Edward Rowe

10-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Localized Prostate Cancer

BACKGROUND The comparative effectiveness of treatments for prostate cancer that is detected by prostate-specific antigen (PSA) testing remains uncertain. METHODS We compared active monitoring, radical prostatectomy, and external-beam radiotherapy for the treatment of clinically localized prostate cancer. Between 1999 and 2009, a total of 82,429 men 50 to 69 years of age received a PSA test; 2664 received a diagnosis of localized prostate cancer, and 1643 agreed to undergo randomization to active monitoring (545 men), surgery (553), or radiotherapy (545). The primary outcome was prostate-cancer mortality at a median of 10 years of follow-up. Secondary outcomes included the rates of disease progression, metastases, and all-cause deaths. RESULTS There were 17 prostate-cancer-specific deaths overall: 8 in the active-monitoring group (1.5 deaths per 1000 person-years; 95% confidence interval [CI], 0.7 to 3.0), 5 in the surgery group (0.9 per 1000 person-years; 95% CI, 0.4 to 2.2), and 4 in the radiotherapy group (0.7 per 1000 person-years; 95% CI, 0.3 to 2.0); the difference among the groups was not significant (P=0.48 for the overall comparison). In addition, no significant difference was seen among the groups in the number of deaths from any cause (169 deaths overall; P=0.87 for the comparison among the three groups). Metastases developed in more men in the active-monitoring group (33 men; 6.3 events per 1000 person-years; 95% CI, 4.5 to 8.8) than in the surgery group (13 men; 2.4 per 1000 person-years; 95% CI, 1.4 to 4.2) or the radiotherapy group (16 men; 3.0 per 1000 person-years; 95% CI, 1.9 to 4.9) (P=0.004 for the overall comparison). Higher rates of disease progression were seen in the active-monitoring group (112 men; 22.9 events per 1000 person-years; 95% CI, 19.0 to 27.5) than in the surgery group (46 men; 8.9 events per 1000 person-years; 95% CI, 6.7 to 11.9) or the radiotherapy group (46 men; 9.0 events per 1000 person-years; 95% CI, 6.7 to 12.0) (P<0.001 for the overall comparison). CONCLUSIONS At a median of 10 years, prostate-cancer-specific mortality was low irrespective of the treatment assigned, with no significant difference among treatments. Surgery and radiotherapy were associated with lower incidences of disease progression and metastases than was active monitoring. (Funded by the National Institute for Health Research; ProtecT Current Controlled Trials number, ISRCTN20141297 ; ClinicalTrials.gov number, NCT02044172 .).

Patient-Reported Outcomes after Monitoring, Surgery, or Radiotherapy for Prostate Cancer

BACKGROUND Robust data on patient-reported outcome measures comparing treatments for clinically localized prostate cancer are lacking. We investigated the effects of active monitoring, radical prostatectomy, and radical radiotherapy with hormones on patient-reported outcomes. METHODS We compared patient-reported outcomes among 1643 men in the Prostate Testing for Cancer and Treatment (ProtecT) trial who completed questionnaires before diagnosis, at 6 and 12 months after randomization, and annually thereafter. Patients completed validated measures that assessed urinary, bowel, and sexual function and specific effects on quality of life, anxiety and depression, and general health. Cancer-related quality of life was assessed at 5 years. Complete 6-year data were analyzed according to the intention-to-treat principle. RESULTS The rate of questionnaire completion during follow-up was higher than 85% for most measures. Of the three treatments, prostatectomy had the greatest negative effect on sexual function and urinary continence, and although there was some recovery, these outcomes remained worse in the prostatectomy group than in the other groups throughout the trial. The negative effect of radiotherapy on sexual function was greatest at 6 months, but sexual function then recovered somewhat and was stable thereafter; radiotherapy had little effect on urinary continence. Sexual and urinary function declined gradually in the active-monitoring group. Bowel function was worse in the radiotherapy group at 6 months than in the other groups but then recovered somewhat, except for the increasing frequency of bloody stools; bowel function was unchanged in the other groups. Urinary voiding and nocturia were worse in the radiotherapy group at 6 months but then mostly recovered and were similar to the other groups after 12 months. Effects on quality of life mirrored the reported changes in function. No significant differences were observed among the groups in measures of anxiety, depression, or general health-related or cancer-related quality of life. CONCLUSIONS In this analysis of patient-reported outcomes after treatment for localized prostate cancer, patterns of severity, recovery, and decline in urinary, bowel, and sexual function and associated quality of life differed among the three groups. (Funded by the U.K. National Institute for Health Research Health Technology Assessment Program; ProtecT Current Controlled Trials number, ISRCTN20141297 ; ClinicalTrials.gov number, NCT02044172 .).

Robot-assisted radical cystectomy with intracorporeal urinary diversion: impact on an established enhanced recovery protocol.

To assess the impact of the introduction of robot‐assisted radical cystectomy (RARC) on an established enhanced recovery programme (ERP) and to examine the effect on mortality and morbidity rates, transfusion rates, and length of stay (LOS).

The status of surgery in the management of high-risk prostate cancer.

Although the optimal treatment for patients with high-risk prostate cancer remains unclear, combined radiotherapy and androgen-deprivation therapy (ADT) has become the standard of care; however, more recently, this paradigm has been challenged. In contemporary surgical series, using a multimodal approach with primary radical prostatectomy and adjuvant radiotherapy, when appropriate, had comparable efficacy in patients with high-risk disease to radiotherapy in combination with ADT. Furthermore, perioperative and postoperative morbidity associated with radical prostatectomy seem to be similar in patients with low-risk, intermediate-risk, or high-risk prostate cancer. Importantly, downstaging and downgrading of a substantial proportion of tumours after surgery suggests that many patients might be overtreated using radiotherapy and ADT. Indeed, the potential benefits of surgery include the ability to obtain tissues that can provide accurate histopathological information and, therefore, guide further disease management, in addition to local control of disease, a potentially reduced risk of developing metastases, and avoidance of long-term ADT. Thus, patients with high-risk disease should be offered a choice of first-line treatments, including surgery. However, effective management of high-risk prostate cancer is likely to require a multimodal approach, including surgery, radiotherapy, and neoadjuvant and adjuvant ADT, although the optimal protocols remain to be determined.

Mortality Among Men with Advanced Prostate Cancer Excluded from the ProtecT Trial

Background Early detection and treatment of asymptomatic men with advanced and high-risk prostate cancer (PCa) may improve survival rates. Objective To determine outcomes for men diagnosed with advanced PCa following prostate-specific antigen (PSA) testing who were excluded from the ProtecT randomised trial. Design, setting, and participants Mortality was compared for 492 men followed up for a median of 7.4 yr to a contemporaneous cohort of men from the UK Anglia Cancer Network (ACN) and with a matched subset from the ACN. Outcome measurements and statistical analysis PCa-specific and all-cause mortality were compared using Kaplan-Meier analysis and Coxs proportional hazards regression. Results and limitations Of the 492 men excluded from the ProtecT cohort, 37 (8%) had metastases (N1, M0 = 5, M1 = 32) and 305 had locally advanced disease (62%). The median PSA was 17 μg/l. Treatments included radical prostatectomy (RP; n = 54; 11%), radiotherapy (RT; n = 245; 50%), androgen deprivation therapy (ADT; n = 122; 25%), other treatments (n = 11; 2%), and unknown (n = 60; 12%). There were 49 PCa-specific deaths (10%), of whom 14 men had received radical treatment (5%); and 129 all-cause deaths (26%). In matched ProtecT and ACN cohorts, 37 (9%) and 64 (16%), respectively, died of PCa, while 89 (22%) and 103 (26%) died of all causes. ProtecT men had a 45% lower risk of death from PCa compared to matched cases (hazard ratio 0.55, 95% confidence interval 0.38–0.83; p = 0.0037), but mortality was similar in those treated radically. The nonrandomised design is a limitation. Conclusions Men with PSA-detected advanced PCa excluded from ProtecT and treated radically had low rates of PCa death at 7.4-yr follow-up. Among men who underwent nonradical treatment, the ProtecT group had a lower rate of PCa death. Early detection through PSA testing, leadtime bias, and group heterogeneity are possible factors in this finding. Patient summary Prostate cancer that has spread outside the prostate gland without causing symptoms can be detected via prostate-specific antigen testing and treated, leading to low rates of death from this disease.

Improvement of an Enhanced Recovery Protocol for Radical Cystectomy

Introduction: Enhanced recovery protocols (ERPs) aim to improve outcome following major abdominal surgery. Our ERP for radical cystectomy focuses on reduced bowel preparation and standardised feeding and analgesic regimens. Although the ERP safely decreased hospital stay, time to return of bowel function has not been affected. The current study aims to assess the addition of chewing gum on return of bowel function as part of an ERP. Patients and methods: We examined the addition of chewing gum to our ERP. Data was obtained retrospectively from 112 consecutive patients, 56 before and 56 after implementing chewing gum in to the EPR. The primary outcome measured was return of bowel function signified by first defecation after surgery. Results: The demographics of the two groups showed no significant difference in age, gender distribution, American Society of Anesthesiologists grade, or type of urinary diversion. A significant reduction in the time to return of bowel function was observed in patients using chewing gum post-operatively (4 versus 6 days, p < 0.0001). The median inpatient stay was 13 days in both groups; however there was a trend to an earlier discharge in those patients receiving chewing gum. Conclusion: The introduction of chewing gum to our ERP is associated with a faster return of bowel function and may lead to a reduced inpatient stay.

Pathological analysis of lymph nodes in anterior prostatic fat excised at robot-assisted radical prostatectomy

Aims To assess the lymph node content of anterior prostatic fat (APF) sent routinely at robot-assisted laparoscopic radical prostatectomy (RALP) and the incidence of positive nodes in the extended pelvic lymph node dissection. Methods Between September 2008 and April 2012, APF excised from 282 patients who underwent RALP was sent for pathological analysis. This tissue was completely embedded and lymph nodes counted. Results In total, 49/282 (17%) patients had lymph nodes in the APF, median lymph node yield in this tissue was 1 (range 1–5). In four patients, the lymph nodes contained metastatic deposits. These patients did not have positive nodes elsewhere in the extended lymph node dissection. Conclusions APF contains lymph nodes in 1 in 6 patients and infrequently these may be malignant. APF should always be removed at radical prostatectomy. APF should be routinely sent for pathological analysis.

Early Recurrence Patterns Following Totally Intracorporeal Robot-assisted Radical Cystectomy: Results from the EAU Robotic Urology Section (ERUS) Scientific Working Group

Recurrence following radical cystectomy often occurs early, with >80% of recurrences occurring within the first 2 yr. Debate remains as to whether robot-assisted radical cystectomy (RARC) negatively impacts early recurrence patterns because of inadequate resection or pneumoperitoneum. We report early recurrence patterns among 717 patients who underwent RARC with intracorporeal urinary diversion at nine different institutions with a minimum follow-up of 12 mo. Clinical, pathologic, radiologic, and survival data at the latest follow-up were collected. Recurrence-free survival (RFS) estimates were generated using the Kaplan-Meier method, and Cox regression models were built to assess variables associated with recurrence. RFS at 3, 12, and 24 mo was 95.9%, 80.2%, and 74.6% respectively. Distant recurrences most frequently occurred in the bones, lungs, and liver, and pelvic lymph nodes were the commonest site of local recurrence. We identified five patients (0.7%) with peritoneal carcinomatosis and two patients (0.3%) with metastasis at the port site (wound site). We conclude that unusual recurrence patterns were not identified in this multi-institutional series and that recurrence patterns appear similar to those in open radical cystectomy series. PATIENT SUMMARY In this multi-institutional study, bladder cancer recurrences following robotic surgery are described. Early recurrence rates and locations appear to be similar to those for open radical cystectomy series.

Incidental acute prostatic inflammation is associated with a lower percentage of free prostate-specific antigen than other benign conditions of the prostate : a prospective screening study

To evaluate the performance of percentage free/total prostate‐specific antigen (f/tPSA) as a screening tool for prostate cancer, and to assess the impact of prostatic inflammation on f/tPSA.

Prostate cancer detection in men with a ‘normal’ total prostate‐specific antigen (PSA) level using percentage free PSA: a prospective screening study

To assess the utility of percentage free/total prostate‐specific antigen (f/tPSA) levels for detecting prostate cancer in a prospectively screened population of men with a ‘normal’ total PSA level.