Should a positive surgical margin following radical prostatectomy be pathological stage T2 or T3? Results from the SEARCH database

PURPOSE: The finding of a positive surgical margin associated with extracapsular extension at radical prostatectomy is a poor prognostic factor. However, whether a positive surgical margin with no documented extracapsular extension portends a similarly poor prognosis is unclear. We examined the significance of the pathological features of positive surgical margin and extracapsular extension for predicting biochemical failure following radical prostatectomy. MATERIALS AND METHODS: We examined data on 1,621 men from the SEARCH Database of patients treated with radical prostatectomy without lymph node metastasis. Patients were separated into 5 groups based on the pathological findings of positive surgical margin, extracapsular extension, and/or seminal vesicle invasion. Preoperative clinical variables were compared across the groups and the groups were compared for time to biochemical recurrence using Cox proportional hazards analysis. RESULTS: Men with seminal vesicle invasion had the highest prostate specific antigen (PSA) recurrence rates, while men with a negative surgical margin and no extracapsular extension had the lowest PSA recurrence rates. There were no differences in PSA failure rates between men with a positive surgical margin and no extracapsular extension versus men with a negative surgical margin and extracapsular extension versus men with extracapsular extension and a positive surgical margin. In this subset of patients with a positive surgical margin and/or extracapsular extension but no seminal vesicle invasion only serum PSA was a significant independent predictor of biochemical recurrence. CONCLUSIONS: Men with a positive surgical margin but no extracapsular extension had PSA recurrence rates similar to those in men with extracapsular extension with or without positive margins. Men with extracapsular extension had similar biochemical recurrence rates whether the surgical margin was positive or negative. If confirmed at other institutions, consideration should be given to modifying the current TNM staging system to reflect these findings.     

Surgical volume is related to the rate of positive surgical margins at radical prostatectomy in European patients

OBJECTIVE: To assess the association between surgical volume (SV) and the rate of positive surgical margins (PSM) after radical prostatectomy (RP) in a large single-institution European cohort of patients. PATIENTS AND METHODS: In all, 2402 men had a RP by a group of 11 surgeons, all of whom were trained by the surgeon with the highest SV; all surgeons used the same surgical technique. Variables assessed before RP were prostate-specific antigen (PSA) level, clinical stage and biopsy Gleason sum; variables assessed after RP were PSA level, extracapsular extension, seminal vesicle invasion, lymph node invasion and pathological Gleason sum. These were used to predict the rate of PSM in models before or after RP. Multivariate models were complemented with SV to test its independent and multivariate statistical significance and to quantify its impact on the model's overall (and 200 bootstrap-corrected) predictive accuracy. RESULTS: The mean (range) SV was 201 (1-1293) RPs; the mean (median, range) rate of PSM was 20.2 (21.4, 0-32.9)%. In multivariate models, SV was a highly statistically significant independent predictor of PSM (P < 0.001) and increased the predictive accuracy in multivariate models both before (2.0%) and after RP (1.5%, both P < 0.001). However, when the surgeon with the highest SV, who contributed to 1293 cases, was removed from the analyses, the multivariate independent prediction and the gains in predictive accuracy related to adding SV, disappeared in the models both before (P = 0.9, accuracy gain 0.1%) and after (P = 0.4, accuracy gain - 0.3%) RP. CONCLUSIONS: These results indicate that patients treated by surgeons with a very high volume can expect to have a significantly lower rate of PSM, after accounting for clinical and pathological case-mix differences. However, SV is not a predictor of PSM when analyses are restricted to intermediate- and low-volume surgeons.     

A low incidence of positive surgical margins in prostate cancer at high risk of extracapsular extension after a modified anterograde radical prostatectomy

OBJECTIVES: To evaluate the incidence of positive surgical margins (and associated risk factors) in patients with localized prostate cancer at high preoperative risk of extracapsular disease treated using a modified anterograde radical retropubic prostatectomy technique. Positive surgical margins are an important risk factor for disease recurrence after radical prostatectomy, particularly in patients with extracapsular disease. PATIENTS AND METHODS: In total, 84 patients with clinically localized prostate cancer and a preoperative prostate-specific antigen (PSA) level > 10 ng/mL and/or a biopsy Gleason score > or = 7 were evaluated. The surgical technique allows easy, wide resection of the posterolateral prostatic pedicles, and good mobilization and exposure of the apex before the urethra transection. Prostatectomy specimens were examined for extracapsular tumour spread and positive surgical margins. Differences in putative risk factors (Gleason score, preoperative PSA level, prostate weight) between the positive- and negative-margin groups were evaluated using the Mann-Whitney test. RESULTS: Overall, 11 of the 84 (13%) patients had positive surgical margins and of these a single site was involved in six. In total, 15 positive-margin sites were identified (five apical, four basal, three posterolateral, two anterior and one posterior). All patients with positive margins had histological extracapsular disease. The preoperative PSA level and Gleason score were significantly higher in the positive- than in the negative-margin group (P = 0.025 and 0.035, respectively). CONCLUSIONS: The anterograde radical prostatectomy minimizes the incidence of positive surgical margins in patients at high risk of extracapsular disease.     

Radical prostatectomy with bladder neck preservation: impact of a positive margin

PURPOSE: Bladder neck preservation during radical prostatectomy has been correlated with improved continence. However, the hazard of a positive margin at this specific site has discouraged many urologists. We evaluated if preservation of the bladder neck at the time of radical prostatectomy jeopardizes surgical cancer control with consequent deleterious outcomes. MATERIALS AND METHODS: 675 consecutive patients underwent radical prostatectomy (RP) by a single surgeon (J.E.P.) at Wayne State University during the 1990s decade. The bladder neck was preserved. Margin-positivity was categorized by location and number. Preoperative, pathological and disease status data was prospectively collected into the Karmanos Cancer Institute multidisciplinary prostate cancer database. RESULTS: Analysis was performed on 555 patients who had RP as monotherapy. Positive margins were found in 178 (32%) of these patients. Correlation between specimen Gleason score, prostatic specific antigen (PSA) and margin status, was encountered (p=0.001). Apical and bladder neck margin-positivity was detected in 104/555 (19%) and 13/555 (2%), respectively. Of those specimens with a positive margin at the bladder neck eight had Gleason score > or =7, three had seminal vesicle invasion and two nodal disease. Only two patients had a positive bladder neck margin as the sole adverse pathological feature. Significant independent predictors of survival included the Gleason score, PSA, pathological stage and presence of positive margins in more than one location. CONCLUSIONS: Anatomical preservation of the bladder neck does not increase the percentage of positive margins at this anatomical location and does not compromise disease-free survival.     

Prostate specific antigen recurrence rates are low after radical retropubic prostatectomy and positive margins

PURPOSE: Treatment in patients with a positive surgical margin after radical retropubic prostatectomy is controversial. Options are observation, radiation therapy and early hormone therapy. Making the appropriate choice should be based on an understanding of the risk of recurrence without treatment. MATERIALS AND METHODS: We reviewed the records of 1,383 patients after radical retropubic prostatectomy was performed by a single surgeon. All specimens were analyzed by a single pathologist. Of the patients 936 met criteria for analysis. RESULTS: Mean followup in these 936 patients was 45.8 months (minimum 12). The overall PSA biochemical recurrence rate was 11.5% (108 of 936 cases). Of the 936 patients 350 (37%) had tumor at an inked margin. These patients had a recurrence rate of 19% (67 of 350), while patients with negative margins had a recurrence rate of 7% (41 of 586). This difference was statistically significant (p <0.01). Multivariate HR analysis revealed that significant risk factors for recurrence in the 936 patients were PSA greater than 20 ng/ml, clinical stage T2 or greater, Gleason 7 or greater, seminal vesicle involvement, extraprostatic extension, a visual estimate of prostate cancer volume of greater than 9.1% and positive surgical margins. Statistically significant risk factors for recurrence in patients with a positive margin on multivariate HR analysis were PSA greater than 20 ng/ml, Gleason score 7 or greater and seminal vesicle involvement. CONCLUSIONS: Although the positive margin rate in this series was 37%, the recurrence rate in these patients was only 19%. It is important to consider other factors, such as PSA, Gleason score, seminal vesicle involvement and extraprostatic extension, when making treatment decisions.     

Risk factors for positive surgical margins following radical prostatectomy: review

The presence of positive surgical margins on radical prostatectomy specimen is an adverse prognostic factor. Parameters supposed to influence surgical margin status includes pathology method analysis, surgical technique, tumoral and non tumoral patient parameters, and neoadjuvant hormonal therapy. Regarding the surgical technique, surgeon's experience and neuro-vascular bundles preservation are the most important factors of margin status, whereas surgical approach, bladder neck conservation, intraoperative frozen analysis, and bleeding are minor factors. Non tumoural patient parameters influencing surgical margin status include patient's age and weight, and prostate gland weight. For tumoural parameters, pathological stage and tumour volume are more important factors than the tumor grade and PSA. Five preoperative tumoral risk factors of positive surgical margins are particularly important, including abnormal digital rectal examination, preoperative PSA 10 ng/mL, biopsy Gleason score >7, number of positive biopsy cores > or = 2, and suspicion of extraprostatic extension on radical prostatectomy specimen.     

Perineural invasion is a prognostic factor for biochemical failure after radical prostatectomy

Objectives:   To identify the prognostic significance of lymphovascular invasion (LVI) and perineural invasion (PNI) in patients undergoing radical prostatectomy for prostate cancer.
Methods:   Overall, 237 patients who had undergone radical prostatectomy for prostate cancer between 1995 and 2004 were analyzed for all clinical and pathological factors. The influence of these two pathological features on biochemical failure-free survival was evaluated by univariate and multivariate analysis.
Results:   Lymphovascular and perineural invasion were identified in 41 (17.2%) and 100 (42.0%) patients, respectively. LVI and PNI were significantly associated with the preoperative prostate-specific antigen (PSA) level, a higher PSA density, a higher pathological stage, a higher Gleason score, a higher frequency of extracapsular extension, a higher frequency of seminal vesicle invasion, and a higher frequency of a positive resection margin. Positive resection margins ( P  = 0.001) and perineural invasion ( P  = 0.011) were identified as independent factors associated with biochemical failure-free survival by the multivariate analysis.
Conclusions:   In this series, PNI was associated with established parameters of biologically aggressive disease, and was an important prognostic factor for biochemical failure-free survival in patients undergoing radical prostatectomy. This finding supports routine evaluation of the PNI status in radical prostatectomy specimens and suggests that patients with PNI should be more closely followed after surgery.     

Preoperative serum prostate specific antigen does not reflect biochemical failure rates after radical prostatectomy in men with large volume cancers

PURPOSE: We compared pathological findings with prostate specific antigen (PSA) failure rates following radical prostatectomy for large volume cancers (6 cc or greater). MATERIALS AND METHODS: A total of 191 men whose radical prostatectomy specimen had a cancer volume of 6 cc or greater were followed for a mean of 3.6 years (range 0.3 to 11.1) and 112 (58.6%) had PSA failure (PSA 0.07 ng./ml. or greater and increasing). Percent Gleason grade 4/5 (the Stanford modified Gleason scale), cancer volume, seminal vesicle invasion, regional lymph nodes, capsular penetration, positive surgical margin, location of the largest cancer in the peripheral or transition zone, prostate weight, patient age, preoperative PSA and clinical stage were analyzed using univariate and multivariate Cox proportional hazards analyses. RESULTS: In univariate regression analysis percent Gleason grade 4/5, lymph node involvement, cancer volume, cancer location in the peripheral zone, capsular penetration and positive surgical margins were significant predictors of biochemical failure. Seminal vesicle invasion, preoperative serum PSA, patient age, prostate weight and clinical stage were not statistically significant. Forward stepwise, multivariate analysis showed that percent Gleason grade 4/5 (p <0.0001, relative risk ratio 2.498), cancer location in the peripheral zone (p = 0.0097, 1.887), cancer volume (p = 0.0157, 1.691) and lymph node involvement (p = 0.0317, 1. 666) were the only independent predictors of biochemical failure. When 52 men with organ confined, large volume prostate cancer were analyzed separately, univariate and multivariate analyses showed that only cancer location in the peripheral zone (p = 0.0021, relative risk ratio 13.473) and percent Gleason grade 4/5 (p = 0. 0449, 4.111) were independent predictors of failure. CONCLUSIONS: Percent Gleason grade 4/5, cancer location in the peripheral zone, cancer volume and lymph node involvement have prognostic value in large volume prostate cancer. Cancer location in the peripheral zone and percent Gleason grade 4/5 are the most powerful predictors of biochemical failure in men whose cancer is 6 cc or greater and contained in the prostatic capsule. Preoperative serum PSA is not helpful in distinguishing biochemical failure rates in these large volume cancers whether they are organ confined or not.     

Prognostic role of perineural invasion in prostate biopsy

IntroductionDespite tumour cell dissemination through the intraprostatic nervous system being considered as a prostate cancer progression mechanism, the significance of perineural invasion in prostate biopsies to predict extraprostatic extension and its use as a potential prognosis factor is controversial.Materials and methodsRetrospective study carried out at an institution on 208 patients treated with radical prostatectomy (January 2007 - July 2010) in which the presence of perineural invasion and the Gleason score in the preoperative biopsy were determined, as well as the clinical stage and the pre-surgery PSA. We classified the patients in risk groups in accordance with the D’Amico classification. We performed bivariate and multivariate statistical analyses to establish the correlations between the different variables.ResultsWe objectified PNI in 18.3% of the prostate biopsies. 71% of the prostatectomy specimens with perineural invasion presented extraprostatic extension in the previous biopsy against 23.1% when this was not found (p < 0.0001) and 47% of the cases showed positive margins with PNI, against 18.3% without perineural invasion (p < 0.0001). In fact, in the multivariate analysis, perineural invasion proved to be an independent risk factor in the presentation of extraprostatic extension and positive margins in the prostatectomy specimen.ConclusionsThe presence of perineural invasion is a useful prognostic factor for predicting extraprostatic extension and the involvement of surgical margin in the radical prostatectomy specimen. We believe that determining it may be a useful tool for improving preoperative diagnosis and planning treatment.     

Serum prostate-specific antigen value adjusted for non-cancerous prostate tissue volume in patients undergoing radical prostatectomy: a new predictor of biochemical recurrence in localized or locally advanced prostate cancer

The aim of this study was to investigate the significance of serum prostate-specific antigen (PSA) value adjusted for total tumor volume (PSA/tumor volume) and serum PSA value adjusted for non-cancerous prostate tissue volume (NCPV) (PSA/NCPV) as a predictor of pathological findings and clinical outcome after radical prostatectomy. Clinical and pathological data of 407 patients (median age: 66.5 years; range: 41.8-85.7 years) were reviewed retrospectively. The median follow-up period was 18.1 months (range: 1.0-107.8 months). Biochemical recurrence was defined as detectable PSA levels (greater than 0.2 ng ml(-1)) and the time of biochemical recurrence was taken to be the first time PSA became detectable. In the multivariate model, PSA/NCPV was an independent predictor of extracapsular extension and positive surgical margin (P<0.05), but PSA/tumor volume was not. Kaplan-Meier curves revealed that PSA/NCPV correlated with biochemical recurrence-free survival (P<0.001; log-rank test) but PSA/tumor volume did not (P=0.275; log-rank test). PSA/NCPV was also a significant independent prognostic factor for biochemical recurrence-free survival on multivariate Cox proportional hazard analysis (P=0.004, relative risk=2.42). Our findings suggest that PSA/NCPV is associated independently with extracapsular extension and surgical margin status and may be an independent prognostic variable of PSA recurrence after radical prostatectomy.     

腹腔镜根治性前列腺切除术后切缘阳性的相关因素分析

目的：分析腹腔镜根治性前列腺切除术后切缘阳性的相关因素。方法：2004年1月～2010年12月,我院完成腹腔镜根治性前列腺切除术188例,平均年龄72岁。患者根治术前均经病理检查确诊为前列腺癌,未发现肿瘤转移征象。采用单因素分析研究各参数对切缘情况的影响,采用多因素Logistic回归分析确定切缘阳性的独立危险因素。结果：除2例患者中转开放手术外,其余患者均在腹腔镜下完成手术。平均手术时间246min,平均出血量309ml。术后病理回报切缘阳性76例,占40．5％。单因素分析提示切缘阳性组与切缘阴性组穿刺Gleason评分、穿刺阳性针数、根治病理Gleason评分、病理分期差异有统计学意义（P〈0．05）。多因素Logistic回归分析显示根治标本Gleason评分、病理分期是切缘阳性的独立相关因素。根治标本Gleason评分8分相对于Gleason评分6分患者切缘阳性风险增高17．1倍（比值比为17．131,95％置信区间为5．237～56．037,P〈0．001）,病理分期T1期相对于T2期患者切缘阳性风险增高9．0倍（比值比为8．970,95％置信区间为4．128～19．493,P〈0．001）。结论：根治标本Gleason评分、病理分期是腹腔镜根治性前列腺切除术后切缘阳性独立危险因素。根治标本Gleason评分为8分、病理分期为T3期患者的切缘阳性率显著增高。     

The extent of biopsy involvement as an independent predictor of extraprostatic extension and surgical margin status in low risk prostate cancer: implications for treatment selection

PURPOSE: We identify predictors of extraprostatic extension and positive surgical margins in patients with low risk prostate cancer (prostate specific antigen [PSA] 10 ng./ml. or less, biopsy Gleason score 7 or less and clinical stage T1c-2b). MATERIALS AND METHODS: From August 1997 to January 1999, 143 previously untreated patients underwent radical retropubic prostatectomy for clinically localized prostate cancer. A total of 62 patients were low risk, with PSA 10 ng./ml. or less, biopsy Gleason score 7 or less and clinical stage T1c-2b, and had sextant biopsy with separate pathological evaluation of each sextant cores. PSA, clinical stage, biopsy Gleason score, average percentage of cancer in the entire biopsy specimen, maximum percentage of cancer on the most involved core, number of cores involved and bilaterality were evaluated for association with extraprostatic extension, seminal vesicle involvement and positive surgical margins. RESULTS: Of the 62 patients 13 (21%) had extraprostatic extension, 6 (10%) seminal vesicle involvement and 20 (32%) positive surgical margins. Average percentage greater than 10% and maximum percentage greater than 25% were associated with extraprostatic extension (p = 0.01 and 0.004, respectively). Average percentage greater than 10%, maximum percentage greater than 25%, more than 2 cores involved and bilaterality were associated with positive surgical margins (p = 0.007, 0.01, 0.002 and 0.03, respectively). On multivariate analysis maximum percentage remained the only independent predictor of extraprostatic extension (p = 0.03), and the number of cores involved remained an independent predictor of positive surgical margins (p = 0.01). Biopsy Gleason score, PSA and clinical stage did not correlate with extraprostatic extension or positive surgical margins in this patient population. CONCLUSIONS: In low risk prostate cancer the extent of biopsy involvement significantly correlates with the risk of extraprostatic extension and positive surgical margins. Biopsy information should be considered when selecting and modifying treatment modalities.     

Prognostic implications of positive margins in radical prostatectomy specimens

To evaluate the histopathologic implication of positive margins of prostatectomy specimens in the biochemical recurrenceMatherial and methodsThe study group consisted of 290 patients with clinically localized prostate cancer who were treated by radical retropubic prostatectomy. Patients with neoadjuvant hormonal therapy and positive lymph nodes were excluded. The mean age at the time of surgery was 63 years (range 47-73); 166 (57.2%) patients were T1c and 124 (42.8%) T2; the average time of folow-up was of 4 years (range 1-12). Positive surgical margins were defined as the presence of cancer cells at the surface inked of prostatectomy specimens. They were classified as: Margin for capsular incision (without extraprostatic extension evidence)/ margin for extraprostatic extension, margin with smooth rounded surface/margin with irregular surface, margin ≤4 mm/margin >4 mm, unifocal margin/multifocal margin. We define biochemical recurrence if the PSA exceeds 0.20 ng/ml in two consecutive determinationsResultsThe overall rate of positive margins was 65/290 (22.4%). The 5-year survival free of biochemical recurrence was as follows: Negative margins 71% vs positive margins 44% (p<0.001); positive margins for capsular incision 84% vs positive margins for extraprostatic extension 33% (p<0.01); positive margins with smooth rounded surface 58% vs positive margins with irregular surface 26% (p<0.01); positive margins ≤4 mm 57% vs positive margins >4 mm 32% (p<0.05); unifocal margins 53% vs multifocal margins 0% (p<0.01). The multivariate analysis revealed that preoperative PSA, Gleason score and pathological classification were the best predictors of biochemical recurrenceConclusionsTwo groups are established of positive margin. The first group with high probability of biochemical recurrence: margin for extraprostatic. The second group with less probability of biochemical recurrence: margin for capsular incision, margin with smooth rounded surface, margin ≤4 mm and unifocal margin     

Pathological features of Gleason score 6 prostate cancers in the low and intermediate range of prostate‐specific antigen level: is there a difference?

OBJECTIVE

To assess the pathological features of Gleason score 6 prostate cancers after radical prostatectomy in the low (<4 ng/mL) and intermediate range of prostate‐specific antigen level (4–10 ng/mL), as such prostate cancers are considered to be well differentiated tumours with a low risk for recurrence after therapy.

PATIENTS AND METHODS

In all, 1354 patients with T1c prostate cancer and PSA levels of <10.0 ng/mL had a radical retropubic prostatectomy. Patients with Gleason score 6 tumours were divided into two groups, those with PSA levels of <4 and 4.0–10.0 ng/mL. Extracapsular extension, positive surgical margins, biochemical recurrence (BCR) and mean time to BCR were evaluated.

RESULTS

Of the 1354 patients, there were 437 (32.3%) with Gleason score 6 prostate cancers. Patients in the low PSA group had less extraprostatic disease than those with a higher level (5.9% vs 14.5%) and both groups had an almost equal proportion of positive surgical margins (9.4% vs 11.0%). In the low PSA group there was statistically significantly shorter BCR than in the high PSA group, with a mean time to BCR of 1.7 vs 3.1 years.

CONCLUSIONS

These results show a statistically significantly higher rate of extraprostatic disease and earlier BCR in men with a high than a low PSA level even in Gleason score 6 prostate cancer. As the rate of BCR and extracapsular extension are significantly related to prostate cancer mortality, these findings further support the concept of screening using low PSA levels.     

Perineural invasion as a predictor of biochemical outcome following radical prostatectomy for select men with clinically localized prostate cancer

PURPOSE: The presence of perineural invasion on the prostate needle biopsy specimen has been suggested to be an independent predictor of prostate specific antigen (PSA) outcome following radical prostatectomy. We evaluated the clinical use of perineural invasion at biopsy for predicting time to PSA failure following radical prostatectomy after controlling for established prognostic factors. MATERIALS AND METHODS: A prospective evaluation using a Cox regression multivariate analysis of 750 men with clinically localized or PSA detected prostate cancer was performed to evaluate the ability of PSA, biopsy Gleason score, perineural invasion on the needle biopsy specimen and the percent of positive prostate biopsies to predict PSA outcome following radical prostatectomy. RESULTS: Multivariate analysis demonstrated that the presence of perineural invasion on the needle biopsy specimen provided additional information regarding 5-year PSA outcome (82% versus 95%, p = 0.04) for patients who were in the low risk group. This difference in PSA outcome could be explained by higher rates of positive surgical margins (25% versus 17%, p = 0.07). Patients whose prostate needle biopsy contained perineural invasion and who had the corresponding neurovascular bundle resected had a significantly lower positive margin rate (11% versus 100%, p = 0.001) compared to those who had the neurovascular bundle spared. The presence of perineural invasion on biopsy was not a significant predictor of PSA outcome following radical prostatectomy for patients in the intermediate or high risk group. CONCLUSIONS: Resection of the neurovascular bundle on the side corresponding to location of perineural invasion on the biopsy may decrease the positive surgical margin rate and improve outcome for low risk patients.     

FAMILIAL PROSTATE CANCER: A DIFFERENT DISEASE?

Purpose

We analyzed the outcome after radical prostatectomy of patients with familial prostate cancer versus patients with sporadic prostate cancer.

Materials and Methods

The study included 720 patients with prostate carcinoma who were treated with prostatectomy between 1987 and 1996. Patients were excluded from the study if they had received adjuvant or neoadjuvant treatment, or had no available pretreatment prostatic specific antigen (PSA) level, no available biopsy Gleason score, incomplete pathological information or no available followup PSA levels. The analysis was performed on 529 cases. Patients were considered to have a positive family history for prostate cancer when the index patient confirmed the diagnosis of prostate cancer in a first degree relative (brother or father). The outcomes of interest were biochemical relapse-free survival, local failure and distant metastases. Proportional hazards were used to analyze the effect of family history and confounding variables (that is age, stage, biopsy Gleason score, initial PSA levels, surgical specimen Gleason score, extracapsular extension, lymph node metastasis, seminal vesicle invasion and surgical margin involvement) on treatment outcome.

Results

Median followup was 30 months. Of all cases 12% had a positive family history. Younger age was the only factor associated with positive family history, with 18% of patients younger than 65 years having a positive family history versus 6% of older patients (chi-square p <0.001). The 5-year biochemical relapse-free survival rate for the entire group was 64%. The 5-year biochemical relapse-free survival rates for patients with negative family history versus positive history were 66% and 46%, respectively (p = 0.001). A multivariate time-to-failure analysis using the proportional hazards model was performed based on family history, age (less than 65 versus 65 to 69 versus 70 or greater, initial PSA (10 or less versus greater than 10), biopsy Gleason score (6 or less versus 7 or greater), clinical T stage (T1-T2 versus T2B-C), prostatectomy specimen Gleason score (6 or less versus 7 or greater), extracapsular extension, seminal vesicle involvement, surgical margin involvement and lymph node involvement. After adjusting for the potential confounding factors, positive family history remained strongly associated with biochemical failure. The clinical failure rate for the entire group was 14%. The 5-year local failure rate was 7%, with positive surgical margins being the only independent predictor of local failure. The 5-year distant metastasis rate was 8%, with family history and initial PSA levels being independent predictors of distant relapse.

Conclusions

Our study suggests that patients with a familial prostate cancer have a higher likelihood of biochemical failure after radical prostatectomy than patients with sporadic cancer. This effect is independent of pretreatment or pathological factors. Our results suggest that the higher failure rates associated with familial prostate cancer are mainly secondary to higher distant relapse rates, and that familial prostate cancer may be more biologically aggressive than sporadic cancers.     

Role of radical prostatectomy in patients with prostate cancer of high Gleason score

BACKGROUND: The routine use of serum prostate-specific antigen (PSA) testing combined with digital rectal examination has lowered tumor volume and clinical-pathological stage of men undergoing radical prostatectomy. Therefore, we may identify more men with poorly differentiated tumors of early clinical stage. In order to identify those who may benefit from radical prostatectomy, we evaluated known prognostic variables in patients with prostate cancer of high Gleason score (8-10). METHODS: Of 652 patients who underwent a radical prostatectomy as monotherapy for clinically localized prostate cancer between March 1991-December 1995, 84 patients with prostatectomy specimen Gleason score 8-10 tumors were identified. Clinical-pathological data were obtained from our prostate cancer database. Gleason score, PSA level, margin status, pathologic stage, and tumor volume were analyzed as general prognostic variables for disease-free survival (DFS). Follow-up ranged from 13-84 months (median, 36.2). Biochemical recurrence was defined as a postoperative PSA elevation greater than 0.4 ng/ml. RESULTS: The DFS for patients with Gleason score 8-10 and pathologically organ-confined disease was 62.5%. DFS was 56.2% for patients with PSA < or =10 ng/ml, compared to 19.2% for patients with serum PSA >10 ng/ml (P = 0.009). Patients with nonspecimen-confined disease (positive margins) had a DFS rate of 26.6% vs. 55% for patients with specimen-confined disease (negative margins) (P = 0.009). On multivariable analysis, only preoperative PSA < or =10 ng/ml (P = 0.02) and surgical margin status (P = 0.04) were significant predictors of DFS. CONCLUSIONS: Surgical margin status and preoperative serum PSA level are independent predictors of DFS for patients with high Gleason score prostate cancer treated by radical prostatectomy as monotherapy. Patients with poorly differentiated prostate cancer treated surgically at an early stage can have a favorable prognosis, especially if negative surgical margins are obtained. A preoperative serum PSA level < or =10 ng/ml carries the greatest likelihood of achieving prolonged DFS in this group of patients.     

Long-term benefits of elective radiotherapy after prostatectomy for patients with positive surgical margins

PURPOSE: The benefit of adjuvant radiotherapy after prostatectomy for patients with pathological risk factors but with an undetectable postoperative PSA remains controversial. In this retrospective study we define the benefits of elective postoperative radiotherapy in this setting. MATERIALS AND METHODS: A total of 44 patients received elective postoperative radiotherapy at a single institution in the PSA era (1989 to 1995) for positive surgical margins and undetectable postoperative PSA. Radiotherapy was delivered to a median dose of 60 Gy. Clinical target volume included the prostate bed. Pelvic nodes were not treated. The four-field box technique with customized blocking of bladder, rectum and small bowels was used and defined the planning target volume. The patients were then compared to a contemporaneous group of 189 patients with positive surgical margins who underwent radical prostatectomy without any adjuvant therapy. Failure was defined as biochemical (PSA) recurrence and was timed from first detectable PSA. RESULTS: The 5 and 10-year biochemical no evidence of disease was 90.9% and 90.9% for the elective postoperative radiotherapy group, and 66.4% and 54.5% for the observation group, respectively (p = 0.0012). Median time to biochemical failure was also longer in the elective postoperative radiotherapy group (88.6 months) compared to the observation group (43.5 months) (p <0.001). Risk factors for biochemical recurrence on multivariate analysis were Gleason score greater than 7 (p = 0.017), established extracapsular extension (p = 0.002) and lack of elective postoperative radiation (p = 0.001). CONCLUSIONS: This is one of the longest followup studies showing that elective postoperative radiation therapy is associated with improved bNED and prolonged time to recurrence. Combined radical prostatectomy and elective postoperative radiotherapy should be considered in the management of high risk prostate cancer, especially in the presence of positive surgical margins despite undetectable PSA.     

Prognostic significance of tumor volume after radical prostatectomy: a multivariate analysis of pathological prognostic factors

OBJECTIVES: To analyze the association between Gleason score, stage and status of surgical margins with tumor volume in prostate cancer progression after radical prostatectomy. METHODS: 200 consecutive radical prostatectomy specimens were analyzed. Preoperative clinical stage, PSA, results of prostate biopsies as well as pathological results were noted. A biochemical recurrence was defined as a single, postoperative detectable PSA level (>0.2 ng/ml). Tumor volume was compared to postoperative staging, Gleason score, and surgical margin status to predict tumor progression. Univariate and multivariate analysis using stepwise logistic regression were used to identify parameters with additional prognostic value. RESULTS: Pathological results of the prostatectomy specimens showed 149 (74.5%) pT2a-b, 29 (14.5%) pT3a and 22 (11%) pT3b tumors. Tumor volume was 0.57 cc for pT2a, 1.2cc for pT2b, 1.7cc for pT3a and 2.9cc for pT3b, respectively (p<0.05). Taken together, mean volume for pT2 and pT3 were 1.06 and 2.2 cc, respectively (p<0.0001). Five-year progression-free actuarial survival was 69.7%. Using univariate analysis, tumor progression correlated with final Gleason score (p<0.0007), positive surgical margins (p=0.02), tumor volume (p=0.009) and stage (p<0.0001). In a multivariate analysis, tumor progression correlated only with the final Gleason score (p=0.04) and stage (p=0.0002). CONCLUSION: Gleason score and pathological stage are independent factors to predict prostate cancer progression after radical prostatectomy. When these parameters are known, tumor volume does not provide additional information.     

PSA density is superior than PSA and Gleason score for adverse pathologic features prediction in patients with clinically localized prostate cancer

Introduction:

Prostate-specific antigen (PSA) and its kinetics have changed prostate cancer screening and diagnosis. The aim of the present study was to evaluate their value in prostate cancer prognosis by determining the predictive potential of PSA density for adverse pathologic features after radical prostatectomy, in terms of positive surgical margins (PSM), extracapsular disease (ECD), seminal vesicle invasion (SVI) and/or lymph node invasion (LNI), and to compare their predictive ability with preoperative PSA and biopsy Gleason score.

Methods:

We retrospectively analysed 285 patients diagnosed with prostate cancer and underwent a retropubic radical prostatectomy for clinically localized disease. Data concerning preoperative PSA, biopsy Gleason score and PSA density were collected and analyzed. PSA density was calculated by dividing preoperative PSA and the pathological volume of the prostate.

Results:

There was a significant difference in PSA density values between patients with PSM, ECD, SVI and LNI. Areas under the curve for PSA density were higher than those of PSA and Gleason score for all parameters of adverse pathology. In multivariate analyses, it was shown that PSA density and Gleason score were the only statistically significant predictors for PSM and ECD, PSA density and PSA for SVI and only PSA density for LNI.

Conclusion:

PSA density is an accurate predictor for adverse pathology prediction in patients undergoing radical prostatectomy. These results demonstrate that this parameter is useful to determine the aggressiveness of prostate cancer and can be used as an adjunct in predicting outcomes after surgery.