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PubMed2006

Clinical and pathologic outcome after radical prostatectomy for prostate cancer patients with a preoperative Gleason sum of 8 to 10.

BACKGROUND: Men with a biopsy Gleason sum of 8 to 10 are considered high-risk. The current study sought to identify whether there was a subset of men with high biopsy Gleason sums who would have a good pathologic and biochemical outcome with surgical monotherapy. To increase the generalizability of the findings, data were used from patients treated at 2 very different practice settings: a tertiary care referral center (Johns Hopkins Hospital) and multiple equal-access medical centers (Shared Equal Access Regional Cancer Hospital [SEARCH] Database). METHODS: The data were retrospectively reviewed from men with biopsy Gleason sums 8 to 10 treated by radical prostatectomy at the Johns Hopkins Hospital (n = 220, 3.8% of total cohort) and within the SEARCH Database (n = 149, 7.7% of total cohort). The preoperative clinical characteristics predicting unfavorable pathologic disease (nonorgan-confined and/or positive surgical margins) and time to biochemical recurrence were determined using logistic regression and Cox proportional hazards analysis, respectively. RESULTS: Favorable pathologic outcome (organ-confined and negative surgical margins) was observed in 21% of the men in the Johns Hopkins cohort and 41% from the SEARCH cohort. On multivariate analysis, higher serum prostate-specific antigen (PSA) was the only variable that significantly predicted an unfavorable pathologic outcome from both the Johns Hopkins (P = .047) and SEARCH cohorts (P = .002). The 5-year and 10-year estimated biochemical-free survival rates in the Johns Hopkins cohort were 40% (95% confidence interval [CI], 33-48%) and 27% (95% CI, 18-36%), respectively, and 32% (95% CI, 22-42%) and 28% (95% CI, 18-38%) in the SEARCH cohort, respectively. Among men with favorable pathologic findings, the 5- and 10-year estimated biochemical-free survival rates in the Johns Hopkins cohort were 79% (95% CI, 62-89%) and 50% (95% CI, 25-71%), respectively, and 49% (95% CI, 32-65%) and 49% (95% CI, 32-65%) in the SEARCH cohort, respectively. No single preoperative variable significantly predicted the risk of biochemical progression in both the SEARCH or Johns Hopkins cohorts. CONCLUSIONS: The majority of men with a biopsy Gleason sum of >or=8, regardless of where the patient is treated, had unfavorable pathologic disease and experienced a biochemical progression after radical prostatectomy. Even among men with organ-confined disease and negative surgical margins or pathologic Gleason sum <8, at least half of the men experienced a PSA recurrence. Patients with biopsy Gleason sum 8 to 10 cancers are good candidates for multimodal therapy. Whereas multimodal therapy has often meant radiation plus hormonal therapy, newer possibilities for multimodal therapy exist such as surgery with neoadjuvant or adjuvant chemohormonal therapy or surgery with adjuvant radiation.

Aged↗

PubMed1992

Fine-needle aspiration of a periurethral Teflon-filled cyst following radical prostatectomy.

Periurethral Teflon injections are being used increasingly for the treatment of urinary incontinence after radical prostatectomy. We report a case of a man who developed increasing obstructive urinary symptoms and stress incontinence following radical retropubic prostatectomy. Six months earlier, he had undergone periurethral Teflon injections. On transrectal ultrasound and magnetic resonance imaging, a 3.2-cm cystic lesion was noted at the prostatic bed near the bladder neck where the Teflon had been injected. Ultrasound-guided transperineal fine-needle aspiration of the cyst yielded a specimen with numerous birefringent crystalline Teflon particles. Although previous reports have described granulomatous tissue reaction, no multinucleated giant cells were present to suggest granuloma formation. To our knowledge, this is the first reported case of Teflon cyst formation following periurethral Teflon injections. The patient's history, imaging studies, cytopathology, and review of the literature are presented in this report.

Aged↗

PubMed2006

Association of vitamin D receptor FokI polymorphism with prostate cancer risk, clinicopathological features and recurrence of prostate specific antigen after radical prostatectomy.

To investigate the effect of vitamin D receptor (VDR) FokI polymorphism on susceptibility to prostate cancer and the outcome of the disease in a Taiwanese population, we genotyped a total of 416 prostate cancer patients, 502 age-matched male controls and 189 non age-matched symptomatic benign prostatic hyperplasia. Although we did not find a significant association between VDR FokI genotypes and overall prostate cancer risk, we found that in men aged less than or equal to the median age of 73 years with VDR FokI F allele specifically had an increased risk of prostate cancer with a marginal significant trend (OR, 2.08; 95% CI, 1.00-4.34, p for trend = 0.056). The FF genotype was also highly associated with more aggressive prostate cancer (Gleason score 8-10) (OR, 2.47; 95% CI, 1.20-5.08) than did the Ff and ff genotypes. After adjusting other covariates, we found that in patients who had localized prostate cancer for which a radical prostatectomy was performed (n = 131), the VDR FokI FF genotype was associated with worse prostate-specific antigen (PSA) recurrence-free survival (hazard ratio = 3.25, 95% CI = 1.32-8.00, p = 0.010). Our findings suggest that the VDR FF genotype may increase the risk of early-onset prostate cancer and is associated with more aggressive disease. Furthermore, the VDR polymorphism could be used as a prognostic marker for localized prostate cancer after radical prostatectomy.

Aged↗

PubMed1992

Pathologic changes occurring in the prostate following transurethral laser prostatectomy.

Serial gross and histopathologic examinations of the prostate following transurethral laser prostatectomy in the canine model demonstrated an immediate well-demarcated sphere of thermal necrosis measuring 2.7 cm in diameter, which, within 24 hours, had begun liquefaction and was showing multiple areas of cavitation. By the end of the 1st week, the areas of cavitation had coalesced to form a central cavity lined by a narrow layer of necrotic tissue clinging to the thin surviving peripheral belt of prostatic glandular parenchyma. At 3 weeks, the bluish-black discoloration resulting from breakdown of blood in the necrotic tissue had subsided, leaving masses of coagulonecrotic tissue within the central cavity. Within 5 weeks, the ectatic central cavity was lined by transitional epithelium. These postmortem pathologic observations confirm our surgical and clinical impressions of being able to satisfactorily perform an effective transurethral prostatectomy using neodymium:YAG (Nd:YAG) laser photoirradiation.

Animals↗

PubMed1994

Prostatectomy by transurethral balloon Laserthermia (PROSTALASE) in the canine.

Prostatectomy by transurethral balloon Laserthermia (PROSTALASE) was performed in a canine model. This balloon device monitored by transrectal ultrasound can cylindrically irradiate with a laser beam. The treatment was performed in 8 canines using 15 watts for 20 minutes at 60 degrees C at a 5 mm depth of the prostate from the urethral surface. Immediately following the laser therapy, an area of coagulation necrosis was observed around the urethra to a depth of 4-5 mm from the surface. After 1 week, cavitation formation was seen in 3 or 4 canines by ultrasound, and the urethral reepithelialization was shown in 1 of 2 canines. After 2 weeks, cavitation formation was observed in both canines, and the urethra was completely reepithelialized in one canine. There was no tissue damage in the bladder neck of urethral sphincter and no urinary incontinence in any animal. This system is thought to be simple and, satisfactorily performed, is an effective transurethral prostatectomy.

Animals↗

PubMed1994

Interstitial laser prostatectomy.

Serial gross and histopathologic examinations of the prostate following interstitial laser prostatectomy in the canine model demonstrated distinct zonal thermal changes around the entire active area of the interstitial thermal therapy (ITT) fiber. A large, well-demarcated area of acute coagulative necrosis immediately surrounded each fiber tract; beyond that were a prominent narrow peripheral zone of marked tissue disruption and an outer zone of hemorrhage. Liquefaction within these coagulative areas was evident within 24 hours, and by 4 days, each lobe of the prostate contained an irregular cavity that became lined by normal-appearing transitional epithelium and that, by 5 weeks, communicated with the prostatic urethra. These postmortem pathologic observations, similar to findings previously reported following transurethral laser prostatectomy, suggest that interstitial laser thermal therapy may provide an additional means for treating benign prostatic hyperplasia in men.

Animals↗

PubMed1994

Pathologic changes following transurethral canine prostatectomy with a cylindrically diffusing fiber.

Transurethral laser prostatectomy was performed on eight mongrel dogs employing a cylindrically diffusing fiber delivery system and a 1.06 mu Nd:YAG laser. Each dog received 15,000 joules of laser energy delivered to the prostate in one continuous dose of 25 watts for 10 minutes. Gross and histopathologic examinations of serial sections of the prostate were performed postoperatively after intervals of 2 hours to 7 weeks. Grossly, a spherical zone of destruction averaging 2.8 cm in diameter was present in dogs except one. Histopathologic changes in the prostate consisted of acute coagulative necrosis with interstitial edema at 2 hours, becoming hemorrhagic by 24 hours. A prominent circular area of acute coagulative necrosis with progressively larger areas of liquefaction and hemorrhage was present in prostates harvested from 4 days to 1 week after lasing. Initial re-epithelization of the resulting cavity was observed at 3 weeks with nearly complete epithelialization 7 weeks after laser treatment. The simplified fiber placement and lack of postoperative complications in this small group of dogs suggest that the cylindrically diffusing fiber could offer significant advantages over laterally deflecting fibers for transurethral prostatectomies in the dog model.

Animals↗

PubMed1995

Transurethral balloon laser prostatectomy in the canine: medium-term, follow-up results.

BACKGROUND AND OBJECTIVE: To demonstrate surgical complications in transurethral balloon laser prostatectomy by medium-term, follow-up observation. STUDY DESIGN/MATERIALS AND METHODS: Three dogs were treated with transurethral laser irradiation using 15 watts for 20 minutes at 60 degrees C at a 5 mm depth of the prostate, one dog was for 5 minutes with same parameters, and one dog was with only laser balloon probe as a control. All animals were followed for 24 weeks. RESULTS: A large cavity in the prostatic urethra was formed in laser-treated animals 4 weeks later, whereas the cavity in the balloon-treated animals was not shown. Cavity volume did not significantly change for 6 months, and there was no bladder neck stricture or urethral stenosis observed in any case. An increase in collagen fibers in the periurethral tissue was barely observed by Mallory staining. CONCLUSION: The risk of bladder neck stricture and urethral stenosis was estimated to be low for transurethral balloon laser prostatectomy.

Aluminum Silicates↗

PubMed1995

Transurethral Nd:YAG laser prostatectomy with a laterally firing fiber: local effects on tissue associated with erectile dysfunction.

BACKGROUND AND OBJECTIVES: Transurethral laser prostatectomy is anticipated to become a recognized alternative to conventional transurethral resection of the prostate. However, the effects of this procedure on the nerves of the pelvic plexus and erectile dysfunction remain unaddressed. The objective of this study was to evaluate the effects of laser energy on extent of prostatic damage as well as injury to periprostatic cavernosal nerves and erectile dysfunction in a canine model. STUDY DESIGN/MATERIALS AND METHODS: Six adult male mongrel dogs underwent transurethral laser prostatectomy at 30 (n = 3) and 40 (n = 3) watt power settings. Total laser energy delivered varied between 6,000 and 13,800 joules. Erectile function was evaluated by pelvic nerve stimulation at 2, 4, and 8 weeks. Animals were then sacrificed to assess histopathology of the prostate at each time point. RESULTS: Histopathologic changes were noted in the prostate in a dose-dependent manner and did not vary with different laser power settings. In dogs that received approximately 10,000 J, substantial prostate ablation confined within the capsule was achieved in every prostate gland. Adequate erectile responses were noted in five of six animals; all received < 10,000 J. In one animal that received a total dose of 13,800 J, an erectile response was not obtained, and histology revealed both prostatic capsule perforation in close proximity to the cavernous nerves and thermal neural damage. CONCLUSIONS: We conclude that cavernous nerve damage may result from excessive doses of laser energy during transurethral laser treatment of the prostate gland. In canines, the upper limit for periprostatic injury is between 10 and 14,000 joules.

Aluminum Silicates↗

PubMed2005

A urodynamics protocol to optimally assess men with post-prostatectomy incontinence.

AIMS: To propose a urodynamic protocol to comprehensively assess all parameters of post prostatectomy incontinence (PPI). METHODS: Sixty men with a history of PPI after radical prostatectomy prospectively underwent a standardized video urodynamics protocol. A 7F urethral catheter was used for standard cystometry, abdominal leak point pressure (ALPP), and pressure flow measurements. The International Continence Society nomogram classified obstruction and further classification of obstruction was based on fluoro voiding cystourethrography and non-invasive flow rates (free Qmax). RESULTS: Twenty-four (40%) men had detrusor overactivity with 8 (13%) also having detrusor overactivity incontinence. Only one patient had impaired compliance. All men had urodynamic stress incontinence, but 21 (35%) men demonstrated it only after removal of the urethral catheter. For men leaking with and without the urethral catheter, the respective ALPP was significantly different, 86.3 and 67 cmH2O, respectively (P = 0.002). The men who leaked only in the absence of the urethral catheter had significantly higher ALPP measurements, P < 0.001. After reclassification using the fluoroscopic images of the bladder outlet and free Qmax, only 13.3% patients were obstructed. CONCLUSIONS: The proposed urodynamic protocol allows for an optimal assessment of bladder and sphincter dysfunction and outlet obstruction in men with PPI.

Aged↗

PubMed2003

Biochemical recurrence following radical prostatectomy: a comparison between prostate cancers located in different anatomical zones.

BACKGROUND: To assess whether differences of biochemical recurrence after radical prostatectomy exist between prostate cancers located in the transition zone (TZ) and peripheral zone (PZ). METHODS: The 5-year biochemical recurrence rate of 307 patients was evaluated. A serum prostate specific antigen (PSA) level > or =0.1 ng/ml was defined as biochemical failure. Cancers were characterized by the location of the largest tumor area as TZ or PZ cancers. Pure PZ cancers were matched to TZ cancers by comparable pathological tumor stage, Gleason score, and surgical margin status. RESULTS: In 63 (20.5%) patients the largest tumor area was located in the TZ. A Kaplan-Meier analysis of the matched pairs calculated an 80% actuarial cure rate of TZ cancers compared to 89% of pure PZ cancers (log-rank test P = 0.742). CONCLUSIONS: TZ and pure PZ cancers matched by comparable pathological tumor stage, Gleason score, and surgical margin status showed no statistical difference in regard to biochemical cure following radical prostatectomy.

Adult↗

PubMed2003

Prognostic value of circulating prostate cells in patients with a rising PSA after radical prostatectomy.

BACKGROUND: To predict poor outcome in patients with a biochemical recurrence (rising PSA) after radical prostatectomy (RP), urologists rely primarily on Gleason score, PSA doubling time, and time from surgery to biochemical (i.e., PSA) recurrence. In the present study, we assess the value of RT-PCR detection circulating prostate cells in blood of patients with a rising PSA. METHODS: RNA from blood samples was obtained from 55 patients with a rising PSA and from 45 patients without evidence of biochemical failure (PSA < 0.1 ng/ml). Both groups were matched for age, Gleason score, pT stage, and interval between radical prostatectomy and PCR testing. RESULTS: PSA positive cells were detected in 1/45 (2%) patients without a PSA recurrence and 19/55 (34%) patients with a PSA recurrence. In the rising PSA group, mean PSA doubling time was significantly shorter in patients with positive RT-PCR (5 months) than in patients with negative RT-PCR (16 months; P = 0.001). An earlier onset of recurrence was also detected in patients with a positive RT-PCR (31 months for positive RT-PCR vs. 50 months for negative RT-PCR) but this result did not achieve statistical significance (P = 0.102). Salvage radiation therapy was administered in 15 patients. Three of the five patients with a positive RT-PCR progressed during radiotherapy whereas 7 of the 10 patients with a negative RT-PCR obtained a complete response and none have progressed. CONCLUSIONS: These preliminary results suggest that RT-PCR detection of prostate cells in blood of patients after RP correlates with rapidly progressing biochemical failure after RP.

DNA, Neoplasm↗

PubMed2004

Expression of p21 cell cycle protein is an independent predictor of response to salvage radiotherapy after radical prostatectomy.

BACKGROUND: To assess whether the expression of p21, p27, and p53 could predict biochemical failure in prostate cancer patients treated with neoadjuvant androgen deprivation prior to salvage radiotherapy for a rising post-radical prostatectomy (RP) prostate-specific antigen (PSA). METHODS: The expression of p21, p27, and p53 was determined by immunohistochemistry in a cohort of 74 formalin-fixed paraffin-embedded prostate cancer samples obtained from RP. Expression of these markers was then correlated with clinicopathological parameters and biochemical failure-free survival after salvage radiotherapy. RESULTS: Expression of p21, p27, and p53 was observed in 20%, 69%, and 74% of prostate cancer specimens, respectively. Overexpression of p21 correlated with a higher Gleason score (>7) (P = 0.024). Of the three markers, only p21 expression was correlated with PSA failure after radiotherapy (P = 0.034). In multivariate analysis, both positive p21 (P = 0.004) and pre-radiation serum PSA > 1 ng/ml (P < 0.0001) were independent predictors of biochemical failure after salvage radiotherapy. Patients with p21- tumors and a serum PSA level < or = 1 ng/ml before salvage radiotherapy had a biochemical failure-free survival at 5 years of 83%, compared to 16% at 5 years for those patients with either p21+ tumor or a PSA > 1 ng/ml. Patients with both p21+ and a PSA level > 1 ng/ml had a much lower biochemical failure-free survival rate of 25% at only 18 months (P < 0.0001). CONCLUSIONS: The expression of p21 in prostatectomy specimens could help predict the likelihood of response to salvage radiotherapy, particularly in patients treated before PSA reaches 1 ng/ml.

Aged↗

PubMed2001

Impact of preoperative serum PSA level from 0 to 10 ng/ml on pathological findings and disease-free survival after radical prostatectomy.

BACKGROUND: To determine the impact of various preoperative serum prostate specific antigen (PSA) levels in the range from 0.1 to 10 ng/ml on pathological stage and disease-free survival after radical prostatectomy. METHODS: We selected a cohort of 585 patients who underwent radical prostatectomy between 1991-1996 for clinically localized prostate cancer and presented with preoperative serum PSA levels from 0.1 to 10 ng/ml. RESULTS: Pathological organ-confined disease was present in 57.6% of patients. The rate of organ-confined disease decreased from an average of 85% for patients with a PSA value < 2 ng/ml, to 46.8% for patients with a PSA value > 7 ng/ml. We found statistically significant correlations between preoperative serum PSA level and overall pathological stage (P = 0.001), pathologically organ-confined disease (P = 0.001), margin positive rates (P = 0.001), extra prostatic extension (P = 0.001), and seminal vesicle invasion (P = 0.001). The overall disease-free survival rate was 87%, with a median follow up of 42.4 months. Disease free survival was significantly better for patients with PSA up to 4 ng/ml (P = 0.005). CONCLUSIONS: Our data suggests that PSA detection programs should strive to detect prostate cancer in men before the PSA level rises above 7 ng/ml. In addition, since patients with a PSA level < 4 ng/ml had better disease-free survival rates than those with a PSA level between 4.1-10 ng/ml, eliminating an arbitrary cutoff of 4 ng/ml, may lead to improved disease-free survival.

Adult↗

PubMed2004

Androgen receptor polymorphisms and risk of biochemical failure among prostatectomy patients.

BACKGROUND: Little is known about the role of inherited genotypes in prostate cancer (PC) progression. This prospective study evaluated the predictive value of androgen receptor (AR) polymorphisms (CAG and GGC repeats) among prostatectomy patients. METHODS: We studied 354 patients registered at M. D. Anderson Cancer Center from 1991 to 2001. Kaplan-Meier and Cox proportional hazard analyses were used. RESULTS: During an average follow-up of 56 months, 66 (19%) post-prostatectomy patients experienced biochemical failure (BF). Patients with higher CAG repeats (CAG > or = 24) had significantly longer BF-free survival (BFFS) than those with fewer repeats (CAG < or = 23) (P = 0.04). Higher CAG repeats were significantly associated with lower BF risk among Whites and African Americans. Among Whites, longer CAG repeats (relative risk (RR) = 0.45, P = 0.03) and Gleason score > or = 8 (RR = 19.33, P = 0.005) remained significant BFFS predictors in multivariate analysis. GGC repeats were not associated with BF. CONCLUSIONS: Our data showed that an inherited polymorphism (CAG repeats) in the AR is related to differences in genetic susceptibility to BF, supporting the hypothesis that increased AR activity may play a role in PC progression.

Adenocarcinoma↗

PubMed2004

Vitamin D receptor gene polymorphisms and disease free survival after radical prostatectomy.

BACKGROUND: Vitamin D has been linked with prostate cancer risk in epidemiologic studies and has antiproliferative, prodifferentiation, and antimetastatic properties in experimental systems. Its hormonal activity is mediated by the vitamin D receptor. We investigated whether germ-line genetic variation in the vitamin D receptor impacts progression of prostate cancer after radical prostatectomy. METHODS: We analyzed BsmI and TaqI polymorphisms using archived specimens from a large series of radical prostatectomy patients at a single institution. Our series included 428 white men (WM) and 310 African-American men (AAM) who were carefully and uniformly staged and followed for 5-10 years. RESULTS: The distribution of polymorphisms varied between WM and AAM. There was little association between genotype and extent of disease at diagnosis, Gleason score, preoperative PSA, or recurrence overall. Among WM with locally advanced disease, however, the BsmI B allele protected against recurrence in models examining gene dose (P = 0.04) and dominant effects (P = 0.05). CONCLUSIONS: Overall vitamin D receptor polymorphisms did not predict pathologic features of prostate cancer but may impact on risk of recurrence among men in certain risk groups. Analysis of polymorphisms may provide clues about the mechanisms through which vitamin D exerts its inhibitory effects on prostate cancer in vivo in men.

Black or African American↗

PubMed2006

The effects of the dual 5alpha-reductase inhibitor dutasteride on localized prostate cancer--results from a 4-month pre-radical prostatectomy study.

BACKGROUND: As dihydrotestosterone (DHT) is the most potent androgen in the prostate, inhibition of the 5alpha-reductase isoenzymes, which convert testosterone to DHT, could be an appropriate target for the treatment of prostate cancer. METHODS: Eighty-one men with clinically localized prostate cancer received daily dutasteride 3.5 or 0.5 mg, or no therapy for 4 months before radical prostatectomy. Histopathological assessments were conducted on prostatectomy specimens. RESULTS: Treatment with dutasteride was associated with reductions in serum and intraprostatic DHT of >or=90%, and a decrease in total prostate and tumor volumes. No effect of dutasteride was noted on Gleason grade. Histopathological effects on benign tissue were similar but less prominent than those seen with androgen ablation, whereas there was no significant difference in cancer histology among the groups. CONCLUSIONS: Dutasteride treatment results in similar but less marked changes compared with androgen ablation.

5-alpha Reductase Inhibitors↗

PubMed1986

Sexual function after radical prostatectomy.

Forty-five patients undergoing radical retropubic prostatectomy by a standard technique modified by the author (JEP) were interviewed regarding their sexual function prior to and after the operation. Thirty-five patients were sexually potent prior to the surgery. Post-operatively, 19 patients retained erectile potency (54%), although in 15 partial erections of varying degrees were noted. In 4 of these patients, erections were not satisfactory for sexual intercourse. It is evident that a significant number of patients retained sexual function after radical prostatectomy, even when no particular attention was made to preserve the neurovascular supply.

Erectile Dysfunction↗