Lionne Venderbos

A longitudinal study on the impact of active surveillance for prostate cancer on anxiety and distress levels

Patients with potentially indolent prostate cancer (PC) can be managed with active surveillance (AS). Our objective was to analyse how anxiety and distress develop in men with untreated PC and whether highly anxious men quit AS.

Change of tumour characteristics and treatment over time in both arms of the European Randomized study of Screening for Prostate Cancer

OBJECTIVE To evaluate a change in tumour characteristics and applied treatments over time in the control arm of all centres of the European Randomized study of Screening for Prostate Cancer (ERSPC) and to compare this with similar data of the screening arm. METHODS Between 1993 and 2003, 182,160 men, aged 50-74 years, were randomised to the screening arm (N=82,816) and the control arm (N=99,184). Men in the screening arm were offered Prostate Specific Antigen (PSA) testing every 4 years whilst men in the control arm received usual care. Tumour characteristics and treatment were evaluated in all men diagnosed with prostate cancer up to December 2006 or the third screening round. Data on the control arm were divided into 3 periods: 1994-1998, 1999-2002 and 2003-2006. RESULTS Tumour characteristics were more favourable over time in both the control and the screening arm, with especially increasing proportions of T1C tumours with 29% in 1994-1998 versus 50% in 2003-2006 and 48% at the initial screening round versus 75% at the third screening round, respectively. Tumour characteristics observed in the last period of the control arm were comparable to tumour characteristics in the initial screening round. In the control arm, treatment changed over time with surgery as the most common treatment in the entire observed period, but almost doubling of expectant management and the combination of hormone therapy and radiotherapy over time. In the initial screening round, surgery was the most common treatment (42%), changing over time to expectant management as the most frequently applied treatment in the third screening round (33%). CONCLUSION Tumour characteristics in the control arm became more favourable over time and show similarity with prostate cancer cases detected at the initial screening round. The most prominent change in treatment over time was an increase of application of expectant management in both arms of the ERSPC. These observations reflect an increasing rate of opportunistic testing over time in men randomised to the control arm.

Informed decision making on PSA testing for the detection of prostate cancer: an evaluation of a leaflet with risk indicator.

BACKGROUND Population-based screening for prostate cancer (PCa) remains controversial. To help men making informed decisions about prostate specific antigen (PSA) screening a risk indicator (www.uroweb.org) was developed. This risk indicator is embedded in a leaflet that informs men about the pros and cons of PCa screening and enables calculation of the individual risk of having a biopsy detectable PCa. AIM To assess the effect of providing a leaflet including individualized risk estimation on informed decision making of men, i.e. knowledge about PCa and PSA screening, attitude towards undergoing a PSA test and intention to have a PSA test. METHODS An intervention study among 2000 men, aged 55-65 years, randomly selected from the population registry of the city of Dordrecht, the Netherlands, in 2008. Men were sent a questionnaire on knowledge of PCa, attitude and intention to have a PSA test. Men without a history of (screening for) PCa were sent the leaflet and Questionnaire 2 within 2 weeks after returning Questionnaire 1. Validated health and anxiety measures were used. RESULTS One thousand and twenty seven of 2000 men completed Questionnaire 1 (51%), of whom 298 were excluded due to a history of (screening for) PCa. Of the 729 remaining men, 601 completed Questionnaire 2 as well. At the second assessment significantly more men met the requirements of informed decision making (15% versus 33%, p<0.001), more men had relevant knowledge (284/601, 50% versus 420/601, 77%, p<0.001) and the intention to have a PSA test had increased (p<0.001). CONCLUSIONS Providing information on PCa screening combined with individualized risk estimation enhanced informed decision making and may be used for shared decision making on PSA screening of physicians and patients.

PSA-based prostate cancer screening： the role of active surveillance and informed and shared decision making

Since the first publication describing the identification of prostate-specific antigen (PSA) in the 1960s, much progress has been made. The PSA test changed from being initially a monitoring tool to being also used as a diagnostic tool. Over time, the test has been heavily debated due to its lack of sensitivity and specificity. However, up to now the PSA test is still the only biomarker for the detection and monitoring of prostate cancer. PSA-based screening for prostate cancer is associated with a high proportion of unnecessary testing and overdiagnosis with subsequent overtreatment. In the early years of screening for prostate cancer, high rates of uptake were very important. However, over time the opinion on PSA-based screening has shifted towards the notion of informed choice. Nowadays, it is thought to be unethical to screen men without them being aware of the pros and cons of PSA testing, as well as the fact that an informed choice is related to better patient outcomes. Now, as the results of three major screening studies have been presented and the downsides of screening are becoming better understood, informed choice is becoming more relevant.

Impact on quality of life of radical prostatectomy after initial active surveillance: more to lose?

Abstract Objective.The aim of this study was to determine whether deferred radical therapy for low-risk prostate cancer has an additionally unfavourable effect on quality of life (QoL). Substantial numbers of patients on active surveillance (AS) are eventually treated. Material and methods. Prostate cancer patients treated with robot-assisted radical prostatectomy (RARP) in the NCI-AvL (Amsterdam, The Netherlands) received systematic QoL questionnaires preoperatively and postoperatively. Questionnaires included the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core Module and Prostate Module (EORTC-QLQ-C30 and EORTC-QLQ-PR25), International Index of Erectile Function-15 (IIEF-15) and International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF). Patients with low-risk prostate cancer who received RARP after an initial period of AS (AS-RARP group) were compared with similar patients who primarily elected surgery (direct-RARP group). Results.The AS-RARP group included 29 patients who received RARP after a median period of 15.4 months of AS (range 3.0–18.8 months). Main reasons for deferred radical therapy were repeat biopsy risk reclassification (45%) and prostate-specific antigen progression (38%). The direct-RARP group included 363 patients treated after 3.3 months (range 0.1–45.5 months). RARP generally resulted in clinically relevant unfavourable changes on different QoL domains in both groups. Preoperatively the AS-RARP group showed more favourable scores on multiple QoL domains (physical functioning, p = 0.004; role functioning, p = 0.001; global health, p = 0.043; sexual activity, p = 0.001; sexual functioning, p = 0.029; IIEF-15, p = 0.042). Postoperatively, most of these more favourable scores in the AS-RARP group had changed to scores similar to the direct-RARP group, except for IIEF-15 (p = 0.027) and urinary symptoms (p = 0.001). When using a 12 month treatment delay threshold, a similar but less distinct effect was seen. Conclusions.Patients with low-risk prostate cancer who choose AS have more favourable preoperative QoL scores than patients who primarily elect radical prostatectomy, but these groups show similar postoperative QoL scores.

Active surveillance: Oncologic outcome

Purpose of review To give insight into recent literature (during the past 12–18 months) reporting on oncologic outcomes of men on active surveillance. Recent findings From recent published trials comparing radical prostatectomy vs. watchful waiting, we learn that radical treatment only benefits a small proportion of men and that a substantial part of men is overtreated. Therefore, active surveillance should aim at postponing treatment for most, but still generate the same disease-specific mortality as radical prostatectomy by treating only those who benefit. In this review some recent published data on prostate cancer-specific mortality under active surveillance as well as intermediate outcomes are described. Summary Prostate cancer-specific mortality under active surveillance is very low; however, longer follow-up is warranted. When deferred radical treatment and immediate radical treatment are compared, results seem to be quite similar, suggesting that postponing treatment does not affect the outcomes of men under active surveillance. Furthermore, in the majority of men active treatment could be avoided completely, without compromising oncologic outcome.

Differences in Treatment and Outcome After Treatment with Curative Intent in the Screening and Control Arms of the ERSPC Rotterdam

UNLABELLED Screening for prostate cancer (PCa) results in a favorable stage shift. However, even if screening did not result in a clinically apparent lower stage or grade, it might still lead to less disease recurrence after treatment with curative intent (radical prostatectomy [RP] and radiation therapy [RT]) because the tumor had less time to develop outside the prostate. The outcome after treatment could also differ because of variations in treatment quality (eg, radiation dosage/adjuvant hormonal therapy). To test these hypotheses, we compared differences in the treatment quality of the screening and control arms of the European Randomized Study of Screening for Prostate Cancer (ERSPC) Rotterdam and disease-free survival (DFS) after curative treatment in PCa patients with similar stage and grade. A total of 2595 men were initially treated with RP or RT. In the control arm, RT was more often combined with hormonal therapy; treatment dosage was often ≥69Gy. This most likely resulted from changes over time in treatment that coincided with the later detection in the control arm. DFS was higher in the screening arm in all risk groups. After correction for lead time, these differences were minimal, however. We concluded that treatment quality differed between the screening and control arms of the ERSPC Rotterdam. RT quality was especially superior in the control arm with higher dosages and more often RT in combination with hormonal therapy. Despite these differences favoring the control arm, DFS differences were minimal. PATIENT SUMMARY We looked at differences in prostate cancer (PCa) treatment and outcome after PCa treatment in men diagnosed after screening and men diagnosed after normal clinical practice. Treatment differed with superior treatment given to men diagnosed in normal clinical practice. We propose a likely explanation for this apparently counterintuitive finding (progressive insight combined with, on average, a later detection of tumors in unscreened men). Although unscreened men received better treatment, this advantage seemed to be outweighed by the advantage associated with the earlier detection, on average, of the tumor in screened men. TRIAL REGISTRATION ISRCTN49127736.

Do Treatment Differences between Arms Affect the Main Outcome of ERSPC Rotterdam

PURPOSE We assessed differences in treatment between the screening and control arms of ERSPC Rotterdam and studied whether possible treatment differences could explain the positive study outcome. MATERIALS AND METHODS In ERSPC Rotterdam men 55 to 74 years old were randomized to a screening arm of 21,210 and a control arm of 21,166. Treatment after diagnosis was at the discretion of the care provider chosen by the patient. Initial treatment was compared in 4 risk groups. The relation between prostate cancer incidence and prostate cancer mortality was assessed by risk group by correlating the incidence RR and the mortality RR. A direct relation would have supported a stage shift as the main cause of changes in prostate cancer mortality. RESULTS Initial treatment differed between the arms in the low, intermediate and high risk groups but not in the metastatic group. The RRs of prostate cancer incidence and mortality per risk group were related 1:1 (regression line slope 1.00, 95% CI 0.30-1.74). Of changes in prostate cancer mortality 94% could be explained by changes in prostate cancer incidence. This made treatment differences unlikely as the reason for the observed decrease in prostate cancer mortality. CONCLUSIONS Differences in treatment between the ERSPC Rotterdam screening and control arms were unlikely to explain the differences in prostate cancer mortality. Results are instead consistent with a decrease in prostate cancer mortality as the result of a favorable stage through screening.

Disease-specific and patient-reported outcomes under active surveillance.

Purpose of review To give insight into literature from the past 12–18 months, reporting on disease-specific and patient-reported outcomes of men under active surveillance for prostate cancer. Recent findings From recently published established active surveillance cohorts, we learnt that medium and long-term follow-up outcome data provide favorable evidence for the feasibility and safety of active surveillance. The mortality rates reported are consistent with expected mortality in favorable-risk patients who were managed with initial radical therapy. More definite conclusions on the safety of active surveillance can only be drawn on the basis of randomized controlled trial data. With respect to quality of life, men on active surveillance seem to do well, also with respect to urinary and erectile function. Further research on this subject is, however, warranted. Summary Prostate cancer-specific mortality under active surveillance is very low. The combination of disease-specific and patient-reported outcomes indicates that active surveillance is feasible. This is also reflected in smaller, population-based studies which confirm the acceptance of active surveillance in clinical practice.

Ethical and Legal Considerations in Active Surveillance for Prostate Cancer

There is a growing body of evidence supporting active surveillance as a preferred treatment strategy for men with low-risk prostate cancer. For various reasons, physicians may still be hesitant in offering active surveillance, one of them being the potential of missing the window of curability and therewith risking medicolegal liability. In this chapter, therefore, considerations will be discussed that give insight into legal components of a potential malpractice process. By providing such an insight, we want to make professionals aware of what they can do to overcome or avert such a process and therewith open the door to offering more active surveillance in the future. To make professionals more confident in offering active surveillance, among others, the role of information provision, the role of patient-physician communication, and the role of guidelines in offering active surveillance will be discussed.