Ultrasensitive Prostate Specific Antigen Assay Following Laparoscopic Radical Prostatectomy – An Outcome Measure for Defining the Learning Curve

INTRODUCTION

Radical retropubic prostatectomy (RRP) performed laparoscopically is a popular treatment with curative intent for organ-confined prostate cancer. After surgery, prostate specific antigen (PSA) levels drop to low levels which can be measured with ultrasensitive assays. This has been described in the literature for open RRP but not for laparoscopic RRP. This paper describes PSA changes in the first 300 consecutive patients undergoing non-robotic laparoscopic RRP by a single surgeon.

OBJECTIVES

To use ultrasensitive PSA (uPSA) assays to measure a PSA nadir in patients having laparoscopic radical prostatectomy below levels recorded by standard assays. The aim was to use uPSA nadir at 3 months'' post-prostatectomy as an early surrogate end-point of oncological outcome. In so doing, laparoscopic oncological outcomes could then be compared with published results from other open radical prostatectomy series with similar end-points. Furthermore, this end-point could be used in the assessment of the surgeon''s learning curve.

PATIENTS AND METHODS

Prospective, comprehensive, demographic, clinical, biochemical and operative data were collected from all patients undergoing non-robotic laparoscopic RRP. We present data from the first 300 consecutive patients undergoing laparoscopic RRP by a single surgeon. uPSA was measured every 3 months post surgery.

RESULTS

Median follow-up was 29 months (minimum 3 months). The likelihood of reaching a uPSA of ≤ 0.01 ng/ml at 3 months is 73% for the first 100 patients. This is statistically lower when compared with 83% (P < 0.05) for the second 100 patients and 80% for the third 100 patients (P < 0.05). Overall, 84% of patients with pT2 disease and 66% patients with pT3 disease had a uPSA of ≤ 0.01 ng/ml at 3 months. Pre-operative PSA, PSA density and Gleason score were not correlated with outcome as determined by a uPSA of ≤ 0.01 ng/ml at 3 months. Positive margins correlate with outcome as determined by a uPSA of ≤ 0.01 ng/ml at 3 months but operative time and tumour volume do not (P < 0.05). Attempt at nerve sparing had no adverse effect on achieving a uPSA of ≤ 0.01 ng/ml at 3 months.

CONCLUSIONS

uPSA can be used as an early end-point in the analysis of oncological outcomes after radical prostatectomy. It is one of many measures that can be used in calculating a surgeon''s learning curve for laparoscopic radical prostatectomy and in bench-marking performance. With experience, a surgeon can achieve in excess of an 80% chance of obtaining a uPSA nadir of ≤ 0.01 ng/ml at 3 months after laparoscopic RRP for a British population. This is equivalent to most published open series.     

Dietary habits and prostate cancer detection: a case–control study

Background

Many studies have suggested that nutritional factors may affect prostate cancer development. The aim of our study was to evaluate the relationship between dietary habits and prostate cancer detection.

Methods

We studied 917 patients who planned to have transrectal ultrasonography–guided prostatic biopsy based on an elevated serum prostate-specific antigen (PSA) level, a rising serum PSA level or an abnormal digital rectal examination. Before receiving the results of their biopsy, all patients answered a self-administered food frequency questionnaire. In combination with pathology data we performed univariable and multivariable logistic regression analyses for the predictors of cancer and its aggressiveness.

Results

Prostate cancer was found in 42% (386/917) of patients. The mean patient age was 64.5 (standard deviation [SD] 8.3) years and the mean serum PSA level for prostate cancer and benign cases, respectively, was 13.4 (SD 28.2) μg/L and 7.3 (SD 4.9) μg/L. Multivariable analysis revealed that a meat diet (e.g., red meat, ham, sausages) was associated with an increased risk of prostate cancer (odds ratio [OR] 2.91, 95% confidence interval [CI] 1.55–4.87, p = 0.027) and a fish diet was associated with less prostate cancer (OR 0.54, 95% CI 0.32–0.89, p = 0.017). Aggressive tumours were defined by Gleason score (≥ 7), serum PSA level (≥ 10 μg/L) and the number of positive cancer cores (≥ 3). None of the tested dietary components were found to be associated with prostate cancer aggressivity.

Conclusion

Fish diets appear to be associated with less risk of prostate cancer detection, and meat diets appear to be associated with a 3-fold increased risk of prostate cancer. These observations add to the growing body of evidence suggesting a relationship between diet and prostate cancer risk.     

Who’s too old to screen? Prostate cancer in elderly men

Introduction:

Prostate cancer is the most common nonskin malignancy affecting men and is the second leading cause of cancer-related death in North America. The incidence of prostate cancer increases dramatically with age. However, many health authorities advocate the cessation of routine prostate cancer testing in men older than 75 because of the belief that most patients will have a clinically insignificant cancer and will not benefit from therapy. The true prevalence of clinically significant prostate cancer in elderly men is not known.

Methods:

We analyzed 1446 needle biopsies of the prostate in men aged 75 or older. All pathological reviews were conducted by the pathology department at the Methodist Hospital in Houston, Tex. Data were collected from pathology reports, hospital and clinic databases, and medical records when available. Data obtained included age at biopsy, serum prostate-specific antigen (PSA) levels, number of positive core biopsies and Gleason grade. Statistical analysis was performed using Stata. Clinically significant cancer was defined by the pathological presence of Gleason grade 6 adenocarcinoma in more than 1 biopsy core or the presence of any Gleason 4 or 5 component in the biopsy.

Results:

The median age of the patients included in the study was 78.8 and 95% of the patients were between the ages of 75 and 85. The mean serum PSA level for patients biopsied was 10.4 μg/L. Of all biopsies reviewed, 53% were positive for prostate cancer and 78% of these would be defined as clinically significant cancer. Regression analysis revealed age to be a significant (p < 0.05) factor for increased Gleason grade in positive biopsies. Logistic regression revealed age as a significant factor (p < 0.05) for clinically significant prostate cancer even when controlling for PSA. A serum PSA threshold value of 6.5 μg/L would have missed 38% of significant cancers and a threshold of 4.0 μg/L would have missed 8% of significant cancers.

Conclusion:

Our findings suggest that the prevalence of clinically significant prostate cancer in the elderly population may be higher than previously thought. As the population continues to live longer and healthier lives, it will become more common to confront prostate cancer morbidity in the eldery population. Using higher serum PSA thresholds to eliminate unnecessary biopsies in older men does not appear to help identify patients at greater risk of having clinically significant prostate cancer. Patients with prostate cancer having aggressive clinical features may benefit from treatment of their prostate cancer well into their eighth and ninth decades of life. Testing and diagnostic recommendations should reflect the potential benefit of identifying patients with aggressive prostate cancer even after age 75.     

Prostate-Specific Antigen fluctuation: what does it mean in diagnosis of prostate cancer?

Objective

To investigate whether prostate-specific antigen (PSA) fluctuation correlates with a prostate cancer and to assess whether PSA fluctuation could be used for diagnosis of prostate cancer.

Materials and Methods

Our study included 229 patients who were performed a prostate biopsy (non-cancer group, 177; prostate cancer group, 52). Enrolled patients were provided twice PSA tests within 6 months. PSA fluctuation (%/month) was defined as a change rate of PSA per a month. Independent t test was used to compare between two groups. Receiver operator characteristic curve was used to assess the availability as a differential diagnostic tool and the correlation. Simple linear regression was performed to analyze a correlation between PSA fluctuation and other factors such as age, PSA, PSA density, and prostate volume.

Results

There were significant differences in PSA, PSA density, percentage of free PSA, and PSA fluctuation between two groups. PSA fluctuation was significantly greater in non-cancer group than prostate cancer group (19.95±23.34%/month vs 9.63±8.57%/month, P=0.004). The most optimal cut-off value of PSA fluctuation was defined as 8.48%/month (sensitivity, 61.6%; specificity, 59.6%; AUC, 0.633; P=0.004). In a simple linear regression model, only PSA level was significantly correlated with PSA fluctuation.

Conclusion

Patients with wide PSA fluctuations, although baseline PSA levels are high, might have a low risk of diagnosis with prostate cancer. Thus, serial PSA measurements could be an option in patients with an elevated PSA level.     

A rapid PSA half-life following docetaxel chemotherapy is associated with improved survival in hormone refractory prostate cancer

Introduction:

Docetaxel chemotherapy prolongs survival in metastatic hormone-refractory prostate cancer (mHRPC), but many patients fail to respond to this therapy and there is potential for serious toxicity. Patients differ in their percent prostate-specific antigen (PSA) decline and rate of PSA decline following treatment. We propose that patients who achieve a rapid rate of PSA decline, measured as a shorter PSA half-life (PSAHL), may experience a longer overall survival (OS) than those who achieve a slower rate of PSA decline.

Methods:

A chart review of patients treated with docetaxel for mHRPC in Alberta from January 2000 to May 2006 was performed. At 42 days (after 2 cycles) and 84 days (after 4 cycles) following chemotherapy, PSA response and PSAHL were determined. PSAHL could only be determined in patients with a PSA drop from baseline. Optimal PSAHL values for OS stratification were determined using the log-rank chi-square statistic. Survival analysis was carried out using Kaplan-Meier curves and regression analysis.

Results:

There were 154 patients who fulfilled the inclusion criteria. Using 42-day postdocetaxel data, no associations with OS could be demonstrated. Using 84-day postdocetaxel data, patients stratified by PSAHL demonstrated a significant difference in OS (15 months vs. 25 months) and this relationship remained following multivariate analysis (hazard ratio 0.08 [0.021–0.34]).

Conclusion:

A more rapid rate of PSA decline (PSAHL <70 days) measured after 4 cycles of chemotherapy was associated with a longer OS. This result was independent of other known markers of survival and allowed for a greater survival differentiation than PSA response.     

Insulin-like growth factor (IgF)-I,IgF binding protein-3, and prostate cancer: correlation with gleason score

Introduction

Non-androgenic growth factors are involved in the growth regulation of prostate cancer (PCa).

Objective

This is the first Brazilian study to correlate, in a population of patients operated for PCa, PSA, total testosterone, insulin-like growth factor-I (IGF-I) and insulin-like growth factor-binding protein-3 (IGFBP-3) with Gleason score and to compare with a control group with benign prostate hyperplasia (BPH).

Materials and Methods

This retrospective single-center study included 49 men with previously diagnosed PCa and 45 with previously diagnosed BPH. PSA, testosterone, IGF-I, IGFBP-3 were determined in both groups.

Results

PSA and IGFBP-3 levels were significantly higher in the PCa group as compared to the BPH group (p<0.001 and p=0.004, respectively). There was a significant difference when we compared the PSA before surgery (p<0.001) and at the inclusion in the study (p<0.001) and IGFBP3 (0.016) among patients with Gleason <7, ≥7 and BPH. In the PCa group, PSA, testosterone, IGF-I and IGFBP-3 levels were comparable between Gleason <7 and ≥7.

Conclusions

Our data suggest that in localized PCa, the quantification of PSA and, not of IGF-1, may provide independent significant information in the aggressiveness. IGFBP-3 could be a biochemical marker of disease control in PCa patients.     

Randomized trial comparing an anterograde versus a retrograde approach to open radical prostatectomy: results in terms of positive margin rate

Objectives:

Surgical technique, patient characteristics and method of pathological review may influence surgical margin (SM) status. Positive surgical margin (SM+) rates of 14% to 46% have been reported in different radical retropubic prostatectomy (RRP) series. We evaluated the effect of an anterograde versus retrograde approach to RRP and specifically focused on the incidence of SM+.

Methods:

From January 2003 to November 2007, we randomly assigned 200 patients with clinically localized prostate adenocarcinomas to undergo a retrograde (Group A) versus an anterograde (Group B) open RRP. All RRPs were performed at our institution by 2 surgeons. For all 200 patients, we evaluated a panel of clinical and pathological variables relating to their association with SM status.

Results:

In Group A, 22% of cases after RRP showed a pT3 tumour and 39% of cases with a Gleason score ≥7 (4+3); in Group B, 20% of cases showed a pT3 tumour and 37% of cases with a Gleason score ≥7 (4+3) (p > 0.10). The incidence of SM+ was 18% in Group A and 14% in Group B (p = 0.0320). In Group A, 22.2% of cases with SM+ had multiple positive margins, whereas no cases in Group B showed multiple SM+. Regarding the localization of SM+, no difference was found between the 2 groups. In the multivariate analysis, only prostate-specific antigen (p = 0.0090 and p = 0.0020, respectively in the 2 groups) and pathological stage (p < 0.0001 in both groups) were significant and independently associated with SM+ occurrence.

Conclusion:

In our experience, the anterograde approach to open RRP is associated with lower SM+ rates and no risk of multiple SM+ when compared with the retrograde approach.     

Developing a Robotic Prostatectomy Service and a Robotic Fellowship Programme – Defining the Learning Curve

Introduction

Robotic radical prostatectomy (RRP) is an established treatment for prostate cancer in selected centres with appropriate expertise. We studied our single-centre experience of developing a RRP service and subsequent training of 2 additional surgeons by the initial surgeon and the introduction of United Kingdom''s first nationally accredited robotic fellowship training programme. We assessed the learning curve of the 3 surgeons with regard to peri-operative outcomes and oncological results.

Patients and Methods

Three hundred consecutive patients underwent RRP between November 2008 and August 2012. Patients were divided into 3 equal groups (Group 1, case 1-100; Group 2, case 101-200; and Group 3, case 201-300). Age, ASA score, preoperative co-morbidities and indications for laparoscopic radical prostatectomy were comparable for all 3 patient groups. Peri-operative and oncological outcomes were compared across all 3 groups to assess the impact of the learning curve for laparoscopic radical prostatectomy. All surgical complications were classified using the Clavien-Dindo system.

Results

The mean age was 60.7 years (range 41-74). There was a significant reduction in the mean console time (p < 0.001), operating time (p < 0.001), mean length of hospital stay (p < 0.001) and duration of catheter (p < 0.001) between the 3 groups as the series progressed. The two most important factors predictive of positive surgical margins (PSM) at RRP were the initial prostate specific antigen (PSA) and tumor stage at diagnosis. The overall PSM rate was 26.7%. For T2/T3 tumors the incidence of PSM reduced as the series progressed (Group 1-22%, Group 2-32% and Group 3-26%). The incidence of major complications i.e. grade Clavien-Dindo system score ≤ III was 2% (6/300).

Conclusion

RRP is a safe procedure with low morbidity. As surgeons progress through the learning curve peri-operative parameters and oncological outcomes improve. This learning curve is not affected by the introduction of a fellowship-training programme. Using a carefully structured mentored approach, RRP can be safely introduced as a new procedure without compromising patient outcomes.Key Words: Robotic radical prostatectomy, Prostate cancer, Learning curve, Fellowship training     

Can the Free/Total PSA Ratio Predict the Gleason Score Before Prostate Biopsy?

Objectives

To determine whether there is a correlation between high Gleason score and free/total (f/t) prostate specific antigen (PSA) in patients newly diagnosed with prostate carcinoma.

Materials and Methods

The study included 272 prostate biopsy patients whose total PSA value ranged from 4–10 ng/ml. The patients were divided into 2 groups according to the f/t PSA ratio: Group 1 ≤ 15% and Group 2 > 15%. Furthermore, the groups were also compared to each other in terms of mild (≤ 6), moderate (= 7), and high (≥ 8) Gleason score.

Results

Group 1 consisted of 135 (49.6%) patients and Group 2 consisted of 137 (50.4%) patients. While 27 (20%) patients had a high Gleason score in Group 1, only 10 (7.3%) patients had a high Gleason score in Group 2 (p = 0.008). Using Spearman''s correlation test, we found that the f/t PSA ratios were observed to decrease significantly in all patients with increased Gleason scores (p = 0.002, r = −0.185).

Conclusion

According to our study, there is a relationship between higher Gleason score and decreased f/t PSA ratio. Therefore, f/t PSA can be an indicator for predicting the Gleason score.Key Words: PSA, Percent free PSA prostate cancer, Gleason score, Prostate biopsy     

Accuracy of medical models made by consumer-grade fused deposition modelling printers

BACKGROUND:

Additive manufacturing using fused deposition modelling (FDM) has become widely available with the development of consumer-grade three-dimensional printers. To be useful in maxillofacial surgery, models created by these printers must accurately reproduce the craniofacial skeleton.

OBJECTIVE:

To determine the accuracy of consumer-grade FDM printers in the production of medical models compared with industrial selective laser sintering (SLS) printers.

METHODS:

Computed tomography images of a dry skull were manipulated using OsiriX (OsiriX, Switzerland) and ZBrush (Pixologic, USA) software. Models were fabricated using a consumer-grade FDM printer at 100 μm, 250 μm and 500 μm layer heights and an industrial SLS printer. Seven linear measurements were made on the models and compared with the corresponding dry skull measurements using an electronic caliper.

RESULTS:

A dimensional error of 0.30% was observed for the SLS models and 0.44%, 0.52% and 1.1% for the 100 μm, 250 μm and 500 μm FDM models, respectively.

CONCLUSION:

Consumer-grade FDM printers can produce medical models with sufficient dimensional accuracy for use in maxillofacial surgery. With this technology, surgeons can independently produce low-cost maxillofacial models in an office setting.     

The Role of Cryosurgery of the Prostate for Nonsurgical Candidates

Introduction:

Technological advancements have reduced the morbidity associated with cryosurgery, leading to an increased interest in this modality for the treatment of organ-confined prostate cancer. In this study, we critically examine the current role of cryoablation of the prostate to better understand how to counsel patients regarding this treatment option.

Methods:

A database was compiled over a 3-year period (2008–2011) of 30 patients who underwent cryoablation for organ-confined prostate cancer. Indications for cryosurgery included primary treatment, focal treatment (institutional review board–approved prospective study), and salvage cryotherapy for radiation failure. The primary outcomes were biochemical response via prostate-specific antigen (PSA) measurement and morbidity associated with cryoablation. Cryotherapy failure was defined as an increasing postcryotherapy PSA level ≥ 2 ng/mL above the post-treatment nadir, a positive prostate biopsy, or radiographic evidence of metastatic disease.

Results:

Of the 30 patients who underwent cryoablation from 2008 to 2011, 26 patients had complete follow-up data for analysis. Of these patients, 17 (65.38%) had total gland cryotherapy, 5 (19.23%) had salvage cryotherapy for radiation failure, and 4 (15.38%) had focal cryotherapy. The mean patient age was 68 years (54–89); median preoperative PSA was 5.5 ng/mL (1.7–15.9); median prostate volume was 35 mL (15–54); mean Gleason score was 7; and the median PSA at study conclusion was 0.7 (0.02–3.4) ng/mL. Of the 17 patients who had total prostate cryotherapy, 11 (64.7%) had significant factors precluding primary treatment by a surgical and/or radiation approach, including neurological disorders (2), morbid obesity (1), rectal cancer treated with radiation (1), kidney/pancreas transplant (2), ileoanal pouch secondary to inflammatory bowel disease (IBD) (1), renal failure (1), and age (3).There were no intra- or postoperative complications. After a median follow-up of 18 months (1–40), none of the patients with multiple comorbidities had biochemical failures. Two patients from the salvage group experienced treatment failure requiring androgen deprivation therapy.

Conclusions:

This critical analysis of a single-surgeon experience at a large academic prostate cancer program revealed that the contemporary role of cryosurgery is, in select patients with comorbidities, preventing surgical and/or radiation therapy. Additionally, cryosurgery has a role in treating radiation failures. Further studies are necessary to investigate focal cryotherapy as an option for primary treatment, but our preliminary results are promising, without any biochemical failures in our focal therapy cohort.     

Does normalizing PSA after successful treatment of chronic prostatitis with high PSA value exclude prostatic biopsy?

Objective

Evaluate male patients with diagnosed chronic prostatitis, elevated serum prostate-specific antigen (PSA) to find out whether medical treatment with antibiotics and anti-inflammatory drugs can lower serum PSA, and consequently decrease the prostate cancer detection rate in patients with post-treatment PSA<4 ng/mL.

Materials and methods

This prospective study evaluated 142 male patients aged 40-73 years whose presented with elevated serum PSA>4 ng/mL and were consequently diagnosed with chronic prostatitis as expressed prostatic excretions examination revealed more than 10 white blood cells per high power field. The Patients underwent treatment with antibiotics and nonsteroidal anti-inflammatory agents for 6-weeks. Subsequently, all patients are Followed-up by serum PSA and performed transrectal ultrasonography-guided prostate biopsy within 2 months of treatment.

Results

Mean patient age was (54.4±13.5) years. The mean PSA pretreatment was (8.11±3.7) ng/mL and after treatment, the mean PSA denoted a significant decrease to (4.7±3.5) ng/mL (P=0.002). The percent of changes in mean PSA was 41.9%. Prostatic biopsy after treatment showed that, cancer prostate in 31 patients (21.8%), chronic prostatitis in 71 patients (50.7%), chronic prostatitis plus benign prostatic hyperplasia (BPH) in 31 (21.8%) and BPH in 9 patients (6.3%) With regard to PSA values, cancer prostate patients were 3/25 (12%) if PSA<2.5 ng/mL, 6/47 (12.7%) if 4.0>PSA≥2.5 and 21/70 (30%) if PSA≥4.0. The numbers of cancer prostate detected patients were 30 (21.1%).

Conclusions

Chronic prostatitis is one of the causes that elevate serum PSA levels. Treatment of chronic prostatitis with elevated PSA by antibiotics and anti-inflammatory agents can decrease the elevated PSA to the normal levels. Nevertheless, the opportunities of potential prostate cancer still exist in patients with a decreased PSA level even also if PSA<2.5 ng/mL.     

Urinary PSA: a potential useful marker when serum PSA is between 2.5 ng/mL and 10 ng/mL

Introduction

Our objective was to evaluate the usefulness of urinary prostate specific antigen (PSA) in the differential diagnosis of benign prostatic hyperplasia (BPH) and prostate cancer.

Methods

We undertook a prospective study and obtained informed consent from 170 men. They provided blood samples to measure serum PSA and 50 mL of first-voided urine to measure urinary PSA. Seventy-seven men were diagnosed with BPH; 42 patients had newly diagnosed prostate cancer; and 51 were selected as age-matched control subjects. Data were analyzed using Wilcoxon signed rank tests, receiver operating characteristic (ROC) curves and logistic regression.

Results

Prostate volume was 35 cm³ and 45 cm³ (p < 0.05), serum PSA was 9.7 ng/mL and 4.5 ng/mL (p < 0.001) and PSA density was 0.28 and 0.11 (p < 0.01) for prostate cancer and BPH patients, respectively. Overall, urinary PSA was not significantly different, but PSA ratio (urinary:serum) was significantly different at 6.7 and 30.6 (p < 0.001) for prostate cancer and BPH patients, respectively. A subgroup with serum PSA between 2.5 ng/mL and 10.0 ng/mL was selected and urinary PSA was significant: 52.6 ng/mL (n = 29) and 123.2 ng/mL (n = 35) (p < 0.05) for prostate cancer and BPH patients, respectively. PSA ratios were also significant (p = 0.007). ROC curves identified a cutoff for urinary PSA at > 150 ng/mL, with a sensitivity of 92.5%. When comparing prostate cancer patients with age-matched control subjects, serum PSA, urinary PSA and PSA ratio were different (p = 0.004).

Conclusion

Our study supports urinary PSA as a useful marker in the differential diagnosis of prostate cancer and BPH, especially when serum PSA is between 2.5 ng/mL and 10 ng/mL. Low urinary PSA and PSA ratios point toward prostate cancer. A urinary PSA threshold of > 150 ng/mL may be used to decrease the number of prostatic biopsies.     

Analysis of monotherapy prostate brachytherapy in patients with prostate cancer. Initial PSA and Gleason are important for recurrence?

Purpose

To evaluate the clinical outcome of a cohort of localized prostate cancer patients treate with 125-I permanent brachytherapy at the São José Hospital – CHLC, Lisbon.

Materials and Methods

A retrospective analysis was carried out on 429 patients with low and intermediate-risk of prostate adenocarcinoma, according to the recommendations of the EORTC, who underwent 125I brachytherapies in intraoperative dosimetry “real-time” system between September 2003 and September 2013.

Results

The mean follow-up was 71.98 months. Biochemical relapse of disease by rising PSA (Phoenix criterion) was observed in 18 patients (4.2%). Through the application of Kaplan-Meier survival curves in this sample, the rate of survival at 6 years without biochemical relapse was higher than 95%. By Iog rank test comparing biochemical relapse with initial PSA (15-10 and <10) and Gleason values (7 and <7), there was no statistical difference (P=0.830) of the initial PSA in the probability of developing biochemical relapse. In relation to Gleason score, it was noted a statistical difference (P<0.05), demonstrating that patients with Gleason 7 are more likely to develop biochemical relapse.

Conclusions

Brachytherapy as monotherapy is at present an effective choice in the treatment of localized prostate adenocarcinoma. Biochemical relapses are minimal. The initial PSA showed no statistically difference in the rate of relapses, unlike the value Gleason, where it was demonstrated that patients with Gleason 7 have a higher probability of biochemical relapse. Cases with PSA bounce should be controlled before starting a salvage treatment.     

Renal and functional outcomes following cystectomy and neobladder reconstruction

Background:

Orthotopic reconstruction following cystectomy has evolved in an attempt to restore anatomy and function to as close as possible to the preoperative state. We review the renal and functional outcomes of patients who underwent cystectomy and neobladder reconstruction at our institution.

Methods:

Between December 2003 and October 2007, 31 patients underwent cystectomy with Studer neobladder reconstruction at the Ottawa Hospital, Ottawa, Ontario, Canada. Follow-up data were obtained regarding renal function (serum creatinine, μmol/L), continence, urinary flow rates and post-void residual (PVR) at 3, 6 and 12 months after surgery. Change in creatinine from preoperative baseline was calculated and analyzed by student t-test to determine if there was a significant rise in creatinine.

Results:

There was a statistically significant increase in creatinine from preoperative baseline, with an average increase of 17.3 μmol/L, 21.8 μmol/L and 26.3 μmol/L at 3, 6 and 12 months, respectively. Six patients developed hydronephrosis. Excluding patients with hydronephrosis, there continued to be a statistically significant rise in creatinine with an average increase of 11.9 μmol/L, 14.7 μmol/L and 19.4 μmol/L at 3, 6 and 12 months, respectively. At 1 year, daytime continence was achieved by 89% of patients; 70% were continent at night.

Interpretation:

Orthotopic neobladders have excellent functional outcomes with low rates of incontinence, which improved throughout follow-up. A significant proportion of patients developed hydronephrosis, highlighting the need for close follow-up to prevent reversible renal deterioration. Creatinine increased during follow-up irrespective of the development of hydronephrosis, but the clinical significance is unknown.     

The association between tumour density and prostate cancer recurrence following radical prostatectomy

Purpose:

Tumour density (TD) may be an independent prognostic factor in men with prostate cancer. The purpose of this study was to evaluate the association between prostate cancer TD and recurrence following radical prostatectomy.

Materials and Methods:

Between 1995 and 2007, 645 patients from The Ottawa Hospital or Memorial Sloan-Kettering Cancer Center who had cancer and prostate volumes measured from radical prostatectomy specimens. Tumour density was defined as the relative tumour to prostate volume (tumour volume/prostate volume) and recurrence was defined as a prostate-specific antigen (PSA) >0.2 ng/mL and rising, or postoperative use of radiation or hormonal therapy. Associations between TD and recurrence are adjusted for preoperative PSA, prostatectomy Gleason sum, tumour stage and margin status.

Results:

Median follow-up was 40.8 months. Tumour density was associated with preoperative PSA, Gleason sum, tumour stage and surgical margin status (all p < 0.0001). As a continuous variable, TD predicted recurrence-free survival (adjusted HR 1.34 per 10% increase in TD; p = 0.04). As a categorical variable, the group of patients with a TD of >10% had a 2.7 times greater hazard of recurrence compared to patients with a TD <5% (95%CI 1.41, 5.19; p = 0.003). Despite the independent association between TD and recurrence, the clinical value of TD remains in question as the discriminative performance (area under the curve) of predictive models only improved from 0.865 to 0.876.

Conclusions:

Prostate cancer TD is associated with known prognostic factors and is also independently predictive of recurrence following radical prostatectomy.     

The 20-core prostate biopsy as an initial strategy: impact on the detection of prostatic cancer

Introduction:

To increase the detection rate of prostate cancer in recent years, we examined the increase in the number of cores taken at initial prostate biopsy. We hypothesized that an increasing number of cores may undermine the accuracy of models predicting the presence of prostate cancer at initial biopsy in patients submitted to 20-core initial biopsy.

Methods:

A total of 232 consecutive patients with prostate-specific antigen (PSA) between 4 and 20 ng/mL and/or abnormal digital rectal examination (DRE) underwent 12-core prostate biopsy protocol (group 1) or 20-core prostate biopsy protocol (group 2). The patients were divided into subgroups according to the results of their serum PSA and prostate volume. We evaluated the cancer detection rate overall and in each subgroup. Clinical data were analyzed using chi-square analysis and the unpaired t-test or 1-way ANOVA with significance considered at 0.05.

Results:

The 2 groups of patients were not significantly different with regard to parameters (age, abnormal DRE and serum PSA), although median prostate volume in group 1 (57.76 ± 26.94 cc) were slighter greater than in group 2. Cancer detection rate for patients submitted to 20 prostate biopsy was higher than patients submitted to 12 prostate biopsy (35.2% vs. 25%, p = 0.095). Breakdown to PSA level showed a benefit to 20 prostate biopsy for PSA <6 ng/mL (37.1% vs. 12.9%, p = 0.005). Stratifying results by prostate volume, we found that the improvement of cancer detection rate with 20 prostate biopsy was significant in patients with a prostate volume greater than 60 cc (55% in 20 prostate biopsy vs. 11.3% p < 0.05). Morbidity rates were identical in groups 1 and 2 with no statistically significant difference. There appeared to be no greater risk of infection and bleeding with 20 prostate biopsy protocol.

Conclusion:

The 20-core biopsy protocol was more efficient than the 12-core biopsy protocol, especially in patients with prostate specific antigen <6 ng/mL and prostate volume greater than 60 cc.     

Prostate gland biopsies and prostatectomies: an Ontario community hospital experience

Objective

Transrectal ultrasound–guided core biopsies of the prostate gland and prostatectomies have become common procedures at many community hospitals in Canada, especially in the era of serum prostate-specific antigen (PSA) screening for prostate cancer. The Gleason grading of prostate cancer in biopsies and prostatectomies is a major determinant used for treatment planning. There is evidence in the literature that suggests important discordance between community hospital pathologists and urological pathologists with respect to the Gleason grading of prostate cancer. Our objective was to determine the diagnostic rates and Gleason scoring patterns for prostate gland biopsies and prostatectomies at our institution compared with the literature.

Methods

We conducted a retrospective review of all prostate gland biopsies and prostatectomies performed at the Grey Bruce Health Services from January 2005 to September 2005. We collected data from 194 biopsies and 44 prostatectomies. We obtained prebiopsy serum PSA levels and digital rectal exam results for all patients from urologists’ office records.

Results

The average age for men having biopsies was 65.8 (standard deviation [SD] 8.6) years, and the average prebiopsy serum PSA level was 8.7 (median 7.1, SD 6.2) μg/L. The rates of diagnosis from prostate gland biopsies of benign (17.6%), high-grade prostatic intraepithelial neoplasia (11.0%), atypical small acinar proliferation suspicious for invasive malignancy (13.2%) and invasive prostatic adenocarcinoma (58.2%) at our institution were significantly different than those reported in the literature (p < 0.001). We observed a significant variation in the rates of these diagnoses among the community hospital pathologists in our study (p = 0.004). There was a strong correlation between the increasing number of positive core biopsy sites and increasing Gleason scores in biopsies (p < 0.001). There was also a strong correlation between increasing pre-biopsy serum PSA levels and increasing Gleason scores in biopsies (p < 0.001). A substantial proportion (21.9%) of the biopsies given the Gleason score of 6 had a Gleason score of 7 in the prostatectomy specimen.

Conclusion

Our results showed a significant difference in prostate gland biopsy categorical diagnoses compared with the literature. There were also significant differences in categorical diagnoses of prostate gland biopsies among the community hospital pathologists in our study. The data identify a strong positive correlation between the increasing number of positive core biopsy sites and increasing Gleason scores in biopsies, as well as a strong positive correlation between increasing prebiopsy serum PSA levels and increasing Gleason scores in biopsies that revealed cancer. We would encourage other community hospital pathologists, in collaboration with their urologists, to review periodically their prostate gland pathology practices in an attempt to improve the uniformity of diagnoses.     

Limited adequacy of thyroid cancer patient follow-up at a Canadian tertiary care centre

Background

We sought to evaluate the adequacy of follow-up of thyroid cancer patients at a Canadian centre.

Methods

We mailed a survey to the family physicians of thyroid cancer patients and analyzed the findings relative to follow-up guidelines published by the American Thyroid Association (ATA). Statistical significance between early and late follow-up patterns was analyzed using the χ² test.

Results

Our survey response rate was 56.2% (91 of 162). The time from operation ranged from 1.24–7.13 (mean 3.96) years, and 87.9% of patients had undergone a physical exam within the previous year. Only 37.4% and 14% of patients had a serum thyroglobulin measurement within 6 and between 6 and 12 months before the survey, respectively. Thyroid simulating hormone (TSH) levels were measured within the prior 6 months in 67% of patients and between 6 and 12 months in 13.2%. The TSH levels were suppressed (< 0.1 μIU/L) in 24.2% of patients, 0.1–2 μIU/L in 44% and greater than 2 μIU/L in 17.6%. Ultrasonography was the most common imaging test performed.

Conclusion

There is significant variation in the follow-up patterns of patients with thyroid cancer, and there is considerable deviation from current ATA guidelines.     

Clinical Effect of Switching from a Luteinizing Hormone-Releasing Hormone Agonist to an Antagonist in Patients with Castration-Resistant Prostate Cancer and Serum Testosterone Level ≥ 20 ng/dl

Introduction

The efficacy of conversion from a luteinizing hormone-releasing hormone agonist to an antagonist was evaluated prospectively in patients with castration-resistant prostate cancer.

Materials and Methods

From October 2012 to December 2014, 8 cases with a serum testosterone level ≥ 20 ng/dl during following androgen deprivation therapy were enrolled and received degarelix monthly. The primary end-pointgoal was to determine the effective prostate-specific antigen response rate. The secondary end-pointgoal was to assess the proportion of cases with a decrease in serum testosterone level to < 20 ng/ml.

Results

One patient achieved a complete response, with a prostate-specific antigen level of 0.02 ng/ml at the nadirend of the study. The effective response rate was 25.0% (2/8), and the proportion of cases with prostate-specific antigen decline was 62.5% (5/8). In 5/8 cases (5/8, 62.5%), serum testosterone levels declined to < 20 ng/dl.

Conclusion

Switching to a luteinizing hormone-releasing hormone antagonist in patients with testosterone levels ≥ 20 ng/dl may be an option in sequential androgen deprivation therapy for some patients.Key Words: Castration-resistant, Degarelix, Prostatic neoplasms, Luteinizing hormone-releasing hormone, Testosterone