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Effect of neoadjuvant androgen deprivation on circulating prostate cells in the bone marrow of men undergoing radical prostatectomy.

Our objective was to determine the effect of neoadjuvant hormonal therapy on the presence of circulating prostate cells in patients undergoing radical prostatectomy for prostate cancer. A total of 60 patients at high risk for extraprostatic disease were analyzed for the presence of circulating prostate cells using reverse transcriptase PCR (RTPCR) amplification of the prostate-specific antigen mRNA. Twenty-nine patients underwent radical prostatectomy for a clinical T2b-c tumor or a stage T1c-T2a tumor and a serum prostate-specific antigen level > or =10ng/ml (radical prostatectomy alone), and 31 similarly staged patients received neoadjuvant hormonal therapy before radical prostatectomy (neoadjuvant). Bone marrow samples were used for RTPCR analysis. Twenty-four percent and 58% of the radical-prostatectomy-alone patients and neoadjuvant patients had organ-confined disease, respectively (P = 0.007). In the radical-prostatectomy-alone group, 77% and 14% of patients with extraprostatic and organ-confined disease were RTPCR positive, respectively (P = 0.03). However, in the neoadjuvant group, 46% and 28% of patients with extraprostatic and organ-confined disease were RTPCR positive, respectively (P = 0.29). For patients that were RTPCR positive, 45 % of the neoadjuvant patients had organ-confined disease compared with 6% in the radical-prostatectomy-alone patients (P = 0.018). These data suggest that a subset of the neoadjuvant patients are converted to organ confined disease without eliminating the prostate cells in the bone marrow. Our data suggest that hormonal therapy before radical prostatectomy decreases the occurrence of extraprostatic disease but, to a lesser degree, the incidence of circulating prostate cells. This may partially explain why hormonal therapy before radical prostatectomy has not improved disease-free survival.

Androgen Antagonists↗

Defining prostate specific antigen progression after radical prostatectomy: what is the most appropriate cut point?

PURPOSE: The most appropriate definition of biochemical progression after radical prostatectomy and radiation therapy is uncertain. We analyzed the effect of using various prostate specific antigen (PSA) end point definitions for defining biochemical progression after radical prostatectomy and attempted to determine the best PSA cut point to use. Aspects of the American Society for Therapeutic Radiology and Oncology (ASTRO) definition of biochemical failure after radiation therapy are also analyzed in our radical prostatectomy cases. MATERIALS AND METHODS: A total of 2,782 men with clinically localized prostate cancer (cT1-T2) who had undergone radical prostatectomy between 1987 and 1993 were reviewed. All patients had regular PSA determinations from surgery through followup. Analysis was limited to patients who did not receive adjuvant treatment within 90 days of radical prostatectomy. Biochemical, PSA progression-free percent after radical prostatectomy was determined by the Kaplan-Meier method using several PSA cut points, including 0.2, 0.3, 0.4 and 0.5 ng./ml. or greater, as well as 0.4 ng./ml. or greater and increasing. Progression-free percent was also assessed using the ASTRO definition, which is 3 increases in PSA. To determine which PSA level was most appropriate to define progression after radical prostatectomy, the percentage of patients with a continued PSA increase after reaching each cut point was determined. The relationship between the maximum PSA within 3 years of surgery and subsequent development of clinical disease was also assessed. RESULTS: Progression-free percent was dependent on the PSA cut point used. Biochemical progression-free percentages for cut points 0.2, 0.3, 0.4 and 0.5 ng./ml. or greater were 62%, 72%, 76% and 78% at 5 years, and 43%, 54%, 59% and 61% at 10 years, respectively. A subsequent increase in PSA was noted in 49%, 62% and 72% of patients who had PSA 0.2, 0.3 and 0.4 ng./ml., respectively. Subsequent clinical progression (local or systemic) was directly related to the maximum PSA attained within 3 years of radical prostatectomy (p=0.0001). Progression-free percent for definitions requiring multiple increases in PSA were dependent on when the event was said to occur. Backdating of events at or before the first PSA (ASTRO definition) resulted in poorer, short-term progression-free percent (78% at 5 years), with little apparent likelihood of long-term failure (78% at 10 years). Coding the event at the last PSA increase when all event criteria had been met resulted in more realistic progression-free percent estimates (85% at 5 and 59% at 10 years). CONCLUSIONS: Biochemical, PSA progression rates vary markedly depending on the method used to define PSA failure. Methods that require multiple increasing PSA values, for example the ASTRO definition, give misleading results, especially if the event time is backdated. Standards for defining PSA progression would allow more consistent and comparable progression estimates after radical prostatectomy. PSA 0.4 ng./ml. or greater may be the most appropriate cut point to use since a significant number of patients with lower PSA do not have a continued increase in it.

Adult↗

Suramin as adjuvant therapy with radical prostatectomy.

Suramin is a newer agent employed in the management of prostate cancer. One suggested method of action is growth factor inhibition. While suramin has been employed to treat advanced disease its adjuvant role remains unexplored. To address this question we have employed a new model: the orthotopic placement of the Dunning AT-3 tumor. The purpose of this research was to assess the efficacy of adjuvant therapy in controlling residual disease. The method consisted of the injection of 2.4 to 2.6 x 10(6) AT-3 cells (harvested from flank tumors) into the ventral prostates of 29 Copenhagen X Fischer rats. The animals were then divided into four groups: 1) untreated controls (6 rats); 2) ventral prostatectomy only (10 rats); 3) ventral prostatectomy plus suramin (300mg/Kg) on post-op day 3 (5 rats); and 4) ventral prostatectomy plus cytoxan (50 mg/Kg) on post-op day 3 (8 rats). Prostatectomies were performed 10-12 days following AT-3 cell inoculation. Animals were sacrificed 10 days following prostatectomy, autopsied, and residual diseased weighed. All operating procedures: tumor cell inoculations, ventral prostatectomies, and necropsies were performed microsurgically employing a Zeiss operating microscope. The results (in mean tumor weights) were: Group 1, 20 +/- 1.4 gms; Group 2, 6.7 +/- 11.5 gms; Group 3, 2.7 +/- 3.8 gms; and Group 4, 2.2 +/- 2.5 gms. The differences between control and all treatment groups were significant: Group 1 vs. Group 2, P < 0.02; and Group 1 vs. Groups 3 and 4, P < 0.001. We conclude that prostatectomy resulted in a diminished weight of residual disease. Of more importance was the fact that adjuvant therapy further reduced residual disease. The orthotopic placement of the Dunning tumor may serve as a model to evaluate the place of suramin following radical prostatectomy.

Animals↗

A comparison of external beam radiation therapy versus radical prostatectomy for patients with low risk prostate carcinoma diagnosed, staged, and treated at a single institution.

BACKGROUND: The authors retrospectively reviewed their institution's long term experience treating a group of comparably staged low risk prostate carcinoma patients with either radical prostatectomy or external beam radiation therapy (RT) to determine whether the method of treatment resulted in significant differences in biochemical control and/or survival. METHODS: From January of 1987 through December of 1994, 382 patients (157 who underwent radical prostatectomy and 225 who received external beam RT) were treated with curative intent for localized prostate carcinoma at William Beaumont Hospital. All patients had a pretreatment serum prostate specific antigen (PSA) level < or =10.0 ng/mL and a biopsy Gleason score </=6. Patients treated with RT received a median dose of 66.6 gray (Gy) (range, 59.2-70.2 Gy) to the prostate. Patients treated surgically underwent radical retropubic prostatectomy with a pelvic lymph node dissection. For surgical patients, biochemical failure was defined as a detectable PSA level > or =0.2 ng/mL at any time after prostatectomy. For RT patients, biochemical failure was defined according to the American Society for Therapeutic Radiology and Oncology Consensus Panel definition. Pretreatment PSA levels and Gleason scores were not significantly different between patients treated with radical prostatectomy or RT. The median follow-up in each treatment group was 5.5 years. RESULTS: The 7-year actuarial rates of biochemical control and cause specific survival were not significantly different between patients treated either with radical prostatectomy or RT (67% vs. 69% for biochemical control and 99% vs. 97% for cause specific survival, respectively). A number of clinical, pathologic, and treatment-related factors were analyzed for an association with biochemical failure (i.e., age, pretreatment PSA, Gleason score, and treatment modality). Only pretreatment PSA and Gleason score were significantly related to outcome in both univariate and multivariate analyses. CONCLUSIONS: Low risk prostate carcinoma patients with similar pretreatment PSA levels and biopsy Gleason scores treated at the same institution with either radical prostatectomy or RT achieved similar 7-year rates of biochemical control and cause specific survival, regardless of treatment technique. These findings suggest that for patients with pretreatment PSA levels </=10 ng/mL and Gleason scores </=6, conventional doses of external beam RT and radical retropubic prostatectomy can be expected to produce comparable treatment results unaffected by age at diagnosis.

Age of Onset↗

Poorly differentiated prostate cancer treated with radical prostatectomy: long-term outcome and incidence of pathological downgrading.

PURPOSE: Patients with high grade (Gleason score 8 to 10) prostate cancer on biopsy are at high risk for cancer recurrence after local treatment, such as radiation therapy and radical prostatectomy. We examined long-term outcomes in patients with high grade prostate cancer on biopsy who were treated with radical prostatectomy alone. We also investigated the impact on outcomes of changes in the radical prostatectomy Gleason score. MATERIALS AND METHODS: Of 5,662 patients who underwent radical prostatectomy during 20 years 238 had a biopsy Gleason score of 8 to 10. We analyzed the rate of biochemical recurrence in this subgroup according to the Gleason grade of cancer in the radical prostatectomy specimen. RESULTS: Ten-year biochemical recurrence-free probability in the cohort was 39%. However, 45% of patients (95% CI 38 to 51%) with Gleason score 8 to 10 cancer on biopsy had a Gleason score of 7 or less in the radical prostatectomy specimen. These patients had a 10-year biochemical recurrence-free probability of 56% compared to 27% in those with a final Gleason score that remained 8 to 10 (p = 0.0004). On multivariate analysis neither prostate specific antigen nor biopsy features, including total number of cores, number of cores with cancer and percent of cancer in the cores, was a significant predictor of downgrading. However, clinical stage and biopsy Gleason score were significant with 58% of cT1c and 51% of biopsy Gleason score 8 cancers downgraded. Almost 65% of cT1c Gleason score 8 cancers were downgraded compared to 11% of cT3 Gleason score 9 cancers. CONCLUSIONS: Patients diagnosed with poorly differentiated prostate cancer (Gleason score 8 to 10) on biopsy do not uniformly have a poor prognosis. Of the patients 39% remain free of cancer recurrence 10 years after radical prostatectomy. Of these cancers 45% have a lower Gleason score in the radical prostatectomy specimen and a correspondingly more favorable long-term outcome. Predictors of downgrading are lower clinical stage (cT1c) and Gleason score 8 in the biopsy specimen.

Cell Differentiation↗

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.

Antineoplastic Agents, Hormonal↗

Lower prostate specific antigen outcome than expected following radical prostatectomy in patients with high grade prostate and a prostatic specific antigen level of 4 ng/ml. Or less.

PURPOSE: We report the estimates of 10-year prostate specific antigen (PSA) outcome following radical prostatectomy in patients with or without grade 4 or 5 disease in the needle biopsy or prostatectomy specimen stratified by the presenting PSA level. MATERIALS AND METHODS: From 1989 to 2001, 2,254 patients treated with radical prostatectomy for clinically localized prostate cancer comprised the study cohort. PSA outcome was estimated using the actuarial method of Kaplan and Meier, and was stratified by the presenting PSA level and needle biopsy and prostatectomy Gleason score. RESULTS: The 10-year estimates of PSA outcome declined significantly (p </=0.002) for patients with biopsy or prostatectomy Gleason score 6 or less as the presenting PSA level increased. This trend was observed for biopsy and prostatectomy Gleason score 7 or higher except for the PSA 4 or less group which did significantly worse (46% versus 62%, p = 0.03) compared to the PSA greater than 4 to 10 ng./ml. group. This finding may be explained by a low serum free testosterone level and the presence of a significantly higher proportion of prostatectomy Gleason score 8 to 10 disease (25% versus 16%, p = 0.03) in the PSA 4 or less versus greater than 4 to 10 ng./ml. group. CONCLUSIONS: Patients with Gleason grade 4 or 5 disease in the radical prostatectomy specimen and a presenting PSA of 4 ng./ml. or less may be androgen deficient and have a significantly lower estimate of 10-year PSA outcome then expected based on the presenting PSA level.

Adult↗

Neoadjuvant hormonal therapy before radical prostatectomy and risk of prostate specific antigen failure.

PURPOSE: To date there is little information on the long-term effect of neoadjuvant hormonal therapy on prostate cancer progression. We performed a prospective study to determine whether patients with prostate cancer receiving neoadjuvant hormonal therapy before radical prostatectomy (hormonal therapy group) have a lower risk of prostate specific antigen (PSA) failure than those treated with radical prostatectomy alone (prostatectomy group). We also evaluated whether type of neoadjuvant hormonal therapy and duration were associated with the risk of PSA failure. MATERIALS AND METHODS: We followed 680 men initially treated for prostate cancer with radical prostatectomy between January 1988 and December 1997 at our university hospital. Of the patients 292 received neoadjuvant hormonal therapy. Median followup was 38 months. Cox regression analysis was used to assess the association between neoadjuvant hormonal therapy and PSA failure (greater than 0.3 ng./ml.) controlling for age, clinical stage, grade, initial PSA and adjuvant therapies. RESULTS: Surgical margins were positive less often in the hormonal therapy (25%) than the prostatectomy (47%) group (p = 0.0001). PSA failure was observed in 163 patients and the 5-year failure rate was 33%. No difference in risk of PSA failure was observed overall between the hormonal therapy and prostatectomy groups (hazards ratio 0.94, 95% confidence interval 0.68 to 1.30). Treatments with antiandrogen alone for any duration, and those combining antiandrogen and luteinizing hormone-releasing hormone analogue for 3 months or less were not associated with improved survival. However, patients receiving combined therapy for more than 3 months had a significantly lower risk of PSA failure than those treated with radical prostatectomy alone (hazards ratio 0.52, 95% confidence interval 0.29 to 0.93). CONCLUSIONS: Prolonged neoadjuvant hormonal therapy combining antiandrogen and luteinizing hormone-releasing hormone analogue may improve disease-free survival after radical prostatectomy.

Adult↗

One-stage laparoscopic pelvic lymphadenectomy and radical perineal prostatectomy.

Laparoscopic pelvic lymph node dissection is currently an accepted procedure for staging adenocarcinoma of the prostate. To assess the feasibility and efficacy of performing laparoscopic pelvic lymph node dissection and radical perineal prostatectomy during the same anesthesia, we retrospectively analyzed 98 patients with clinically localized adenocarcinoma of the prostate who were candidates for radical prostatectomy. Of the patients 12 (12%) underwent laparoscopic pelvic lymph node dissection only since they had metastatic disease to the pelvic lymph nodes on frozen section evaluation (the Gleason pathological grade was 2 to 4 in 2 patients, 5 to 7 in 8 and 8 in 2). Of the remaining 86 patients who underwent radical perineal prostatectomy for definitive management 76 (88%) underwent 1-stage radical perineal prostatectomy immediately after laparoscopic pelvic lymph node dissection, while 10 (12%) in the initial stages of our series underwent delayed perineal prostatectomy following laparoscopic pelvic lymph node dissection (2-stage). The average postoperative hospital stay in the 1-stage group was 3.11 days, yet 19 (25%) patients were discharged from the hospital within 48 hours and another 39 (51%) within 72 hours. Thus, 76% of the patients were discharged from the hospital within 72 hours of laparoscopic pelvic lymph node dissection and radical perineal prostatectomy. The advent of laparoscopic pelvic lymph node dissection and radical perineal prostatectomy has found a resurgence at our institutions, with its lower morbidity rate and more rapid return to normal activity for these patients. Based on our results, we recommend laparoscopic pelvic lymph node dissection followed by radical perineal prostatectomy as a 1-stage treatment option for localized adenocarcinoma of the prostate.

Adenocarcinoma↗

Why do sicker patients cost more? A charge-based analysis of patients undergoing prostatectomy.

Hospitals are reimbursed a greater amount for Medicare patients undergoing prostate surgery who have comorbid and complicating conditions than for patients without these conditions, since the former have been shown to have higher hospital costs and charges. We attempted to determine whether the higher hospital charges are due to duration of hospital stay and/or intensity of services. We analyzed hospital discharge data from 799 patients undergoing radical or transurethral prostatectomy during a 3-year period (1988 to 1991) at 2 major teaching hospitals by examining length of stay (duration), charges per hospital day (intensity) and total charges per stay. Mean lengths of stay were significantly longer for sicker versus healthier patients undergoing radical prostatectomy (7.4 versus 6.8 days at hospital 1 and 8.9 versus 7.8 days at hospital 2, p < 0.05) and transurethral prostatectomy (3.5 versus 2.8 days at hospital 1 and 3.5 versus 2.5 days at hospital 2, p < 0.05). Total hospital charges were significantly higher for sicker versus healthier patients undergoing radical prostatectomy ($14,557 versus $13,357 at hospital 1 and $17,864 versus $16,080 at hospital 2, p < 0.05) and transurethral prostatectomy ($6,446 versus $5,012 at hospital 1 and $5,468 versus $3,710 at hospital 2, p < 0.05). However, sicker and healthier patients had similar charges per day for radical prostatectomy ($1,959 versus $1,961 at hospital 1 and $2,006 versus $2,073 at hospital 2, p not significant) and for transurethral prostatectomy ($1.839 versus $1,800 at hospital 1 and $1.544 versus $1,488 at hospital 2, p not significant). On specified hospital days the charges per day for room/nursing, medical/surgical supplies, laboratory services and pharmacy services were similar for patients with and without comorbid conditions. Patients who are more ill at admission remain hospitalized longer after prostatectomy. However, they do not receive more intense care during their stays. For these procedures duration and not intensity appears to be the primary determinant of higher hospital charges for sicker patients.

Comorbidity↗

An analysis of urinary prostate specific antigen before and after radical prostatectomy: evidence for secretion of prostate specific antigen by the periurethral glands.

We investigated whether urinary prostate specific antigen (PSA) might be a useful marker to detect locally recurrent tumor after radical prostatectomy. We also investigated whether PSA in the first 1 to 5 cc of voided urine is a more useful indicator of urinary PSA levels than the midstream urine PSA, since the first portion of the voided urine contains the highest concentration of prostatic and urethral secretions. To determine the response of urinary PSA to radical prostatectomy, we obtained first voided and midstream urine PSA levels in 18 patients with adenocarcinoma of the prostate before and after surgery. Mean first voided urine PSA levels decreased from 915.1 ng./ml. (range 21 to 2,853) preoperatively to 21.4 ng./ml. (range 0.9 to 88) postoperatively, while mean midstream urine PSA levels decreased from 245.9 ng./ml. (range 5 to 1,312) preoperatively to 1.8 ng./ml. (range 0 to 20.4) postoperatively. We also obtained postoperative first voided and midstream urine PSA levels in 9 prostate cancer patients who had undergone radical prostatectomy, and were considered to be cured by rigid clinical and histological criteria. To distinguish bladder versus urethral sources of urinary PSA in patients without a prostate, we additionally studied 11 patients without prostate cancer who had undergone cystoprostatectomy with orthotopic bladder substitution and who had undetectable serum PSA levels by the ultrasensitive assay. In the cured prostatectomy patients the mean first voided urine PSA level was 40.2 ng./ml. (range 2.8 to 100) and the mean midstream urine PSA level was 3.4 ng./ml. (range 0.1 to 15.2), while in the cystoprostatectomy patients these levels were 15.5 ng./ml. (range 0.8 to 49.9) and 1.2 ng./ml. (range 0 to 6.4), respectively. We conclude that the first voided urine sample better reflects local PSA production by the prostate than the midstream sample, first voided urine PSA decreases significantly in response to radical prostatectomy but is still present in measurable amounts even in surgically cured prostate cancer patients and urethral secretion of low levels of PSA persists after radical prostatectomy. This finding diminishes the chance that the first voided urine PSA level will be a useful marker to detect locally recurrent tumor after radical prostatectomy. Further studies are needed to determine if there is a critical level of first voided urine PSA after radical prostatectomy above which there is an increased likelihood of locally recurrent tumor but overall urinary PSA is highly unlikely to be clinically useful.

Adenocarcinoma↗

A population-based study of prostatectomy: outcomes associated with differing surgical approaches.

Data from the universal health insurance system in Manitoba, Canada were used to describe the short-term (2 years) and long-term (8 years) outcomes associated with prostatectomy for nonmalignant conditions (all 2,699 procedures were performed from 1974 to 1976). In a system with high quality urological care (more than 90 per cent of the procedures were performed by urologists) no superior operative results for transurethral procedures were found. Postoperative mortality rates following transurethral prostatectomy were similar to or higher than rates for open procedures, and the rate of repeat prostatectomy, was considerably higher following transurethral resection. Dilation for urethral stricture was most common after suprapubic prostatectomy and least common after retropubic prostatectomy. Patients were followed for 8 years and those who underwent transurethral prostatectomy required an additional prostatic operation at a constant rate (2 per cent per year). By the end of the followup period 16.8 per cent of the transurethral prostatectomy patients had undergone a second prostatectomy compared to 7 per cent or less of those who initially underwent an open procedure.

Adult↗

Complications after radical retropubic prostatectomy in the medicare population.

OBJECTIVES: Radical prostatectomy is the standard of care for the treatment of clinically localized prostate cancer in the appropriate patient. However, the morbidity associated with this procedure remains controversial, since complications from centers of excellence are low but nationwide surveys have reported a much higher risk of complications. This study reports the complication rates after radical retropubic prostatectomy (RRP) for men in the Medicare population. METHODS: All men in the Medicare population who underwent RRP in 1991 were identified. All inpatient, outpatient, and physician (Part B) Medicare claims for these men for 1991 to 1993 were then analyzed to determine outcomes. Procedures performed for complications resulting from RRP were recorded, as were the diagnosis codes that may have heralded a complication after RRP. RESULTS: In 1991, 25,651 men in the Medicare population underwent RRP. The mean age of these men was 70.5 years. Procedures for the relief of bladder outlet obstruction or urethral strictures after RRP occurred in 19.5% of these men. A penile prosthesis was implanted in 718 men (2.8%) after prostatectomy, and 593 men (2.3%) had an artificial urinary sphincter placed after prostatectomy. A diagnosis of urinary incontinence was reported in 5573 men (21.7%) after radical prostatectomy, but only 2025 of these men (7.9%) continued to carry this diagnosis more than 1 year after prostatectomy. A diagnosis of erectile dysfunction was reported in 5510 men (21.5%) after radical prostatectomy, but only 3276 of these men (12.8%) continued to carry this diagnosis more than 1 year after surgery. CONCLUSIONS: A review of a large, nationwide, heterogenous cohort of men revealed a morbidity rate that is slightly higher than that reported by major centers that perform large numbers of radical retropubic prostatectomies but is lower than complication rates obtained by patient surveys. The limitations of claim information in determining patient outcomes, however, must be considered when evaluating these data.

Aged↗

Does urethral-sparing prostatectomy risk residual prostate cancer?

OBJECTIVES: Urethral length after radical prostatectomy has correlated positively with postoperative urinary continence. Because sparing the prostatic urethra may improve continence after prostatectomy, we evaluated anatomic and pathologic consequences of urethral-sparing surgery. METHODS: From February to October 1999, 12 patients with clinically localized prostate cancer received a bladder neck-sparing radical retropubic prostatectomy by one surgeon. At the time of operation, the prostatic urethra was anatomically dissected from the prostatectomy specimen and sent separately to pathology to evaluate for the presence of adenoma or prostate cancer. RESULTS: All patients had clinically localized prostate cancer with routine preoperative evaluations, including negative bone scans for prostate-specific antigen (PSA) greater than 10 or Gleason score higher than 7. Pathologic specimens confirmed localized prostate cancer in 7 of 12 specimens. Positive margins were identified in 5, including 2 patients with locally advanced disease. All 12 urethral specimens showed residual prostate adenoma but no prostate cancer. Follow-up ranged from 8 to 16 months with a zero PSA for all evaluated. CONCLUSIONS: Residual prostate adenoma is found on dissected urethral specimens during radical retropubic prostatectomy. Although urethral-sparing prostatectomy may improve continence after radical prostatectomy, residual adenoma may confound follow-up PSA results. Furthermore, the malignant potential of the benign periurethral adenoma is unknown. The patient and clinician must understand the implications of residual prostatic tissue when performing urethral-sparing radical retropubic prostatectomy.

Adenoma↗

Concurrent assessment of obstructive/irritative urinary symptoms and incontinence after radical prostatectomy.

OBJECTIVES: To concurrently evaluate urinary obstructive symptoms and incontinence in men after radical prostatectomy and to determine the effects of these components on urinary impairment and satisfaction. METHODS: Two hundred twenty-eight men after radical prostatectomy were age-matched and zip code-matched to a random sample of 228 men without prostate cancer. Urinary incontinence was assessed by the urinary function domain of the Prostate Cancer Index, and obstructive symptoms were assessed by the American Urological Association Symptom Index. Regression models were constructed to evaluate the impact of obstructive and incontinence symptoms on urinary impairment and satisfaction. RESULTS: The control group reported greater urinary continence (P <0.0001) and less impairment (P <0.0001) than the prostatectomy group, but a difference was not observed for obstructive symptoms. Obstructive urinary symptoms were associated with impairment for both the prostatectomy and the control groups (P <0.0001), and incontinence symptoms were more strongly associated with impairment in the prostatectomy group than in the control group (P = 0.01). Greater obstructive/irritative and incontinence symptoms were associated with lower satisfaction (P <0.0001). CONCLUSIONS: Urinary incontinence was more common in the radical prostatectomy group, but differences were not seen for obstructive symptoms. In addition to incontinence symptoms, obstructive symptoms were associated with urinary impairment and dissatisfaction in the prostatectomy group, suggesting that these symptoms should also be assessed after radical prostatectomy.

Adult↗

Comparison of biochemical disease-free survival of patients with localized carcinoma of the prostate undergoing radical prostatectomy, transperineal ultrasound-guided radioactive seed implantation, or definitive external beam irradiation.

PURPOSE: This retrospective study compares the long-term biochemical disease-free survival for patients undergoing radical prostatectomy, transperineal ultrasound-guided (125)Iodine implantation, or external beam irradiation alone in a tertiary referral community-based hospital. METHODS AND MATERIALS: Five hundred forty patients were available for evaluation, which included: external beam, 132; (125)I, 186; and radical prostatectomy, 222. For the 318 patients referred to the Department of Radiation Oncology, those with T3 disease underwent external beam irradiation while patients with T1 or T2 underwent (125) 0.2 ng/mL or if they had three consecutive increases in their PSA or an increase in their postoperative PSA warranting intervention with androgen ablation or external beam irradiation to the pelvis. RESULTS: Patients were stratified by pretreatment risk groups predicting for post-treatment PSA recurrence. Patients were considered to be at a low or intermediate risk for recurrence if their clinical stage was T1c, T2a, T2b, pretreatment PSA level was </= 20 or their biopsy. Gleason score was </= 6, Patients were considered to be at high risk for failure if they were clinically stage T2c, T3, PSA at diagnosis > 20, or Gleason score was >/= 7. For 132 patients undergoing external beam irradiation, 28 of 37 low or intermediate risk obtained a 1 year nadir PSA of < 1 (76%) while 40% of high risk patients obtained nadir < 1. Of 186 patients undergoing (125)I, 112 of 147 low or intermediate risk (76%) obtained a nadir PSA < 1. Twenty of 39 (51%) high risk obtained a nadir PSA < 1. Of the 222 patients undergoing prostatectomy, 83 of 88 (94%) low or intermediate risk had undetectable levels of PSA at 1 year. One hundred seventeen of 134 (86%) were high risk and had undetectable levels of PSA at 1 year. The biochemical disease-free survival for patients with low or intermediate risk at 5 years is approximately 70% with no significant difference between those patients treated with radical prostatectomy, external beam, or (125)I. For those patients with high risk factors for recurrence, there is no significant difference between ultrasound-guided implant or external beam, but there is a significant improvement in biochemical disease-free survival with radical prostatectomy. CONCLUSION: For patients with low or intermediate risk disease, external beam, ultrasound-guided (125)I, or a radical prostatectomy give comparable long-term biochemical disease-free survival. For patients with high risk disease, a radical prostatectomy provides a significantly improved biochemical disease-free survival. Our current protocols utilize androgen ablation in combination with conformal three-dimensional external beam irradiation or androgen ablation in conjunction with external beam irradiation and (103)Pd seed implantation for patients at high risk for extra capsular disease. It is too early to determine if this combination therapy will give results comparable to radical prostatectomy. For patients who obtain a 1 year nadir PSA of < 1, the biochemical disease-free survival is durable with little risk of subsequent recurrence.

Aged↗

Preoperative prediction of Gleason grade in radical prostatectomy specimens: the influence of different Gleason grades from multiple positive biopsy sites.

The Gleason score of prostate adenocarcinomas is an important preoperative predictor of cancer behavior, and is used to help guide treatment. In the setting of more than two positive biopsy sites, pathologists usually grade the tumor at each site separately, and the Gleason score may differ from each positive site. This study seeks to determine if the highest Gleason score in all biopsy sites, or the Gleason score in the site with the highest tumor volume on the needle biopsy is the best predictor of final Gleason score in the radical prostatectomy specimens. Various preoperative biopsy findings were analyzed. All 151 patients had at least two positive biopsy sites and underwent radical prostatectomy. Primary and secondary Gleason pattern grades were assigned for each positive biopsy site. The tumor volume in the needle biopsy site was defined by the percentage of areas of biopsy cores involved by cancer. The radical prostatectomy specimens were completely embedded and processed in the whole-mount method. The Gleason score from both the biopsy site with the highest Gleason score and the biopsy site with the highest tumor volume on the needle biopsy correlated equally well with final Gleason score at radical prostatectomy (Spearman correlation coefficient =0.54 for both, P<0.001). The Gleason score from both the biopsy site with the highest Gleason score and the biopsy site with the highest tumor volume on the needle biopsy also correlated with primary Gleason pattern grade at radical prostatectomy (Spearman correlation coefficient =0.53 for both, P<0.001). Secondary Gleason pattern grade from the biopsy site with the highest tumor volume on the needle biopsy correlated with secondary Gleason pattern grade at radical prostatectomy slightly better than those from the biopsy site with the highest Gleason score (Spearman correlation coefficient, 0.32 vs 0.24; both P<0.001). Our data indicate that the highest Gleason score from all sites and the Gleason score from the site with the highest tumor volume on the needle biopsy are equally and significantly predictive of final Gleason score on radical prostatectomy. Both methods of prediction are significantly predictive of primary and secondary Gleason pattern grade on radical prostatectomy. We recommend that the highest Gleason score from all positive biopsy sites should be used when assigning an initial score using needle biopsies.

Adenocarcinoma↗

Population-based study of relationships between hospital volume of prostatectomies, patient outcomes, and length of hospital stay.

BACKGROUND: Despite the large number of prostatectomies performed annually, few data exist regarding relationships between the volume of prostatectomies handled by a hospital, the length of a patient's stay in the hospital, and patient outcomes. We examined the effect of hospital prostatectomy volume and changes in the hospital volume on patient outcomes and the length of a patient's stay. METHODS: We collected data on 101 604 prostatectomies from Medicare claims filed from 1991 through 1994. By use of logistic regression and analysis of variance, we examined relationships between hospital load of prostatectomies, length of a patient's hospital stay, surgical complications, readmission rate, and mortality rate in a 30-day period following surgery. Statistical tests were two-sided. RESULTS AND CONCLUSIONS: Cross-sectional analyses revealed that, compared with high-volume hospitals, low-volume, medium-low-volume, and medium-high-volume hospitals had higher relative risks of readmission by 30% (95% confidence interval [CI] = 21%-39%), 16% (95% CI = 7%-25%), and 8% (95% CI = -1% to 17%), respectively; higher relative risks of serious complications by 43% (95% CI = 37%-48%), 25% (95% CI = 19%-31%), and 9% (95% CI = 3%-15%), respectively; and higher relative risks of mortality by 51% (95% CI = 25%-77%), 43% (95% CI = 17%-69%), and 42% (95% CI = 16%-68%), respectively. The mean length of a patient's stay in a low-volume hospital was 9% longer than that in a high-volume hospital (8.51 days [95% CI = 8.47-8.56] versus 7.81 days [95% CI = 7.77-7.85]; P for trend across all volume categories =.0001). Within-hospital longitudinal analyses revealed that hospitals with a relative increase in prostatectomy volume had a 57% greater reduction in the length of a patient's stay compared with those with a relative decrease in volume (P =.005). Changes in prostatectomy volume did not affect the frequency of complications, mortality, and readmission. These findings suggest that an increase in a given hospital's prostatectomy volume may facilitate a decrease in the length of a patient's stay without an adverse impact on patient outcomes.

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