Lymphovascular invasion is an independent prognostic factor in prostatic adenocarcinoma

PURPOSE: Gleason grade and tumor stage are well established prognostic factors in prostate cancer. Histological demonstration of tumor in lymphovascular spaces has been associated with poor prognosis in many tumor types but it is not included in current prostate cancer grading and staging schemes. Whether lymphovascular invasion is an independent prognostic factor for disease progression in prostate cancer is uncertain. We retrospectively investigated lymphovascular invasion as a predictive factor for biochemical failure and cancer specific survival following radical prostatectomy. MATERIALS AND METHODS: The records of 504 patients with prostatic adenocarcinoma undergoing radical prostatectomy were reviewed for lymphovascular invasion. Clinical followup data were available on 459 cases. Mean followup was 44 months (range 1.5 to 144). Multivariate analysis was performed using the Cox model. RESULTS: Lymphovascular invasion was identified in 106 cases (21%). Univariate analysis showed a significant association between lymphovascular invasion and higher preoperative serum prostate specific antigen (PSA), advanced pathological stage, higher Gleason score, positive surgical margins, extraprostatic extension, seminal vesicle invasion, lymph node metastasis and perineural invasion (each p <0.001). No association was observed between lymphovascular invasion and patient age at surgery, prostate weight or high grade prostatic intraepithelial neoplasia. Lymphovascular invasion was an independent predictor of PSA recurrence (HR 1.6, 95% CI 1.12 to 2.38, p = 0.01) and cancer specific survival (HR 2.75, 95% CI 1.04 to 2.28, p = 0.041) after controlling for tumor stage, surgical margins and Gleason grade on multivariate analysis. Five-year cancer specific survival was 90% in men with lymphovascular invasion compared to 98% in those without lymphovascular invasion (p <0.001). CONCLUSIONS: Lymphovascular invasion can be identified in approximately 20% of prostate cancer cases. Lymphovascular invasion is an independent risk factor for PSA recurrence and cancer death in patients with prostate cancer.     

PSA-related parameters in prostate cancer relapsed after endocrine therapy

PURPOSE: Prostate cancer is generally controlled by endocrine therapy even in an advanced state, but relapse may occur in many cases. Generally, the prognosis of a relapsed case is poor, but the prognosis differs case by case. We experienced 74 cases of prostate cancer relapsed after effective endocrine therapy, and investigated the relationship between the PSA-related parameters, clinical stage and prognosis. PATIENTS AND METHODS: We investigated 74 prostate cancer patients whose PSA declined 10 ng/ml or lower by the treatment consisting of endocrine therapy, but relapsed later. Pre-treatment PSA, the value of PSA nadir, the period from the start of treatment to PSA nadir, the period from the start of treatment to relapse, PSA doubling time (PSA-DT) at relapse and PSA response to the second line therapy at relapse were calculated, and compared with the clinical stage and prognosis. The relationship between each PSA parameter and clinical stage was tested using the Kruskal-Wallis test and chi 2 test. Cancer-specific survival after relapse in stage D patients was calculated by the Kaplan-Meier method and differences in prognosis were tested using the Logrank test. RESULTS: Pre-treatment PSA was significantly (p < 0.01) high, while the period from the start of treatment to relapse (p < 0.05) and PSA-DT at relapse (p < 0.01) was significantly short as the stage progressed. According to PSA response to the second line therapy at relapse, the rate of CR + PR was significantly (p < 0.05) high in clinical stage B + C group compared to clinical stage D group. The prognosis after relapse was significantly poorer in patients with relapse within 10 months after start of treatment than in those with relapse later, and in patients whose PSA-DT at relapse was shorter than 2 months than in those with a longer PSA-DT. CONCLUSIONS: The period from the start of treatment to relapse, and PSA-DT at relapse were useful PSA-related parameters for predicting prognosis after relapse, and for determining the strategy of cancer therapy after relapse. Using these data, the physician can inform the family and the patient of the prognosis more accurately, so that they can adjust future plans.     

Implications of circulating chromogranin A in prostate cancer

OBJECTIVE: To evaluate whether measurement of circulating chromogranin A (CgA) levels provides clinicopathological and prognostic information in prostate cancer. MATERIAL AND METHODS: Plasma CgA levels were measured in 57 patients with histologically confirmed prostate cancer (stage B or less, n=22; stage C, n=10; stage D1, n=2; hormone-naive D2, n=12; hormone-refractory D2, n=11) and in 22 with undetected prostate cancer using an enzyme-linked immunoabsorbent assay. RESULTS: Median plasma CgA levels were significantly higher in patients with prostate cancer than in those with undetected cancer (p=0.0271). Higher stage (p<0.0001) and higher grade (p=0.0412) tumours were also significantly associated with higher plasma CgA levels. Above-normal CgA levels were also detected in 4/27 patients (15%) who underwent radical prostatectomy. Postoperative clinical failure was not reported in the prostatectomy patients; however, prostate-specific antigen (PSA) failure was reported in 44% of patients after a median follow-up period of 20.3 months. Multivariate analysis revealed that the pathological stage of the tumour was the only independent predictive variable for postoperative PSA failure (p=0.0494). Preoperative plasma CgA levels had no impact on postoperative PSA failure in the subgroup (prostatectomy patients). Elevated plasma CgA levels were associated with a poor survival prognosis in patients with stage D2 prostate cancer after a median follow-up period of 22.5 months (p=0.0416). CONCLUSIONS: It was demonstrated in this study that plasma CgA levels in prostate cancer increase with the severity of the disease, especially for progressive hormone-refractory prostate cancer (HRPC), after hormone therapy. Although this cross-sectional study involved only a small number of patients, we believe that plasma CgA levels may effectively predict HRPC status and prognosis in metastatic cases.     

The prognostic value of different forms of prostate specific antigen and their ratios in patients with prostate cancer

OBJECTIVE: To assess the prognostic value for patient survival of different forms of PSA and ratios thereof, before treatment for prostate cancer, by considering the forms and ratios both as independent markers and by comparing them with other commonly used prognostic markers, e.g. tumour grade, local stage (T-stage) and absence or presence of skeletal metastases (M-stage). PATIENTS AND METHODS: Blood samples were collected consecutively from men diagnosed with prostate cancer at our department in 1988. From this group, 66 men were followed until death, or for >/=9 years. Twenty-five patients died from their prostate cancer and 21 from other causes during the follow-up period. Forty-eight patients received hormonal treatment, whereas 18 remained untreated or received no treatment for their cancer before they died from other causes. Assays measuring the serum levels of free prostate specific antigen (fPSA), PSA complexed to alpha1-antichymotrypsin (PSA-ACT), and total PSA (tPSA) were used to calculate the percentage of free to total PSA (f/tPSA) fPSA/ACT and ACT/tPSA at diagnosis. Based on the initial levels or ratios of the PSA forms, the patients were divided into three numerically comparable groups (tertiles) for survival analysis. Prognostic factors predicting patient survival were evaluated using univariate (Kaplan-Meier life-tables with the log-rank test) and multivariate techniques (Cox proportional hazards regression model). RESULTS: Univariate analysis using the log-rank test showed that the serum level of each molecular form of PSA, i.e. tPSA (P=0.001), PSA-ACT (P<0.001) and fPSA (P<0.001), as well as grade (P<0.001), T-stage (P=0.00355) and M-stage (P<0.001), provided statistically significant prognostic information. Log-rank tests showed that none of the ratios, i.e. f/tPSA, fPSA/ACT and ACT/tPSA, were informative of prognosis (P>0.05). However, in a multivariate analysis regression model, not only M-stage (risk ratio 4.2; P=0. 026) and grade (risk ratio 2.6; P=0.022), but also f/tPSA (risk ratio 1.8; P=0.037), provided significant prognostic information. CONCLUSION: The values of tPSA, fPSA and PSA-ACT, as well as grade and T- and M-stage, are all independent prognostic factors of prostate cancer survival. In a multivariate analysis, not only M-stage and grade but also f/tPSA provided significant prognostic information.     

PSA doubling time in prostate cancer relapsed after endocrine therapy

PURPOSE: The PSA level of prostate cancer patients generally declines after endocrine therapy, but elevates when the cancer relapses in most cases. However, the rate of elevation differs with the case. We investigated the PSA doubling time (PSA-DT) of the prostate cancer patients whose PSA declined after endocrine therapy and later re-elevated, and investigated the relationship with other parameters. PATIENTS AND METHODS: We investigated 55 prostate cancer patients who underwent endocrine therapy between 1991 and 1998. Their PSA re-elevated continuously after their PSA fell below 10 ng/ml after the endocrine therapy as the first line treatment. First, the correlation coefficients with time and PSA were calculated in order to decide whether their PSA elevation was exponential or linear. PSA-DT was calculated thereafter, and compared with the clinical stage, pathological differentiation, clinical relapse style, time from the beginning of the therapy to PSA relapse, pre-treatment PSA value, and prognosis. The relationship between PSA-DT and each clinical parameter was tested using the Kruskal-Wallis test. Differences in survival rates and PSA-DT were calculated using the log-rank test. RESULTS: PSA elevated exponentially after cancer relapsed. PSA-DT in all cases ranged from 0.5 to 26.3 months, with an average of 4.4 +/- 4.8 (S.D.) months and the median was 2.5 months. PSA-DT was significantly (p < 0.01) short when the pre-treatment clinical stage was high, the time from the beginning of the therapy to PSA relapse was short, or the pre-treatment PSA value was high. PSA-DT tended to be short when the pre-treatment pathological differentiation was low, but not significantly. PSA-DT tended to be short when the cancer relapsed as distant metastasis rather than regional relapse, but not significantly. Prognosis from the initial treatment and PSA relapse was significantly poor when the PSA-DT was short. CONCLUSIONS: PSA elevated exponentially in the relapsed prostate cancer patients after the endocrine therapy. PSA-DT was distributed in a very wide range, and this value was considered to reflect the malignant potential and prognosis of the cancer. PSA-DT may be useful for determining the strategy after relapse.     

Prognostic value of neuroendocrine serum markers and PSA in irradiated patients with pN0 localized prostate cancer

BACKGROUND: The prognosis of patients with localized prostate cancer depends on clinical stage, histological grade, and pretreatment prostate-specific antigen (PSA). We evaluated the additional prognostic impact of serum levels of neuron-specific enolase (NSE) and chromograninA (CgA) after curative radiotherapy and the importance of serum PSA, analyzed 3 months after irradiation. METHODS: From 1988 to 1995, 161 patients with localized T1-4, pN0M0, prostate adenocarcinoma were treated with external radiation (66Gy, 2Gy/5 fractions per week). Frozen serum samples were assessed for CgA, NSE, and PSA before and 3 months after radiotherapy. CgA was analyzed in only 100 patients. NSE and CgA were determined by a immunometric assay. Total PSA was measured by a time-resolved fluoro-immunometric assay. RESULTS: Prior to radiotherapy CgA was elevated in 16 of 100 patients, and NSE was elevated in 33 of the 161 patients. There was no association between grade, T category or pretreatment PSA and the levels of neuroendocrine markers. Pretreatment-elevated serum NSE, but not initial CgA, identified patients with an unfavorable prognosis. A < 50% reduction of PSA 3 months after radiotherapy was associated with decreased failure-free 10 years urvival. Multivariate analysis demonstrated an increased risk of failure for patients with elevated pretreatment NSE and PSA values, T3 category, and decline of PSA less than 50% 3 months after radiotherapy. The presence of none or several risk factors (1-4) defined clearly separable groups. CONCLUSIONS: Together with T category and pretreatment serum PSA values, serum NSE values before radiotherapy and decrease of serum PSA 3 months after radiotherapy represent easily assessable prognostic parameters in patients undergoing curative radiation treatment for prostate cancer.     

Pattern of progression and survival in hormonally treated metastatic prostate cancer

BACKGROUND: Patients with prostate cancer generally respond to androgen ablation therapy, but progression to androgen-independence is frequently observed. To further evaluate disease progression, the pattern of progression and survival in hormonally treated metastatic prostate cancer was examined. METHODS: One hundred and ninety-three patients with untreated metastatic prostate cancer (TxNxM ) who received endocrine therapy between 1986 and 1995 were included in the present study. The pattern of progression was evaluated in these patients. RESULTS: One hundred and eighteen of the 193 patients (61.1%) had disease progression: 33 had local progression, 73 had distant progression and 12 had distant with local progression. Patients with only local progression had a longer interval to disease progression and longer survival than those with distant progression. The interval from disease progression to death in patients with local progression was longer than in those with distant progression. The patients whose prostate-specific antigen (PSA) had not been normalized 3 months after the start of endocrine therapy had a tendency to progression either into the prostate or into distant sites. Patients with extent of disease (EOD) scores of 3 and 4 progress, especially to distant sites, after endocrine treatment. CONCLUSIONS: In untreated metastatic prostate cancer, patients with a poor response of PSA levels and patients with a high volume of bone metastasis (i.e. EOD 3, 4) were in the high-risk group for progression, especially to distant sites. Progression into distant sites was a poor prognostic factor for patients with recurrence to endocrine therapy.     

Prognostic significance of changes in short-term prostate volume and serum prostate-specific antigen after androgen withdrawal in men with metastatic prostate cancer

OBJECTIVE: Endocrine therapy is the standard treatment for metastatic prostate cancer although progression to androgen independence is inevitable. To evaluate prognostic factors in metastatic prostate cancer, patients who had been treated with endocrine therapy were investigated especially for the change in prostate volume. METHODS: Fifty-nine patients with untreated metastatic prostate cancer who received endocrine therapy were included in the present study. Blood chemistry, histological grade, extent of bony metastasis, clinical response to hormone therapy including the short-term change in prostate volume and serum prostate-specific antigen (PSA), and prognosis of the patients were evaluated. RESULTS: With univariate analysis, hemoglobin concentration, serum alkaline phosphatase, lactate dehydrogenase (LDH), histological grade, extent of bony disease, the short-term change of prostate volume and response of PSA at 3 months were shown to be significant prognostic factors. Response of PSA, LDH and the change in prostate volume were significant for predicting prognosis with multivariate analyses. Five-year survival rate in patients whose prostate had regressed 20% or more at 1 month and whose PSA had been normalized at 3 months was 67%, whereas that in patients whose prostate had regressed less than 20% and whose PSA had not been normalized was 0%. CONCLUSIONS: The patients in whom PSA had not been normalized at 3 months and the prostate volume had regressed less than 20% at 1 month were in the high-risk group. New or more aggressive treatment should be considered.     

Radical prostatectomy for pathological Gleason 8 or greater prostate cancer: influence of concomitant pathological variables.

PURPOSE: We evaluated the long-term outcome of radical prostatectomy for pathological Gleason score 8 or greater prostate cancer and characterized the prognostic significance of other pathological variables. MATERIALS AND METHODS: A total of 6,419 patients underwent radical prostatectomy between 1987 and 1996. There were 407 patients classified as having pathological Gleason 8 or greater, including 8 in 48%, 9 in 49% and 10 in 3%. Adjuvant treatment was used in 45% of patients and adjuvant hormonal therapy was administered to 155 (38%). Progression-free, including local or systemic, and/or prostate specific antigen (PSA) 0.4 ng./ml. or greater, and cancer specific survival were determined by the Kaplan-Meier method. The effect of pathological grade and stage, preoperative PSA, DNA ploidy, margin status, tumor dimension, seminal vesicle invasion, and adjuvant treatment was assessed with the univariate and multivariate analyses. RESULTS: Pathological stage distribution was pT2 in 26% of patients, pT3 48% and pTxN+ 27%. Overall and progression-free survival at 10 years was 67% and 36%, respectively, compared to cancer specific survival 85%. Adjuvant treatment, pathological stage, preoperative PSA and pathological grade were significant (less than 0.05) univariate predictors of progression-free survival. Pathological stage, margin status and ploidy were univariately associated with cancer specific survival. Progression-free survival at 10 years of those patients who did and did not receive adjuvant treatment was 52% and 23%, respectively. In the multivariate analysis pathological grade (p=0.02), preoperative PSA (p <0.0001), adjuvant therapy (p <0.0001) and pathological stage (p=0.036) were significant independent predictors of progression-free survival. CONCLUSIONS: High grade prostate cancer can be controlled with radical prostatectomy in some patients with disease confined pathologically, and 10-year cause specific survival is 96%. Predictors of outcome in patients with Gleason 8 disease or greater are similar to established predictors derived by using all grades. Although adjuvant hormonal therapy appears to improve disease progression rates after radical prostatectomy on the basis of this nonrandomized study, it may not affect prostate cancer death rates within 10 years in patients with high grade cancer.     

The independent value of tumour volume in a contemporary cohort of men treated with radical prostatectomy for clinically localized disease

Study Type – Prognosis (case series)
Level of Evidence 4

OBJECTIVE

To determine if prostate tumour volume is an independent prognostic factor in a contemporary cohort of men who had a radical prostatectomy (RP) for clinically localized disease, as the effect of tumour volume on prostate cancer outcomes has not been consistently shown in the era of widespread screening with prostate‐specific antigen (PSA).

PATIENTS AND METHODS

The study included 856 men who had RP from 1998 to 2007 for localized prostate cancer. Tumour volume based on pathology was analysed as a continuous and categorized (<0.26, 0.26–0.50, 0.51–1.00, 1.01–2.00, 2.01–4.00, >4.00 mL) variable using Cox proportional hazards regression and Kaplan‐Meier analysis. A multivariable analysis was also conducted controlling for PSA level, Gleason grade, surgical margins, and pathological stage.

RESULTS

Tumour volume had a positive association with grade and stage, but did not correlate with biochemical recurrence‐free survival on univariate analysis as a continuous variable (hazard ratio 1.00, P = 0.09), and was only statistically significant for volumes of >4 mL as a categorical variable. No tumour volume was an independent predictor of prostate cancer recurrence on multivariate analysis. There was no difference between tumour volume and time to cancer recurrence for organ‐confined tumours using Kaplan‐Meier analysis. In low‐risk patients (PSA level <10 ng/mL, Gleason score ≤6, clinical stage T1c/T2a) tumour volume did not correlate with biochemical recurrence‐free survival in univariate or multivariable analysis.

CONCLUSIONS

There is no evidence that tumour volume is an independent predictor of prostate cancer outcome and it should not be considered as a marker of tumour risk, behaviour or prognosis.     

Prognostic significance of the nadir prostate specific antigen level after hormone therapy for prostate cancer

PURPOSE: We determine whether the nadir prostate specific antigen (PSA) level after hormone therapy can be used to predict the progression to hormone refractory prostate cancer. MATERIALS AND METHODS: We reviewed the progressive status and survival of 177 patients with stage C or D prostate cancer who had received hormone therapy at our institution. The overall survival rate, incidence of progression to hormone refractory prostate cancer and interval until progression were analyzed with reference to the nadir PSA level. Multiple regression analysis was used to analyze the predictive factors for progression to hormone refractory prostate cancer, and the relative efficacy of the nadir PSA level in predicting progression was evaluated by receiver operating characteristics analysis. RESULTS: Median followup was 39 months (range 3 to 89) and 85.4% of patients (151) responded to treatment, of whom 77.5% (117) had progression to hormone refractory prostate cancer. Median time until nadir PSA levels were reached after hormone therapy was 8.1 months and median time until hormone refractory prostate cancer was 24.0 months. Nadir PSA levels were less than 0.2 ng./ml. in 31% of respondents, 0.2 to 1.0 ng./ml. in 23%, 1.1 to 10 ng./ml. in 42% and greater than 10 ng./ml. in 5%. These groups had similar clinicopathological characteristics. Nadir PSA levels correlated significantly with pretreatment PSA levels, Gleason scores and progression to hormone refractory prostate cancer (p = 0.01, p <0.01 and p <0.001, respectively), and inversely correlated with the interval to the establishment of hormone refractory prostate cancer (r = -0.465, p <0.05). By univariate analysis bone metastasis, nadir PSA, PSA at 6 months after treatment and pretreatment PSA were significantly associated with progression to hormone refractory prostate cancer. Only the nadir PSA was calculated to be an independent factor by multivariate analysis. Receiver operating characteristics analysis indicated that nadir PSA predicted progression to hormone refractory prostate cancer after 2 years with an accuracy of 86.2%. With the lower limit of the nadir PSA level set to 1.1 ng./ml., sensitivity was 80.3% and specificity was 83.8%, and these levels were deemed the most appropriate. Furthermore, nadir PSA after hormone therapy was an independent prognosticator for survival, as were initial levels of hemoglobin and alkaline phosphatase. CONCLUSIONS: The nadir PSA level after hormone therapy may be the most accurate factor predicting the progression to hormone refractory prostate cancer and is an independent prognostic factor for survival. Furthermore, a lower limit for the nadir PSA level of 1.1 ng./ml. gives optimal sensitivity and specificity.     

前列腺癌组织中蛋白表达与内分泌治疗后进展的相关性研究

目的 探讨前列腺癌内分泌治疗前癌组织中多种蛋白标记表达与内分泌治疗后发生进展的相关性,筛选内分泌治疗后进展的预测因子.方法 收集116例接受内分泌治疗的前列腺癌患者的临床病理资料,检测患者内分泌治疗前癌组织中雄激素受体(AR)、上皮型钙黏附索(E-cad-herin)、嗜铬粒蛋白A(CgA)、核增殖抗原(Ki67)、凋亡抑制蛋白(Survivin)、EZH2、hepsin蛋白表达,应用Cox比例风险模型进行多因素分析.结果 Ki67、EZH2、Survivin 3种蛋白表达与传统临床病理学因素存在Spearman等级相关.单因素分析中发现临床分期(P<0.001)、Gleason评分(P=0.005)、治疗前血清PSA值(P<0.001)以及Ki67(P=0.032)、Survivin蛋白(P=0.002)表达与内分泌治疗后的进展相关,多因素分析结果 显示临床分期(T_x N_+/M_+)(P<0.001)、高病理分级(Gleason评分≥8分)(P-0.038)和Survivin蛋白高表达(p＝0.031)是内分泌治疗后进展的重要危险因素.其中T_x N_+/M_+者67例(57.8%),Gleason评分≥8分者56例(48.3%),Survivin蛋白高表达者91例(78.4%). 结论 临床分期、病理分级、Survivin蛋白表达对于预测前列腺癌内分泌治疗后进展有重要意义.     

Skewing towards neuroendocrine phenotype in high grade or high stage androgen-responsive primary prostate cancer

OBJECTIVE: The prognostic influence of neuroendocrine (NE) differentiation in prostate cancer patients is not yet properly established. In a series of primary hormone-naive prostate cancers from a patient population that underwent radical prostatectomy, we wanted to determine the relationship between NE phenotype expression and Gleason sum, disease stage, and serum PSA concentration. METHODS: Chromogranin A (CgA) expression was scored and compared in 105 consecutive primary prostate cancers with their homologous preoperative tumor prostate biopsies. RESULTS: High grade or high stage prostate cancers expressed a significantly higher CgA score than low grade or localized diseases (p < 0.005). Both the CgA score of the surgical specimens and the PSA level in the serum increased linearly (p = 0.001). In the samples of many corresponding tumor biopsies no significant CgA staining was found. CONCLUSION: NE differentiation in primary untreated prostate cancer is closely associated with the major prognostic parameters of survival. This association cannot be shown by evaluating the CgA staining in tumor biopsies.     

The role of pretreatment serum albumin to predict pathological stage and recurrence among radical prostatectomy cases

Serum albumin level has been implicated as a prognostic factor in various cancers, however it has not been studied in early stage prostate cancer. We examine the clinical prognostic value of the readily available pretreatment albumin level as a marker for determining staging and prognosis for men undergoing radical prostatectomy. A retrospective review was performed on 354 patients who underwent a radical prostatectomy at a tertiary facility from 15 April, 1990 until 3 December, 1996 who had a pretreatment serum albumin within 6 months prior to surgery. Albumin levels were analyzed and compared to the values of standard prognostic factors to assess the ability of albumin to predict pathological stage and serological recurrence by PSA level after radical prostatectomy. Albumin level was not of value in predicting serological disease recurrence, but interestingly was an independent prognostic factor in predicting risk of nonorgan-confined disease (T3 or T4). Our data also showed that, as expected, grade and pretreatment PSA levels were independent predictors of pathological stage. Albumin appears to be of clinical utility to augment assessment of pretreatment pathological stage. However, it is not of value in predicting serological disease recurrence following radical prostatectomy. Further study in other cohorts and in using additional analysis such as neural networks is indicated. Prostate Cancer and Prostatic Diseases (2000) 3, 186-190     

Prognostic features in men who died of prostate cancer

PURPOSE: Since the advent of widespread prostate specific antigen (PSA) based screening in the United States, the risk of over diagnosis as well as delayed diagnosis due to existing PSA thresholds has become a concern. Treatment decision planning is generally linked to prognostic variables, most notably PSA, clinical stage and Gleason grade. We examined these and other prognostic variables in a cohort of men who ultimately died of prostate cancer. MATERIALS AND METHODS: Of 413 men with prostate cancer in a cohort in San Antonio, Texas between 1993 and 2003 who died of disease we identified 211 who died as a direct result of prostate cancer. In these cases we assessed presenting symptoms, PSA history, tumor stage and Gleason score at diagnosis. RESULTS: Of the 211 men 141 (67%) underwent screening for prostate cancer prior to diagnosis. Of 190 men with PSA data at diagnosis available 7 (3.7%) had PSA less than 4.0 ng/ml and 27 (14%) had PSA 4.0 to 10.0 ng/ml. Clinical stage distribution was cT1 in 21.1% of cases, cT2 in 50.7% and cT3 in 26.8%. Of 167 men for whom biopsy Gleason grade was available 16.8%, 16.2%, 24% and 43.1% had Gleason sum 5 or less, 6, 7 and 8 or higher, respectively. CONCLUSIONS: While most men who ultimately die of prostate cancer have poor prognostic features, a substantial number have features associated with a potentially good prognosis, including low PSA and low Gleason grade. Many men who died of prostate cancer had undergone prior screening. These data demonstrate the need for improved markers of prognosis and continued assessment of the efficacy of screening with PSA.     

Prognostic factors for survival of patients with pathological Gleason score 7 prostate cancer: differences in outcome between primary Gleason grades 3 and 4

PURPOSE: We evaluated differences in clinical and pathological outcomes between Gleason 3 + 4 and 4 + 3 prostate cancer. MATERIALS AND METHODS: The radical prostatectomy whole mounted specimens from 263 men with pathological Gleason 7 tumors were identified. Gleason 3 + 4 and 4 + 3 tumors were compared in regard to pathological variables and outcome. Significance of clinical and pathological data on progression-free survival was analyzed. RESULTS: Of the tumors 34% had a primary Gleason grade of 4, and were more likely than those with primary grade 3 to have seminal vesicle involvement (34% versus 18%, p = 0.006), a higher pathological stage (pT3 55% versus 42%, N+ 13% versus 3%, 0.001), extraprostatic extension (58% versus 38%, 0.001) and higher median preoperative prostate specific antigen (PSA) (13.5 versus 9.0 ng./ml., respectively <0.001). Mean followup plus or minus standard deviation was 6.8 +/- 1.9 years. The overall 10-year crude, cancer specific and progression-free survival rates were 83%, 99% and 58%, respectively. Primary Gleason grade was significantly associated with progression-free (risk ratio 1.6, 95% confidence interval 1.08 to 2.5, p = 0.02) but not crude and cancer-specific survival. Univariately, primary Gleason grade 4 was associated with progression-free survival, as were percent Gleason 4, seminal vesicle invasion, lymph node involvement, pT stage, margin status, DNA ploidy, preoperative PSA, cancer volume and extent of extraprostatic extension. Multivariately, only preoperative PSA (p <0.001), seminal vesicle invasion (<0.001) and DNA ploidy (0.002) were associated with progression-free survival. Primary Gleason grade and percent Gleason 4 were not identified as independently associated with progression-free survival. CONCLUSIONS: In patients with Gleason 7 score prostate cancer primary Gleason grade 3 and 4 cancers are different in pathological parameters and prognosis. However, primary Gleason grade does not provide any additional information than other known prognostic factors, such as preoperative PSA, seminal vesicle invasion and DNA ploidy.     

PSA decline is an independent prognostic marker in hormonally treated prostate cancer.

OBJECTIVE: The aim of this study was to estimate the prevalence of primary hormone-refractory prostate cancer and to evaluate the prognostic value of decline of prostate-specific antigen (PSA) after primary hormonal therapy. MATERIAL AND METHODS: The material consisted of 236 consecutive, hormonally treated prostate cancer patients, whose clinicopathological findings, as well as serum PSA values, were retrieved from patient files. Multivariate analysis was performed based on the PSA decline at 12 months from the commencement of therapy and patients were thereafter categorised into four groups: complete response (CR), partial response (PR), stable disease (SD), and no response (NR) according to the biochemical response. RESULTS: Only 14 (5.9%) of the patients were included in the NR group, i.e. PSA declined less than 50%, suggesting that primary androgen-independent prostate cancer is uncommon. The PSA decline was significantly (p < 0.001) associated with cancer-specific survival. Patients with CR had a median survival of more than 6 years, whereas those with NR had a median survival of only 14 months. In multivariate analysis, PSA decline showed independent prognostic value together with M-stage and histological grade. CONCLUSIONS: Primary prostate cancer is probably even more sensitive to hormonal treatment than previously assumed, and PSA decline seems to be useful in predicting disease outcome after hormonal therapy.     

Tumor angiogenesis is associated with progression after radical prostatectomy in pT2/pT3 prostate cancer

BACKGROUND: The clinical relevance of tumor angiogenesis has been investigated in several human tumor types. Angiogenesis (measured as microvessel density; MVD) was recently correlated with tumor stage, grade, and clinical course in prostate cancer (PC). However, considerable controversy remains concerning the prognostic value of angiogenesis in PC. METHODS: We examined MVD in primary PCs to further establish the prognostic relevance of angiogenesis in this tumor entity. In 98 paraffin-embedded PCs of various stages, 5 prostate adenomas, and 20 normal prostate tissues, MVD was determined immunohistochemically using a polyclonal antibody against factor VIII. The findings were correlated with the clinical data of the patients. RESULTS: Normal prostate tissue and prostate adenomas had a low MVD. In PC, MVD increased significantly with tumor stage and grade (P < 0.001). The Wilcoxon rank statistics showed significant differences for MVD (P < 0.0001), tumor stage (P < 0. 0027), and grade (P < 0.0001), but not for preoperative prostate-specific antigen values in PC patients with and without tumor progression subsequent to treatment, respectively. Importantly, multivariate survival analysis revealed that MVD and tumor grade were the only independent markers for progression in prostate carcinoma. CONCLUSIONS: In this study, tumor angiogenesis measured by MVD was associated with a dismal pathologic appearance and a negative clinical prognosis in PC after radical prostatectomy.     

Percentage of cancer in prostate biopsies as prognostic factor for staging and postoperative biochemical failure after radical prostatectomy

OBJECTIVE: To assess if the percentage of cancer in prostate needle biopsies provides independent prognostic information for predicting pathological stage and/or biochemical relapse after radical prostatectomy. METHODS: One hundred and forty prostate cancer patients who underwent radical prostatectomy were evaluated. Preoperative parameters analyzed were patient age, PSA, clinical stage, and the information obtained from sextant biopsies (Gleason score, maximum percentage of cancer in a core, percentage of tissue with cancer in all biopsies and the number of cores positive for cancer). Univariate and multivariate analyses (logistic regression) for the dependent variables (prostate cancer, organ-confined and biochemical relapse) were performed. RESULTS: The tumor was organ-confined in 73.6% of patients. In those patients studied for disease progression (n = 126), no biochemical recurrence was observed in 76.2%. In the multivariate analysis for organ-confined disease, the total percentage of biopsy tissue with cancer, the preoperative PSA level, the Gleason score and the clinical stage were the most accurate predictive factors of pathological stage. The multivariate analysis for the study of biochemical failure indicated that only the total percentage of biopsy tissue with cancer, the preoperative PSA level and the Gleason score were independent predictive factors. According to the logistic regression analysis for disease recurrence, 3 risk groups could be identified: low risk (less than 10% probability of disease progression), intermediate risk (30%) and high risk (more than 70%). CONCLUSIONS: The percentage of cancer in prostate biopsy provides independent prognostic information for predicting pathological stage and the risk of biochemical failure after radical prostatectomy.