Proposed Hydrogel-Implant Quality Score and a Matched-Pair Study for Prostate Radiation Therapy.

PURPOSE: SpaceOAR hydrogel has been Food and Drug Administration approved to reduce rectal toxicity in prostate radiation therapy. Training and certification for this procedure is performed by the manufacturer, without independent quality measures. We propose a Hydrogel-Implant Quality Score (HIQS) as a surrogate to quantify hydrogel placement accuracy, to assist clinicians in tracking their implant proficiency, and to support quality improvement. A matched-pair study was designed to investigate the benefit of SpaceOAR in rectal dose reduction for low-dose-rate brachytherapy and to validate the principle of the proposed HIQS. METHODS: Eighty-one prostate patients were retrospectively selected for this study. Each patient had SpaceOAR implantation under manufacturer supervision. Postprocedure computed tomography and T2-weighted magnetic resonance imaging were acquired for radiation planning. A HIQS system was proposed to evaluate the hydrogel placement quality. Hydrogel implantation was performed immediately after LDR seed placement. For each LDR patient, a non-SpaceOAR patient was matched based upon intraoperative rectal dose and prostate coverage. Intraoperative and postoperative rectal dose reduction was compared between SpaceOAR and non-SpaceOAR groups. RESULTS: The average HIQS was 77 ± 10.8 (range, 49-97). Rectal anatomic distortions were seen in 17 cases. Significant rectal dose reductions between intraoperative and postoperative plans were found for SpaceOAR patients compared with non-SpaceOAR patients (25.1 Gy vs -5.0 Gy for ΔD2cc and 65.7 Gy vs 13.0 for ΔD0.1cc). Additional rectal dose reductions (8.4 Gy for ΔD2cc and 12.7 Gy for ΔD0.1cc) were found for patients without rectal distortion when SpaceOAR was used. CONCLUSIONS: The proposed HIQS system measured the hydrogel placement quality and provided insights into clinician learning and DVH outcome. SpaceOAR was shown to be effective in reducing rectal dose for LDR patients.

Erectile function following unilateral cavernosal nerve replacement.

INTRODUCTION: With nerve-sparing techniques, patients undergoing a radical prostatectomy may avoid the morbidity of erectile dysfunction. Certain patients who are not candidates for nerve-sparing procedures may be eligible for nerve interposition grafts. While bilateral cavernosal nerve grafting after radical prostatectomy has shown efficacy, the effect of unilateral nerve grafting following prostatectomy remains unclear. We evaluate a large group of patients who underwent a unilateral cavernosal nerve replacement. METHODS: Forty patients underwent unilateral nerve sparing surgery with concomitant contralateral cavernosal nerve replacement. Patients were selected for this procedure based upon preoperative nomogram risk assessment, endorectal MRI evidence of extra capsular disease (ECE) or intraoperative histology demonstrating margin positivity. Age, demographic data, Gleason score, clinical and pathologic stage and pre and post operative IIEF data was collected and prospectively analyzed. RESULTS: Median follow-up was 19 months. Median change in IIEF scores was 7.5. Twenty-one of 29 patients (72%) report being able to penetrate after prostatectomy. Sixteen of those 21 (76%) continue to require PDE-5 inhibitors to facilitate penetration. Four of the 6 patients (67%) who were unable to have intercourse following cavernosal nerve replacement received adjuvant hormonal and/or radiation therapy. Twenty-eight patients (97%) reported numbness at the graft harvest site. One patient experienced a graft site infection. Two of 29 (7%) patients reported pain at the harvest site. CONCLUSION: Unilateral sural nerve grafting is a feasible and well-tolerated approach for patients who must undergo wide resection of a NVB. While men do show a decrease in their IIEF score, 76% are able to achieve penetration following surgery. The majority of men continue to require PDE-5 inhibitors to facilitate intercourse.

Post-operative drain output as a predictor of bladder neck contracture following radical prostatectomy.

BACKGROUND: Bladder neck contracture (BNC) following prostatectomy has been reported in 0.5-32% of cases. While the etiology of a BNC is unclear, several factors have been associated with this complication, including blood loss, devascularization of bladder neck tissue, poor mucosal apposition and urinary extravasation. To study the impact of urinary extravasation on BNC formation, we used postoperative drain output as a surrogate measure for anastomotic leakage. METHODS: All patients undergoing a radical retropubic prostatectomy (RRP) or a robotic assisted radical prostatectomy (RARP) from January 2000 to April 2006 have been entered into a prospective review board-approved database. All RRP patients had their anastomosis performed in an interrupted fashion using six monofilament 2-0 sutures. All robotic-assisted radical prostatectomy anastomoses were performed in a running fashion using 2-0 monofilament sutures. A single, closed suction Jackson Pratt drain was placed over the surgical bed at the conclusion of the case. Post-operative drain outputs were recorded. All patients were evaluated at 3, 6, 9, 12 and 24 months post-operatively. All patients who reported a diminished urinary stream or incontinence were evaluated by office cystoscopy. The inability to navigate an 18 French cystoscope through the bladder neck was defined as a bladder neck contracture. RESULTS: A total of 576 patients underwent a radical prostatectomy over this time span. Complete records were available for 535 (93%) of these patients. There were 21 bladder neck contractures (3.9%) overall. The post-operative drain output ranged from 5-5,465 ml (median 119 ml). Eight patients who had drain outputs less than 119 ml developed a BNC while 13 BNC developed in patients with Jackson Pratt drain output > 119 ml (P = 0.343). In patients who underwent an open RRP, 19/424 (4.5%) developed contractures while 2/108 (1.9%) RARP patients developed a BNC (P = 0.105). CONCLUSION: The amount of post-operative drain output is not statistically associated with the development of a bladder neck contracture.

Mechanical failure rate of da Vinci robotic system.

INTRODUCTION: Robotic-assisted laparoscopic radical prostatectomy (RLRP) is playing an increasing role in the surgical management of prostate cancer. The benefits of minimally invasive surgery, enhanced surgeon familiarity with the instrumentation, and increased patient demand has led to the popularity of this surgical technique. There are, however, shortcomings specifically associated with this technology. Notably, instrumentation failure associated with robotic procedures represents a new and unique problem in urological surgery. We examine the rate of mechanical failure of the da Vinci robotic system and its impact on our prostate cancer program. MATERIALS AND METHODS: We reviewed our prospective, institutional review board-approved database of the first 350 RLRP procedures that were scheduled for surgery at our institution. We identified all cases in which mechanical failure of the da Vinci robotic system resulted in surgery being cancelled, postponed, or converted to a conventional laparoscopic or an open radical prostatectomy. RESULTS: Nine of the 350 (2.6%) scheduled RLRPs were unable to be completed robotically secondary to device malfunction. Six of the malfunctions were detected prior to anesthesia induction and surgery was rescheduled. Three other malfunctions occurred intraoperatively and were converted either to a conventional laparoscopic (1 case) or an open surgical approach (2 cases). The etiology of the malfunctions included the following: set-up joint malfunction (2), arm malfunction (2), power error (1), monocular monitor loss (1), camera malfunction (1), metal fatigue/ break of surgeon's console hand piece (1) and software incompatibility (1). CONCLUSIONS: Although uncommon, malfunction of the da Vinci robotic system does occur and may lead to psychological, financial, and logistical burdens for patients, physicians, and hospitals. Patients should be carefully counseled preoperatively regarding the possibility of robotic mechanical failure.

Experience improves staging accuracy of endorectal magnetic resonance imaging in prostate cancer: what is the learning curve?

INTRODUCTION: Accurate clinical staging is critical in guiding treatment for patients with prostate adenocarcinoma. Endorectal magnetic resonance imaging (MRI) has been advocated to improve staging accuracy. In order to assess the learning curve for endorectal MRI interpretation, we compared two cohorts of patients with high-risk prostate who underwent endorectal MRI at a center with limited prior exposure to this imaging modality. MATERIALS AND METHODS: Data for all patients who received a preoperative endorectal MRI followed by radical prostatectomy were prospectively collected. MRI was performed in patients with a high level of suspicion for extracapsular disease based on biopsy Gleason score, prostate specific antigen level, and digital rectal examination or if the Memorial Sloan-Kettering nomogram predicted a greater than 30% likelihood of extracapsular disease. The MRI results of our first 40 patients (group 1) and our second 40 patients (group 2) were compared to assess for improvement. RESULTS: Between October 2003 and September 2005, 80 patients underwent an endorectal MRI followed by radical prostatectomy. Mean age and median PSA were 58.4 (range 43 - 74) and 6.4 (range 0.048 -115.0), respectively. MRI findings were compared to the pathological findings from the radical prostatectomy specimen. Sensitivity, specificity, positive predictive value, and negative predictive value for detection of extracapsular disease were 31.3% versus 64.7%, 70.8% versus 78.3%, 41.7% versus 68.8%, and 60.7% versus 75.0%, respectively in group 1 versus group 2. The accuracy of MRI for detecting extracapsular extension was 52.5% in group 1 compared to 72.5% in group 2. CONCLUSIONS: In our series, endorectal MRI initially did not accurately predict tumor stage in patients with prostatic adenocarcinoma. With further experience, the accuracy of MRI substantially improved and approached the results from centers with significant experience in the interpretation of endorectal prostate MRI.

Development and external validation of an extended repeat biopsy nomogram.

PURPOSE: We hypothesized that the outcome of repeat biopsy could be accurately predicted. We tested this hypothesis in a contemporary cohort from 3 centers. MATERIALS AND METHODS: The principal cohort of 1,082 men from Hamburg, Germany was used for nomogram development as well as for internal 200 bootstrap validation in 721 and external validation in 361. Two additional external validation cohorts, including 87 men from Milan, Italy and 142 from Seattle, Washington, were also used. Predictors of prostate cancer on repeat biopsy were patient age, digital rectal examination, prostate specific antigen, percent free prostate specific antigen, number of previous negative biopsy sessions and sampling density. Multivariate logistic regression models were used to develop the nomograms. RESULTS: The mean number of previous negative biopsies was 1.5 (range 1 to 6) and the mean number of cores at final repeat biopsy was 11.1 (range 10 to 24). Of the men 370 (30.2%) had prostate cancer. On multivariate analyses all predictors were statistically significant (p < or =0.028). After internal validation the nomogram was 76% accurate. External validation showed 74% (Hamburg), 78% (Milan) and 68% (Seattle) accuracy. CONCLUSIONS: Relative to the previous nomograms (10 predictors or 71% accuracy) our tool relies on fewer variables (6) and shows superior accuracy in European men. Accuracy in American men is substantially lower. Racial, clinical and biochemical differences may explain the observed discrepancy in predictive accuracy.

An abnormal digital rectal examination is an independent predictor of Gleason > or =7 prostate cancer in men undergoing initial prostate biopsy: a prospective study of 790 men.

OBJECTIVE: To evaluate our experience with a referral population of 790 patients undergoing initial prostate biopsy in the prostate-specific antigen (PSA) era, to assess the role of a digital rectal examination (DRE) in predicting the outcome of prostate needle biopsy (PNB) and to evaluate if DRE findings were associated with cancer grade. PATIENTS AND METHODS: We analysed 790 consecutive men who had an initial PNB from September 1999 to July 2005 by one urologist (C.P.). All data were collected in a prospective database. Multivariate logistic regression analysis was used to determine the relationship between an abnormal DRE and the presence of cancer and cancer grade on PNB. RESULTS: An abnormal DRE was an independent predictor for prostate cancer on multivariate analysis (odds ratio 2.18, 95% confidence interval 1.53-3.10, P < 0.001). In all patients biopsied, an abnormal DRE was associated with a Gleason sum of > or = 7 on multivariate analysis (odds ratio 3.39, 2.07-5.53, P = 0.001). CONCLUSION: A DRE is a useful and important tool to use when assessing patients for a PNB. An abnormal DRE independently predicted high-grade disease in these men. These results might have important implications in the prediction of men with other than indolent prostate cancer.

External beam radiation helps prevent heterotopic bone formation in patients with a history of heterotopic ossification.

The aim of this study was to determine if radiation prevents heterotopic ossification (HO) in HO-forming patients after total hip arthroplasty (THA) or HO excision alone. Patients with HO in the ipsilateral hip (63 treated with THA revision and 25 treated with HO excision alone) and HO in the contralateral hip (36 treated with primary THA) were termed HO-forming patients. They underwent radiation to prevent HO. After excluding patients with inadequate follow-up, 84 patients were studied to determine if radiation prevents significant HO (Brooker Grade 3-4). For patients with ipsilateral hip HO, 12.3% developed significant HO. In patients with contralateral hip HO, 10.5% developed significant HO after THA. Sixty percent who received 6 Gy in 3 fractions after excision of ipsilateral HO developed significant HO, which was higher than for all dose-fractionation schemes combined (P = .01). In contrast, patients who received 7 Gy in 1 fraction developed significant HO 13.8% of the time, which was equivalent to all dose-fractionation schemes combined (P = not significant). Radiation prevents HO in HO-forming patients.

Vinorelbine, doxorubicin, and prednisone in androgen-independent prostate cancer.

BACKGROUND: Ultimately, patients with metastatic prostate cancer progress on androgen ablation therapy. The investigation of new chemotherapeutic regimens for the treatment of androgen-independent prostate cancer (AIPC) is essential. The authors conducted a Phase II trial with vinorelbine, doxorubicin, and daily prednisone (NAP) to investigate the antitumor activity and palliative response of this regimen in patients with AIPC. METHODS: Forty-six patients entered this Phase II combination chemotherapy trial. Patients were treated with both vinorelbine and doxorubicin at doses of 20 mg/m2 on Days 1, 8, and 15 every 28 days and prednisone 5 mg twice daily. Endpoints included prostate-specific antigen (PSA) response and palliation, as measured by the Functional Assessment of Cancer Therapy-Prostate (FACT-P) instrument, the Brief Pain Inventory Scale, and a narcotic analgesic log. RESULTS: The median follow-up for all 46 patients was 13.4 months. Fifty-two percent of patients had impaired performance status at baseline. One responding patient remained on NAP and was progression-free at 11.5 months. Thirty-nine patients progressed, 3 patients died prior to response assessment, and 3 patients refused therapy. The median overall survival was 57 weeks (95% confidence interval [95% CI], 36-76 weeks), and the median time to disease progression was 17 weeks (range, 11-24 weeks). The PSA response among the 36 patients who completed 3 cycles of NAP was 42% (95% CI, 26-59%). There was a statistically significant improvement in quality of life measured both by the FACT-General instrument (P = .03) and the FACT-P instrument (P = .0006) over the 3 months compared with baseline measurements. Pain medicine use also improved: The median morphine equivalents among patients who were taking pain medications at the time of study enrollment showed a substantial decline after 1 cycle of treatment that was maintained. Pain (as assessed by the Brief Pain Inventory) improved compared with baseline pain at the 2nd-month assessment (worst pain, P = .08; least pain, P = .02; and average pain, P = .003). Overall, the regimen was tolerated well. The most common side effects were mild fatigue and gastrointestinal complaints (all of which were Grade 1 or 2 [according to Version 2.0 of the Expanded Common Toxicity Criteria]). Seventeen patients (37%) experienced Grade 3 or 4 neutropenia. Five patients (11%) developed a cardiac ejection fraction of <50% during treatment and had doxorubicin discontinued. No patients developed clinical congestive heart failure. CONCLUSIONS: The NAP combination produced substantive palliation and a moderate response rate in men with AIPC.

Phase I-II prospective dose-escalating trial of lycopene in patients with biochemical relapse of prostate cancer after definitive local therapy.

OBJECTIVES: To report a prospective trial of lycopene supplementation in biochemically relapsed prostate cancer. METHODS: A total of 36 men with biochemically relapsed prostate cancer were enrolled in a dose-escalating, Phase I-II trial of lycopene supplementation. Six consecutive cohorts of 6 patients each received daily supplementation with 15, 30, 45, 60, 90, and 120 mg/day for 1 year. The serum levels of prostate-specific antigen (PSA) and plasma levels of lycopene were measured at baseline and every 3 months. The primary endpoints were PSA response (defined as a 50% decrease in serum PSA from baseline), pharmacokinetics, and the toxicity/tolerability of this regimen. RESULTS: A total of 36 patients were enrolled. The median age was 74 years (range 56 to 83), with a median serum PSA at entry of 4.4 ng/mL (range 0.8 to 24.9). No serum PSA responses were observed, and 37% of patients had PSA progression. The median time to progression was not reached. Toxicity was mild, with 1 patient discontinuing therapy because of diarrhea. Significant elevations of plasma lycopene were noted at 3 months and then appeared to plateau for all six dose levels. The plasma levels for doses between 15 and 90 mg/day were similar, with additional elevation only at 120 mg/day. CONCLUSIONS: Lycopene supplementation in men with biochemically relapsed prostate cancer is safe and well tolerated. The plasma levels of lycopene were similar for a wide dose range (15 to 90 mg/day) and plateaued by 3 months. Lycopene supplementation at the doses used in this study did not result in any discernible response in serum PSA.

Repetitive ureteral stenting for management of transplant graft ureteral obstruction.

PURPOSE: To review the use of repetitive stenting in the management of patients with ureteral obstruction after renal transplantation, with an emphasis on technique and functional graft outcome. MATERIALS AND METHODS: Five adult renal allograft recipients with ureteral obstruction were managed with repetitive ureteral stenting. Their hospital records, office notes, and operative reports were reviewed. RESULTS: All patients were successfully managed with retrograde ureteral stenting. They underwent an average of 8.8 stent changes over a mean 34.5 month follow up. No decline in renal function was observed. CONCLUSIONS: Repetitive stenting is a viable treatment option for select patients with renal allograft ureteral obstruction.

Robotic-assisted laparoscopic radical prostatectomy: an objective assessment and review of the literature.

Robotic-assisted laparoscopic radical prostatectomy (RLRP) has become an accepted treatment option for men with prostate cancer. A search of the available literature through January 2006 was performed to analyze the surgical technique, outcomes data, and other unique issues regarding RLRP. While prospective, randomized trials and long-term data are lacking, short-term data from single institution series have demonstrated outcomes for RLRP that appear to be equivalent to those for open radical prostatectomy (ORP). Although not yet proven, some encouraging data suggest that RLRP may be able to achieve improved cancer control, postoperative urinary control, and erectile function compared to open surgery for prostate cancer. Definite advantages of RLRP over ORP are not yet established. Future studies will determine the role of RLRP in the surgical treatment of men with prostate cancer.

Bladder cancer.

PURPOSE OF REVIEW: This article reviews the recent literature concerning important issues in the management of patients with bladder cancer. A brief overview of all aspects of bladder cancer including the etiology, diagnosis, and treatment are discussed with a focus on recent advances. RECENT FINDINGS: Bladder cancer is a significant cause of morbidity and mortality. The treatment for bladder cancer should be based on individual patient risk assessment and should include a multidisciplinary approach. In patients with superficial bladder cancer, research has focused on improving and optimizing intravesical therapy to reduce tumor recurrence and progression as well as on methods to better select the most appropriate treatment for patients with high-risk features. The important prognostic and therapeutic role of lymphadenectomy during radical cystectomy has become apparent and recent work has attempted to better define what should be considered the standard for lymph node dissection. Finally, in an attempt to improve survival, advances have been made using systemic chemotherapy in both the perioperative settings as well as for treatment of metastatic bladder cancer. SUMMARY: Research continues to improve our understanding of bladder cancer. This ongoing investigation is currently being translated to the bedside with refinements in the diagnosis and treatment of patients with bladder cancer.

Bladder cancer.

PURPOSE OF REVIEW: This article reviews recent advances in the diagnosis and management of bladder cancer. RECENT FINDINGS: Bladder cancer is a significant cause of morbidity and mortality. Recent research has attempted to improve the care of patients with this disease. Evidence suggests that bacillus Calmette-Guerin is the most effective intravesical therapy for the treatment of superficial bladder cancer and that maintenance therapy is superior to an induction course alone. In patients with muscle-invasive disease, nodal status and extent of lymphadenectomy have been shown to correlate with survival after radical cystectomy. The role of chemotherapy in the treatment of bladder cancer continues to evolve as well. Neoadjuvant chemotherapy has recently demonstrated a survival benefit, and trials are ongoing to define the optimal regimen of chemotherapy for urothelial carcinoma. SUMMARY: Improved understanding and advancements in the management of all stages of bladder cancer continue to improve the care of patients with this disease.

Bladder cancer.

Bladder cancer is a significant public health problem responsible for more than 130,000 deaths annually worldwide. Disease prevalence is also remarkable, with more than 500,000 patients carrying the diagnosis in the United States alone. Significant progress has been made in understanding the underlying molecular and genetic events in bladder cancer. However, there remains a great need for the development of reliable markers that can provide clinically useful information regarding diagnosis and prognosis and to facilitate the selection of appropriate therapy in the individual patient. Ongoing and future investigation is anticipated to refine treatment of patients with high-risk superficial disease, to determine the role of neoadjuvant and adjuvant chemotherapy for high-risk invasive disease, and to improve the efficacy of chemotherapy for patients with metastatic bladder cancer.