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Five-year outcomes after prostatectomy or radiotherapy for prostate cancer: the prostate cancer outcomes study.

BACKGROUND: Men treated for clinically localized prostate cancer with either radical prostatectomy or external beam radiotherapy usually survive many years with the side effects of these treatments. We present treatment-specific quality-of-life outcomes for prostate cancer patients 5 years after initial diagnosis. METHODS: The cohort consisted of men aged 55-74 years who were newly diagnosed with clinically localized prostate cancer in 1994-1995 and were treated with radical prostatectomy (n = 901) or external beam radiotherapy (n = 286). We used clinical and quality-of-life data previously collected at the time of diagnosis (i.e., baseline) and at the 2-year follow-up and data newly collected at 5 years after diagnosis to compare urinary, bowel, and sexual function and to examine temporal changes in those functions. Odds ratios (ORs) and adjusted percentages were calculated by logistic regression. All statistical tests were two-sided. RESULTS: At 5 years after diagnosis, overall sexual function declined in both groups to approximately the same level. However, at 5 years after diagnosis, erectile dysfunction was more prevalent in the radical prostatectomy group than in the external beam radiotherapy group (79.3% versus 63.5%; OR = 2.5, 95% confidence interval [CI] = 1.6 to 3.8). Approximately 14%-16% of radical prostatectomy and 4% of external beam radiotherapy patients were incontinent at 5 years (OR = 4.4, 95% CI = 2.2 to 8.6). Bowel urgency and painful hemorrhoids were more common in the external beam radiotherapy group than in the radical prostatectomy group. All of these differences remained statistically significant after adjustment for confounders and for differences between treatment groups in some baseline characteristics. CONCLUSIONS: At 5 years after diagnosis, men treated with radical prostatectomy for localized prostate cancer continue to experience worse urinary incontinence than men treated with external beam radiotherapy. However, the two treatment groups were more similar to each other with respect to overall sexual function, mostly because of a continuing decline in erectile function among the external beam radiotherapy patients between years 2 and 5.

Aged↗

30-day mortality and major complications after radical prostatectomy: influence of age and comorbidity.

BACKGROUND: Radical prostatectomy is associated with excellent long-term disease control for localized prostate cancer. Prior studies have suggested an increased risk of short-term complications among older men who underwent radical prostatectomy, but these studies did not adjust for comorbidity. METHODS: We examined mortality and complications occurring within 30 days following radical prostatectomy among all 11,010 men who underwent this surgery in Ontario, Canada, between 1990 and 1999 using multivariable logistic regression modeling. We adjusted for comorbidity using two common comorbidity indices. Statistical tests were two-sided. RESULTS: Overall, 53 men (0.5%) died, and 2195 [corrected] (19.9%[corrected]) had one or more complications within 30 days of radical prostatectomy. In models adjusted for comorbidity and year of surgery, age was associated with an increased risk of 30-day mortality (odds ratio = 2.04 per decade of age, 95% confidence interval [CI] = 1.23 to 3.39). However, the absolute 30-day mortality risk was low, even in older men, at 0.66% (95% CI = 0.2 to 1.1%) for men aged 70-79 years. In adjusted models, age was associated with an increased risk of cardiac (Ptrend < .001), respiratory (Ptrend = .01), and miscellaneous medical (Ptrend = .058) complications. Similarly, increasing comorbidity was associated with a higher risk of all categories of complications. CONCLUSIONS: Increasing comorbidity is a stronger predictor than age of almost all categories of early complications after radical prostatectomy. The risk of postoperative mortality after radical prostatectomy is relatively low for otherwise healthy older men up to age 79.

Age Factors↗

Biochemical (prostate specific antigen) recurrence probability following radical prostatectomy for clinically localized prostate cancer.

PURPOSE: We retrospectively reviewed the clinical followup for a large series of men with clinically localized prostate cancer who underwent radical retropubic prostatectomy to identify clinical and/or pathological indicators of biochemical (prostate specific antigen [PSA]) recurrence. We then used those indicators to develop multivariate models for determination of recurrence probability following radical retropubic prostatectomy. MATERIALS AND METHODS: From 1982 to 1999, 2,091 consecutive men underwent radical retropubic prostatectomy and pelvic lymphadenectomy for clinically localized adenocarcinoma of the prostate (clinical stage T1c or T2 disease with Gleason score 5 or greater). Actuarial analysis was performed comparing freedom from biochemical recurrence after radical retropubic prostatectomy (PSA 0.2 ng./ml. or greater.) using the Kaplan-Meier method. Event time distributions for the time to recurrence were compared using the log rank statistic or the Cox proportional hazards regression model. The first model was developed using preoperative variables only and the second model using all available variables. Observed and predicted recurrence-free survival curves for different models were compared to select a model for calculation of predicted recurrence-free probabilities and confidence intervals. RESULTS: With a median followup of 5.9 years (range 1 to 17) 360 men (17%) had biochemical recurrence. Overall actuarial 5, 10 and 15-year biochemical recurrence-free survival rates were 84%, 72% and 61%, respectively. The relative risk of biochemical recurrence following surgery decreased with time, even after adjusted for other perioperative parameters. Variables identified for the preoperative model were biopsy Gleason score, clinical TNM stage and PSA. Variables identified for the postoperative model were prostatectomy Gleason score, PSA and pathological organ confinement status. Nomograms were generated and corrected for the decreasing relative risk of biochemical recurrence over time. CONCLUSIONS: Using 3 preoperative or postoperative parameters, these nomograms can easily be used to determine the 3, 5, 7 and 10-year biochemical recurrence-free survival probabilities among men who undergo radical retropubic prostatectomy for clinically localized prostate cancer in the modern era.

Adenocarcinoma↗

Comparison of preoperative prostate specific antigen density and prostate specific antigen for predicting recurrence after radical prostatectomy: results from the search data base.

PURPOSE: Prostate specific antigen (PSA) density based on the surgical weight of the radical prostatectomy specimen has previously been shown to be an independent predictor of biochemical recurrence after radical prostatectomy. We determined whether preoperative PSA density calculated using transrectal ultrasound prostate volume was a better predictor of advanced pathological findings or biochemical recurrence after radical prostatectomy relative to PSA. MATERIALS AND METHODS: We examined 552 men from the newly established Shared Equal Access Regional Cancer Hospital data base of men treated with radical prostatectomy at equal access medical centers to determine whether preoperative PSA density was a significant predictor of an adverse pathological condition or PSA recurrence after radical prostatectomy. Models using PSA density were compared with models using PSA to determine whether PSA density improved risk stratification relative to PSA. PSA density was examined as a continuous and a categorical variable using cutoffs to separate patients into groups at different risks for PSA failure. RESULTS: PSA density and PSA were significant predictors of adverse pathological findings on univariate analysis. Using PSA density in the multivariate model resulted in slightly better but statistically insignificant improvement in prediction of positive surgical margins (p = 0.134) and extracapsular extension (p = 0.771) relative to using PSA in the model. Neither PSA nor PSA density were significant independent predictors of seminal vesicle invasion. Area under the ROC curves for predicting biochemical recurrence for PSA and PSA density were not significantly different (0.589 and 0.58, respectively, p = 0.691). On separate multivariate analyses PSA density and PSA were significant independent predictors of biochemical failure. The multivariate model using PSA density provided only slight improvement in risk assessment relative to the model using PSA (index C = 0.589 and 0.581, respectively). To determine whether using PSA density as a categorical variable would result in improved prognostication we evaluated PSA density to determine the cutoff points that would provide the greatest risk stratification. PSA density cutoffs of less than 0.4, 0.4 to 1 and greater than 1 ng./ml./cc separated patients into 3 distinct groups at increasing risk for biochemical failure (p <0.001). While these cutoffs provided better risk stratification than when PSA density was examined as a continuous variable (index C = 0.684 versus 0.58), they provided only marginal improvement relative to the standard PSA cutoffs of less than 10, 10 to 20 and greater than 20 ng./ml. (index C = 0.676). CONCLUSIONS: The use of preoperative PSA density relative to PSA provided only slight improvement for predicting adverse pathological findings and biochemical recurrence after radical prostatectomy. The minimal and statistically insignificant improvement in preoperative risk assessment provided by PSA density does not justify the time and effort necessary to calculate this value.

Humans↗

A prospective study measuring penile length in men treated with radical prostatectomy for prostate cancer.

PURPOSE: Some patients report that the penis is smaller after radical retropubic prostatectomy for prostate cancer. We performed a prospective study which measured penile length before and after radical retropubic prostatectomy. MATERIALS AND METHODS: A total of 124 men consented to penile measurements before radical prostatectomy performed by the same surgeon. Repeat measurements were performed at 3-month intervals following surgery. Penile measurements (cm.) consisted of flaccid length, stretched length, depth of prepubic fat pad and circumference. Statistical analysis of penile measurements was performed using the paired samples and independent Student's t test, Pearson's correlation and analysis of variance. RESULTS: Mean patient age was 59.1 (range 42 to 76). No patient had a penile abnormality, for example Peyronie's disease, or history of penile or urethral surgery. The size of the penis was significantly smaller after prostatectomy, and there was a significant difference for flaccid (p <0.001), stretched (p <0.001), prepubic fat pad (p = 0.02) and circumference measurements (p <0.01). Twelve patients (19%) had a 15% or greater decrease in stretched penile length. When dichotomizing groups at the cut point of 15% decrease, the independent t test of prostate size was not significant (t[df 36.7] = -1.83, p = 0.076). Nerve sparing was not significant in relation to change in penile stretched length, (F[df 2, 62] = 0.501, p = 0.609). CONCLUSIONS: Our findings support observations of decreased penile length after radical prostatectomy. Men should be counseled before radical prostatectomy that penile shortening may occur.

Adult↗

Preoperative p27 status is an independent predictor of prostate specific antigen failure following radical prostatectomy.

PURPOSE: p27 is an important cell cycle regulator, and decreased expression in radical prostatectomy specimens is associated with an increased risk of prostate specific antigen (PSA) failure. To our knowledge no prior study has shown that preoperative p27 status independently predicts recurrence after radical prostatectomy. MATERIALS AND METHODS: The prostate needle biopsy specimens of 161 men treated with radical prostatectomy were examined for p27 expression using immunohistochemistry. Various p27 cut points were examined for their ability to separate patients into groups with different risk for time to biochemical recurrence following radical prostatectomy. The best p27 cut point was compared to other clinical variables (PSA, clinical stage, age, biopsy Gleason score and percent of prostate needle biopsy with cancer) on multivariate analysis to determine which variables independently predicted biochemical failure. RESULTS: A p27 cut point of less than 45% positive staining cells resulted in significant preoperative risk stratification for time to PSA failure (HR 2.41, p = 0.010). On multivariate analysis serum PSA (HR 1.04, p = 0.011), biopsy Gleason score (HR 1.51, p = 0.011), percent of biopsy tissue with cancer (HR 10.01, p = 0.001) and less than 45% p27 positive cells (HR 2.44, p = 0.014) were all independent predictors of biochemical recurrence. CONCLUSIONS: Preoperative p27 expression is an independent predictor of time to biochemical recurrence following radical prostatectomy. Patients with less than 45% p27 positive cells in the prostate needle biopsy specimen have almost a 2.5-fold increased risk of biochemical recurrence. To our knowledge this study is the first to show that p27 status of the prostate needle biopsy specimen can be used before radical prostatectomy to predict biochemical failure.

Aged↗

Laparoscopic [correction of laproscopic] management of rectal injury during laparoscopic [correction of laproscopic] radical prostatectomy.

PURPOSE: Rectal injury is a potential complication of radical prostatectomy. Because laparoscopic radical prostatectomy is still a challenging procedure, we review the incidence and management of rectal injury in 1,000 cases of consecutive laparoscopic radical prostatectomy performed at our institution. MATERIALS AND METHODS: Of the first 1,000 laparoscopic transperitoneal radical prostatectomies performed between January 1998 and April 2002, 13 (1.3%) were complicated by rectal injury. Mean patient age was 66.5 years (range 58 to 76) and mean prostate specific antigen was 12.9 ng./ml. (range 2.9 to 26). Clinical stage was T1c, T2a and T2b in 5, 7 and 1 patient, respectively. Mean preoperative Gleason score was 5.8 (range 3 to 8). Once recognized the rectal defect was closed laparoscopically in 2 layers and tested for the absence of leakage. Broad-spectrum intravenous antibiotics were given for 7 days. Oral liquids were started the day after surgery with a low residue diet, and a regular diet was started on postoperative day 5. Healing of the vesicourethral anastomosis was confirmed by voiding cystourethrogram on postoperative day 5. RESULTS: All patients underwent a non-nerve sparing procedure except 1 in whom unilateral neurovascular bundle preservation was done. Of 13 injuries 11 were diagnosed and repaired intraoperatively, and 2 were diagnosed postoperatively. Of the 11 cases of intraoperative diagnosis and repair 9 healed primarily without colostomy and peritonitis was diagnosed in the remaining 2 on days 3 and 4, respectively. Of the latter 2 patients 1 required repair of a small rectal defect without colostomy while the other required colostomy. Colostomy was performed in the 2 patients with delayed diagnosis on days 3 and 4 but even then a rectourethral fistula developed in 1, necessitating secondary repair. Average urethral catheterization time was 8.6 days for the 9 patients with an uneventful immediate postoperative course and mean hospital stay was 6.8 days. For the remaining 4 patients urethral catheterization duration was 12, 13, 15 and 120 days, and hospital stay was 7, 16, 21 and 27 days, respectively. There was no perioperative mortality. CONCLUSIONS: Rectal injury during laparoscopic radical prostatectomy requires meticulous intraoperative repair in 2 layers, which allows primary healing without diversion colostomy. For injury prevention scrupulous attention is required during non-nerve sparing radical prostatectomy, particularly at the posterior surface of the prostatic apex.

Aged↗

A longitudinal assessment of bowel related symptoms and fecal incontinence following radical perineal prostatectomy.

PURPOSE: Recent studies have suggested an increased incidence of fecal incontinence following radical perineal prostatectomy. We provide a prospective and longitudinal assessment of bowel related symptoms of patients undergoing radical perineal prostatectomy. MATERIALS AND METHODS: A total of 78 patients who underwent radical perineal prostatectomy between January 1 and December 31, 2001 and had a minimal followup of 6 months were included in the analysis. Patient information was obtained from the chart and the bowel domain specific questions of a validated quality of life questionnaire, the Expanded Prostate Cancer Index Composite. The questionnaire was administered to the candidates preoperatively, at 4 weeks following surgery and subsequently at 3-months intervals. A mean bowel function, bother and summary health related quality of life score was calculated at each interval. The duration of new or worsened symptoms with respect to baseline was evaluated using Kaplan-Meier analysis. RESULTS: Symptoms of involuntary stool leakage and rectal urgency were reported by 11.5% (9 of 78) and 19.2% (15) of patients preoperatively. While all bowel related symptoms transiently increased following surgery, rectal urgency was the most persistent symptom, yet normalized in more than 90% of patients within 9 1/2 months. Compared to individual baseline 15.4%, 7.7%, 5.1% and 3.9% of patients reported worsened symptoms of fecal incontinence after 3, 6, 9 and 12 months, respectively. In the subset of 69 patients who denied preoperative fecal incontinence the incidence of involuntary stool leakage was 2.9% by 12 months following radical perineal prostatectomy. Of 10 patients 9 recovered individual health related quality of life score by 6 months after prostatectomy. CONCLUSIONS: Longitudinal assessment of self-reported questionnaire data suggests that fecal incontinence and bowel related symptoms are more prevalent following radical perineal prostatectomy compared to baseline, yet resolve in the majority of patients with time in the early postoperative period.

Adult↗

Critical surgical techniques for radical perineal prostatectomy.

PURPOSE: Radical perineal prostatectomy was historically the surgical treatment of choice for localized adenocarcinoma of the prostate until the 1980s when radical retropubic prostatectomy began to gain popularity. Nevertheless, the perineal approach possesses advantages that prompt resurgence in the interest of this classic operation. We review the relevant anatomy and our modified technique of performing a successful radical perineal prostatectomy. MATERIALS AND METHODS: The English literature pertaining to the different surgical approaches to radical perineal prostatectomy was reviewed through PubMed. Attention was paid to its indications, anatomical significance and various surgical techniques. RESULTS: Studies demonstrate no difference in the incidence of positive surgical margins and biochemical recurrence between radical retropubic and perineal prostatectomies. Furthermore, the perineal approach avoids the dorsal venous complex and better facilitates the vesicourethral anastomosis in the face of minimal pain and requirement for transfusion. We use a modified Belt approach, aiming to yield the most optimal outcome with minimal morbidity. A meticulous anatomical approach is warranted if complications such as rectal injury, incontinence and erectile dysfunction are to be minimized. CONCLUSIONS: With careful preoperative evaluation, selected patients should benefit from radical perineal prostatectomy for the management of localized prostate cancer. Familiarity with this specialized technique should be an immeasurable addition to any armamentarium in the therapy of prostatic diseases.

Equipment Design↗

Prostate specific antigen progression in men with lymph node metastases following radical prostatectomy: results of long-term followup.

PURPOSE: We examined the clinical outcome of patients with lymph node metastases found at prostatectomy with the goal to identify factors that predict freedom from prostate specific antigen (PSA) progression. MATERIALS AND METHODS: We retrospectively reviewed the records of 3,264 consecutive men with clinically localized prostate cancer who underwent extended pelvic lymphadenectomy and radical prostatectomy performed by a single surgeon between April 1982 and March 2003. Patients with pathologically confirmed lymph node metastases and no history of adjuvant treatment were identified. Clinical and histopathological factors were analyzed for an association with time to PSA progression using univariate and multivariable analyses. RESULTS: Of the 143 patients (4.4% of total) in the study with nodal involvement 24 (16.8%) were free of disease at last followup (median 6 years). Median time to failure was 2 years with PSA progression occurring as late as 11 years postoperatively in 2 patients. The 5 and 7-year PSA progression free rate in all lymph node positive patients was 26.5% and 10.9%, respectively. A 15% or greater incidence of positive nodes (p = 0.0008) and high prostatectomy Gleason score (ie score 8 to 10, p = 0.008) were independent predictors of PSA progression in multivariate Cox proportional hazards models. Seminal vesicle invasion (HR 1.45, p = 0.063) or positive surgical margins (HR 1.43, p = 0.063) were marginally significant in the multivariate model. The 5-year PSA progression-free rate was 52% in men with less than 15% positive lymph nodes, prostatectomy Gleason score 7 or less and negative seminal vesicle invasion. CONCLUSIONS: While the incidence of lymph node positive disease in patients undergoing radical prostatectomy is infrequent in the PSA era, patients with nodal involvement may experience disease progression as remote as 1 decade after surgery. Pathological factors such as the percent of positive lymph nodes, prostatectomy Gleason score and seminal vesicle invasion appear to predict an increased risk of PSA failure in this population.

Disease Progression↗

Perineural invasion in radical prostatectomy specimens: lack of prognostic significance.

PURPOSE: The prognostic significance of perineural invasion in radical prostatectomy specimens is uncertain. We evaluated the relationship between perineural invasion and other pathological characteristics in whole mount radical retropubic prostatectomy specimens as well as prostate specific antigen (PSA) recurrence postoperatively. MATERIALS AND METHODS: Between 1999 and 2003, 364 consecutive patients were treated with radical prostatectomy for localized prostate cancer. Radical prostatectomy specimens were processed by the whole mount technique. The relationship of perineural invasion and various clinicopathological characteristics to PSA recurrence was analyzed. RESULTS: Perineural invasion was present in 287 specimens (79%). Specimens with perineural invasion were associated with smaller prostate weight (p <0.0001), greater pathological stage (p <0.0001), larger tumor volume (p <0.0001), higher Gleason score (p <0.0001), a higher incidence of extraprostatic extension (p <0.0001) and seminal vesicle invasion (p = 0.02), and a higher positive surgical margin rate (p = 0.01). Perineural invasion did not correlate with preoperative PSA (p = 0.96), lymph node metastases (p = 0.35), multifocality (p = 0.21), high grade prostatic intraepithelial neoplasia (p = 0.12) or PSA recurrence (p = 0.24). CONCLUSIONS: While perineural invasion in the radical prostatectomy specimen significantly correlated with multiple adverse pathological factors, it did not predict which patients will have early PSA recurrence following radical prostatectomy.

Aged↗

Preoperative prediction of small volume cancer (less than 0.5 ml) in radical prostatectomy specimens.

PURPOSE: The detection of low volume and early stage prostate cancer has increased with the widespread use of prostate specific antigen screening for prostatic adenocarcinoma. This increased detection has led to efforts to stratify patient risk and the potential benefits of various treatments based on preoperative clinical and biopsy data. We examined various clinical parameters and prostate biopsy features to determine which variables are most predictive of small volume (less than 0.5 ml) cancer at prostatectomy. MATERIALS AND METHODS: We studied 336 patients who underwent prostatectomy for prostate cancer. Radical prostatectomy specimens were completely embedded and whole mounted. Final tumor volume in the radical prostatectomy specimens was determined by the grid method. Clinical data were gathered by a review of patient charts. Various preoperative clinical and biopsy findings were analyzed to determine factors predictive of small volume cancer at prostatectomy. RESULTS: A total of 55 patients (16%) were found to have small volume cancer (less than 0.5 ml). On univariate logistic regression certain variables were significant predictors of small volume cancer, namely the highest Gleason score from all positive biopsy sites (p = 0.001), the Gleason score from the biopsy site with the highest percent of adenocarcinoma (p = 0.006), the highest percent of adenocarcinoma at any biopsy site (p <0.0001), the percent of adenocarcinoma at the biopsy site with the highest Gleason score (p <0.0001), the highest percent of cores positive for adenocarcinoma at any biopsy site (p = 0.001), the percent of cores with carcinoma at the site with the highest Gleason score (p = 0.002), the number of positive sites (p <0.0001) and tumor bilaterality (p <0.0001). None of the clinical parameters that we studied, including preoperative prostate specific antigen (p = 0.52), clinical stage (p = 0.62) or patient age (p = 0.94), was predictive of small volume cancer. On multivariate analysis the highest percent of adenocarcinoma at any site (adjusted OR 0.95, 95% CI 0.92 to 0.97, p <0.0001) and the number of positive biopsy sites (adjusted OR 0.97, 95% CI 0.96 to 0.99, p <0.0001) were significant predictors of small volume cancer. CONCLUSIONS: The number of positive biopsy sites and the highest percent of adenocarcinoma at any biopsy site are significant predictors of small volume cancer in radical prostatectomy specimens.

Adenocarcinoma↗

Update on laparoscopic and robotic radical prostatectomy.

PURPOSE OF REVIEW: Laparoscopic and robotic-assisted prostatectomy have been proposed as alternatives to traditional open retropubic prostatectomy. In this review, we update the more recent data concerning the results, technical trends and controversies regarding these novel, minimally invasive procedures. RECENT FINDINGS: As a result of improved patient selection, a better understanding of surgical anatomy, and refinements in surgical techniques, traditional retropubic prostatectomy set the standards very high, leaving little room for improvement. In this review, the results of laparoscopic prostatectomy are compared with contemporary in addition to historical series. Besides the transperitoneal laparoscopic approach, which was almost exclusively used in the initial series, the introduction and development of the extraperitoneal laparoscopic approach meant a significant change in the surgical strategy of a number of teams worldwide. The relative merits of the transperitoneal and extraperitoneal approaches are discussed. Robotic radical prostatectomy is a promising technical innovation that allows us to overcome many of the inherent limitations of laparoscopic surgery. As a result of financial constraints, the experience has been limited to a few centres worldwide. SUMMARY: Although long-term results are still lacking, novel minimally invasive techniques seem to fulfil the highest standards of radical prostatectomy in terms of early oncological cure, functional results and morbidity. A standardization of data collection and evaluation methodology will be indispensable for a better comparison of the different series.

Blood Loss, Surgical↗

Symptoms versus flow rates versus urodynamics in the selection of patients for prostatectomy.

Many prostatectomies are performed on the basis of symptoms alone; 39% of patients referred by their family doctors and 23% of patients who were on waiting lists for prostatectomy of other hospitals, but who had not undergone any urodynamic investigations, were found to be unobstructed on urodynamic criteria. A screening peak urinary flow rate of 12 ml/s or less was associated with urodynamic evidence of obstruction in 95% of cases; 35% of patients with symptoms of outflow obstruction and a flow rate greater than 12 ml/s were also found to be obstructed. One year post-operatively, 84% of patients who were selected for surgery on combined symptomatic and urodynamic criteria were pleased symptomatically with their result. The failure of detrusor instability to resolve following prostatectomy was associated with symptomatic failure of treatment. Residual obstruction was demonstrated in 5 patients who had undergone prostatectomy and were asymptomatic at this time. This study illustrates that objective measures are necessary in the assessment of patients prior to prostatectomy in order to select only patients who are obstructed. The importance of a screening flow rate is emphasised. All patients who underwent surgery had cystometric evidence of obstruction but the symptomatic results of surgery were no better than the results in patients who had been assessed according to non-urodynamic selection criteria. We have thus failed to identify a need for routine cystometry in the pre-operative assessment of these patients. Cystometry does, however, have a role in assessing patients with pre-operative flow rates greater than 12 ml/s and in those who remain symptomatic following prostatectomy.

Humans↗

Intra-operative myocardial ischaemia detected by biplane transoesophageal echocardiography during transurethral prostatectomy.

Recent studies have shown an increased late mortality rate due to cardiovascular causes after transurethral compared with open prostatectomy. This has been linked to the demonstration of haemodynamic changes during transurethral prostatectomy, which may cause ischaemic myocardial injury. We used transoesophageal echocardiography (currently the most sensitive modality for detecting myocardial ischaemia) to study 26 patients during prostatectomy under general anaesthesia. Evidence of myocardial ischaemia (as shown by the development of new regional wall motion abnormalities of the left ventricle) occurred in 4 of 22 patients during transurethral and in 3 of 4 patients during retropubic prostatectomy. An intra-operative fall in systolic as well as diastolic blood pressure occurred in 21 of 22 patients during the transurethral procedure and in all 4 patients during retropubic prostatectomy. The duration of anaesthesia and the operation, and the intra-operative blood loss did not differ significantly between patients with and without evidence of intra-operative myocardial ischaemia. However, the maximum intra-operative fall in systolic and diastolic blood pressure, as well as the mass of the prostatic tissue removed, were significantly greater in patients with than in those without evidence of intra-operative myocardial ischaemia, suggesting that the latter may be related to the extent of surgery and the degree of intraoperative hypotension. In this study, 7 of 26 patients (27%) showed evidence of myocardial ischaemia during prostatectomy. However, it remains difficult to explain why intra-operative myocardial ischaemia should result in an increased cardiovascular mortality rate several years after the operation.

Aged↗

Salvage radical prostatectomy in the management of locally recurrent prostate cancer after 125I implantation.

OBJECTIVE: To define the role of salvage prostatectomy in patients who have locally recurrent prostate cancer following pelvic lymph node dissection and 125I implantation. PATIENTS AND METHODS: Over 1000 patients underwent 125I implantation for localized prostate cancer at the Memorial Sloan Kettering Cancer Center between 1970 and 1986. Salvage radical prostatectomy was performed in a highly selected group of 10 patients with locally recurrent disease. RESULTS: Three of the 10 patients had organ-confined residual prostate cancer following salvage radical prostatectomy. The remaining seven patients had extra-prostatic disease including four patients with positive surgical margins. Two patients with organ-confined disease and one with extracapsular tumour had no evidence of locally recurrent or metastatic disease and continue to have undetectable prostate-specific antigen (PSA) levels at 50, 44, and 31 months following salvage radical prostatectomy. After a mean follow-up of 30 months, the remaining seven patients had a rising PSA level consistent with locally persistent and/or metastatic disease (median 5 ng/mL; range 1.0-144). This PSA elevation occurred within 20 months of salvage radical prostatectomy (median 6 months). Two of these patients developed clinically evident bone metastases. CONCLUSION: Salvage radical prostatectomy, although technically feasible in highly selected patients, should not be widely advocated as an effective treatment option for patients with locally recurrent prostate cancer after 125I implantation.

Aged↗

Gleason scores from prostate biopsies obtained with 18-gauge biopsy needles poorly predict Gleason scores of radical prostatectomy specimens.

OBJECTIVES: Prostate cancer is the most frequent cancer among men in the US. Histological grading is an important part of the diagnostic evaluation aside from clinical staging and serum PSA. The most commonly used grading system is the one described by Gleason. From a prognostic point of view, it is of considerable interest to know how accurate the needle biopsy Gleason score is in predicting the final score of the radical prostatectomy specimen. From an outcome research point of view, it is important to recognize that a stratification of patients by Gleason score may prove correct in patients undergoing radical prostatectomy, while in patients undergoing radiation or conservative management some of the well-differentiated cancers could actually be moderately and poorly differentiated, and some of the moderately differentiated might be poorly differentiated, thus favoring radical prostatectomy in a direct comparison of treatment efficacy. We aimed to determine (1) whether such undergrading exists, (2) what the magnitude of the bias is, and (3) whether it is common and similar in different institutions. MATERIALS AND METHODS: We retrospectively reviewed the records of 415 patients who underwent radical prostatectomy in three Dallas area hospitals, excluding patients who received neoadjuvant therapy prior to surgery. Data of Gleason grades and score were collected from the needle biopsy and the radical prostatectomy specimen. Analysis was done using three categorization schemes for mild, moderate and poor differentiation for the three individual hospitals and the entire group. RESULTS: The most common Gleason score by needle biopsy and prostatectomy was five. 37.2% of all patients had no change in score assignment, while 12.7% were 'overgraded' and 50.1% 'undergraded' by needle biopsy. The most common undergrading was by 1 or 2 score points. Only 23.7% of the category 'well' cancers remained so after surgery. Between 65.0 and 88.4% of the category 'moderate' cancers remained so after surgery. To determine the degree of agreement between needle biopsy and surgery category, kappa statistics were employed. The kappa value ranged from 0.148 to 0.328 for all categories and classification schemes indicating poor reproducibility. Serum prostate-specific antigen was not helpful in predicting Gleason score upgrading. CONCLUSIONS: Independent of the setting, about 50% of all Gleason score assignments made on needle biopsy specimen are revised in the direction of a worse score/category. It is important for clinicians to realize this phenomenon when consulting with patients regarding treatment choices if the grade is taken into consideration. For outcome research purposes, it is important to realize that this introduces a bias into direct comparisons between surgical and nonsurgical (radiation and watchful waiting) series favoring the outcomes of surgical series as the nonsurgical series suffer from a less favorable patient mix.

Biopsy↗

Angiogenesis, p53, bcl-2 and Ki-67 in the progression of prostate cancer after radical prostatectomy.

Within the past 5 years, research has increasingly addressed molecular alterations in prostate cancer (CaP). Mutations of tumor suppressor gene p53 have been found in a variety of cancers, including urologic neoplasms. Several studies have been conducted on CaP specimens, citing frequencies of p53 alterations in localized cancers ranging from 4 to 60% and with more advanced hormone refractory disease, as high as 94%. The majority of studies have revealed a low percentage of p53 abnormalities in early-stage (clinically organ-confined) CaP. The overwhelming bulk of evidence suggests that the frequency of p53 abnormalities does increase with disease progression and is highest in tissues from patients with hormone-refractory prostate cancer. More recently, our group and others have found that focal p53 expression in the primary tumor by immunohistochemistry is predictive of cancer recurrence after radical prostatectomy. bcl-2 is an oncogene critically involved in the apoptosis, or programmed cell death. Overexpression of bcl-2 protein by immunohistochemistry has been commonly detected in advanced hormone refractory CaP. Our group recently has also shown that bcl-2 protein expression in primary CaP is a predictor of cancer recurrence after radical prostatectomy. Furthermore, the combination of p53 and bcl-2 protein expression were both independent predictors of recurrence after surgery. Most recently, we have shown that even though p53 and bcl-2 are predictive biomarkers when sampling the radical prostatectomy specimen, they are not useful to predict postoperative recurrence when sampling the pretreatment needle biopsy. Ki-67 is an antigen of cellular proliferation. Immunohistochemical staining for Ki-67 in archival material can be performed using the MIB-1 antibody. Unlike our results with p53 and bcl-2, Ki-67 protein expression by immunohistochemistry using MIB-1 was not an independent prognostic marker for cancer recurrence after radical prostatectomy although it may have clinical utility in subsets of patients. Assessment of MIB-1 staining in CaP needle biopsy samples is underway. Tumor neovascularity, or angiogenesis, is necessary for cancers to grow and metastasize. Angiogenesis in CaP as a prognostic marker has received recent attention. Most studies have used factor VIII immunohistochemical staining and increased angiogenesis has been suggested as a staging and prognostic marker. Our group has recently conducted a large study of radical prostatectomy patients and used CD34 antigen immunohistochemistry to assess neovascularity. We did not find that this biomarker assessment was an independent prognostic marker of cancer recurrence after radical prostatectomy. Further work is being conducted in needle biopsy samples. More research is needed to assess new biomarkers and, most importantly, to standardize the methodology for sampling and assaying biomarkers in heterogeneous and multifocal prostate cancer.

Biomarkers, Tumor↗