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ABSTRACT: We assessed risk stratification in patients with low grade prostate cancer managed by active surveillance using a 20-core saturation biopsy technique.
A total of 135 consecutive patients with low risk prostate cancer were prospectively entered in an active surveillance program in a 10-year period. The study entrance requirement and progression definition followed Epstein criteria using only pathological parameters, ie fewer than 3 positive cores, Gleason score 6 or less and 50% or less of any single core involved. All patients were monitored by restaging 20-core saturation biopsy every 12 to 18 months. A total of 120 patients with at least 1 rebiopsy form the basis of this report.
Of the cohort 30% progressed during a median of 2.4 years. Three multivariate analyses were performed. The first analysis used variables only at diagnosis biopsy and revealed that prostate specific antigen density greater than 0.08 ng/ml/cc and prostate cancer family history were significant predictors of progression. When combined in a 3-level risk factor score, they were significant (p = 0.003). The second multivariate analysis considered changes in characteristics between diagnosis biopsy and first rebiopsy. Prostate specific antigen velocity along with prostate specific antigen density and family history highly predicted progression according to a 4-level risk factor score (p <0.0001). The third multivariate analysis validated the previously reported prostate specific antigen density cutoff of 0.08 ng/ml/cc at first rebiopsy as a significant predictor of subsequent progression (HR 3.16, 95% CI 1.12, 8.93; p = 0.03).
Risk factor stratification can be used to significantly predict the outcome in patients on active surveillance. Prostate specific antigen density 0.08 ng/ml/cc at first rebiopsy was validated as a significant predictor of subsequent progression.
The Journal of urology 02/2011; 185(2):471-6. · 4.02 Impact Factor
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ABSTRACT: Robot-assisted partial nephrectomy (RAPN) is emerging as a viable minimally invasive surgical technique for small renal tumors. The warm ischemia time (WIT) during laparoscopic partial nephrectomy has been reduced using an early unclamping (EU) technique. We present our technique of EU technique in RAPN. From November 2009 to June 2010, 12 consecutive RAPNs were performed by a single surgeon (A.W.) using EU technique. The median operative time was 227 minutes (176-315); median WIT, 16 minutes (11-25). Median estimated blood loss was 150 mL (50-500) and length of stay 2 days. There were no intraoperative or postoperative complications. RAPN using EU technique is a safe and feasible option in experienced hands, allowing for a shorter WIT without increasing blood loss. This approach requires a highly skilled bedside assistant who is imminently familiar with the robotic system and advanced laparoscopic techniques.
Journal of endourology / Endourological Society 01/2011; 25(2):305-8. · 1.75 Impact Factor
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ABSTRACT: We determined the relationship between age adjusted free T, and stage, grade and the biochemical-free survival rate in patients with surgically treated prostate cancer.
A retrospective cohort study was done between 1995 and 2001 in 333 patients treated for clinically localized prostate cancer with radical retropubic prostatectomy by a single surgeon at our institution. The study cohort consisted of 279 patients (84%) who had free T levels available. Free T was assessed by single cutoff value of 1.5 ng/dl or less, as suggested by the assay manufacturer, or by age adjusted free T. The relationship of low free T as a single cutoff value and age adjusted reference ranges with clinical and pathological measures of disease progression were assessed using the Fisher exact and Wilcoxon rank sum tests with the outcome assessed by the log rank test.
Using the assay manufacturer suggested single cutoff value of 1.5 ng/dl or less to define low free T 57% of patients with prostate cancer in the cohort were categorized as hypogonadal. However, using age adjusted free T reference ranges only 2.5% of patients with prostate cancer were categorized as hypogonadal, which is more logical and representative of clinically significant hypogonadism in the general population. Poorly differentiated prostate cancer was associated with low free T when measured by a single cutoff value of 1.5 ng/dl or less, or by age adjusted free T (p = 0.017 and 0.04, respectively).
Low age adjusted free T as well as single cutoff free T correlates with poorly differentiated prostate cancer in surgically treated patients.
The Journal of Urology 05/2006; 175(4):1341-5; discussion 1345-6. · 3.75 Impact Factor
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ABSTRACT: Carcinoma-associated fibroblasts (CAF) promote tumor progression of pre-neoplastic epithelial cells. To investigate the basis of this phenomenon, we compared the properties of fibroblasts cultured from normal human prostate (NHPF) to prostate CAF. NHPF and CAF were assayed for growth potential, cell death and proliferative capacity by measuring population doubling time, cell cycle distribution and capability to form colonies in soft agar. Resistance to genotoxic (UV radiation: 0-50 J/cm2) and chemotoxic (0-200 nM Taxol) agents were compared between CAF and NHPF by measuring cell viability and cell cycle analysis. Transforming growth factor beta1 (TGF-beta1) immunoreactivity was assessed in non-malignant and malignant prostatic tissue. No detectable differences were found when comparing CAF and NHPF with respect to population doubling time, cell cycle distribution and response to genotoxic and chemotoxic agents. The mean number of colonies in soft agar was 120.5 for CAF vs. 18.2 for NHPF (p < 0.05). Because TGF-beta1 and matrix metalloproteinase (MMP)-9 have been associated with growth of fibroblasts in soft agar and tumor promotion, we measured the expression of these factors in NHPF and CAF by ELISA. There was no difference in expression of MMP-9; however, TGF-beta1 was expressed in higher concentrations in CAF than in NHPF (p < 0.0014). Furthermore, TGF-beta1 expression was higher in the carcinoma-associated stroma of prostate cancer tissue than stroma of non-malignant prostatic tissue. Increased capability of CAF as compared to NHPF to form colonies in soft agar may be due to a higher expression of TGF-beta1 and correlates with the ability of CAF to promote malignant progression of prostate epithelial cells.
International Journal of Cancer 11/2004; 112(2):213-8. · 5.44 Impact Factor
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ABSTRACT: We examined the prognostic significance of clinical and pathological variables on outcome following radical retropubic prostatectomy (RRP) in a cohort of patients in the post-prostate specific antigen (PSA) era.
We reviewed the clinical and pathological data on a cohort of 476 patients who underwent RRP for localized prostate cancer between January 1990 and July 2001 by 1 urologist (WCD). Median age, preoperative PSA and followup were 61 years, 5.8 ng/ml and 49 months, respectively. We used Cox proportional hazard modeling to evaluate the prognostic significance of clinical and pathological variables for cancer recurrence, defined as 2 successive PSA determinations 0.3 ng/ml or greater.
Of the 476 patients 53 (11%) had recurrence. Estimated cancer nonprogression probability was 86% (95% CI 83 to 90) and 76% (95% CI 68 to 86) at 5 and 10 years, respectively. Two multivariate analyses were performed. The first analysis, using only preoperative indicators, found that the percent of biopsy cores positive for cancer and biopsy Gleason score were the best predictive indicators of recurrence. The second multivariate analysis, using preoperative and postoperative indicators, found that the percent of biopsy cores positive for cancer, RRP Gleason score and the combined pathological stage/margin status variable were the best predictive indicators of recurrence. PSA was not found to be an important predictor of recurrence on either multivariate analysis. Patients with a percent of biopsy cores in the upper half of the distribution (greater than 28% positive) were at significantly increased risk for recurrence compared with those in the lower half of the distribution (28% or less positive) (HR 3.86, p <0.001).
The percent of cores positive for cancer was a better predictor of cancer recurrence than PSA in this post-PSA era RRP series. In addition, surgical Gleason score and pathological stage/surgical margins were also independent predictors of cancer recurrence after RRP. These 3 predictors are displayed in a nomogram-type format to summarize estimated 5 and 10-year recurrence-free probabilities.
The Journal of Urology 04/2004; 171(4):1492-9. · 3.75 Impact Factor
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ABSTRACT: We examined the concordance of Gleason scores in prostate needle biopsy specimens and the corresponding radical retropubic prostatectomy specimens in a cohort of patients grouped according to the number of cores obtained during diagnostic needle biopsy.
We reviewed clinical and pathological data on a cohort of 466 men diagnosed with localized prostate cancer by needle biopsies who underwent radical retropubic prostatectomy between January 1, 1990 and July 31, 2001. Two study groups were identified, including 126 patients diagnosed with prostate cancer by extended needle biopsies (10 or more cores) and 340 diagnosed with cancer by nonextended needle biopsies (9 or fewer cores). Mean age was 60 years and median prostate specific antigen was 5.8 ng./ml. The median number of cores in the extended and nonextended biopsy groups was 12 and 6, respectively. The concordance of Gleason score in the needle biopsy and prostatectomy specimens was compared and correlated with the number of cores on needle biopsy.
In the whole cohort 311 patients (67%) had identical Gleason scores on the needle biopsy and prostatectomy specimens, while 53 (11%) were over graded and 102 (22%) were under graded on needle biopsy. In patients who underwent extended needle biopsies the accuracy rate for Gleason scoring was 76% with 10% over and 14% under graded. The highest accuracy rates were in patients with 13, 14 and 16 cores (89%, 87% and 100%, respectively). No patients in the extended needle biopsy group had a discrepancy of more than 2 Gleason units in grade in the biopsy and surgical specimens. In those who underwent nonextended needle biopsies the accuracy rate for Gleason scoring was 63% with 12% over and 25% under graded. There were significantly different rates of accuracy (p = 0.008) and under grading (p = 0.01) in the 2 needle biopsy groups. Patients with a needle biopsy Gleason score of less than 7 had significantly higher concordance with the prostatectomy Gleason score when extended biopsies were done compared with nonextended biopsies (p = 0.001).
Prostate cancer grading by extended needle biopsy is a better predictor of the final Gleason score than nonextended needle biopsy, as determined by radical prostatectomy histological evaluation. Therefore, extended prostate needle biopsy provides better guidance to determine the appropriate treatment in patients with prostate cancer.
The Journal of Urology 02/2003; 169(1):136-40. · 3.75 Impact Factor
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ABSTRACT: We investigated the relationship between prostate volume and cancer detection by needle biopsy, and determined the effect of an increased number of cores on the sampling error of needle biopsy on large prostate glands.
The study cohort included 750 consecutive patients who underwent first time transrectal ultrasound guided prostate needle biopsy from January 1995 to August 2001. Prostate volumes were divided into quartiles (13 to 34, 34.1 to 45, 45.1 to 64 and 64.1 to 244 cc). Multivariate analysis controlling for age, prostate specific antigen (PSA) and biopsy indication was performed to determine the effect of the number of cores and prostate volume on prostate cancer detection.
Patients diagnosed with prostate cancer were older (p = 0.0035) and had higher PSA levels (p = 0.0002) than those with no cancer on biopsy. Decreasing cancer detection rates were seen with increasing prostate volume (p = 0.0074). The OR of detection for each additional core was 0.99 (95% CI 0.93, 1.06), suggesting that increasing the number of biopsy cores did not increase the rate of prostate cancer detection. Multivariate analysis revealed that patients with larger prostates had the same, or possibly lower, cancer detection rate as the number of biopsy cores was increased. Patients with larger prostates were older (p <0.0001), had higher PSA levels (p <0.0001) and were even more likely to have undergone biopsy for increased PSA rather than abnormal digital rectal examination alone (p <0.0001).
Our study suggests that the lower cancer detection rate for men with large prostates may be due to a decrease in the use of increased serum PSA for prostate cancer detection in larger prostates in addition to other factors such as sampling error. Increased serum PSA levels in cases of larger prostates, although a risk factor for prostate cancer warranting biopsy, may also be due to nonmalignant sources such as benign prostatic hyperplasia.
The Journal of Urology 01/2003; 169(1):130-5. · 3.75 Impact Factor
