Prasad Bollina

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

BACKGROUNDnThe comparative effectiveness of treatments for prostate cancer that is detected by prostate-specific antigen (PSA) testing remains uncertain.nnnMETHODSnWe 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.nnnRESULTSnThere 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).nnnCONCLUSIONSnAt 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

BACKGROUNDnRobust 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.nnnMETHODSnWe 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.nnnRESULTSnThe 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.nnnCONCLUSIONSnIn 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 .).

Development of a complex intervention improved randomization and informed consent in a randomized controlled trial

OBJECTIVEnMulticenter randomized trials are required for pragmatic evaluations of health care interventions, but recruitment is difficult. Systematic reviews failed to identify robust strategies to improve recruitment. We developed and evaluated a complex intervention to increase levels of randomization and informed consent.nnnSTUDY DESIGN AND SETTINGnThe ProtecT (Prostate testing for cancer and Treatment) trial compares radical surgery, radical conformal radiotherapy, and active monitoring for men aged 50-69 years with localized prostate cancer. The intervention was developed using qualitative research methods (content, thematic and conversation analysis). Rates of randomization and immediate acceptance of allocation were measured every 6 months to evaluate the impact of the intervention.nnnRESULTSnThe complex intervention comprised reviews of centers falling below study targets, training programmes, documents and individually tailored feedback. Over 65% of eligible participants consented to randomization. Trial participants became increasingly well informed as immediate acceptance of allocation rose from 65% to 81% between 2001 and 2005.nnnCONCLUSIONnThis complex intervention resulted in high levels of randomization and informed consent in a difficult trial. The generic aspects of the intervention could be applied to other trials to maximize randomization and informed consent, and allow the mounting of trials previously considered too difficult.

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.

Selective Interactions between Prostate Fibroblast and Epithelial Cells in Co-Culture Maintain the BPH Phenotype

Paracrine interactions between primary cultured prostate epithelial cells and stromal fibroblasts were investigated in relation to morphology, growth, androgen sensitivity and secretory activities using co-cultures in which the two populations were separated by a microporous membrane. In this new model system, both cell types maintained several aspects of the differentiated phenotype including the capacity to express 5α-reductase iso-enzymes and androgen receptors, to respond to androgens and to secrete prostate-specific antigen by the epithelial cells. Morphological studies demonstrated that the cells grown in co-culture exhibited round nuclei, tonofibrils and microvilli in epithelial cells and elongated nuclei, large amounts of Golgi apparatus and cilia in the fibroblasts, all indicative of the differentiated state. The co-culture system highlights the importance of the metabolic co-operation between prostate fibroblast and epithelial cells for preserving the phenotypic characteristics associated with the human prostate in vivo.

Endoscopic extraperitoneal radical prostatectomy: critical analysis of outcomes and learning curve.

Study Type – Therapy (case series)u2028Level of Evidenceu20034

Exploring the feasibility and acceptability of couple-based psychosexual support following prostate cancer surgery: study protocol for a pilot randomised controlled trial

BackgroundMen who undergo surgery for prostate cancer frequently experience significant side-effects including urinary and sexual dysfunction. These difficulties can lead to anxiety, depression and reduced quality of life. Many partners also experience psychological distress. An additional impact can be on the couple relationship, with changes to intimacy, and unmet psychosexual supportive needs in relation to sexual recovery and rehabilitation. The aim of this exploratory randomised controlled trial pilot study is to determine the feasibility and acceptability of a novel family-relational-psychosexual intervention to support intimacy and reduce distress among couples following prostate cancer surgery and to estimate the efficacy of this intervention.Methods/DesignThe intervention will comprise six sessions of psychosexual and relationship support delivered by experienced couple-support practitioners. Specialist training in delivering the intervention will be provided to practitioners and they will be guided by a detailed treatment manual based on systemic principles. Sixty-eight couples will be randomised to receive either the intervention or standard care (comprising usual follow-up hospital appointments). A pre-test, post-test design will be used to test the feasibility of the intervention (baseline, end of intervention and six-month follow-up) and its acceptability to couples and healthcare professionals (qualitative interviews). Both individual and relational outcome measures will assess sexual functioning, anxiety and depression, couple relationship, use of health services and erectile dysfunction medication/technologies. An economic analysis will estimate population costs of the intervention, compared to usual care, using simple modelling to evaluate the affordability of the intervention.DiscussionGiven the increasing incidence and survival of post-operative men with prostate cancer, it is timely and appropriate to determine the feasibility of a definitive trial through a pilot randomised controlled trial of a family-relational-psychosexual intervention for couples. The study will provide evidence about the components of a couple-based intervention, its acceptability to patients and healthcare professionals, and its influence on sexual and relational functioning. Data from this study will be used to calculate sample sizes required for any definitive trial.Trial registrationClinicalTrials.gov Identifier: NCT01842438.Registration date: 24 April 2013; Randomisation of first patient: 13 May 2013

Couple-Based Psychosexual Support Following Prostate Cancer Surgery: Results of a Feasibility Pilot Randomized Control Trial.

INTRODUCTIONnSurgery for prostate cancer can result in distressing side effects such as sexual difficulties, which are associated with lower levels of dyadic functioning. The study developed and tested an intervention to address sexual, relational, and emotional aspects of the relationship after prostate cancer by incorporating elements of family systems theory and sex therapy.nnnAIMSnTo develop and test the feasibility and acceptability of relational psychosexual treatment for couples with prostate cancer, determine whether a relational-psychosexual intervention is feasible and acceptable for couples affected by prostate cancer, and determine the parameters for a full-scale trial.nnnMETHODSnForty-three couples were recruited for this pilot randomized controlled trial and received a six-session manual-based psychosexual intervention or usual care. Outcomes were measured before, after, and 6 months after the intervention. Acceptability and feasibility were established from recruitment and retention rates and adherence to the manual.nnnMAIN OUTCOME MEASURESnThe primary outcome measurement was the sexual bother subdomain of the Expanded Prostate Cancer Index Composite. The Hospital Anxiety and Depression Scale and the 15-item Systemic Clinical Outcome and Routine Evaluation (SCORE-15) were used to measure emotional and relational functioning, respectively.nnnRESULTSnThe intervention was feasible and acceptable. The trial achieved adequate recruitment (38%) and retention (74%) rates. The intervention had a clinically and statistically significant effect on sexual bother immediately after the intervention. Small decreases in anxiety and depression were observed for the intervention couples, although these were not statistically significant. Practitioners reported high levels of adherence to the manual.nnnCONCLUSIONnThe clinically significant impact on sexual bother and positive feedback on the studys feasibility and acceptability indicate that the intervention should be tested in a multicenter trial. The SCORE-15 lacked specificity for this intervention, and future trials would benefit from a couple-focused measurement.

Midterm oncological outcome and clinicopathological characteristics of anterior prostate cancers treated by endoscopic extraperitoneal radical prostatectomy

PurposeThe purpose of the study is to characterise the clinicopathological characteristics of anterior prostate cancer (APC) compared to posterior prostate cancer (PPC)s and to determine the midterm oncological outcomes of patients with APCs undergoing endoscopic extraperitoneal radical prostatectomy (EERPE).MethodsA retrospective review was carried out on all EERPEs performed in 2009. Pathology reports (transrectal ultrasound biopsy and surgical specimen), specimen photographs, demographic details and oncological outcome data from a prospectively maintained database were reviewed. Unpaired t test, chi-squared test and Kaplan–Meier curves were used for the analysis.ResultsOf 139 patients identified, 53 were APCs (38xa0%) and 86 were PPCs (62xa0%). Significantly, greater number of repeat biopsies were required to diagnose APCs (pxa0=xa00.02) and they had significantly fewer positive biopsy cores (pxa0=xa00.0005). The APC group had a significantly higher PSA density (PSAd) with (<5 and 5–25xa0%) tumour involvement in positive cores compared to PPCs (pxa0=xa00.036 and 0.024, respectively). APCs had higher positive surgical margin (PSM) rates (pxa0=xa0ns), the apical margin more likely positive than PPCs (pxa0=xa00.0006). Biochemical recurrence-free survival (BRFS) for APCs at 1, 2 and 3xa0years was lower than PPCs, although not statistically significant (pxa0=xa00.16).ConclusionIn our study, APCs proved more difficult to diagnose and stage, had a higher PSM rate and a trend towards a worse bRFS than PPCs. Additionally, the use of PSAd low core involvement biopsies might aide clinicians to investigate this cohort of patients more thoroughly before advising active surveillance.

Could prostate biopsies be avoided in men older than 75 years with raised PSA

Objectives: Our purpose was to review current practice regarding the use of prostate biopsies in men older than 75 years with raised PSA by presenting the results of a retrospective audit and to identify these older men who really benefit from prostate biopsies. Methods: A high-volume tertiary center’s prospectively maintained prostate biopsy database of contemporary biopsies was reviewed. Men were stratified by age and PSA. Logistic regression analysis, Mantel-Haenszel and Fisher’s exact tests were used for statistical analysis. Results: Overall, 1,593 men underwent prostate biopsies between April 2004 and August 2006. Of these, 293 patients (18.4%) with a mean age of 82.62 years and mean PSA of 30.37 ng/ml were eligible for the study with an overall incidence of prostate cancer of 73.7%. Elderly men with PSA >20 ng/ml had a prostate cancer detection rate of 91%. They were more likely to have-high grade disease (OR = 5.4, 95% CI = 2.8–10.8, p < 0.0001) and receive hormone deprivation therapy (RR = 3.0, 95% CI = 2.1–4.3, p < 0.0001). Elderly men with PSA <20 ng/ml had a 3-fold risk of being placed on active monitoring. Almost 20% of them had 1 complication following biopsy, of whom 12 (4.1%) needed hospitalization. Conclusions: Given the high probability of detecting prostate cancer and receiving conservative treatment, prostate biopsies can be omitted in men >75 years with PSA >20 ng/ml. However, they are still useful in fit men >75 and <80 years with PSA <20 ng/ml who can be the potential candidates for treatment with curative intent.