Bladder neck involvement in pathological stage pT4 radical prostatectomy specimens is not an independent prognostic factor

PURPOSE: Bladder neck invasion by prostate cancer in radical prostatectomy specimens is uncommon and, thus, its influence on disease recurrence has not been well defined. Consequently the classification of bladder neck invasion in the TNM staging system is controversial. We studied our cohort of patients with stage pT4 disease and bladder neck invasion to clarify the true clinical behavior and prognostic significance of bladder neck invasion in radical prostatectomy specimens. MATERIALS AND METHODS: The study group consisted of 4,090 consecutive patients treated with radical prostatectomy at one of our institutions between 1983 and 2001. Median followup was 53.1 months (range 1 to 189). After excluding from analysis patients treated with neoadjuvant androgen withdrawal or preoperative irradiation 72 of the remaining 2,571 (2.8%) with bladder neck invasion were classified with stage pT4 disease and their specimens were reviewed. Progression-free probability was determined by Kaplan-Meier analysis. Using the Cox proportional hazards model the independent prognostic significance of bladder neck invasion was assessed after controlling for pretreatment prostate specific antigen, final Gleason sum, extracapsular extension, surgical margins status, seminal vesicle invasion and lymph node involvement. RESULTS: Of the 72 patients categorized with stage pT4 disease 14 (19%) had poorly differentiated Gleason sum 8 to 10 cancer, 38 (53%) had established extracapsular extension, 24 (33%) had seminal vesicle invasion and 8 (11%) had lymph node involvement. However, 26 patients (36%) had cancer confined to the prostate and 28 (39%) had negative surgical margins except for the bladder neck site. The mean 5-year progression-free probability plus or minus SD in all stage pT4 cases was 68% +/- 7%, which was better than in cases of seminal vesicle invasion (52% +/- 5%, log rank test p = 0.0156) but worse than in those of extracapsular extension (84% +/- 4.1%). Univariate analysis of the stage pT4 cohort revealed that higher prostatectomy Gleason sum, more extensive extracapsular extension and seminal vesicle invasion were significantly associated with an adverse prognosis. However, in a multivariate model that included all radical prostatectomy cases the finding of bladder neck invasion or stage pT4 disease did not independently predict prostate specific antigen recurrence. CONCLUSIONS: Stage pT4 disease comprises a heterogeneous group of tumors with various pathological features and inconsistent outcomes. Assigning the pT4 stage to cases of microscopic bladder neck invasion provides no independent ability for predicting disease progression after adjusting for other adverse disease features. Due to this and previously reported data the definition of stage pT4 disease should be modified in the next version of the TNM staging system.     

Nondissection of pelvic lymph nodes does not influence the results of perineal radical prostatectomy in selected patients

OBJECTIVES: Retrospective studies have shown that pelvic lymph node dissection can be dispensed with in selected men undergoing radical prostatectomy. We prospectively evaluated the influence of nondissection of pelvic lymph nodes on tumor progression in our first 100 perineal prostatectomies. METHODS: From October 1992 to February 1998, 100 patients underwent radical perineal prostatectomy for localized prostate cancer. Preoperative PSA, the Gleason score of positive biopsies and age at surgery were noted. Forty-three of the 100 patients (group 1) did not undergo pelvic lymph node dissection because their preoperative PSA level was below 10 ng/ml (Hybritech assay, normal value 4 ng/ml) and the Gleason score of their positive biopsies was below 7. These 43 patients were compared with 25 of the 114 patients operated on during the same period by the retropubic approach and who had pelvic node dissection and the same preoperative criteria (PSA <10 ng/ml and a Gleason score of positive biopsies <7; group 2). All prostatectomy specimens were processed according to the Stanford protocol: prostate weight, Gleason score, capsular, seminal vesicle, lymph node and surgical margin status, and tumor volume were studied. Postoperative followup was based on routine serum PSA assays after 1 and 3 months and then half-yearly. Biological progression was defined as PSA level which was detectable postoperatively (>/=0.2 ng/ml). Kaplan-Meier analysis was used to evaluate the likelihood of biochemical recurrence. Results were compared by using Fisher's test, the Mann-Whitney test and the log-rank test. Differences were considered significant when the p value was <0.05. RESULTS: No differences in preoperative characteristics were observed; in groups 1 and 2, mean age was 65.9 and 64.7 years, PSA was 6.7 and 5.11 ng/ml, and the Gleason biopsy score was 5.7 vs. 5.0, respectively. In groups 1 and 2, specimen weight was 44.5 and 54.3 g (p = 0.04), the Gleason score was 6.2 and 5.6, tumor volume was 0.91 and 0.8 ml, 81.4 and 84% of patients were in stage pT2, 13.9 and 12% had extracapsular disease, 4.6 and 0% had seminal vesicle invasion, and 13.9 and 16% had positive surgical margins, respectively. The mean follow-up was 2.74 years (0.27-5.59 years). The actuarial 5-year recurrence-free rate was 78% in group 1 and 80% in group 2 (p>0.05). CONCLUSION: The lack of pelvic lymph node dissection does not influence the intermediate term results of perineal radical prostatectomy in selected patients (preoperative PSA <10 ng/ml and Gleason score for positive biopsies <7).     

The significance of microscopic bladder neck invasion in radical prostatectomies: pT4 disease?

Introduction  It is controversial whether microscopic invasion of the bladder neck (BN) has a high risk for biochemical progression following radical prostatectomy (RP). The tumor, node, and metastasis (TNM) classification for prostate cancer considers BN involvement to be pT4 disease, equivalent to rectal or external sphincter invasion, however, it does not specify whether the invasion is macroscopic or microscopic. Materials and methods  Clinicopathological findings were studied from 290 patients submitted to RP. The time to biochemical (prostate-specific antigen, PSA) progression-free outcome for patients with BN invasion was compared to patients with extraprostatic extension (EPE) or seminal vesicle invasion (SVI). A univariate Cox proportional hazards model was created and a final multivariate Cox proportional hazards model was developed to assess the influence of several variables simultaneously. Results  BN invasion was present in 55/290 (18.96%) surgical specimens and 18/290 (6.2%) also showed positive surgical margins. Patients with microscopic BN invasion had significantly higher preoperative PSA, higher Gleason score, higher apical and circumferential positive surgical margins, more advanced pathological stage, and more extensive tumors. At 5 years 42%, 40%, and 27% of the patients with BN invasion, extraprostatic extension (EPE), and seminal vesicle invasion (SVI), respectively, were free of biochemical recurrence following RP. In multivariate analysis, BN invasion did not contribute for a higher relative hazard of PSA recurrence when added to EPE or SVI. Conclusion  BN invasion is associated with adverse clinicopathological findings. However, the biochemical-free outcome following RP is similar to patients with EPE but significantly better than patients with SVI. The findings of this study do not favor considering microscopic bladder neck invasion as stage pT4 but, probably, stage pT3a.     

Prognostic indicators for long term outcome following radical retropubic prostatectomy for prostate cancer involving the seminal vesicles

Seminal vesicle involvement at the time of radical prostatectomy (RP) for prostate cancer has been equated with metastatic disease. We review our biochemical freedom from disease results following RP in patients with seminal vesicle involvement with particular attention to identifying variables that may be predictive of disease recurrence. We retrospectively reviewed our surgical database and identified patients with pT3b (2002 AJCC) prostate cancer at RP [corrected]. There were 70 cases without lymph node involvement and with available clinical follow-up identified. Any patient receiving androgen deprivation therapy, radiation therapy, or with a sustained PSA elevation greater than 0.2 ng/mL was considered a biochemical failure. Results were calculated using the Kaplan-Meier method. Mean age was 63.4 (range 45.7-79.5) years, mean preoperative PSA was 11.3 ng/mL (range 2-60), mean biopsy Gleason score was 7.2 (range 4-9), mean RP Gleason score was 7.5 (range 5-9), and median follow-up time was 61.5 months (range 2.3-160.6). Overall, 33/70 (47%) patients were without evidence of disease without further therapy. For patients with pT3bN0Mx prostate cancer, margin status, capsular invasion, and PSA were not statistically significant risk factors for disease progression. Gleason score and major Gleason grade were the only statistically significant variables that predicted disease progression. A specimen Gleason score of greater than 7 and major Gleason grades greater than 3 were associated with an increased rate of disease progression in this patient group.     

Complete embedding and close step-sectioning of radical prostatectomy specimens both increase detection of extra-prostatic extension,and correlate with increased disease-free survival by stage of prostate cancer patients

The objectives of this work were to evaluate the efficacy of controlled close step-sectioned and whole-mounted radical prostatectomy specimen processing in prediction of clinical outcome as compared to the traditional processing techniques. Two-hundred and forty nine radical prostatectomy (RP) specimens were whole-mounted and close step-sectioned at caliper-measured 2.2-2.3 mm intervals. A group of 682 radical prostatectomy specimens were partially sampled as control. The RPs were performed during 1993-1999 with a mean follow-up of 29.3 months, pretreatment PSA of 0.1-40, and biopsy Gleason sums of 5-8. Disease-free survival based on biochemical or clinical recurrence and secondary intervention were computed using a Kaplan-Meier analysis. There were no significant differences in age at diagnosis, age at surgery, PSA at diagnosis, or biopsy Gleason between the two groups (P<0.05). Compared with the non-close step-sectioned group, the close step-sectioned group showed higher detection rates of extra-prostatic extension (215 (34.1%) vs, 128 (55.4%), P<0.01), and seminal vesicle invasion (50 (7.6%) vs 35 (14.7%), P<0.01). The close step-sectioned group correlated with greater 3-y disease-free survival in organ-confined (P<0.01) and specimen-confined (P<0.01) cases, over the non-uniform group. The close step-sectioned group showed significantly higher disease-free survival for cases with seminal vesicle invasion (P=0.046). No significant difference in disease-free survival was found for the positive margin group (P=0.39) between the close step-sectioned and non-uniform groups. The close step-sectioned technique correlates with increased disease-free survival rates for organ and specimen confined cases, possibly due to higher detection rates of extra-prostatic extension and seminal vesicle invasion. Close step-sectioning provides better assurance of organ-confined disease, resulting in enhanced prediction of outcome by pathological (TNM) stage.     

Radical prostatectomy can provide a cure for well-selected clinical stage T3 prostate cancer

OBJECTIVE: Radical prostatectomy is commonly believed not to achieve the eradication of locally advanced disease. This retrospective study aimed to elucidate the role of radical prostatectomy in this condition. METHODS: A retrospective study of 158 patients surgically treated for clinical stage T3N0M0 prostate cancer was undertaken. Thirty patients had postoperative hormonal treatment, rendering prostate-specific antigen (PSA) follow-up unreliable, and were considered to be progressive at 1 month. Eighteen other patients received postoperative radiotherapy. One hundred and ten patients had radical prostatectomy only. PSA-relapse-free survival was analyzed. The mean follow-up time was 30 months. RESULTS: Seventy-nine percent of the resected specimens were pathologically T3 (pT3), and about 25% were pT3c. Thirteen percent were pT2 and 8% were pT4. Ninety-five specimens (60%) had positive surgical margins. There was poor accordance between the biopsy Gleason score and that of the specimen. A multivariate analysis showed that seminal vesicle and nodal invasion, margin status and a PSA level above 10 ng/ml were independent prognostic factors. In 47 cT3a patients with PSA <10 ng/ml, the PSA-free survival rate exceeded 70% at 24 months and the 5-year estimated PSA-free survival rate was more than 60%. CONCLUSIONS: Radical prostatectomy has a place in the treatment of clinical stage T3 prostate cancer patients with a PSA value lower than 10 ng/ml. There is a need to definitively rule out nodal or seminal vesicle invasion in order to select those patients that can benefit from surgery.     

Use of Gleason score, prostate specific antigen, seminal vesicle and margin status to predict biochemical failure after radical prostatectomy

PURPOSE: We determine the importance of clinical and pathological variables for predicting biochemical progression in patients after surgery for specimen confined prostate cancer. We developed a simple scoring algorithm for biochemical progression in node negative cases and tested the algorithm performance on an independent group. MATERIALS AND METHODS: Our study included 2,518 patients with pT2N0 or pT3N0 disease treated between 1990 and 1993. Gleason score, preoperative prostate specific antigen (PSA), margin status, extraprostatic extension, seminal vesicle involvement, DNA ploidy and adjuvant treatment were primary variables analyzed univariately. The Cox proportional hazards model was used on 2,000 randomly selected patients to develop a multivariate scoring algorithm for the aforementioned factors to predict biochemical progression-free survival. The final model included Gleason score, preoperative PSA, margin status, seminal vesicle involvement and adjuvant treatment. The prognostic score derived from this model was validated by applying it to the remaining 518 patients. Harrell's measure of concordance (C) was used to compare competing models. RESULTS: For patients who did not receive adjuvant therapy the derived score based on the Cox model coefficient was Gleason +1 (PSA 4 to 10), +2 (PSA 10.1 to 20), +3 (PSA greater than 20), +2 (positive seminal vesicle) and +2 (positive margin). The score was reduced by 4 if adjuvant hormonal therapy was given and by 2 for only adjuvant radiotherapy. The 5-year progression-free survival was 94% for scores less than 5, 60% for 10 and 32% for greater than 12 (C = 0. 718). Applying the score to the independent validation data set (518) resulted in 5-year progression-free survival of 96% for scores less than 5, 53% for 10 and 30% for greater than 12 (C = 0.759). CONCLUSIONS: Progression-free survival determined by the model score group identified a wide range of risk levels for patients with specimen confined prostate cancer. This simple predictive model allows identification of patients at high risk for cancer progression with specimen confined disease who may be targeted for closer surveillance and adjuvant therapy, while those at lower risk may be simply observed.     

Prognostic impact of lymphovascular invasion in radical prostatectomy specimens

OBJECTIVE: To estimate the prognostic value of lymphovascular invasion (LVI) in patients with node-negative prostate cancer treated by radical prostatectomy (RP). PATIENTS AND METHODS: In all, 412 patients with prostatic adenocarcinoma who had RP and pN0 status were analysed for all established standard pathological factors and LVI. The influence of these pathological findings on biochemical failure was evaluated by multivariate analysis with the Cox model. The mean (range) follow-up was 52.5 (10-116) months. RESULTS: LVI was identified in 42 patients (10.2%) and significantly associated with a high preoperative prostate-specific antigen (PSA) level, a high PSA density, high percentage of positive biopsy cores, high Gleason score, and seminal vesicle invasion. Of the 42 patients with LVI, 33 (79%) had a Gleason score of > or = 7 and 27 (64%) had pathological stage pT3. The 5-year biochemical-free survival was 87.3% for patients with no LVI and 38.3% with LVI on the RP specimen (P < 0.001). By multivariate analysis, LVI and Gleason score were independent predictors of biochemical failure. CONCLUSION: These results show that in addition to the Gleason score, only LVI is strongly correlated with biochemical failure after RP. These findings support the routine evaluation of LVI status in RP specimens and provide the option for its incorporation into nomograms predictive of oncological outcome.     

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.     

Are PSA density and PSA density of the transition zone more accurate than PSA in predicting the pathological stage of clinically localized prostate cancer?

PURPOSE: To assess whether PSA density (PSAD) and PSA density of the transition zone (PSADTZ) are more accurate than PSA alone in predicting the pathological stage of prostate cancer. MATERIALS AND METHODS: One hundred and nine consecutive patients with clinically localized prostate cancer and preoperative PSA values over the whole range, treated with radical retropubic prostatectomy and limited pelvic lymph node dissection were included in this prospective study. Total prostate and transition zone volumes were measured by transrectal ultrasound using the prolate ellipsoid method. PSA, PSAD, and PSADTZ were compared to percentage of positive biopsy cores (% PC), biopsy and surgical Gleason score, and pathological stage, using univariate and multivariate analysis. RESULTS: Pathological stage was pT2a, pT2b, pT3a, and pT3b in 25.6%, 37.7%, 25.6%, and 11.1% of patients, respectively. Lymph node metastases were found in 4.6% of patients. PSA, PSAD, and PSADTZ were significantly related to % PC, biopsy, and surgical Gleason score and pathological stage (P < 0.001), and were equally able to predict higher pathological stage, i.e., seminal vesicle invasion and lymph node metastases. Only by adding % PC in multivariate analysis was it possible to discriminate intra- from extracapsular tumors. CONCLUSIONS: The results of the present study demonstrate that PSAD and PSADTZ failed to outperform PSA in preoperative stage prediction of prostate cancer, possibly because the formula used to calculate them does not eliminate the contribution to total PSA of the nonmalignant portion of the gland.     

Histological characteristics and clinical significance of Japanese prostate cancer with low levels of prostate specific antigen of 4.0 ng/ml or lower]

PURPOSE: They set a normal limit of prostate specific antigen (PSA) to 4.0 ng/ml in Tandem R assay at most institutions. We investigated clinical and histological characteristics of prostate cancer based on whole mount step-section histology of radical prostatectomy specimens, and taking notice of Japanese prostate cancer whose levels of PSA are less than 4.0 ng/ml in normal levels. MATERIALS AND METHODS: One hundred and twenty-two patients underwent radical prostatectomy for clinically resectable prostate cancer at University Hospital from February 1992 to April 1997. Clinicopathological findings were stratified according to the preoperative PSA levels in 111 patients without preoperative endocrine therapy. Immunohistochemical study for PSA was conducted in 7 randomly selected patients. RESULTS: Of the patients 22 (19.8%) had normal (4.0 ng/ml or lower) preoperative serum PSA. Mean tumor volume in this PSA range was 1.5 cm3 with one pT 0 case included. Pathologically organ confined, potentially curable disease (< pT 3) was found in 17 (77.3%) patients and extracapsular extension and seminal vesicle invasion in 5 (23.8%), respectively. No patients had positive pelvic lymph nodes. Well differentiated tumors of Gleason scores 2-4 were found in 9 (40.9%) of the patients, moderately differentiated tumors (Gleason scores 5, 6) in 5 (22.7%) and poorly differentiated histology (Gleason scores 7-10) in 7 (31.8%). Sixteen (72.7%) patients had clinically significant tumors (> 0.5 cm3, Gleason score > or = 7). All 7 patients had positive staining for PSA, but its intensity did not correlate with serum PSA levels. CONCLUSIONS: Many prostate cancers found in surgical specimens were clinically significant despite the low levels of PSA and potentially curable by definitive treatment. Age, co-morbidity and other clinicopathological variables as well as PSA levels should all be taken into account when treatment options are discussed.     

Flap endonuclease 1 is overexpressed in prostate cancer and is associated with a high Gleason score

OBJECTIVE: To investigate the expression and potential clinical usefulness of structure-specific flap endonuclease 1 (FEN-1) in human primary prostate cancer using tissue microarray technology, as FEN-1 was recently identified to be overexpressed in CL1.1, the most aggressive clone generated from the hormone-refractory prostate cancer cell line CL1. MATERIALS AND METHODS: Immunohistochemistry was performed on tissue microarrays constructed from paraffin-embedded specimens of primary prostate cancer from 246 patients who had had a radical prostatectomy. Prostatic intraepithelial neoplasia (PIN), benign prostatic hyperplasia (BPH) and normal prostate epithelium were represented on the array. FEN-1 nuclear expression was scored based on the percentage of target cells staining positively, and correlated with Gleason score, preoperative prostate-specific antigen (PSA) level and pathological stage. The time to PSA recurrence was also analysed. RESULTS: The mean expression of FEN-1 was significantly higher in cancer (36.7%) than in normal (13.2%), BPH (4.5%) and PIN (15.4%) specimens (P < 0.001). FEN-1 expression was significantly correlated with Gleason score (ó = 0.23, P = 0.002). A higher preoperative serum PSA level (P = 0.015), Gleason score > or = 7 (P < 0.001), seminal vesicle invasion (P < 0.001) and capsular involvement (P = 0.004) were associated with PSA recurrence, whereas FEN-1 expression was not. In a multivariate analysis, only Gleason score > or = 7 (P < 0.001), seminal vesicle invasion (P = 0.005) and capsular involvement (P = 0.009) were retained as independent predictors for PSA recurrence. CONCLUSIONS: FEN-1 is overexpressed in prostate cancer compared with matched normal prostate, and its expression increases with tumour dedifferentiation, as shown by increasing Gleason score. These results suggest that FEN-1 might be a potential marker for selecting patients at high risk, and a potential target for prostate cancer diagnosis and therapy.     

Iatrogenic and non-iatrogenic positive margins: incidence,site, factors involved,and time to PSA progression following radical prostatectomy

Introduction There are conflicting data regarding the incidence, site and prognostic significance of positive margins resulting from iatrogenic incision into the prostate (pT2+) or non-iatrogenic inability to excise extraprostatic extension (EPE) of tumor. Materials and methods The surgical specimens were whole-mount processed. Nerve-sparing, tumor extension and Gleason score were considered possible factors involved in positive margins. Time to PSA progression was studied using a Kaplan–Meier product-limit analysis. Results Positive margins resulted from iatrogenic incision in 61/230 (26.52%) prostates and from EPE in 34/230 (14.78%) prostates. The site most frequently involved in pT2+ prostates was the posterolateral quadrants (40.98%); in cases with EPE both anterolateral and posterolateral quadrants (67.65%) were most frequently involved. Positive margins occurred equally in patients with and without nerve-sparing in both groups. Tumors were significantly more extensive and with higher Gleason score in patients with EPE. Time to PSA progression was similar in patients with pT2+ versus EPE and no invasion of the seminal vesicle, but was significantly shorter in patients with EPE and invasion of the seminal vesicle. Conclusion The frequency of positive margins in our institution was similar to others with large experience in performing radical prostatectomies. The higher frequency of posterolateral quadrants in iatrogenic positive margins is probably related to the preservation of adjacent vital structures and not to nerve-sparing surgery. A trend for a decreasing frequency of non-iatrogenic surgical margins may be explained by the marked increase of clinical stage T1c in recent years. More-extensive tumors and higher Gleason scores seem to influence only non-iatrogenic positive margins. Biochemical (PSA) progression in EPE must be studied by stratifying the patients into two groups: with and without seminal vesicle invasion.     

Long-term prognostic significance of primary Gleason pattern in patients with Gleason score 7 prostate cancer: impact on prostate cancer specific survival

PURPOSE: We determined the long-term clinical significance of primary Gleason pattern in patients with Gleason score 7 prostate cancer. MATERIALS AND METHODS: We reviewed the records of all patients who underwent bilateral pelvic lymph node dissection and radical retropubic prostatectomy for Gleason score 7 prostate cancer at our institution. All patients who underwent adjuvant hormonal or radiation therapy were excluded from analysis. Patients were monitored for biochemical failure, that is PSA progression, systemic recurrence and cancer specific survival. RESULTS: We identified 1,688 patients who met admission criteria, of whom 1,256 (74.4%) had primary Gleason pattern 3 and 432 (25.6%) had primary Gleason pattern 4. Median followup was 6.9 years. At 10 years primary Gleason pattern 3 was associated with increased biochemical recurrence-free survival (48% vs 38%, p <0.001), lower systemic recurrence (8% vs 15%, p <0.001) and higher cancer specific survival (97% vs 93%, p = 0.013) for Gleason primary grades 3 and 4, respectively. All of these end points remained significant on multivariate analysis when controlling for preoperative PSA, seminal vesicle involvement, margin status, DNA ploidy and TNM staging. PSA doubling time was shorter in patients with primary Gleason pattern 4 (1.64 vs 1.01 years). Systemic recurrence and cancer specific survival were associated with a PSA doubling time of less than 1 year. CONCLUSIONS: Gleason score 7 prostate cancer is a heterogeneous entity. We should continue to stratify patients according to primary Gleason pattern. Patients with Gleason score 4 + 3 prostate cancer have more aggressive disease and experience higher rates of biochemical failure, systemic recurrence and cancer specific death.     

The percentage of free prostate-specific antigen does not predict extracapsular disease in patients with clinically localized prostate cancer before radical prostatectomy

OBJECTIVE: To determine whether the percentage of free/total prostate-specific antigen (f/tPSA) can predict the pathological features in patients with clinically localized prostate cancer before radical prostatectomy. PATIENTS AND METHODS: Univariate and multivariate logistic regression was used to analyse data from 171 untreated patients who underwent radical prostatectomy. Variables included the total PSA (tPSA), fPSA, f/tPSA, biopsy Gleason score, clinical stage and patient age. RESULTS: In 115 patients with pathologically organ-confined tumours ( pT2N0) the mean (SD) tPSA value was 6.9 (5.6) ng/mL; in 56 patients with extracapsular disease ( pT3pN0/N+) it was 10.2 (7.6) ng/mL; the respective f/tPSA values were 14.9 (8.1)% and 14.2 (12.9)%. In the univariate and multivariate analysis, tPSA and biopsy Gleason score were highly significant in predicting extracapsular disease (P < 0.001 and 0.002) but the f/tPSA was not (P = 0.18). There was no significant difference between the mean f/tPSA and final Gleason scores. CONCLUSION: The f/tPSA does not predict extracapsular disease in patients with clinically localized prostate cancer before radical prostatectomy. Knowing the f/tPSA provides no significant additional information in predicting extracapsular disease when the biopsy Gleason score and tPSA are known.     

Prediction of Capsular Perforation and Seminal Vesicle Invasion in Prostate Cancer

Purpose

Capsular perforation and seminal vesicle invasion are unfavorable, prognostic factors in prostate cancer. Accurate preoperative prediction of these factors would be clinically useful for planning treatment, especially in patients being considered for radiation therapy, nerve sparing radical prostatectomy and watchful waiting. However, current methods are imprecise at predicting the presence and extent of these factors. We determined which combination of commonly available preoperative variables provides the best prediction of capsular perforation and seminal vesicle invasion in patients with clinically localized prostate cancer.

Materials and Methods

We reviewed the preoperative medical records and biopsy findings from 314 patients with clinical stages T1cN0M0 to T2cN0M0 cancer who underwent radical retropubic prostatectomy and bilateral pelvic lymphadenectomy between September 1991 and June 1993. Radical prostatectomy specimens were embedded and evaluated by whole mount sections.

Results

Capsular perforation was observed in 104 patients (33.1 percent) and seminal vesicle invasion was noted in 46 (14.6 percent). Preoperative variables predictive of capsular perforation and seminal vesicle invasion on univariate analysis were serum prostate specific antigen (PSA) concentration, clinical stage, Gleason primary and secondary patterns, Gleason score, nuclear grade, perineural invasion and percent cancer in the biopsy specimens. On multivariate analysis independent prognostic factors for capsular perforation and seminal vesicle invasion were PSA, Gleason score and percent cancer in the biopsy specimens.

Conclusions

The combination of serum PSA concentration, Gleason score and percent cancer in the biopsy specimens provides the best prediction of capsular perforation and seminal vesicle invasion. Models based on this combination of factors may be clinically useful to stratify patients for nonoperative treatment.     

Perineural invasion on prostate needle biopsy: an independent predictor of final pathologic stage

Objectives. To examine the significance of perineural invasion (PNI) in predicting pathologic findings in patients treated by radical prostatectomy, because a recent study concluded that PNI on needle biopsy has no independent predictive value.Methods. Between 1993 and 1998, radical prostatectomy was performed in 319 consecutive patients. Prostate needle biopsies were reviewed in all cases. We compared PNI with other preoperative parameters, including digital rectal examination, PSA, and biopsy Gleason score, for the ability to predict tumor stage. Clinical records and pathologic findings were reviewed for all cases. Tumor stage was defined as either pT2 (organ confined) or pT3 (extraprostatic extension and/or seminal vesicle invasion).Results. The median age was 61.4 years (range 40 to 75.6). Seventy-two percent of the 95 men with nonpalpable disease and 67% of the 224 men with palpable disease had organ-confined prostate cancer on final pathologic staging. Of 205 men with a Gleason score on biopsy of 6 or less, 159 (78%) had organ-confined disease compared with 59 (52%) of 114 with a Gleason score of 7 to 9 (P <0.001, chi-square test). PNI was identified in 77 (24%) of 319 patients, with 83% specificity and 40% sensitivity for Stage pT3 disease (odds ratio 3.49). Of men with pT3 disease on final pathologic staging, 18%, 27%, and 56% had preoperative PSA levels of 0 to 4, more than 4 to 10, and greater than 10 ng/mL, respectively (P <0.001, Mantel-Haenszel chi-square test). On multivariate analysis, PNI (P = 0.0031), PSA (P = 0.0004), and Gleason score (P = 0.0003) independently predicted stage (pT3 disease).Conclusions. PNI is an important preoperative predictor of pathologic stage and should be reported when adenocarcinoma is diagnosed on prostate needle biopsies.     

Die erweiterte, radikale perineale Prostatektomie

One hundred and twenty-five consecutive patients with prostate cancer underwent an extended, radical perineal prostatectomy according to the technique described by VE Weldon. This technique was modified by an initial complete mobilization of the posterior aspect of the prostate and seminal vesicles from the rectum and pelvic wall, incision of the endopelvic fascia, and partial resection of the dorsal vein complex after suture ligature. The perioperative morbidity was low. An operative revision was necessary in four (3.2%) patients because of arterial bleeding from a drainage channel (n = 1), wound infection (n = 2), and rectocutaneous fistula (n = 1). The in-dwelling catheter was removed on day 4-8 in 104 (83%) patients. Positive surgical margins were diagnosed in 22 (17.6%) patients only. These patients had pT3 (n = 17) and pT4 (n = 5) tumors with a Gleason score > or = 7 (n = 17) mostly; extensive, multifocal capsular penetration (n = 18); seminal vesicle invasion (n = 11); and lymph node metastases (n = 4). The unifocal positive margins were localized at the apex (n = 3), dorsolateral (n = 6) aspect, and bladder neck (n = 4). In nine patients, multifocal positive surgical margins were noted. The risk for a positive surgical margin depends on the serum PSA level, Gleason score, and tumor volume. In case potency preservation is not considered, the extended, radical perineal prostatectomy with the above mentioned modifications should be considered to guarantee a low rate of surgical margins.     

Does the Tertiary Gleason Pattern Influence the PSA Progression-Free Interval after Retropubic Radical Prostatectomy for Organ-Confined Prostate Cancer?

INTRODUCTION: The Gleason sum is an important prognostic parameter for patients treated with radical prostatectomy for localized prostate cancer. However, frequently more than two predominant Gleason patterns are present in one specimen. In this study we investigated the prognostic significance of tertiary Gleason patterns in radical prostatectomy specimens. PATIENTS AND METHODS: Between 1994 and 2001, 277 patients underwent radical retropubic prostatectomy (RRP) for clinically localised prostate cancer in our institute. We collected information on Gleason score and cancer volume (CV) for all tumour localizations, clinical and pathological stage, seminal vesicle invasion (SVI) and extra capsular extension (ECE). In case one pattern was seen in more than 95% of the tumour, this pattern was used both for the primary and secondary Gleason pattern, and any other pattern (actually the secondary pattern) was called tertiary. Charts were examined retrospectively for clinical follow up. PSA progression was defined as two subsequent rising PSA measurements above 0.10 ng/ml. Kaplan-Meier time to PSA progression was compared between patients with and without a tertiary pattern. RESULTS: Overall, of the 223 patients, 106 (48%) were found to have a tertiary pattern, which on average, was 7% of the total tumour volume. Patients with a tertiary pattern had a 5-year risk of PSA progression of 37.3% versus 12.6% in case no tertiary Gleason pattern was present (log rank p=0.0002). There was no prognostic difference between patients with a higher-grade tertiary pattern as compared to those with a lower grade tertiary pattern. CONCLUSIONS: If present, a tertiary Gleason pattern, whether better or worse than the primary or secondary pattern, is an indication for a worse outcome, as indicated by a shorter time to PSA progression. This suggests that tumour multifocality, rather than the presence of a higher-grade tertiary Gleason pattern has prognostic value.     

Comparison of Gleason scores from sextant prostate biopsies and radical prostatectomy specimens.

OBJECTIVES: We compared the Gleason scores obtained from sextant prostate biopsy and radical prostatectomy (RP) specimens in patients with localized prostate cancer. PATIENTS AND METHODS: Sixty-one patients having a clinical diagnosis of localized prostate cancer underwent needle biopsy under transrectal ultrasonography (TRUS) and RP. Grading and staging were assigned based on Gleason scores and the TNM system, respectively. RESULTS: Mean patient age was 65.5 +/- 13.43 years and mean PSA level was 14.69 +/- 3.95. Mean Gleason score for prostate biopsy and RP specimen were 5.85 +/- 0.7 and 6.34 +/- 1.44, respectively. With respect to clinical stage, there were 20 patients in stage 1 and 41 patients in stage 2 prostate cancer. Comparing the Gleason scores, the biopsy score was lower in 26 (42.26%) and higher than RP specimens in 7 (11.84%) cases, and there was agreement between the biopsy and RP specimens in 28 (45.9%) patients. The difference between the two Gleason scores was +/- 1 for 18 patients (29.5%) and +/- 2 or more for 17 patients (27.86%). CONCLUSION: In our study, high Gleason score biopsies with elevated PSA level (>10 ng/ml) were risk factors for extraprostatic extension, and we demonstrated that Gleason scores were significantly correlated with seminal vesicle and lymph node invasion (p < 0.05). The Gleason scores of biopsy and RP specimens agreed with 45.9% of TRUS-guided sextant prostate biopsies, and this ratio was 91.1% in moderately differentiated tumors Copyright 2001 S. Karger AG, Basel