A phase IIb randomized placebo-controlled trial testing the effect of MAG-EPA long-chain omega-3 fatty acid dietary supplement on prostate cancer proliferation.

BACKGROUND: High prostate eicosapentaenoic fatty acid (EPA) levels were associated with a significant reduction of upgrading to grade group (GG) ≥ 2 prostate cancer in men under active surveillance. We aimed to evaluate the effect of MAG-EPA long-chain omega-3 fatty acid dietary supplement on prostate cancer proliferation. METHODS: A phase II double-blind randomized placebo-controlled trial was conducted in 130 men diagnosed with GG ≥ 2 prostate cancer and undergoing radical prostatectomy between 2015-2017 (Clinicaltrials.gov: NCT02333435). Participants were randomized to receive 3 g daily of either MAG-EPA (n = 65) or placebo (n = 65) for 7 weeks (range 4-10) prior to radical prostatectomy. The primary outcome was the cancer proliferation index quantified by automated image analysis of tumor nuclear Ki-67 expression using standardized prostatectomy tissue microarrays. Additional planned outcomes at surgery are reported including plasma levels of 27 inflammatory cytokines and fatty acid profiles in circulating red blood cells membranes and prostate tissue. RESULTS: Cancer proliferation index measured by Ki-67 expression was not statistically different between the intervention (3.10%) and placebo (2.85%) groups (p = 0.64). In the per protocol analyses, the adjusted estimated effect of MAG-EPA was greater but remained non-significant. Secondary outcome was the changes in plasma levels of 27 cytokines, of which only IL-7 was higher in MAG-EPA group compared to placebo (p = 0.026). Men randomized to MAG-EPA prior to surgery had four-fold higher EPA levels in prostate tissue compared to those on placebo. CONCLUSIONS: This MAG-EPA intervention did not affect the primary outcome of prostate cancer proliferation according to nuclear Ki-67 expression. More studies are needed to decipher the effects of long-chain omega-3 fatty acid dietary supplementation in men with prostate cancer.

It is thought that our diet can impact our risk of cancer and affect outcomes in patients with cancer. Omega-3 fatty acids, mostly found in fatty fish, might be beneficial by protecting against prostate cancer and its adverse outcomes. We conducted a clinical trial to test the effects of an omega-3 dietary supplement (MAG-EPA) in men with prostate cancer. We randomly allocated 130 men to receive either MAG-EPA or a placebo for 7 weeks before their prostate cancer surgery. We measured a marker of how much tumor cells were proliferating (or growing in number) at the point of surgery, which might indicate how aggressive their disease was. However, the supplement did not affect tumor cell proliferation. The supplement was therefore not beneficial in this group of patients and further studies  are needed to test and confirm the effects of MAG-EPA on prostate cancer cells.

Effects of omega-3 supplementation on psychological symptoms in men with prostate cancer: Secondary analysis of a double-blind placebo-controlled randomized trial.

BACKGROUND: In the general population, a higher omega-3 polyunsaturated fatty acids intake is associated with lower levels of several psychological symptoms, especially depression. However, the existing evidence in cancer is equivocal. METHODS: This phase IIB double-blind, placebo-controlled trial was aimed at comparing the effects of eicosapentaenoic acid monoacylglyceride (MAG-EPA) supplementation and high oleic acid sunflower oil (HOSO; placebo) on depression levels (primary outcome) and other symptoms (anxiety, fear of cancer recurrence, fatigue, insomnia, perceived cognitive impairments; secondary outcomes). Participants, recruited in a prostate cancer clinic, were randomized to MAG-EPA (3.75 g daily; n = 65) or HOSO (3.75 g daily; n = 65) for 1 year post-radical prostatectomy (RP), starting 4-10 weeks before surgery. Patients completed self-report scales at baseline (before RP) and 3, 6, 9, and 12 months after: Hospital Anxiety and Depression Scale (HADS), Fear of Cancer Recurrence Inventory (FCRI), Insomnia Severity Index (ISI), Fatigue Symptom Inventory (FSI), and Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog). RESULTS: Analyses showed significant reductions in HADS-depression, HADS-anxiety, FCRI, ISI, FSI-number of days, and FACT-Cog-impact scores over time. A significant group-by-time interaction was obtained on FACT-Cog-Impact scores only; yet, the temporal change was significant in HOSO patients only. CONCLUSIONS: Several symptoms significantly decreased over time, mainly within the first months of the study. However, MAG-EPA did not produce greater reductions than HOSO. Omega-3 supplementation does not seem to improve psychological symptoms of men treated with RP.

Effects of Concentrated Long-Chain Omega-3 Polyunsaturated Fatty Acid Supplementation on Quality of Life after Radical Prostatectomy: A Phase II Randomized Placebo-Controlled Trial (RCT-EPA).

Prostate cancer (PCa) and associated treatments incur symptoms that may impact patients' quality of life. Studies have shown beneficial relationships between diet, especially omega-3 fatty acids, and these symptoms. Unfortunately, only few data describing the relationship between long-chain omega-3 fatty acids (LCn3) and PCa-related symptoms in patients are available. The purpose of this study was to evaluate the effects of LCn3 supplementation on PCa-specific quality of life in 130 men treated by radical prostatectomy. Men were randomized to receive a daily dose of either 3.75 g of fish oil or a placebo starting 7 weeks before surgery and for up to one-year post-surgery. Quality of life was assessed using the validated EPIC-26 and IPSS questionnaires at randomization, at surgery, and every 3 months following surgery. Between-group differences were assessed using linear mixed models. Intention-to-treat analyses showed no significant difference between the two groups. However, at 12-month follow-up, per-protocol analyses showed a significantly greater increase in the urinary irritation function score (better urinary function) (MD = 5.5, p = 0.03) for the LCn3 group compared to placebo. These results suggest that LCn3 supplementation may improve the urinary irritation function in men with PCa treated by radical prostatectomy and support to conduct of larger-scale studies.

Perception and satisfaction of patients after telemedicine urology consultations: A matched analysis with physicians' perspective.

INTRODUCTION: During the first regional COVID-19 lockdown in March 2020, we conducted a study aimed at evaluating completeness of telemedicine consultation in urology. Of 1679 consultations, 67% were considered completely managed by phone. The aim of the present study was to assess patients' experience and satisfaction with telemedicine and to compare them with urologists' perceptions about quality and completeness of the telemedicine consultation. METHODS: We contacted a randomly selected sample of patients (n=356) from our previous study to enquire about their experience. We used a home patient experience questionnaire, inspired by the Patient Experiences Questionnaire for Out-of-Hours Care (PEQOHC) and the Consumer Assessment Health Profile Survey (CAHPS). RESULTS: Of 356 patients contacted, 315 agreed to complete the questionnaire. Urological consultations were for non-oncological (104), oncological (121), cancer suspicion (41), and pediatric (49) indications. Mean patient satisfaction score after telemedicine consultation was 8.8/10 (median 9/10) and 86.3% of patients rated the quality of the consultation as either excellent (54.6%) or very good (31.7%). Consultations regarding cancer suspicion had the lowest score (8.3/10). Overall, 46.7% of all patients would have preferred an in-person visit outside of the pandemic situation. Among patients whose consultations were rated suboptimal by urologists, almost a third more (31.2%) would have preferred an in-person visit (p=0.03). CONCLUSIONS: Despite high reported patient satisfaction rates with telemedicine, it is noteworthy that nearly half of the patients would have preferred an in-person visit. Post-pandemic, it will be important to incorporate telemedicine as an alternative, while retaining and offering in-person visits.

Effects of omega-3 fatty acids supplementation on perioperative blood loss and complications after radical prostatectomy.

BACKGROUND AND AIMS: Many dietary supplements, including omega-3 fatty acids (ω3), are suspected to affect blood coagulation and platelet function. Despite no clinical evidence, discontinuation is recommended before radical prostatectomy. However, long-chain ω3 (LCω3) appear beneficial against prostate cancer progression. Here, we aim to determine the effect of LCω3 supplements on perioperative bleeding, hemoglobin, platelets, and postoperative complications after radical prostatectomy. METHODS: This is a planned exploratory analysis of 130 patients diagnosed with prostate cancer grade group 2 or greater enrolled in a randomized controlled trial (NCT02333435) testing the effects of LCω3, on prostate cancer biological and pathological outcomes at radical prostatectomy as main outcomes. The LCω3 intervention (MAG-EPA 3 g daily) or equivalent placebo was given 4-10 weeks prior to radical prostatectomy. An intention-to-treat analysis approach was used with bi-variate statistical testing of bleeding and complications outcomes. We also estimated the difference between groups using linear regression and non-parametric quantile regression models. All models were adjusted for confounding variables selected on clinical relevance. RESULTS: We found no clinically significant effect of LCω3 versus placebo on perioperative bleeding, laboratory tests or postoperative complications. In contrast, as expected, we found a significant increase in perioperative bleeding in open retropubic radical prostatectomy compared to robot-assisted radical prostatectomy (adjusted difference 115.8 mL, p = 0.04). CONCLUSIONS: Our results suggest that ω3 supplements can be safely taken before radical prostatectomy without increasing surgical bleeding risk. These findings are relevant since ω3 may beneficially affect prostate cancer evolution.

18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) is accurate for high-grade prostate cancer bone staging when compared to bone scintigraphy.

INTRODUCTION: In this study, we compared 18F-fluorodeoxyglucose (18F-FDG)-positron emission tomography/computed tomography (PET/CT) and bone scintigraphy accuracies for the detection of bone metastases for primary staging in high-grade prostate cancer (PCa) patients to determine if 18F-FDG-PET/CT could be used alone as a staging modality. METHODS: Men with localized high-grade PCa (n=256, Gleason 8-10, International Society of Urological Pathology [ISUP] grades 4 or 5) were imaged with bone scintigraphy and 18F-FDG-PET/CT. We compared, on a per-patient basis, the accuracy of the two imaging modalities, taking inter-modality agreement as the standard of truth (SOT). RESULTS: 18F-FDG-PET/CT detected at least one bone metastasis in 33 patients compared to only 26 with bone scan. Of the seven false-negative bone scintigraphies, four (57.1%) were solitary metastases (monometastatic), three (42.9%) were oligometastatic (2-4 lesions), and none were plurimetastatic (>4 lesions). Compared to SOT, 18F-FDG-PET/CT showed higher sensitivity and accuracy than bone scintigraphy (100% vs. 78.8%, and 98.7% vs. 98.2%) for the detection of skeletal lesions. CONCLUSIONS: 18F-FDG-PET/CT appears similar or better than conventional bone scans to assess for bone metastases in patients newly diagnosed with high-grade PCa. Since intraprostatic FDG uptake is also a biomarker for failure of radical prostatectomy and that FDG-PET/CT has been shown to be accurate in detecting PCa lymph node metastasis, FDG-PET/CT has the potential to be used as the sole preoperative staging modality in high-grade PCa.

A prospective, multisite study analyzing the percentage of urological cases that can be completely managed by telemedicine.

INTRODUCTION: The COVID-19 pandemic has accelerated the development of telemedicine due to confinement measures. However, the percentage of outpatient urological cases that could be managed completely by telemedicine outside of the COVID-19 pandemic remains to be determined. We conducted a prospective, multisite study involving all urologists working in the region of Quebec City. METHODS: During the first four weeks of the regional confinement, 18 pediatric and adult urologists were asked to determine, after each telemedicine appointment, if it translated into a complete (CCM), incomplete (ICM), or suboptimal case management (SCM, adequate only in the context of the pandemic). RESULTS: A total of 1679 appointments representing all urological areas were registered. Overall, 67.6% (95% confidence interval [CI] 65.3; 69.8), 27.1% (25.0; 29.3), and 4.3% (3.5; 5.4) were reported as CCM, SCM, and ICM, respectively. The CCM ratio varied according to the reason for consultation, with cancer suspicion (52.9% [42.9; 62.8]) and pediatric reasons (38.0% [30.0; 46.6]) showing the lowest CCM percentages. CCM percentages also varied significantly based on the setting where it was performed, ranging from 61.1% (private clinic) to 86.8% (endourology and general hospital). CONCLUSIONS: We show that two-thirds of all urological outpatient cases could be completely managed by telemedicine outside of the pandemic. After the pandemic, it will be important to incorporate telemedicine as an alternative for a patient's first or followup visit, especially those with geographical, pathological, and socioeconomic considerations.

Increased Prostate Cancer Glucose Metabolism Detected by 18F-fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Localised Gleason 8-10 Prostate Cancers Identifies Very High-risk Patients for Early Recurrence and Resistance to Castration.

BACKGROUND: The accuracy of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) to stage prostate cancer (PCa) is limited. However, Gleason 8-10 PCa and more aggressive metastatic PCa have been shown to exhibit a higher glycolytic activity. OBJECTIVE: To evaluate the potential of intraprostatic FDG uptake to prognose Gleason 8-10 PCa patients prior to prostatectomy, based on tumour intrinsic biology. DESIGN, SETTING, AND PARTICIPANTS: FDG-PET/CT and a bone scan were performed as a staging procedure prior to prostatectomy in 148 consecutive patients diagnosed with PCa with a Gleason sum of ≥8 at biopsy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The FDG-PET/CT images were blind reviewed. Lymph node (LN) metastasis and intraprostatic FDG uptake were systematically recorded, and correlated with the patients' clinicopathological characteristics. RESULTS AND LIMITATIONS: FDG-PET/CT detected foci of intraprostatic FDG uptake in 66% of patients. An intraprostatic FDG uptake of maximum intraprostatic standardised uptake value (SUVmax) of ≥4.6 was statistically significantly associated with a higher pathological Gleason ≥8, extracapsular extension, seminal vesicle invasion, and pathological LN metastasis. In multivariate analysis, an intraprostatic SUVmax of ≥4.6 was associated with a two-fold increased risk of biochemical recurrence in the year following surgery. Patients with an intraprostatic SUVmax of ≥4.6 had estimated median biochemical recurrence-free survival (BFS) of 11.3mo compared with 49.5mo for those with a lower SUVmax. Finally, high intraprostatic FDG uptake was associated with shorter time to castration resistance following radical prostatectomy (RP). CONCLUSIONS: Preoperative intraprostatic FDG uptake is an integrator of adverse pathological prognostic factors, predicting BFS and castration resistance following RP in patients with a Gleason score ≥8 PCa at biopsy. These results support the use of preoperative FDG-PET/CT as a tool to distinguish at diagnosis very high-risk Gleason 8-10 PCa patients in whom novel neoadjuvant or adjuvant therapies should be explored. PATIENT SUMMARY: This study shows that an increased use of glucose by prostate cancer cells detected by 18F-fluorodeoxyglucose positron emission tomography molecular imaging can identify aggressive prostate cancers.

Prognostic value of urinary prostate cancer antigen 3 (PCA3) during active surveillance of patients with low-risk prostate cancer receiving 5α-reductase inhibitors.

OBJECTIVES: To determine the clinical performance of the urinary prostate cancer antigen 3 (PCA3) test to predict the risk of Gleason grade re-classification amongst men receiving a 5α-reductase inhibitor (5ARI) during active surveillance (AS) for prostate cancer. PATIENTS AND METHODS: Patients with low-risk prostate cancer were enrolled in a prospective Phase II study of AS complemented with prescription of a 5ARI. A repeat biopsy was taken within the first year and annually according to physician and patient preference. In all, 90 patients had urine collected after digital rectal examination of the prostate before the first repeat biopsy. The PCA3 test was performed in a blinded manner at a central laboratory. RESULTS: Using a PCA3-test score threshold of 35, there was a significant difference (P < 0.001) in the risk of being diagnosed with Gleason ≥7 cancer during a median of 7 years of follow-up. Adjusted Cox regression and Kaplan-Meier analyses also showed a significantly higher risk of upgrading to Gleason ≥7 during follow-up for those with a higher PCA3-test score. CONCLUSION: The urinary PCA3 test predicted Gleason grade re-classification amongst patients receiving a 5ARI during AS for low-risk prostate cancer.

FDG-PET/CT for pre-operative staging and prognostic stratification of patients with high-grade prostate cancer at biopsy.

BACKGROUND: The role of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in prostate cancer (PCa) has not been well defined yet. Because high-grade PCa tends to exhibit increased glycolytic rate, FDG-PET/CT could be useful in this setting. The aim of this study was to assess the value of FDG-PET/CT for pre-operative staging and prognostic stratification of patients with high-grade PCa at biopsy. METHODS: Fifty-four patients with a Gleason sum≥8 PCa at biopsy underwent FDG-PET/CT as part of the staging workup. Thirty-nine patients underwent radical prostatectomy (RP) and pelvic lymph node (LN) dissection, 2 underwent LN dissection only, and 13 underwent non-surgical treatments. FDG-PET/CT findings from clinical reports, blinded reading and quantitative analysis were correlated with clinico-pathological characteristics at RP. RESULTS: Suspicious foci of increased FDG uptake were found in the prostate, LNs and bones in 44, 13 and 6% of patients, respectively. Higher clinical stage, post-RP Gleason sum and pattern, and percentage of cancer involvement within the prostate were significantly associated with the presence of intraprostatic FDG uptake (IPFU) (P<0.05 in all cases). Patients without IPFU who underwent RP were downgraded to Gleason≤7 in 84.6% of cases, as compared to 30.8% when IPFU was reported (P=0.003). Qualitative and quantitative IPFU were significantly positively correlated with post-RP Gleason pattern and sum, and pathological T stage. Absence and presence of IPFU were associated with a median 5-year cancer-free survival probability of 70.2 and 26.9% (P=0.0097), respectively, using the CAPRA-S prognostic tool. CONCLUSION: These results suggest that, among patients with a high-grade PCa at biopsy, FDG-PET/CT could improve pre-treatment prognostic stratification by predicting primary PCa pathological grade and survival probability following RP.

The impact of solitary and multiple positive surgical margins on hard clinical end points in 1712 adjuvant treatment-naive pT2-4 N0 radical prostatectomy patients.

BACKGROUND: Positive surgical margins (PSMs) increase the risk of biochemical recurrence (BCR) after radical prostatectomy (RP), but their impact on hard clinical end points is a topic of ongoing discussion. OBJECTIVE: To evaluate the influence of solitary PSMs (sPSMs) and multiple PSMs (mPSMs) on important clinical end points. DESIGN, SETTING, AND PARTICIPANTS: Data from 1712 patients from the Centre Hospitalier Universitaire de Québec with pT2-4 N0 prostate cancer (PCa) and undetectable prostate-specific antigen after RP were analyzed. INTERVENTION: RP without neoadjuvant or adjuvant treatment. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Kaplan-Meier analysis estimated survival functions, and Cox proportional hazards models addressed predictors of clinical end points. RESULTS AND LIMITATIONS: Median follow-up was 74.9 mo. A total of 1121 patients (65.5%) were margin-negative, 281 patients (16.4%) had sPSMs, and 310 patients (18.1%) had mPSMs. A total of 280 patients (16.4%) experienced BCR, and 197 patients (11.5%) were treated with salvage radiotherapy (SRT). Sixty-eight patients (4.0%) received definitive androgen deprivation therapy, 19 patients (1.1%) developed metastatic disease, and 15 patients (0.9%) had castration-resistant PCa (CRPC). Thirteen patients (0.8%) died from PCa, and 194 patients (11.3%) died from other causes. Ten-year Kaplan-Meier estimates for BCR-free survival were 82% for margin-negative patients, 72% for patients with sPSMs, and 59% for patients with mPSMs (p<0.0001). Time to metastatic disease, CRPC, PCa-specific mortality (PCSM), or all-cause mortality did not differ significantly among the three groups (p=0.991, p=0.988, p=0.889, and p=0.218, respectively). On multivariable analysis, sPSMs and mPSMs were associated with BCR (hazard ratio [HR]: 1.711; p=0.001 and HR: 2.075; p<0.0001), but sPSMs and mPSMs could not predict metastatic disease (p=0.705 and p=0.242), CRPC (p=0.705 and p=0.224), PCSM (p=0.972 and p=0.260), or all-cause death (p=0.102 and p=0.067). The major limitation was the retrospective design. CONCLUSIONS: In a cohort of patients who received early SRT in 70% of cases upon BCR, sPSMs and mPSMs predicted BCR but not long-term clinical end points. Adjuvant radiotherapy for margin-positive patients might not be justified, as only a minority of patients progressed to end points other than BCR. PCSM was exceeded 15-fold by competing risk mortality.

ImmunoCyt/uCyt+ improves the sensitivity of urine cytology in patients followed for urothelial carcinoma.

ImmunoCyt/uCyt is a fluorescent test combining three monoclonal antibodies. In this study, it has been tested as a complement to cytology in the detection of urothelial carcinoma in urine. It has been performed simultaneously with standard cytology and cystoscopy on 870 urine analyses from one hospital. In 136 cases, one or more bladder tumors were found. Overall sensitivity of cytology, ImmunoCyt/uCyt and combined analyses reached 29, 74 and 84%, respectively, and overall specificity was 98, 62 and 61%. The negative predictive value of cytology, ImmunoCyt/uCyt and both analyses was 88, 93 and 95%, respectively, and the positive predictive value was 70, 26 and 29%. The sensitivity of cytology for low malignant potential neoplasms, low- and high-grade papillary carcinomas was 6, 18 and 53%, while it reached 71, 79 and 93% when combined with ImmunoCyt/uCyt. The sensitivity of cytology for stages Ta, T1, T2 and over and Tis tumors was 12, 67, 47 and 50%, while it reached 78, 83, 79 and 100% when combined with ImmunoCyt/uCyt. In the absence of tumor on cystoscopy but with positive ImmunoCyt/uCyt, 18% of patients developed a tumor, 2-6 months later. Of the 109 cases diagnosed as suspicious for malignancy by cytology, a tumor was present in 30 cases and ImmunoCyt/uCyt was positive in 22 (73%) of them. In conclusion, ImmunoCyt/uCyt may be used to postpone cystoscopies in patients followed for bladder cancer and may help to save cytologist and pathologist screening time.

Safety and outcome of early catheter removal after radical retropubic prostatectomy.

OBJECTIVES: To assess the outcomes of patients who underwent radical retropubic prostatectomy (RRP) and had their indwelling urinary catheter removed on postoperative day 4 or later. METHODS: The medical records of 342 consecutive patients undergoing RRP by a single surgeon were retrospectively reviewed. None of these patients had received radiotherapy, transurethral resection, or simple prostatectomy before RRP. The 342 patients were categorized into two groups according to the length of catheterization. Group 1 (n = 127) had the urethral catheter removed on postoperative day 4, and group 2 (n = 215) had the catheter removed later than postoperative day 4. Removal of the urinary catheter was only done if control cystography failed to demonstrate anastomotic extravasation. In the case of acute urinary retention, home care nurses and emergency room personnel reinserted the urinary catheter without cystoscopic assistance. Incontinence was rated according to the number of protective pads used in a 24-hour period as follow: none, mild (1 pad/day), moderate (more than 1 but 3 or fewer pads/day), and severe (more than 3 pads/day). RESULTS: The mean age of the study population was 61.5 +/- 6.1 years. Acute urinary retention after catheter removal occurred in 11 patients (3%), 4 from group 1 and 7 from group 2. None of the patients requiring catheter reinsertion presented with complications related to this event. The overall continence rate was 58%, 85%, and 92% at 3, 9, and 12 months, respectively. The continence rates at 3, 9, and 12 months were higher for group 1 than for group 2 (P = 0.0002, P = 0.011, and P = 0.044, respectively). Bladder neck contracture was encountered in 14 patients (4%), 2 (2%) from group 1 and 12 (6%) from group 2. The only factor predicting continence was the duration of bladder catheterization. CONCLUSIONS: Bladder catheters can be safely removed on postoperative day 4 in patients with normal cystograms after RRP. The continence and anastomotic stricture rates were improved in patients with 4 days of indwelling catheterization.

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.

Routine nasogastric tubes are not required following cystectomy with urinary diversion: a comparative analysis of 430 patients.

PURPOSE: Postoperative nasogastric tube (NGT) use has been shown to increase postoperative morbidity in patients undergoing nonurological abdominal surgery. We examine the omission of NGTs as a method of decreasing postoperative gastrointestinal complications and hospital stay in patients undergoing cystectomy with urinary diversion. MATERIALS AND METHODS: Between January 1983 and December 2001, 430 patients underwent cystectomy with urinary diversion at our institution. We retrospectively compared patients who received postoperative NGTs with those who did not with regard to gastrointestinal recovery time, gastrointestinal complications and hospital stay. RESULTS: After correcting for confounding factors using ANCOVA the time to first bowel sounds, time to first flatus and the duration of hospitalization were shorter in patients not receiving NGTs (p = 0.006, 0.001 and 0.032, respectively). Omitting NGTs did not increase the risk of ileus, bowel obstruction, wound dehiscence, anastomotic leakage or aspiration pneumonia and it did not result in more frequent postoperative NGT placement. CONCLUSIONS: The results of the current study suggest that gastric decompression with NGTs following cystectomy with urinary diversion may prolong gastrointestinal recovery, which may be a factor leading to increased duration of hospitalization. We propose that postoperative NGTs should not be used routinely in the management of cystectomy cases.

Neoadjuvant hormone therapy before salvage radiotherapy for an increasing post-radical prostatectomy serum prostate specific antigen level.

PURPOSE: We retrospectively evaluated the benefit of neoadjuvant androgen deprivation therapy administered before salvage external beam radiation treatment in patients with biochemical failure following retropubic radical prostatectomy (RRP). MATERIALS AND METHODS: A total of 81 patients were treated with neoadjuvant androgen deprivation therapy before salvage external beam radiation treatment because of an increased prostate specific antigen (PSA) level following RRP. Preoperative, pathological, postoperative, and pre-salvage treatment parameters and radiation therapy dosage were examined for influence on outcome. Biochemical failures after RRP or salvage external beam radiation treatment were defined as a PSA greater than 0.3 ng/ml on 2 consecutive measurements. Median radiation dose delivered was 60 Gy. Neoadjuvant androgen deprivation therapy consisted of a 3 month injection of a luteinizing hormone releasing hormone analogue. Median followup was 38 months (range 12 to 102) after completion of external beam radiation treatment and 91 months (range 20 to 163) after radical prostatectomy. RESULTS: The actuarial free biochemical failure rates at 3 and 5 years were 75% and 50%, respectively. Two patients (2%) died of prostate cancer. Significant predictors of response to salvage external beam radiation treatment on a univariate analysis were a pre-radiation serum PSA less than 1 ng/ml and a pathological Gleason score less than 7. However, only pre-radiation PSA remained statistically significant on a multivariable analysis. CONCLUSIONS: External beam radiation with neoadjuvant androgen deprivation therapy is a viable option for patients with an increasing post-prostatectomy serum PSA. The most powerful predictor of biochemical failure was pre-radiation serum PSA.

Prognostic value of bone scan in patients with metastatic prostate cancer treated initially with androgen deprivation therapy.

PURPOSE: We analyzed whether classifying bone prostate cancer metastases correlates with survival in patients treated primarily with androgen deprivation. MATERIALS AND METHODS: We identified 86 patients with bone metastases who were followed between September 1988 and September 1999. Only those treated initially with androgen deprivation as monotherapy were included in this study. Clinical, pathological and radiological information were obtained by patient chart review. The 86 patients were divided into 2 groups according to metastasis grade on bone scan at diagnosis. Group 1 included patients with metastases on the axial skeleton and group 2 included those with bone metastases on the appendicular skeleton. In addition to our classification, we stratified patients according to the Soloway and Crawford et al classifications, and analyzed survival. RESULTS: There were no statistical differences in the groups with axial versus appendicular metastases in terms of patient age, biopsy Gleason score, serum prostate specific antigen or clinical stage. Median survival was 53 and 29 months in patients with axial and appendicular bone metastases, respectively. Those with axial disease had better survival than those with appendicular bone metastases (p = 0.048). No statistical difference was observed when grading bone scan according to the Soloway and Crawford et al classifications. CONCLUSIONS: Classifying bone scans according to the site of metastases (axial versus appendicular) had many advantages. It is easy to understand and helps urologist better predict the patient prognosis. Axial metastases carries a better prognosis than appendicular metastasis.

Prognostic markers in muscle invasive bladder cancer.

Current tumor, node, and metastasis (TNM) staging and grading systems are insufficient to accurately predict the evolution of most invasive bladder cancers irrespective of treatment. Predicting which invasive tumors will or will not recur or metastasize early is crucial in order to dictate initial therapy and to better counsel the patient. A need for tumor markers that could be incorporated into clinical practice to add prognostic information to the conventional TNM and grading systems in terms of treatment response and prognosis is crucial. This review provides an update on the most promising reported single markers and pathways, including the cell cycle markers p53, p21 and p27, and potential targets for novel therapies, such as cyclooxygenase 2 (COX 2) and factors of angiogenesis. The critical steps remain the availability of large and well-characterized data sets to validate the combination of markers, as well as high throughput methods to study tumor molecular fingerprints, such as DNA microarrays.

[Main grade of Gleason's 7 score of the surgical sample correlated with biologic progression in patients treated for total prostatectomy]. / Le grade principal du score 7 de Gleason de la pièce opératoire corrélé à la progression biologique des patients traités par prostatectomie totale.

OBJECTIVES: To analyse the influence of the main grade of Gleason score 7 of the operative specimen correlated with the blood PSA level on the laboratory progression-free survival of patients treated by radical prostatectomy. MATERIALS AND METHODS: 331 patients consecutively treated by radical prostatectomy and presenting a Gleason score 7 were analysed. Exclusion criteria were the use of radiotherapy and/or preoperative and/or postoperative endocrine therapy. The main grade (3 or 4), histological stage, and blood PSA level were analysed for their predictive value of laboratory progression-free survival. The mean follow-up was 3.5 years (range: 13.6 to 72.8 months). Laboratory recurrence was defined by a PSA > 0.4 ng/ml. RESULTS: The main grade of Gleason score 7 was 3 in 199 (60%) patients and 4 in 132 (40%) patients with a mean follow-up of 3.6 years. Laboratory progression-free survival rates were 89% and 72% for main grades 3 and 4, respectively (p = 0.03). When the cancer was confined to the prostate, the progression-free survival rates were 96% and 88% for main grades 3 and 4, respectively (p = 0.01). For a PSA < 10 ng/ml, main grade 3 was associated with a better laboratory progression-free survival rate than main grade 4 (p = 0.0007). No difference in terms of laboratory progression was observed in the presence of extraprostatic extension or PSA > 10 ng/ml. CONCLUSION: A high correlation was observed between the main grade of Gleason score 7 and laboratory progression-free survival. Main grade 3 constituted a factor of better prognosis than main grade 4.