSA and prostatic acid phosphatase concentrations in patients. Immunohistochemical localization of mouse or rabbit anti-cathepsin B (CB) antibody IgG and mouse antihuman stefin (cystatin) A IgG was quantified using a computer-based image analysis system equipped with Metamorph software. RESULTS: CB and stefin A identified aggressive and less aggressive clones of PCs within an individual Gleason score. Tumors with a Gleason Score of 6 that are similar histologically and morphologically were heterogeneous with respect to the ratios of CB to stefin A (CB > stefin A, CB = stefin A, and CB < stefin A). We also found a significant positive association (P = 0.0066) between ratios of CB and stefin A (CB > stefin A) and the incidence of pelvic lymph node metastases, but not with ratios of CB less than stefin A and/or ratios of CB equal to stefin A. Patients with Gleason 7 PCs had a higher incidence of positive lymph nodes than those with Gleason Score 6 tumors. Our data indicated that mortality rates increased in patients when the ratios of CB were greater than stefin A. CONCLUSIONS: PC within an individual Gleason score is a heterogeneous tumor that contains clones or subpopulations of aggressive and less aggressive tumors that can be defined by the ratios of CB to stefin A. PC with an aggressive clone can be identified when the ratio of CB is greater than that of stefin A. Less aggressive clones are identified when the ratio of CB is less than that of stefin A or when the ratio of CB is equal to that of stefin A. The ratios of CB to stefin A can be used in the differential diagnosis and treatment of patients with PC. This is the first report to identify phenotypes of aggressive and less aggressive PCs within a Gleason score.     

Metastatic prostate carcinoma to bone: clinical and pathologic features associated with cancer-specific survival

BACKGROUND: The objective of this study was to examine the clinical and pathologic features of metastatic prostate carcinoma to bone in a large cohort of men, and the associations of these features with outcome. METHODS: Sixty-eight men who underwent surgery for metastatic prostate carcinoma to bone for stabilization of a pathologic fracture or impending fracture were studied. Clinical characteristics included the type of treatment for the primary and metastatic prostate carcinoma, age and serum prostate specific antigen (PSA) at the diagnosis of the metastatic prostate carcinoma, radiographic findings of the metastasis (osteoblastic, osteolytic, or mixed), and the number of metastatic sites at the time of the surgery for the metastasis. Pathologic features examined included Gleason score of the metastatic prostate carcinoma. Immunohistochemical stains for MIB-1, cytokeratin, PSA, synaptophysin, chromogranin A, serotonin, estrogen receptor, progesterone receptor, and androgen receptor were performed for all cases. The Kaplan-Meier method was used to estimate cancer-specific survival. The duration of follow-up was defined as the interval from the date of surgery for the metastasis to the date of death or last follow-up. Univariate and multivariate Cox proportional hazards models were fit to assess the features that were associated with death from prostate carcinoma. RESULTS: The average (standard deviation) time from the surgery for the metastasis to death from prostate carcinoma was 1.5 (1.9) years, ranging from 0 days to 10 years, with a median of 1 year. The estimated cancer-specific survival rates at 1 year, 2 years, and 3 years were 54.3%, 28.8%, and 22.9%, respectively. Median cancer-specific survival occurred at 1.1 years. After 4 years of follow-up, there were only seven patients left at risk for death from prostate carcinoma. Features that were found to be significantly associated with death from prostate carcinoma univariately included the interval between the diagnosis of metastasis and the surgery for metastasis (P < 0.001), androgen deprivation therapy before surgery for the metastasis (P = 0.002), presentation with metastasis (P = 0.003), the number of metastatic sites (P = 0.034), Gleason score of the metastasis (P = 0.002), and tumor positivity for chromogranin A (P = 0.041). On multivariate analysis, the interval between the diagnosis of metastasis and the surgery for metastasis (P < 0.001), Gleason score of the metastasis (P < 0.001), and tumor positivity for chromogranin A (P = 0.009) were associated significantly with death from prostate carcinoma. CONCLUSIONS: Although cancer-specific survival for patients after surgery for prostate carcinoma metastatic to bone is poor, assessments of tumor differentiation of the metastasis and chromogranin A positivity provide prognostic information.     

Serum insulin level,disease stage,prostate specific antigen (PSA) and Gleason score in prostate cancer

In the present study, we assessed the relationship of serum insulin levels and three surrogate markers of recurrence, T stage, PSA, and Gleason score, in men with localized prostate cancer. Participants in our study were found through urology and radiation oncology clinics, and all eligible patients were asked to take part. All patients were asymptomatic and had been initially diagnosed on the basis of rising PSA or abnormal physical examination. Histological confirmation of diagnosis was obtained for all subjects. Serum insulin levels were determined by chemoluminescent assay with a standard, commercially available instrument. Patients were divided into three previously defined risk groups: Low risk: PSA < or =10, stage < or =T2a, or Gleason grade < or =6. Medium risk: 10 7, tumour in seminal vesicle biopsy, PSA >15 or stage T2c or T3. One hundred and sixty-three men with prostate cancer were studied. There was a significant increase in serum insulin with risk group (P=0.003, one way anova). Tukey's multiple range test showed that the insulin levels of high risk patients were significantly higher than the insulin levels of medium and low risk patients (P=0.05) but the insulin levels of medium and low risk patients were not significantly different from one another. Multivariate linear regression, with insulin as the dependent variable, Gleason score, PSA, and T stage (T1, T2, T3) as the independent variables, was significant overall (P<0.001, r(2)=0.120). Increased T stage was independently correlated with increased serum insulin levels (P<0.001). Gleason score was negatively, insignificantly correlated with serum insulin level (P=0.059). The positive correlation of PSA and insulin level was not significant (P=0.097). To assure normal distribution of insulin and PSA values, the regression was repeated with log (insulin) as the dependent variable, log (PSA), T stage (T1, T2, T3), and Gleason score as independent variables. The regression was significant overall (P=0.002, r(2) =0.095). Increased T stage was independently correlated with increased log (insulin level) (P=0.026). Gleason score was negatively, insignificantly correlated with log (insulin) level (P=0.728). The positive correlation of log (PSA) and log (insulin) levels was significant (P=0.010). The relationship between increased insulin level and advanced tumour stage in prostate cancer we describe here is biologically quite plausible, since insulin is a growth factor. Further studies may document whether serum insulin levels might be a useful biomarker of prostate cancer stage.