Prognostic significance of Gleason pattern in patients with Gleason score 7 prostate carcinoma

BACKGROUND: In the current study, the authors sought to further stratify the prognosis of patients with Gleason score (GS) 7 prostate carcinoma. They assessed the influence on outcome of a predominant poorly differentiated Gleason pattern (primary Gleason pattern [GP] 4) and/or a coincident small focus of poorly differentiated tumor of higher grade (tertiary GP 5). METHODS: The authors studied 412 patients (mean postoperative follow-up, 33 months) with GS 7 tumors treated with radical prostatectomy at a single Australian campus between November 1989 and December 2002. The chi-square test, Kaplan-Meier method, and Cox proportional hazards analyses were used to evaluate the correlation between primary GP 4 and tertiary GP 5 with the occurrence of adverse pathologic features and disease recurrence. RESULTS: In this cohort, 307 patients (75%) had primary GP 3 tumors, 105 (25%) had primary GP 4 tumors, and 17 (2.3%) had a tertiary element of high-grade tumor (GP 5). Patients with primary GP 4 tumors displayed higher rates of seminal vesicle involvement and extraprostatic extension and, along with patients with tertiary GP 5, had significantly shorter times to disease recurrence. Univariate analysis demonstrated that primary GP 4 (P = 0.0003) and tertiary GP 5 (P < 0.0001) were strong predictors of disease recurrence. Primary GP 4 (P = 0.0122) remained an independent predictor of disease recurrence on stepwise multivariate analysis. CONCLUSIONS: Primary GP 4 tumors represented an aggressive subset of GS 7 prostate carcinomas. Primary GP was an easily accessible and clinically relevant predictor of disease recurrence in patients with GS 7 prostate carcinoma.     

Clinical utility of endorectal MRI in determining PSA outcome for patients with biopsy Gleason score 7, PSA <or=10, and clinically localized prostate cancer

PURPOSE: Although the optimal management for patients with high-grade clinically localized prostate cancer is undefined, radical prostatectomy (RP) or external beam radiotherapy (EBRT) is performed. The clinical utility of the pretreatment prostrate-specific antigen (PSA) level (10 ng/mL) and endorectal MRI (erMRI) stage (T3 vs. T2) to stratify PSA outcome after RP in these patients was evaluated. METHODS AND MATERIALS: erMRI was performed in 147 men with biopsy Gleason score >or=7 and 1992 AJCC clinical Stage T1c or T2a disease before RP. Enumerations of the biopsy and prostatectomy Gleason scores, pathologic stage, and margin status were performed for each pretreatment group on the basis of erMRI findings and PSA level. Comparisons were made using a chi-square metric. The median follow-up was 4.5 years (range 1-10 years). Comparisons of the actuarial freedom from PSA failure (bNED) were made using the log-rank test. RESULTS: erMRI Stage T2 and T3 disease was found in 132 and 15 patients, respectively. On stratification by PSA level, patients with erMRI T3 disease had similar bNED outcomes (p = 0.46), regardless of the PSA level. The 3-year bNED rate was 82%, 64%, and 25% (p <0.0001) for Group 1 (erMRI T2 and PSA 10 ng/mL), and Group 3 (erMRI T3 with any PSA level), respectively. The rates of prostatectomy T3 disease, biopsy and prostatectomy Gleason score 8-10, and positive surgical margins were significantly higher (p or=7, PSA 相似文献   

Importance of margin extent as a predictor of outcome after adjuvant radiotherapy for Gleason score 7 pT3N0 prostate cancer

PURPOSE: To evaluate, in Gleason score 7, pT3N0 prostate cancer patients with positive surgical margins, the predictors of progression-free survival and to identify a patient subgroup that would benefit from immediate adjuvant postoperative radiotherapy (ART). METHODS AND MATERIALS: Between November 1989 and August 1998, 76 men underwent radical prostatectomy and were found to have capsular penetration (pT3N0), surgical Gleason score 7, tumor present at the resection margin, and an undetectable postoperative prostate-specific antigen (PSA) level. All surgical specimens underwent whole-mount serial sectioning to determine the degree of margin positivity (focal vs. extensive). Of the 76 men, 45 underwent early ART (within 6 months with a median dose of 64.8 Gy), and 31 had no immediate treatment. We defined freedom from PSA failure (bNED) as the absence of two consecutive PSA rises >0.2 ng/mL. RESULTS: The median follow-up time was 5.1 years (range, 2-10 years). The ART and non-ART patients were similar with respect to preoperative PSA level, Gleason score (4 + 3 vs. 3 + 4), presence of seminal vesicle invasion, and margin extent. On univariate analysis, margin extent was predictive for improved bNED (5-year bNED rate of 92% vs. 58%, p = 0.010, for men with focal and extensive margins, respectively). Gleason score (4 + 3 vs. 3 + 4), seminal vesicle invasion, and ART were not statistically significant predictors. On multivariate analysis, the preoperative PSA level, margin extent, and ART were independent significant factors. In the group with extensive surgical margins, men receiving ART had a significantly greater 5-year bNED survival rate compared with the non-ART patients (73% vs. 31%, p = 0.004). CONCLUSION: These data suggest that the amount of microscopic residual tumor significantly affects bNED after radical prostatectomy for Gleason score 7, pT3N0 prostate cancer. In addition, men with pathologic evidence of microscopic local disease appear to benefit from early ART compared with untreated controls.     

Pretreatment prostate-specific antigen and Gleason score predict the risk of extracapsular extension and the risk of failure following radiotherapy in patients with clinically localized prostate cancer

The purpose of this study is to evaluate the use of a relatively simple equation for predicting the risk of extracapsular extension (ECE) based on the pretreatment prostate-specific antigen (PSA) and Gleason score (GS) in patients with clinically localized prostate cancer. Three hundred and seventy-four patients who underwent radical prostatectomy between 1988 and 1994 and 521 men undergoing definitive radiotherapy during a similar time period were eligible for this analysis. Surgically treated patients were considered eligible if the pathological stage, preoperative PSA, and GS were available. Among these patients, the median preoperative PSA was 8.1 ng/mL (range, 0 to 195 ng/mL), and the median preoperative GS was 6 (range, 2 to 10). The empirically derived equation tested was (1.5 x PSA + [GS - 3] x 10). For this equation, the range of calculated risk was limited to 0% to 100%. Using the empirically derived equation, patients with a low calculated risk (CR) of < or = 33% had an average calculated risk (ACR) of 21.9% and an observed incidence (OI) of ECE was 17.8%. Patients with a moderate CR of 34% to 66% had an ACR of 46.3%, and an OI of ECE was 46.7%. Patients with a CR of 67% to 100% had an ACR of 83.7% and an OI of ECE of 66.7%. Of the 21 patients who had a PSA < or = 4 and a GS < or = 4, only 1 patient (4.8%) was found to have ECE. Men with an estimated risk of ECE of <33%, 33% to 67%, and >67% had a 4-year risk of biochemical failure following radiotherapy of 29%, 56%, and 78% (P < .00001). This empirically derived data appears to be reasonably accurate at estimating the incidence of ECE in patients with at low or intermediate risk before surgery. The risk of biochemical failure following radiotherapy also correlated the risk of ECE. Future staging systems for prostate cancer should use similar approach for defining risk groups.     

Pathologic findings and prostate specific antigen outcome after radical prostatectomy for patients diagnosed on the basis of a single microscopic focus of prostate carcinoma with a gleason score </= 7

BACKGROUND: Whether patients who are diagnosed on the basis of a single microscopic focus of prostate carcinoma with a Gleason score 相似文献   

Prostate specific antigen and Gleason score in men with prostate cancer at a private diagnostic radiology centre in Western Jamaica

Background: Prostate cancer is the most common malignant tumour in men and the second most commoncause of male cancer death. The study examines the clinicopathological features of patients with prostate cancerconsecutively diagnosed at a private Diagnostic Radiology Centre in Western Jamaica over a 6-year period.Method: The medical records, including the pathology reports of 423 consecutive patients who had transrectalultrasonography (TRUS) - guided prostate biopsy between January 2006 and December 2011 were reviewed.Results: The mean age at diagnosis of the 191 men with prostate adenocarcinoma was 68.5 ± 0.59 years withthe majority in the 70 - 79 year age group (43.5%). Moderately differentiated carcinomas (Gleason score of 6)comprised the largest group with 72 cases (37.9%); poorly differentiated cancers with Gleason scores of 8 - 10comprised 49 cases (25.8%). The PSA levels increased with Gleason score. The mean PSA levels for men withGleason score of 6 was 50.1 ± 30.0 ng/mL compared with 136.5 ± 59.9 ng/mL in patients with Gleason score of 8and 140.5 ± 31.8 ng/mL in patients with Gleason score of 9. Perineural invasion was present in 7.85% of the casesoverall; high-grade prostatic intraepithelial neoplasia (HGPIN) was present in 4.71% of the biopsies. Conclusion:Although the majority of patients had moderate, and moderate to poor differentiated carcinomas, the numberwith poorly differentiated carcinoma was high. This is a reflection of the patients’ late clinical presentation atthe time of diagnosis.     

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。     

Radiation dose response in patients with favorable localized prostate cancer (Stage T1-T2, biopsy Gleason < or = 6, and pretreatment prostate-specific antigen < or = 10)

PURPOSE: To study the radiation dose response as determined by biochemical relapse-free survival in patients with favorable localized prostate cancers, i.e., Stage T1-T2, biopsy Gleason score (bGS) < or = 6, and pretreatment prostate-specific antigen (iPSA) < or = 10 ng/mL. METHODS AND MATERIALS: A total of 292 patients with favorable localized prostate cancer were treated with radiotherapy alone between 1986 and 1999. The median age was 69 years. Sixteen percent of cases (n = 46) were African-American. The distribution by clinical T stage was as follows: T1/T2A, 243 (83%); and T2B/T2C, 49 (17%). The distribution by iPSA was as follows: < or = 4 ng/mL, 49 (17%); and > 4 ng/mL, 243 (83%). The mean iPSA level was 6.2 (median, 6.4). The distribution by bGS was as follows: or = 5 in 89 cases (30%) and 6 in 203 cases (70%). The median radiation dose was 70.0 Gy (range, 63.0-78.0 Gy). Doses of < or = 70.0 Gy were delivered in 175 cases, 70.2-72.0 Gy in 24 cases, 74 Gy in 30 cases, and 78 Gy in 63 cases. For patients receiving < 72 Gy, the median dose was 68 Gy, vs. 78 Gy for patients receiving > or = 72 Gy. A conformal technique was used in 129 (44%) of cases. The median follow-up was 43 months (range, 3-153). RESULTS: For the entire cohort, the projected 5- and 8-year biochemical relapse-free survival (bRFS) rates were both 81%. For patients receiving > or = 72 Gy, the 5- and 8-year bRFS rates were both 95% vs. only 77% for patients receiving < 72 Gy, p = 0.010. For patients receiving 74 Gy, the 4-year bRFS rate was 94% vs. 96% for patients receiving 78 Gy, p = 0.90. A multivariate analysis for factors affecting bRFS rates using Cox proportional hazards was performed for all cases using the following variables: age (continuous variable), race (black vs. white), iPSA (continuous variable), bGS (< or = 5 vs. 6), Stage (T1-2A vs. T2B-C), radiation dose (continuous variable), and radiation technique (conformal vs. standard). From the multivariate analysis, only iPSA (p = 0.017, chi(2) = 5.7), and radiation dose (p = 0.021, chi(2) = 5.3) were independent predictors of outcome. Age (p = 0.94), race (p = 0.89), stage (p = 0.45), biopsy GS (p = 0.40), and radiation technique (p = 0.45) were not. CONCLUSION: There is a clear radiation dose response in patients with favorable localized prostate cancers (i.e., Stage T1-T2, biopsy Gleason score < or = 6, and iPSA < or = 10 ng/mL). At least 74 Gy should be delivered to the prostate and periprostatic tissues. With our cohort of patients, longer follow-up will be needed to assess the importance of doses exceeding 74 Gy.     

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.     

Factors affecting recurrence rates after prostatectomy or radiotherapy in localized prostate carcinoma patients with biopsy Gleason score 8 or above

BACKGROUND: To review the biochemical recurrence-free survival (bRFS) rates of treatment with either external beam radiotherapy or radical prostatectomy in patients with biopsy Gleason score 8 or above in the prostate specific antigen (PSA) era. METHODS: A total of 297 localized prostate carcinoma patients diagnosed with biopsy Gleason score 8 or above were treated between 1987 and 2000 at the Cleveland Clinic with either prostatectomy or radiotherapy (RT). All patients had pretreatment PSA (iPSA) levels. Androgen deprivation was given as part of the initial treatment in 154 patients (52%). Radical prostatectomy (RP) was the primary treatment in 115 patients (39%) and 182 patients (61%) received RT.The median radiation dose was 70.2 Gy (range, 60.0-78.0 Gy). The median follow-up time was 42 months (range, 1-153 months). RESULTS: For the 297 patients, the 5 and 8-year bRFS rates were 45% (95% confidence interval [CI] 38-52%) and 31% (95% CI 20-42%), respectively. The 5-year bRFS rates for iPSA 10 or less versus. iPSA above10 were 66% (95% CI 54-78%) versus 31% (95% CI 22-40%), respectively (P < 0.001). The 5-year bRFS rates for use of androgen deprivation versus no androgen deprivation were 62% (95% CI 52-72%) versus 35% (95% CI 27-42%), respectively (P < 0.001). The 5-year bRFS rates for RT patients versus RP patients were 47% (95% CI 38-57%) versus 42% (95% CI 31-53%), respectively (P = 0.051). For RT patients, the 5-year bRFS rates for use of androgen deprivation versus no androgen deprivation were 71% versus 29%, respectively (P < 0.001). For RP patients, the 5-year bRFS rates for use of androgen deprivation versus no androgen deprivation were 39% versus 43%, respectively (P = 0.90). Multivariate time-to-failure analysis using the proportional hazards model showed iPSA level (P < 0.001) and the use of androgen deprivation (P = 0.001) to be the only independent predictors of biochemical recurrence. Age (P = 0.44), race (P = 0.80), clinical T stage (P = 0.10), biopsy Gleason scores (P = 0.39), and treatment modality (P = 0.13) were not independent predictors of biochemical failure. A total of 104 patients had Stage T1 or T2 disease, low iPSA levels (/= 8). For all 104 patients, the 5-year bRFS rate was 64%. For 52 of the 104 patients who received 6 months of androgen deprivation or less, the 5-year bRFS rate was 78%. CONCLUSION: Patients with localized prostate carcinoma with a biopsy Gleason score 8 or less have lower recurrence rates if iPSA levels are 10 or less. Biochemical control rates were encouraging for patients with biopsy Gleason score 8 or above, clinical Stage T1-T2, and iPSA levels less than or equal to 10 ng/mL treated with adjuvant androgen deprivation given only for 6 months or less. If longer follow-up confirms these findings, these patients might not need prolonged androgen deprivation for periods exceeding 6 months following local therapy.     

Outcome and predictive factors for patients with Gleason score 7 prostate carcinoma treated with three-dimensional conformal external beam radiation therapy

BACKGROUND: The purpose of this study was to determine the biochemical outcome and factors predictive of outcome in prostate carcinoma patients with Gleason score 7 tumors who were treated with three-dimensional conformal radiation therapy (3DCRT). METHODS: Between August 1990 and October 1997, 163 T1-T3NXM0 prostate carcinoma patients with Gleason score 7 were treated with definitive 3DCRT alone. The median follow-up, International Commission on Radiological Units dose, and pretreatment prostate specific antigen (PSA) for the entire group were 50 months, 76 grays (Gy), and 11.4 ng/mL, respectively. Independent predictors based on multivariate results were used to stratify the patients into prognostic groups for which biochemical no evidence of disease (bNED) control was reported. Biochemical NED failure was defined according to the American Society for Therapeutic Radiology and Oncology Consensus Panel definition. RESULTS: The 5-year bNED control for all patients was 66%. Stratified by pretreatment PSA, 5-year bNED control rates were 83%, 65%, and 21% for 0-9.9 ng/mL, 10-19.9 ng/mL, and > or =20 ng/mL, respectively. Dose to the central axis was found to be a significant treatment factor, with patients receiving > or =76 Gy experiencing 76% 5-year bNED control versus 54% when treated with <76 Gy to isocenter. Pretreatment PSA, dose, and palpation stage were significant independent predictors for bNED control upon multivariate analysis. Patients with a PSA <10 ng/mL who received a dose of > or =76 Gy had excellent 5-year bNED control of 100% compared with 50% bNED if patients had PSA >10 ng/mL or received radiation therapy doses of <76 Gy. CONCLUSIONS: Patients with Gleason score 7 adenocarcinoma who had a pretreatment PSA <10 ng/mL and received doses of > or =76 Gy had excellent 5-year bNED control, emphasizing the importance of higher central axis doses in treating Gleason 7 tumors. Patients with intermediate PSA (10-19.9 ng/mL) also required doses > or =76 Gy. Pretreatment PSA > or = 20 ng/mL portends a very poor bNED outcome for Gleason 7 patients treated with radiation therapy alone, and thus efforts should be directed toward multimodal or long term hormonal treatment strategies.     

Predictive modeling for the presence of prostate carcinoma using clinical, laboratory, and ultrasound parameters in patients with prostate specific antigen levels < or = 10 ng/mL

BACKGROUND: The objective of the current study was to develop a model for predicting the presence of prostate carcinoma using clinical, laboratory, and transrectal ultrasound (TRUS) data. METHODS: Data were collected on 1237 referred men with serum prostate specific antigen (PSA) levels < or = 10 ng/mL who underwent an initial prostate biopsy. Variables analyzed included age, race, family history, referral indication(s), prior vasectomy, digital rectal examination (DRE), PSA level, PSA density (PSAD), and TRUS findings. Twenty percent of the data were reserved randomly for study validation. Logistic regression analysis was performed to estimate the relative risk, 95% confidence interval, and P values. RESULTS: Independent predictors of a positive biopsy result included elevated PSAD, abnormal DRE, hypoechoic TRUS finding, and age 75 years or older. Based on these variables, a predictive nomogram was developed. The sensitivity and specificity of the model were 92% and 24%, respectively, in the validation study for which the predictive probability > or = 10% was used to indicate the presence of prostate carcinoma. The area under the receiver operating characteristic curve (AUC) for the model was 73%, which was significantly higher compared with the prediction based on PSA alone (AUC, 62%). If it was validated externally, then application of this model to the biopsy decision could result in a 24% reduction in unnecessary biopsy procedures, with an overall reduction of 20%. CONCLUSIONS: Incorporation of clinical, laboratory, and TRUS data into a prebiopsy nomogram significantly improved the prediction of prostate carcinoma over the use of individual factors alone. Predictive nomograms may serve as an aid to patient counseling regarding prostate biopsy outcome and to reduce the number of unnecessary biopsy procedures.     

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.     

Introducing a prognostic score for pretherapeutic assessment of seminal vesicle invasion in patients with clinically localized prostate cancer.

PURPOSE: To identify prostate cancer patients who will have the most likely benefit from sparing the seminal vesicles during 3D conformal radiation therapy. METHODS AND MATERIALS: From 1988 to 2001, 532 patients underwent radical prostatectomy for clinically localized prostate cancer. Primary endpoint was the pathological evidence of seminal vesicle invasion. Variables for univariate and multivariate analyses were age, prostate weight, clinical stage, PSA level, Gleason score, number and site of positive prostate sextant biopsies. Multivariate logistic regression with backward stepwise variable selection was used to identify a set of independent predictors of seminal vesicle invasion, and the variable selection procedure was validated by non-parametric bootstrap. RESULTS: Seminal vesicle invasion was reported in 14% of the cases. In univariate analysis, all variables except age and prostate weight were predictors of seminal vesicle invasion. In multivariate analysis, only the number of positive biopsies (P<0.0001), Gleason score (P<0.007) and PSA (P<0.0001) were predictors for seminal vesicles invasion. Based on the multivariate model, we were able to develop a prognostic score for seminal vesicle invasion, which allowed us to discriminate two patient groups: A group with low risk of seminal vesicles invasion (5.7%), and the second with a higher risk of seminal vesicles invasion (32.7%). CONCLUSIONS: Using the number of positive biopsies, Gleason score and PSA, it is possible to identify patients with low risk of seminal vesicles invasion. In this population, seminal vesicles might be excluded as a target volume in radiation therapy of prostate cancer.     

The correlation of serial prostate specific antigen measurements with clinical outcome after external beam radiation therapy of patients for prostate carcinoma

BACKGROUND: The authors analyzed retrospectively their institution's experience in treating patients with localized prostate carcinoma with external beam radiation therapy (EBRT) to determine the correlation of various biochemical failure (BF) definitions with clinical failure and cause specific survival (CSS). METHODS: Between January 1987 and December 1997, 1,094 patients with clinical T1-T3N0M0 prostate carcinoma were treated with definitive EBRT alone at William Beaumont Hospital, Royal Oak, Michigan. All patients received EBRT alone (no adjuvant hormones) to a median total prostate dose of 66.6 grays (Gy) (range, 59.4-70.4 Gy). Multiple BF definitions were tested for their correlation with clinical failure and cause specific death (CSD = 1-CSS). All BF definitions were tested for sensitivity, specificity, and accuracy of predicting subsequent clinical failure and CSD. Positive and negative predictive values were calculated in the form of 10-year actuarial clinical failure and CSD rates. Analyses were performed on all 1,094 patients as well as for those 727 patients who had at least 5 post-RT prostate specific antigen (PSA) level measurements and who did not receive hormonal therapy for post-RT PSA elevations. The median PSA follow-up was 4.0 years for the entire population and 4.5 years for those 727 patients included in the second analysis. RESULTS: In the entire population, 167 patients (15%) experienced clinical failure corresponding to 5- and 10-year actuarial rates of 16% and 34%, respectively. The correlation of various BF definitions with outcome was calculated in those 727 patients who did not receive hormonal therapy. For these patients, BF (as defined by the American Society for Therapeutic Radiology and Oncology Consensus Panel) yielded a 73% sensitivity, 76% specificity, and 75% overall accuracy for predicting clinical failure and a 74% sensitivity, 69% specificity, and 69% overall accuracy for predicting CSD. The 10-year clinical failure rate for those 251 patients demonstrating 3 consecutive PSA rises (BF) was 64% versus 14% for those patients who did not meet these criteria (biochemically controlled [BC]). As expected, definitions requiring only two rises were more sensitive but less specific in predicting clinical failure than those definitions requiring three or four rises. Because there were dramatically more clinically controlled patients (85%) than clinical failures (15%), the overall accuracy for each definition more closely approximated its specificity. The definitions classifying BF as a postnadir increase of > or = 3 or > or = 4 ng/mL above the nadir yielded the highest accuracies of 87% and 88%, respectively. In addition, these definitions also appeared to provide the greatest separation in clinical failure rates between BC and BF patients, an absolute difference of 77% and 76%, respectively. CONCLUSIONS: The correlation between BF and clinical failure and CSD varies markedly depending on the BF definition used. Definitions incorporating a fixed baseline (the nadir level) and the postnadir PSA profile may have better correlation with clinical failure than definitions using the nadir only or a specific number of consecutive rises in which a variable baseline "resets" after a PSA decrease.     

The impact of the biopsy Gleason score on PSA outcome for prostate cancer patients with PSA < or = 10 ng/ml and T1c,2a: implications for patient selection for prostate-only therapy

PURPOSE: This study was performed to determine the ability of the biopsy Gleason score, prostate-specific antigen (PSA) level, and the 1992 American Joint Commission on Cancer (AJCC) clinical T-stage for predicting time to postoperative PSA failure for patients with a PSA < or =10 ng/ml and T1c or T2a disease. Specific attention is given to the patient subgroup with biopsy Gleason 3 + 4 vs. 4 + 3. METHODS AND MATERIALS: A concordance map of the biopsy and prostatectomy Gleason grades and a clinical-pathologic correlation of the PSA, biopsy Gleason score, and 1992 AJCC T-stage and pathologic stage were performed. A Cox regression multivariable analysis was used to evaluate the ability of the biopsy Gleason score, PSA, and 1992 AJCC T-stage to predict time to PSA failure for 457 men managed with a radical prostatectomy (RP). RESULTS: The absence of prostatectomy Gleason grade 4 or 5 disease was noted in 71%, 50%, and 11% of patients with biopsy Gleason score 2-6, 3 + 4, and > or =4 + 3 disease respectively while pathologic evidence of seminal vesicle invasion was noted in 2%, 4%, and 17% of these patients respectively. Estimates of 5-year PSA failure-free survival rates were not statistically different for patients with biopsy Gleason score 2-6 vs. 3 + 4 (79% vs. 81%; p = 0.93), but were significantly different for patients having biopsy Gleason score 2-6 vs. 4 + 3 (79% vs. 62%; p = 0.04) or 2-6 vs. 8-10 (79% vs. 18%; p = 0.0001) prostate cancer. CONCLUSION: Based on the pathologic stage and PSA control data following RP, patients with biopsy Gleason 3 + 4 disease and PSA < or =10 ng/ml and 1992 AJCC T1c or T2a disease may be suitable candidates for radiation therapy directed at the prostate only.     

Observations of prostate specific antigen doubling time in Japanese patients with nonmetastatic prostate carcinoma.

BACKGROUND: To understand better the natural history and biology of prostate carcinoma occurring in Japanese patients, the authors attempted to define changes with time in prostate specific antigen (PSA) measurements in 48 men with clinically resectable T1-T3 nonmetastatic disease. METHODS: The authors analyzed PSA changes prospectively in prostate carcinoma patients who were managed by watchful waiting. PSA doubling time was calculated by linear regression. These values and their distribution were compared with clinical parameters and with published series of prostate carcinoma patients. RESULTS: The mean age of the 48 patients at the time of diagnosis was 74.2 years. The median follow-up from the time of diagnosis was 24.0 months. The median PSA doubling time was 35.7 months. In 27.1% of patients, there was no increase in the PSA level over the observation period. A rapid rise in PSA (doubling time of <2 years) was observed in 29.2% of patients. These results in Japanese patients are virtually the same as those reported in Western countries. There was no statistically significant relation between calculated PSA doubling time and clinical disease stage, tumor grade, PSA level at the time of diagnosis, probability of extraprostatic disease, patient age at diagnosis, or prostate volume (P > 0.05). CONCLUSIONS: Prostate carcinoma may not differ significantly by race once it becomes clinically manifest. The magnitude of positive changes in PSA over a given period of observation may not be helpful in determining the need for therapy. The previously reported incidence of clinically insignificant prostate carcinoma, which primarily was based on pathologic findings in surgical specimens, may have been an underestimation.