Maxwell V. Meng

The Changing Face of Low-Risk Prostate Cancer: Trends in Clinical Presentation and Primary Management

PURPOSE Early intervention for prostate cancer is associated with excellent long-term survival, but many affected men, especially those with low-risk disease characteristics, might not experience adverse impact to survival or quality of life were treatment deferred. We sought to characterize temporal trends in clinical presentation and primary disease management among patients with low-risk prostate cancer. METHODS Data were abstracted from the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE), a disease registry of 8,685 men with various stages of prostate cancer. Included were 2,078 men who were diagnosed between 1989 and 2001 and had a serum prostate specific antigen </= 10 ng/mL, Gleason sum </= 6, and clinical T stage </= 2a. Trends in risk distribution, tumor characteristics, and primary treatment were evaluated. RESULTS The proportion of patients with low-risk tumor characteristics rose from 29.8% in 1989 to 1992, to 45.3% in 1999 to 2001 (P <.0001). There have been sharp increases in the use of brachytherapy and androgen deprivation monotherapy, from 3.1% and 3.1%, to 12.0% and 21.7%, respectively. Utilization rates for prostatectomy, external-beam radiotherapy, and observation have fallen accordingly, from 63.8%, 16.1%, and 13.8%, to 51.6%, 6.8%, and 7.9% (P <.0001 for all except prostatectomy [P =.0019]). Age and socioeconomic status were significantly associated with treatment selection, but overall, the treatment trends were echoed on subgroup analysis of patients 75 years or older. CONCLUSION Low-risk features characterize a growing proportion of prostate cancer patients, and there have been significant shifts in the management of low-risk disease. Overtreatment may be a growing problem, especially among older patients.

Active surveillance for the management of prostate cancer in a contemporary cohort

Active surveillance followed by selective treatment for men who have evidence of disease progression may be an option for select patients with early‐stage prostate cancer. In this article, the authors report their experience in a contemporary cohort of men with prostate cancer who were managed with active surveillance.

Outcomes of Active Surveillance for Men With Intermediate-Risk Prostate Cancer

PURPOSE Active surveillance (AS) is an option for the initial management of early-stage prostate cancer. Current risk stratification schema identify patients with low-risk disease who are presumed to be most suitable for AS. However, some men with higher risk disease also elect AS; outcomes for such men have not been widely reported. PATIENTS AND METHODS Men managed with AS at University of California, San Francisco, were classified as low- or intermediate-risk based on serum prostate-specific antigen (PSA), Gleason grade, extent of biopsy involvement, and T stage. Clinical and demographic characteristics, and progression in terms of Gleason score, PSA kinetics, and active treatment were compared between men with low- and intermediate-risk tumors. RESULTS Compared to men with low-risk tumors, those with intermediate-risk tumors were older (mean, 64.9 v 62.3 years) with higher mean PSA values (10.9 v 5.1 ng/mL), and more tumor involvement (mean, 20.4% v 15.3% positive biopsy cores; all P < .01). Within 4 years of the first positive biopsy, the clinical risk group did not differ in terms of the proportions experiencing progression-free survival, (low [54%] v intermediate [61%]; log-rank P = .22) or the proportions who underwent active treatment (low [30%] v intermediate [35%]; log-rank P = .88). Among men undergoing surgery, none were node positive and none had biochemical recurrence within 3 years. CONCLUSION Selected men with intermediate-risk features be appropriate candidates for AS, and are not necessarily more likely to progress. AS for these men may provide an opportunity to further reduce overtreatment of disease that is unlikely to progress to advanced cancer.

Changes in Prostate Cancer Grade on Serial Biopsy in Men Undergoing Active Surveillance

PURPOSE Active surveillance is now considered a viable treatment option for men with low-risk prostate cancer. However, little is known regarding changes in Gleason grade on serial biopsies over an extended period of time. PATIENTS AND METHODS Men diagnosed with prostate cancer between 1998 and 2009 who elected active surveillance as initial treatment, with 6 or more months of follow-up and a minimum of six cores at biopsy, were included in analysis. Upgrading and downgrading were defined as an increase or decrease in primary or secondary Gleason score. Means and frequency tables were used to describe patient characteristics, and treatment-free survival rates were determined by life-table product limit estimates. RESULTS Three hundred seventy-seven men met inclusion criteria. Mean age at diagnosis was 61.9 years. Fifty-three percent of men had prostate-specific antigen of 6 ng/mL or less, and 94% had Gleason score of 6 or less. A majority of men were cT1 (62%), had less than 33% of biopsy cores involved (80%), and were low risk (77%) at diagnosis. Median number of cores taken at diagnostic biopsy was 13, mean time to follow-up was 18.5 months, and 29% of men had three or more repeat biopsies. Overall, 34% (129 men) were found to have an increase in Gleason grade. The majority of men who experienced an upgrade (81%) did so by their second repeat biopsy. CONCLUSION A proportion of men experience an upgrade in Gleason score while undergoing active surveillance. Men who experience early upgrading likely represent initial sampling error, whereas later upgrading may reflect tumor dedifferentiation.

Contemporary patterns of androgen deprivation therapy use for newly diagnosed prostate cancer.

Although once reserved for the management of metastatic prostate cancer, androgen deprivation therapy (ADT) is being used increasingly to treat lower stages of disease. We sought to assess patterns of ADT use in a contemporary cohort of men newly diagnosed with prostate cancer. Men with newly diagnosed prostate cancer who had > or =12 months of follow-up evaluation were identified in a national disease registry of patients with prostate cancer. The patterns of ADT use, both primary and secondary, were characterized and stratified by risk according to prostate-specific antigen levels, clinical stage, and Gleason score. In a cohort of 1485 men, 46% underwent ADT at some point during their treatment: 41% as primary therapy (either sole therapy or neoadjuvant therapy), and 5% as secondary therapy. In all, 50% of men receiving initial ADT had low- or intermediate-risk disease characteristics. Among patients treated with radical prostatectomy and radiation therapy, neoadjuvant ADT was administered in 20% and 48% of patients, respectively. Secondary hormonal manipulation was observed in 5% and 7% of patients treated initially with surgery or radiation, respectively. ADT is commonly used to treat men with prostate cancer. Much of the use of ADT is in men with low- and intermediate-risk disease characteristics. The appropriateness of such therapy requires further study, including its effect, not only on disease endpoints, but also on resource utilization and health-related quality of life.

Laparoscopic linear cutting stapler failure

OBJECTIVES To characterize the frequency and nature of problems with linear cutting staplers to help prevent complications in the future. These devices are often used during laparoscopic urologic procedures. METHODS We retrospectively reviewed the experience with laparoscopic linear cutting staplers at two institutions routinely performing urologic laparoscopy and analyzed the difficulties with any staplers. Data from the Food and Drug Administration Center for Devices and Radiological Health were also examined to determine the prevalence and types of reported problems. RESULTS In performing approximately 460 laparoscopic cases, we encountered 5 problems (1%) with endovascular gastrointestinal anastomosis staplers. Fifty-five additional cases in 50 patients were documented in the Food and Drug Administration database. Of the 55 patients, 15 (27%) required open conversion to manage the problem, 8 (15%) received blood transfusions, and 2 (4%) died postoperatively. Twenty-two events occurred during 19 laparoscopic donor nephrectomies (35%) without associated graft dysfunction, damage, or loss. All phases of instrument use were subject to problems; however, abnormal firing of the stapler and improper staple formation were the most common and morbid aspects of device malfunction. CONCLUSIONS Despite the general reliability of linear cutting staplers, difficulties were encountered in every step of use. Most situations were successfully managed by prompt identification and appropriate intracorporeal maneuvers. Nevertheless, significant morbidity may occur, and conversion to an open operation should be considered. Many potential problems can be avoided by surgeon and staff education, and one should be aware of the alternative methods of tissue ligation currently available.

Urinary stone disease

Urinary stone disease , Urinary stone disease , کتابخانه دیجیتالی دانشگاه علوم پزشکی و خدمات درمانی شهید بهشتی

A First in Human Phase 1 Study of CG0070, a GM-CSF Expressing Oncolytic Adenovirus, for the Treatment of Nonmuscle Invasive Bladder Cancer

PURPOSE We assessed the safety, pharmacokinetics and anticancer activity of intravesical CG0070, a cancer selective, replication competent adenovirus, for the treatment of nonmuscle invasive bladder cancer. MATERIALS AND METHODS A total of 35 patients received single or multiple (every 28 days × 3 or weekly × 6) intravesical infusions of CG0070 at 1 of 4 dose levels (1 × 10(12), 3 × 10(12), 1 × 10(13) or 3 × 10(13) viral particles). Response to treatment was based on cystoscopic assessment and biopsy or urine cytology. Urine and plasma CG0070, and granulocyte-monocyte colony-stimulating factor were measured in all patients. A subset of 18 patients was assessed for retinoblastoma phosphorylation status. RESULTS Grade 1-2 bladder toxicities were the most common adverse events observed. A maximum tolerated dose was not reached. High levels of granulocyte-monocyte colony-stimulating factor were detected in urine after administration in all patients. Virus replication was suggested based on an increase in urine CG0070 genomes between days 2 and 5 in 58.3% of tested patients (7 of 12). The complete response rate and median duration of the complete response across cohorts was 48.6% and 10.4 months, respectively. In the multidose cohorts the complete response rate for the combined groups (every 28 days and weekly × 6) was 63.6% (14 of 22 patients). In an exploratory, retrospective assessment patients with borderline or high retinoblastoma phosphorylation who received the multidose schedules had an 81.8% complete response rate (9 of 11). CONCLUSIONS Intravesical CG0070 was associated with a tolerable safety profile and antibladder cancer activity. Granulocyte-monocyte colony-stimulating factor transgene expression and CG0070 replication were also suggested.

PURE LAPAROSCOPIC ENTEROCYSTOPLASTY

The realm of laparoscopic surgery has expanded from simple extirpative operations to more complicated reconstructive procedures, such as dismembered pyeloplasty and ileal conduit creation. There has been recent interest in using laparoscopic techniques to augment the bladder with bowel.1, 2 To date only 1 case of enterocystoplasty, using the stomach, has been accomplished entirely by laparoscopy.3 To our knowledge we report the first case of ileal enterocystoplasty performed completely by laparoscopy. CASE REPORT A 31-year-old paraplegic woman with a C6 spinal cord injury developed worsening voiding dysfunction during the 2 years preceding presentation. She had managed previously with clean intermittent catheterization every 4 hours and remained dry. Video urodynamic studies demonstrated detrusor instability at bladder volumes of 40 to 50 ml. and a maximum bladder capacity of 85 ml. The patient did not desire urinary diversion or a continent cutaneous reservoir, and opted instead for laparoscopic ileal bladder augmentation. Mechanical and antibiotic bowel preparation was performed, and externalized ureteral stents were initially placed. The remainder of the operation duplicated open augmentation cystoplasty using an ileal segment. Briefly, 5 ports were used and the ileum was identified 15 cm. from the ileocecal valve. An endoscopic gastrointestinal anastomosis stapler was used to isolate a 15 to 20 cm. segment of ileum, and the mesentery was incised with ultrasonic coagulating shears. Bowel continuity was restored in a side-to-side fashion using a gastrointestinal anastomosis stapler, with the enterotomy closed in a single layer with interrupted 2-zero silk Lembert sutures. Monopolar electrocautery was used to remove the staples from both ends of the isolated ileal segment and detubularize it on its antimesenteric border. The ileum was sutured into a U-shaped configuration using a single layer of running 3-zero polyglactin sutures prior to mid sagittal cystotomy. The ileal patch was sutured to the bladder in quadrants using running 3-zero polyglactin sutures. Drainage was provided by a 20Fr urethral catheter and a 10 mm. Blake drain brought out through a lateral port site. No suprapubic catheter was placed. Watertight closure was confirmed by intraoperative irrigation of the bladder. Estimated blood loss was 100 ml. and there were no intraoperative complications. On the third postoperative day the drain was removed and the patient resumed liquid intake. However, she remained hospitalized due to prolonged ileus for 13 days. She returned to work and normal activity 1 week after being discharged. A cystogram performed 4 weeks postoperatively, at the time of catheter removal, demonstrated a bladder capacity of at least 250 ml. (see figure). Presently, the patient is continent between catheterizations with urinary volumes approximating 400 ml. DISCUSSION

The Relationship Between Prostate Specific Antigen Change and Biopsy Progression in Patients on Active Surveillance for Prostate Cancer

PURPOSE We assessed whether an association exists between a change in prostate specific antigen and biopsy progression in men on active surveillance. MATERIALS AND METHODS A cohort of patients undergoing active surveillance for prostate cancer was identified from the urological oncology database at our institution. Multivariate logistic regression was performed to determine whether prostate specific antigen velocity, defined as the change in ln(prostate specific antigen) per year, is associated with biopsy progression, defined as a Gleason upgrade or volume progression on repeat biopsy within 24 months of diagnosis. RESULTS A total of 241 men with a mean ± SD age of 61 ± 7 years and mean prostate specific antigen 4.9 ± 2.2 ng/ml met study inclusion criteria. Median time to repeat biopsy was 10 months (IQR 6-13). Biopsy progression developed in 55 men (23%), including a Gleason score upgrade in 46 (19%), greater than 33% positive cores in 11 (5%) and greater than 50% maximum single core positive in 12 (5%). The median prostate specific antigen ratio per year was 1.0 (IQR 0.95-1.03), although 1 man had a ratio of greater than 1.26 (doubled over 3 years) and 7 had a ratio of less than 1/1.26 (halved over 3 years). On multivariate analysis prostate specific antigen doubling within 3 years was associated with a 1.4-fold increase in the odds of biopsy progression (OR 1.4, 95% CI 0.6-3.4, p = 0.46). CONCLUSIONS There is little change in prostate specific antigen during the first 24 months of surveillance in men with well staged, low risk prostate cancer. We believe that these findings highlight the importance of repeat biopsy during surveillance.