Clustered p53 immunostaining: a novel pattern associated with prostate cancer progression

Abnormal p53 protein accumulation is typically defined as present when greater than 5 or 10% of cancer cells stain positively. We present a novel approach whereby immunopositivity is defined when 15 or more cells within a 300 x 400-micrometer(2) field exhibit p53 protein accumulation; a feature that we have called "clustered" staining. We assessed p53 immunostaining of moderately differentiated, clinically localized prostate cancers derived from two patient groups: those without cancer recurrence 5 years after radical prostatectomy, and those in whom cancer had recurred following radical prostatectomy. Clustered p53 immunopositivity was present in 10 (63%) of 16 patients in the recurrent group and in only 7 (21%) of 33 in the nonrecurrent group. Clustered p53 staining was clearly associated with cancer recurrence (P < 0.01). This refinement of a commonly used assay may help define the biological aggressiveness of a cancer.     

HpSS: a new silver staining method for Helicobacter pylori

Fifty-seven patients with clinically localized prostate cancer were treated by radical prostatectomy or external radiation therapy following pelvic lymphadenectomy. Comparing the outcome of radiotherapy with that of prostatectomy in 42 T2 patients without lymph node metastasis, the 5-year cause-specific survival did not differ between the radical prostatectomy group (n = 31) and radiotherapy group (n = 11). The 5-year disease-free survival of the prostatectomy group, however, was superior to that of radiotherapy group (p = 0.01). To cure patients with T2 prostate cancer, therefore, it is supposed that radical prostatectomy should be performed. To improve the treatment outcome after radiotherapy, stereotactic radiosurgery for prostate cancer has been attempted in our institution. Phantom experiments using a linear accelerator demonstrated a round dose distribution, and high reproducibility of prostate positioning was confirmed by CT when a thermoplastic immobilization device was used to fix the pelvis. In one patient with localized prostate cancer treated by radiosurgery, acute complication has not been recognized during the 5 week follow-up. Radiosurgery may be available to treat clinically localized prostate cancer.     

Radical prostatectomy for prostate cancer: the perineal approach increases the risk of surgically induced positive margins and capsular incisions

PURPOSE: We compare the incidence of positive surgical margins in patients who underwent perineal or retropubic radical prostatectomy for clinically localized (stage T1, T2) prostate cancer. MATERIALS AND METHODS: In this retrospective, nonrandomized study we reexamined the specimens of 94 consecutive patients who underwent radical perineal (48) or retropubic (46) prostatectomy for clinically localized prostate cancer (stage T1, T2) and with pathological stage pT2 (intracapsular), pT3A (established extracapsular extension without positive margins) or pT3B (extracapsular extension with positive margins) without lymph node involvement (N0). We assessed the presence or absence of extracapsular cancer with or without positive margins, incisions of the prostatic capsule exposing cancer (surgically induced positive margins) or benign glandular tissue. Patients were followed for 3 to 66 months (mean 25) using an ultrasensitive prostate specific antigen assay with a lower detection limit of less than 0.05 ng./ml. RESULTS: The overall incidence of positive margins in cancer tissue was 56% in the perineal and 61% in the retropubic group, and biochemical failure-free survival was 67% each. However, surgically induced positive margins in patients with organ confined disease were more frequent in the perineal than retropubic group (43 versus 29%, p < 0.05) and associated with a 37% risk of biochemical failure (prostate specific antigen greater than 0.1 ng./ml.) at mean followup. In addition, capsular incisions exposing benign tissue were more frequent in the perineal than retropubic group (90 versus 37%, p < 0.05) irrespective of pathological stage. CONCLUSIONS: Although overall positive margins and biochemical failure rates are similar or identical for the perineal and retropubic approaches for organ confined prostate cancer, the perineal approach is associated with a significantly higher risk of capsular incisions and surgically induced positive margins and, thus, a higher risk of biochemical failure.     

The effects of FR167653 in extended liver resection with ischemia in dogs

PURPOSE: We assess the neovascularity of clinically localized prostate cancer by immunohistochemistry using the monoclonal antibody CD34 in an attempt to identify associations between angiogenesis and disease progression following radical prostatectomy. MATERIALS AND METHODS: Microvascularity was evaluated using the CD34 monoclonal antibody in archival paraffin embedded radical prostatectomy specimens from 149 patients followed from 3 to 10 years (mean 6.6). Vessels were quantified by counting a minimum of 2 selected microscopic fields (200x, 0.754 mm.2) from each tumor, area of prostatic intraepithelial neoplasia and prostatic hyperplasia, and given a numerical value representing the microvessel density count. RESULTS: Mean microvessel density count did not vary significantly with age or race. There was a significant association between the count and nuclear grade, Gleason sum and pathological stage. Cox survival analysis shows that microvessel density is significantly related to time to recurrence when considered as a continuous variable (p=0.03) as well as dichotomous variable (p=0.007) (microvessel density count less than 90 and 90 or greater). The 5-year recurrence-free survival was significantly higher for patients with a count less than 90 (71%) than for those with a count 90 or greater (51%) (p=0.006). The 5-year recurrence-free survival was also significantly different when microvessel density was used as a continuous variable (p=0.02). Controlling for stage, Gleason sum, race and nuclear grade, microvessel density remained significant in predicting recurrence (p=0.03) but when pretreatment prostate specific antigen was included in the model the count was no longer significant. The microvessel density count in the tumor area significantly increased with increasing Gleason sum and nuclear grade but it did not increase significantly in the adjacent benign prostate or areas of prostatic intraepithelial neoplasia in the same specimen. CONCLUSIONS: Microvascularity or neovascularity as measured by the CD34 antigen may be a prognostic marker of recurrence for prostate cancer patients after radical prostatectomy but more study in prostate specific antigen era patients with sufficient followup is needed.     

Outcome based staging for clinically localized adenocarcinoma of the prostate

PURPOSE: Some patients with clinically localized prostate cancer are not cured after radical prostatectomy because of the presence of occult systemic disease. The American Joint Commission on Cancer staging classification for prostate cancer does not reliably distinguish between clinically localized patients who are likely or unlikely to be cured after local therapy. This project was undertaken to develop a staging system capable of predicting long-term outcome after radical prostatectomy on the basis of the clinical parameters obtained routinely during the standard workup for patients with adenocarcinoma of the prostate. MATERIALS AND METHODS: A total of 688 clinically localized prostate cancer patients managed with a radical retropubic prostatectomy for adenocarcinoma of the prostate between 1989 and 1996 was evaluated for clinical features predictive of time to prostate specific antigen (PSA) failure using a Cox regression multivariate analysis. A recently defined clinical factor called the calculated prostate cancer volume and its ability to predict time to PSA failure in conjunction with PSA, biopsy Gleason score and clinical stage were evaluated. RESULTS: The calculated prostate cancer volume (p <0.0001) and the pretreatment PSA (p <0.001) provided the optimal staging system for predicting freedom from PSA failure after radical prostatectomy. CONCLUSIONS: The calculated prostate cancer volume and PSA may provide clinically useful information regarding outcome after radical prostatectomy, enabling the selection of a therapeutic approach for an individual patient with clinically localized disease. Validation of this staging system is needed.     

Predictors of pathological stage before neoadjuvant androgen withdrawal therapy and radical prostatectomy. The Canadian Urologic Oncology Group

PURPOSE: This prospective randomized trial was used to compare predictive factors for organ confined margin negative status after radical prostatectomy with and without a 3-month course of neoadjuvant androgen withdrawal therapy. MATERIALS AND METHODS: A total of 213 patients with localized adenocarcinoma of the prostate were randomized to radical prostatectomy with or without a 3-month course of 300 mg. neoadjuvant cyproterone acetate daily. Multivariate logistic regression analysis was used to determine significant predictors of organ confined margin negative status after radical prostatectomy in both groups. Parameters evaluated included baseline prostate specific antigen (PSA 4 or less, 4.1 to 10, greater than 10 ng./ml.), clinical stage (T2c versus T2b or less), biopsy Gleason score and percentage of surface area of biopsies involved with cancer. The multivariate analysis was repeated with PSA density and the natural logarithm of PSA to optimize the model. RESULTS: In the radical prostatectomy alone arm a model incorporating only PSA density was the best predictor of organ confined margin negative status. In the neoadjuvant androgen withdrawal therapy arm a model incorporating biopsy Gleason score, PSA density and clinical stage was the best predictor. CONCLUSIONS: The conventional predictors of pathology at radical prostatectomy, biopsy Gleason score, PSA density and clinical stage retain significance as predictors in patients treated with a 3-month course of neoadjuvant androgen withdrawal therapy before radical prostatectomy.     

Experience with radical prostatectomy as treatment of localized cancer of the prostate at the Fundación Santa Fe de Bogotá, Colombia

OBJECTIVE: To analyze the experience of the Fundación Santa Fe de Bogotá with radical prostatectomy in the treatment of localized prostatic cancer. METHODS: A retrospective study was conducted on 108 patients with localized carcinoma of the prostate stage T1-T2NxM0 submitted to radical prostatectomy from 1989 to 1994. RESULTS: Preoperatively, 50% of the patients had a PSA < 10 ng/ml and 14% had values that fell within the normal ranges of 0-4 mg/ml. A family history of prostate cancer was detected in 9.3% of the patients. The prostate cancer was clinically understaged in 75% of the patients, particularly those with stages T2a and T2b, and less significantly in those with stage T2c. Considering only those patients in whom the pathological staging had disclosed the cancer was not localized, this incidence accounted for 52% (n = 57). The presence of surgical margins was approximately 36%. The tumor recurrence rate was 26.9% and the complication rate was 6.8%. CONCLUSION: The relatively low complication rate in the present series shows that radical prostatectomy is a safe procedure that achieves good results if the cases are carefully selected and the diagnostic test are widely utilized.     

Impact of androgen deprivation prior to radical prostatectomy for T1, T2 prostate cancer on the likelihood of curative surgery

BACKGROUND: Extracapsular extension is commonly seen in patients undergoing radical prostatectomy for localized prostate cancer due to understaging of disease. One possible approach to reduce the likelihood of extracapsular disease is androgen deprivation prior to radical prostatectomy, neoadjuvant therapy. However, adequate application is not clear. We analyzed the outcome of neoadjuvant therapy and radical prostatectomy in an attempt to expand our understanding on indications of neoadjuvant therapy. METHODS: Forty-six selected patients with clinical T1 or T2 prostate cancer were retrospectively reviewed. Twenty-two patients underwent neoadjuvant therapy (group N) that mainly consists of LH-RH agonist. The duration of neoadjuvant therapy, varied from 1 to 12 months with the mean being 4 months. Twenty-four underwent radical prostatectomy alone (group S). RESULTS: In the group N and group S, 59% and 33% had either organ confined disease (OCD) or specimen confined disease (SCD) respectively. When the patients had OCD or SCD, they were defined as surgically cured patients. In the patients with clinical stage T1b, T1c, and T2 disease, likelihood of surgical cure were 100%, 50%, 46.7% in group N, 100%, 20%, 11%, in group S respectively. In the patients with initial serum PSA less than 10 ng/ml and more than 10.1 ng/ml, likelihood of surgical cure were 83.3% and 50% in group N, 63.6% and 15.4% in group S, respectively. Likelihood of surgical cure was higher in the patients with well differentiated carcinoma both in group N and group S. All the patients with serum PSA less than 0.1 ng/ml after neoadjuvant therapy had OCD. CONCLUSION: Neoadjuvent therapy could be beneficial either in the patients with moderately or in the poorly differentiated adenocarcinoma of prostate especially in the group with initial serum PSA more than 10.1 ng/ml. However, in patients both with well differentiated adenocarcinoma and the initial serum PSA less than 10 ng/ml, no evidence of beneficial effect on the likelihood of OCD or SCD was observed. PSA after neoadjuvant therapy could be useful predictor for the pathological outcome.     

p53 nuclear protein overexpression in colorectal cancer: a dominant predictor of survival in patients with advanced hepatic metastases

PURPOSE: To determine whether p53 protein expression is similar within primary colorectal cancer (CRC) and synchronous regional and distant metastases and to assess whether p53 nuclear protein expression could predict outcome in patients with synchronous unresectable liver metastases treated by hepatic artery infusional (HAI) chemotherapy. MATERIALS AND METHODS: Paraffin sections from tumor and corresponding normal mucosa representative of 50 consecutive advanced CRC cases were examined for p53 nuclear protein expression by immunohistochemistry using the monoclonal antibody PAb 1801. Patterns of p53 nuclear expression were correlated with standard clinicopathologic variables and outcome, including response to HAI and survival. In a subset analysis, the pattern of nuclear p53 immunoreactivity was compared between primary CRC and lymph node and liver metastases. RESULTS: Positive nuclear immunoreactivity for p53 protein was found in 72% of cases. The pattern of p53 protein expression in lymph node and liver metastases was identical to that of the primary tumor. The median survival time was 21.0 months in patients with p53-positive tumors and 53.2 months in patients with p53-negative tumors (Wilcoxon test P = .038). Two-year survival rates were 41.7% and 78.6%, respectively (P < .01). No significant difference was found in the response rates to HAI chemotherapy between the two groups. By multivariate analysis, p53 protein status was the single best predictor of survival, with a relative risk of 6.312. CONCLUSION: Our results indicate that nuclear p53 protein status in primary CRC is similar to that in metastatic sites and may be the dominant predictor of survival in patients with advanced hepatic metastases.     

Pathological features and prognostic significance of prostate cancer in the apical section determined by whole mount histology

PURPOSE: We test the hypothesis that cancer in the apical section of the prostate is an important independent factor in predicting the progression of clinically localized prostate cancer. MATERIALS AND METHODS: We analyzed clinical data and whole mount histological step sections for 500 patients who had undergone radical retropubic prostatectomy for clinically localized prostate cancer. RESULTS: Cancer was in the apex of the prostate in 175 patients (35%). These patients had a larger cancer and higher incidence of positive surgical margins, and were more likely to have a poorly differentiated cancer than the 325 patients without cancer in the apex. However, the presence of apical cancer was not a significant predictor of clinical or prostate specific antigen progression in either univariate or multivariate Cox proportional hazards models when analyzed for the entire group or only in patients with tumor confined to the prostate. CONCLUSIONS: Apical cancer in a radical prostatectomy specimen is simply a sign of a larger volume cancer and is not independently associated with an increased risk of clinical or prostate specific antigen progression.     

Reduced space hidden Markov model training

OBJECTIVE: To analyze trends in the clinical stage and pathologic outcome of patients with prostate cancer who underwent radical prostatectomy at a large referral practice during the prostate-specific antigen (PSA) testing era. MATERIAL AND METHODS: Between January 1987 and June 1995, 5,568 patients with prostate cancer (4,774 with clinically localized disease of stage T2c or less) underwent pelvic lymphadenectomy and radical retropubic prostatectomy at our institution. Patient age, preoperative serum PSA level, clinical stage, pathologic stage, Gleason score, and tumor ploidy were assessed. Outcome was based on clinical and PSA (increases in PSA level of 0.2 ng/mL or more) progression-free survival. RESULTS: Patient age (65 to 63 years old; P<0.001) and serum PSA level (median, 8.4 to 6.8 ng/mL; P<0.001) decreased during the study period. The percentage of patients with clinical stage T1c prostate cancer increased from 2.1% in 1987 to 36.4% in 1995 (P<0.001), and clinical stage T3 cancer decreased from 25.3% to 6.5% (P<0.001). Nondiploid tumors decreased from 38.3% to 24.6% (P<0.001), and the proportion of patients with pathologically organ-confined disease increased from 54.9% to 74.3% (P<0.001). More cT1c than cT2 tumors were diploid (80% versus 72%; P<0.001), had a Gleason score of 7 or less (75% versus 65%; P<0.001), and were confined to the prostate (75% versus 57%; P<0.001). Five-year progression-free survival was 85% and 76% for patients with clinical stage T1c and T2, respectively (P<0.001). CONCLUSION: Since the advent of PSA testing, patients referred to our institution for radical prostatectomy have shown a significant migration to lower-stage, less-nondiploid, more often organ-confined prostate cancer at the time of initial assessment. Cancer-free survival associated with PSA-detected cancer (cT1c) is superior to that with palpable tumors (cT2). Whether these trends translate into improved long-term cancer-specific survival remains to be confirmed with longer follow-up.     

One core positive prostate biopsy is a poor predictor of cancer volume in the radical prostatectomy specimen

PURPOSE: In view of the recent increase in patients presenting with only 1 core positive for prostate carcinoma, we examined the correlation in tumor volume between the biopsy and the subsequent radical prostatectomy specimen. MATERIALS AND METHODS: We studied a total of 169 consecutive prostate biopsies with matched radical prostatectomy specimens and selected 48 patients with only 1 positive core. RESULTS: Cancers found in the biopsy regardless of their size were associated with a wide range of cancer volume in the radical prostatectomy specimens, and the amount of cancer in the biopsy was a poor predictor of the volume of cancer in the prostatectomy specimen. Even with a cancer of 3 mm. or less in the biopsy, 57% of patients had cancer of clinically significant volume (greater than 0.5 ml.). Other modalities for the evaluation of prostate cancer such as Gleason score and clinical stage were not helpful in segregating patients with clinically significant from those with insignificant volume of cancer. However, when combined with a preoperative serum prostate-specific antigen higher than 10 ng./ml., 1 core positive biopsy could reliably predict the presence of cancer of significant volume. CONCLUSIONS: One core only positive prostate biopsy, when accompanied by an elevated serum prostate specific antigen value (greater than 10 ng./ml.), strongly suggests the presence of clinically significant cancer.     

The contemporary value of pretreatment prostatic acid phosphatase to predict pathological stage and recurrence in radical prostatectomy cases

PURPOSE: We examine the clinical prognostic value of the currently available simple and inexpensive immunoenzymatic prostatic acid phosphatase (PAP) assay for the staging and prognosis of radical prostatectomy cases. MATERIALS AND METHODS: Between February 1, 1990 and May 3, 1996 pretreatment PAP was measured in 295 patients who underwent radical prostatectomy. From February 1, 1990 to May 17, 1992 the Hybritech Tandem-E assay was used in 75 cases, from May 18, 1992 to February 28, 1993 the Abbott EIA assay was used in 49 and from March 1, 1993 to May 3, 1996 the Abbott IMx assay was used in 171. PAP assays were analyzed individually and the results were combined with pretreatment prostate specific antigen (PSA) values to assess the ability to predict organ confined prostate cancer and serological recurrence after radical prostatectomy. RESULTS: PAP testing was not of value for predicting organ confined disease or positive margins. However, this test was useful for predicting the first serological PSA recurrence in the 3 periods (77 to 85% correct) and overall (82% correct, p < 0.001, odds ratio 6.06). The Kaplan-Meier disease-free survival rate at 4 years was 78.8% for men with PAP less than 3 ng./ml. and 38.8% for those with PAP 3 ng./ml. or greater, which was significant when pretreatment PSA was less than 10 ng./ml. (p = 0.047), 10 ng./ml. or greater (p = 0.012) and overall (p < 0.001). PAP testing added prognostic information to pretreatment PSA values and it was an independent predictor of recurrence. CONCLUSIONS: The widely available and inexpensive PAP assays of the 1990s are predictors of recurrence after radical prostatectomy. They should be included in future studies of prostate cancer recurrence modeling. However, they do not predict pathological stage or margin status.     

Racial differences in clinically localized prostate cancers of black and white men

PURPOSE: Tumor grade, deoxyribonucleic acid (DNA) ploidy, proliferation, p53 and bcl-2 expression were examined in clinically localized prostate cancers of black and white American men to learn whether these features showed racial differences. MATERIALS AND METHODS: A total of 117 prostate cancers (43 black and 74 white patients) obtained at radical prostatectomy for clinically localized disease were assigned Gleason scores by a single pathologist. Enzymatically dissociated nuclei from archival prostate cancers were examined by DNA flow cytometry using propidium iodide staining and the multicycle program to remove debris and sliced nuclei and to perform cell cycle analysis. For immunostaining after microwave antigen retrieval we used a DO-1/DO-7 monoclonal antibody cocktail for p53 and the clone 124 antibody for bcl-2. RESULTS: Significantly more black than white men had Gleason score 7 tumors. The DNA ploidy distribution of Gleason 6 or less tumors was similar for both races. As anticipated, the ploidy distribution of higher grade prostate cancer in white men was more abnormal but, unexpectedly, this was not found for higher grade prostate cancer in black men. No significant racial differences were found in S phase fractions, p53 or bcl-2 immunopositivity. However, for prostate cancer in black men there was a significant association between bcl-2 immunopositivity and higher S-phase fractions. CONCLUSIONS: The aggressive prostate cancers of black men may be characterized by the 2 features of high proliferation and a block to programmed cell death.     

Cathepsin D and chromogranin A as predictors of long term disease specific survival after radical prostatectomy for localized carcinoma of the prostate

BACKGROUND: The accumulation of chromogranin A (Chr A) and cathepsin D (Cath D) gene products may be important in prostate carcinoma progression. This study assessed whether the levels of immunoreactivity for Chr A and Cath D are better predictors of disease specific survival than conventional pathologic parameters of the primary tumor such as Gleason score, capsular penetration, seminal vesicle invasion, and percent tumor in the specimen for patients with clinically localized prostate carcinoma managed by radical prostatectomy. METHODS: Seventy-one patients with modified Jewett clinical stages A1 to B2 adenocarcinoma of the prostate underwent a radical prostatectomy after a negative metastatic workup. No neoadjuvant or adjuvant treatments were given and all disease recurrences and causes of death were recorded. Analysis of prostatectomy specimens was undertaken to determine the conventional pathologic parameters of the primary tumor and Chr A and Cath D immunohistochemical staining. Univariate and multivariate analyses were performed to determine the independent contributions of Chr A and Cath D in predicting survival. RESULTS: On univariate analysis Chr A was the only variable that reached statistical significance for disease specific survival (P = 0.035). Cath D nearly reached significance with a P value of 0.079 for disease specific survival. On multivariate analysis, the only independent factor predicting disease specific survival was the Chr A staining score (P < 0.05). In patients with unequivocal foci of Chr A immunoreactivity, the 14-year disease specific survival was 50% compared with 68% for patients lacking such foci. CONCLUSIONS: The level of Chr A immunohistochemical staining is a strong predictor of disease specific survival and is superior to standard pathologic prognostic factors. Such findings lay the groundwork for future prospective study of the utility of such markers on biopsy specimens to predict patient outcome.     

The role of cyclic guanylate monophosphate in nitric oxide-induced injury to rat small intestinal epithelial cells

PURPOSE: Biostatistical models predicting the risk of recurrence after radical prostatectomy for clinically localized prostate cancer are necessary. Identifying these high risk patients shortly after surgery, while tumor burden is minimal, makes them candidates for possible adjuvant therapy and/or investigational phase II clinical trials. This study builds on previously proposed models that predict the likelihood of early recurrence after radical prostatectomy. MATERIALS AND METHODS: In our analysis we evaluate age, race, prostatic acid phosphatase and nuclear grade with the established prognostic variables of pretreatment prostate specific antigen, postoperative Gleason sum and pathological stage. RESULTS: After multivariable Cox regression analysis using only statistically significant variables that predicted recurrence we developed an equation that calculates the relative risk of recurrence (Rr) as: Rr = exp[(0.51 x Race) + (0.12 x PSAST) + (0.25 x Postop Gleason sum) + (0.89 x Organ Conf.). These cases are then categorized into 3 distinct risk groups of relative risk of recurrence of low (< 10.0), intermediate (10.0 to 30.0) and high (> 30.0). Kaplan-Meier survival analysis of these 3 risk groups reveals that each category has significantly different risks of recurrence (p < 0.05). This model is validated with an independent cohort of radical prostatectomy patients treated at a different medical center by multiple primary surgeons. CONCLUSIONS: This model suggests that race, preoperative prostate specific antigen, postoperative Gleason sum and pathological stage are important independent prognosticators of recurrence after radical prostatectomy for clinically localized prostate cancer. Race should be considered in future models that attempt to predict the likelihood of recurrence after surgery.     

Induction androgen deprivation plus prostatectomy for stage T3 disease: failure to achieve prostate-specific antigen-based freedom from disease status in a phase II trial

OBJECTIVES: There is interest in treating prostate cancer with induction androgen deprivation prior to radical prostatectomy. Data on long-term prostate-specific antigen (PSA)-based survival analyses among patients treated with neoadjuvant hormonal therapy (NHT) and prostatectomy are limited. In 1991 we instituted a pilot study for T3 disease based on endorectal coil magnetic resonance imaging (eMRI), mandatory negative laparoscopic nodal dissection prior to hormonal manipulation, and prostatectomy followed by pathologic and PSA-based outcome determinations. METHODS: Of 26 patients, 21 had negative laparoscopic lymphadenectomy followed by 4 months of NHT (leuprolide +/- flutamide) prior to radical prostatectomy. eMRI was performed at the time of diagnosis and following hormonal treatment. Serum PSA was determined at 3-month intervals. Prostatectomy specimens were evaluated by 3-mm whole-mount step sections. RESULTS: Prior to prostatectomy, biochemical response was documented in all patients and downsizing was observed by eMRI in 57%. Pathologic downstaging to a lower stage (T2c or lower) was achieved in 48%. However, the actuarial 3-year freedom from biochemical relapse rate was only 24%. CONCLUSIONS: Using laparoscopy to exclude node-positive patients and 4 months of NHT appears to result in pathologic and initial biochemical evidence of regression. These factors have not translated into improved freedom from biochemical relapse among patients with Stage T3 disease treated with NHT and prostatectomy. Recent data strongly suggest a beneficial effect in patients with clinical T2 disease treated with NHT and radical prostatectomy. The NGT and radical prostatectomy approach appeared to offer no clear advantage when compared with PSA-based benchmarks achieved with conformal irradiation or NHT followed by external beam treatment among patients with clinical T3 disease.     

Hormonal treatment before radical prostatectomy: a 3-year followup

PURPOSE: Hormonal treatment administered before radical prostatectomy has been shown to decrease the rate of positive surgical margins. We determine whether preoperative hormonal treatment has any impact on the subsequent failure rate. MATERIALS AND METHODS: We prospectively evaluated 122 patients with stages T1bNxM0 to T3aNxM0, grades 1 to 3 prostate cancer, including 64 randomly assigned to immediate radical retropubic prostatectomy and 58 randomly assigned to radical retropubic prostatectomy preceded by 3 months of pretreatment with a gonadotropin-releasing hormone agonist. We performed intention to treat analysis on the data with failure defined as lymph node involvement, serum prostate specific antigen greater than 0.5 ng./ml., or the need for postoperative hormonal or radiation adjuvant treatment. RESULTS: The positive margin rate was 23.6 versus 45.5% in the pretreatment plus prostatectomy versus prostatectomy only groups (p = 0.016). There were 20 failures (34.5%) in the pretreatment plus prostatectomy subgroup and 26 (40.6%) in the prostatectomy only group (p = 0.48). A negative surgical margin was associated with a significantly lower risk of progression than a positive surgical margin (20.8 versus 50.0%, p = 0.0016), and progression was delayed by approximately 1 year after hormonal pretreatment. However, at a median followup of 38 months there was no difference in progression-free survival (p = 0.57). CONCLUSIONS: Although hormonal pretreatment significantly decreased the positive margin rate, it did not result in any difference in progression-free survival when followup exceeded 3 years. Thus, our current results do not support the routine administration of hormonal treatment before radical prostatectomy.