Erik van Muilekom

Active Surveillance for Low-Risk Prostate Cancer Worldwide: The PRIAS Study

BACKGROUND Overdiagnosis and subsequent overtreatment are important side effects of screening for, and early detection of, prostate cancer (PCa). Active surveillance (AS) is of growing interest as an alternative to radical treatment of low-risk PCa. OBJECTIVE To update our experience in the largest worldwide prospective AS cohort. DESIGN, SETTING, AND PARTICIPANTS Eligible patients had clinical stage T1/T2 PCa, prostate-specific antigen (PSA) ≤ 10 ng/ml, PSA density <0.2 ng/ml per milliliter, one or two positive biopsy cores, and Gleason score ≤ 6. PSA was measured every 3-6 mo, and volume-based repeat biopsies were scheduled after 1, 4, and 7 yr. Reclassification was defined as more than two positive cores or Gleason >6 at repeat biopsy. Recommendation for treatment was triggered in case of PSA doubling time <3 yr or reclassification. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Multivariate regression analysis was used to evaluate predictors for reclassification at repeat biopsy. Active therapy-free survival (ATFS) was assessed with a Kaplan-Meier analysis, and Cox regression was used to evaluate the association of clinical characteristics with active therapy over time. RESULTS AND LIMITATIONS In total, 2494 patients were included and followed for a median of 1.6 yr. One or more repeat biopsies were performed in 1480 men, of whom 415 men (28%) showed reclassification. Compliance with the first repeat biopsy was estimated to be 81%. During follow-up, 527 patients (21.1%) underwent active therapy. ATFS at 2 yr was 77.3%. The strongest predictors for reclassification and switching to deferred treatment were the number of positive cores (two cores compared with one core) and PSA density. The disease-specific survival rate was 100%. Follow-up was too short to draw definitive conclusions about the safety of AS. CONCLUSIONS Our short-term data support AS as a feasible strategy to reduce overtreatment. Clinical characteristics and PSA kinetics during follow-up can be used for risk stratification. Strict monitoring is even more essential in men with high-risk features to enable timely recognition of potentially aggressive disease and offer curative intervention. Limitations of using surrogate end points and markers in AS should be recognized. TRIAL REGISTRATION The current program is registered at the Dutch Trial Register with ID NTR1718 (http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1718).

Quality of Life in Patients with Low-Risk Prostate Cancer. A Comparative Retrospective Study: Brachytherapy Versus Robot-Assisted Laparoscopic Prostatectomy Versus Active Surveillance

PURPOSE To investigate the quality of life (QoL) after different treatment modalities for low-risk prostate cancer, including brachytherapy, robot-assisted laparoscopic prostatectomy (RALP), and active surveillance (AS) with validated questionnaires. MATERIALS AND METHODS From a prospective database, we selected a total of 144 men with low-grade localized prostate cancer including 65 (45.1%) patients with RALP, 29 (20.2%) with brachytherapy, and 50 (34.7%) whose cancer was managed with AS. QoL was routinely evaluated with validated questionnaires: The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30), EORTC-QLQ-Prostate Module (PR)25, International Index of Erectile Function (IIEF)-15, International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF) with a minimum follow-up of 1 year. RESULTS In comparison with baseline scores, the brachytherapy group showed a significant decrease of QoL domain scores of voiding complaints (P=0.010), use of incontinence aids (P=0.011), sexual functioning domain (P=0.011), and erectile function (P≤0.001). In the RALP group, sexual function (P≤0.001), incontinence (P≤0.001), and erectile function were significantly affected. A decrease in sexual function was observed in 71% of men after RALP and 59% after brachytherapy. In 30% of men under AS, a decrease of erectile function score during follow-up was reported. Overall, no significant decrease in general QoL was observed neither for men under AS nor for men treated by brachytherapy or RALP. Clinical factors such as age, prostate size, prostate-specific antigen level, and nerve preservation during RALP were nonpredictive of overall QoL after treatment for the individual patient (P=0.676). CONCLUSION Patients with low-risk prostate cancer who are treated with brachytherapy or RALP report deterioration of QoL of specific domains such as voiding, continence, and sexual functioning in comparison with AS patients. A decrease of erectile function was also observed during AS. Overall QoL was similar for all three treatments options.

Robot-Assisted Laparoscopic Prostatectomy: Nodal Dissection Results During the First 440 Cases by Two Surgeons

BACKGROUND Although many studies address the learning curve for robot-assisted laparoscopic prostatectomy (RALP), little is known concerning the results for pelvic lymph node dissection (LND) during RALP. PATIENTS AND METHODS Between 2006 and 2011, two surgeons performed 904 RALP procedures. LND was performed in 440 (48.6%) cases based on the European Association of Urology guidelines. Both surgeons had extensive experience with open LND for both prostate and bladder cancer. Clinical data were prospectively recorded into an online database. Complications were reported using the Clavien-Dindo system and documented prospectively. RESULTS For both surgeons, the operative time for LND decreased over time during the first 150 LND procedures. After that, a mean plateau of operative time of 49 minutes for LND was reached. Nodal yield increased from a mean of 10 nodes for the first 50 cases to 14 for cases 351 to 400. The percentage of positive nodes increased significantly in these intervals from 4% to 23.1% (P<0.001, Mann Whitney U test). Overall complications by grade were not significantly different between RALP with or without LND. In 440 LND cases, 5 (1.5%) grade IIIb complications occurred. All were infection related with bowel perforation in one. Symptomatic lymphoceles necessitating drainage were present in five (1.5%) men. Thromboembolic events (0% vs 1.5%) and anastomosis dehiscence (0.2% vs 1.1%) were more common in men with LND. During the learning curve, the incidence of Clavien grade I and II but not grade III and IV complications decreased. CONCLUSION An improvement pattern for LND during RALP is observed for operative time, nodal yield node positivity rate, and complication rate during the first 400 cases of LND.

Selecting men diagnosed with prostate cancer for active surveillance using a risk calculator: a prospective impact study

Study Type – Prognosis (cohort series)

Extended Nodal Dissection Reduces Sexual Function Recovery After Robot-Assisted Laparoscopic Prostatectomy

BACKGROUND AND PURPOSE Considering the anatomic proximity of the internal iliac lymph nodes and the pelvic plexus, it may be expected that more extensive pelvic nodal dissection is associated with an increased risk of damage to the small pelvis neural and vascular structures. We evaluate whether nodal dissection is associated with functional outcome after robot-assisted radical prostatectomy (RARP). PATIENTS AND METHODS In a series of 798 RARP procedures, 325 (40.7%) patients underwent a lymph node dissection. Continence, sexual function, and lower urinary tract symptoms (LUTS) were assessed using the International Consultation of Incontinence Questionnaire short form (ICIQ)-SF), International Index of Erectile Function-15, and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ)-PR25 questionnaires before and at 6 months intervals after RARP. RESULTS Preoperative ICIQ-SF, IIEF-15, and PR25-LUTS scores were similar for men with and without nodal dissection. Normal postoperative erectile function (IIEF-EF >24) at 6 months was reported by 1.7%, 9.1%, and 50.4% of men with no, unilateral, and bilateral nerve preservation and normal preoperative erectile function. All domains of the IIEF-15 score showed a negative correlation with the number of removed lymph nodes. In 70 of 325 (21%) cases with nodal dissection, more than 10 nodes were removed. Men with more than 10 nodes removed had lower IIEF-15 domain scores compared with men with 1 to 10 removed lymph nodes. The postoperative ICIQ-SF and PR25-LUTS scores were not associated with extent of nodal dissection. Nodal metastases were found in 5.9% and 15.7% of men with ≤ 10 nodes and >10 nodes removed (P=0.005). In a multivariate analysis, extent of fascia preservation (FP-score), preoperative IIEF-EF, and number of removed nodes were the strongest independent predictors of postoperative erectile function recovery. CONCLUSION More extensive nodal dissection was associated with impaired postoperative sexual function recovery but not continence and voiding function after RARP, independent of preoperative function and nerve preservation.

Interview-Based Versus Questionnaire-Based Quality of Life Outcomes Before and After Prostatectomy

INTRODUCTION Functional outcome and quality of life (QOL) domains are important outcomes after curative therapy for prostate cancer. Although useful for scientific purposes, QOL questionnaires may be too extensive for daily routine, and single questions or interview-assessed outcomes may be more practical alternatives. The QOL outcomes of these measures were compared. MATERIALS AND METHODS The QOL of patients undergoing Robot-Assisted Radical Prostatectomy (RARP) in our hospital was monitored before and after treatment using both brief standardized interview questions, as well as more extensive validated questionnaires. The interview questions address erectile function and urinary continence with only one question on each subject (both four response items). Questionnaires included a total of 74 questions (EORTC-QLQ-C30, EORTC-QLQ-PR25, international index of erectile function-15, and international consultation on incontinence questionnaire-short form). RESULTS In 925 RARP patients, pre- and postoperative interview and questionnaire QOL data were available with a median follow up of 20 months. Improvement in both erectile function and continence scores occurred up till 2 years after the RARP for both interview- and questionnaire-based evaluations. On an individual patient basis, interview scores poorly correlated with questionnaire-based domains for continence and erectile function. Single questions from the questionnaire showed better correlation with domain scores. Functional recovery of continence after 1 year was worse when assessed by questionnaire than by interview evaluation. A decrease in physical (8%) and overall QOL (12%) after prostatectomy as assessed by the EORTC-QLQ-C30 questionnaire was better predicted by questionnaire-based than interview-based scores. Continence scores had a greater impact on physical and overall QOL scores than on erectile function scores. CONCLUSION Interview/assessed continence and erectile function outcome after RARP showed limited association with questionnaire-based evaluation and may overestimate functional recovery. Continence scores for both interviews and questionnaires were stronger correlated with physical and overall QOL than erectile function scores.

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.

Patterns of Benign Prostate Hyperplasia Based on Magnetic Resonance Imaging Are Correlated With Lower Urinary Tract Symptoms and Continence in Men Undergoing a Robot-assisted Radical Prostatectomy for Prostate Cancer

OBJECTIVE To investigate the association between benign prostatic hyperplasia (BPH) patterns, classified by magnetic resonance imaging (MRI), with lower urinary tract symptoms (LUTS) or continence, preoperatively and after robot-assisted laparoscopic radical prostatectomy (RARP). MATERIALS AND METHODS This retrospective study included 49 prostate cancer patients, with prostate size >47 cm3, who underwent an endorectal MRI followed by RARP. Five BPH patterns were identified according to Wasserman, and additional prostate measurements were recorded. LUTS were assessed using the International Prostate Symptom Score and the PR25-LUTS-Questionnaire score. Continence was assessed using the International Consultation of Incontinence Questionnaire-Short Form. RESULTS BPH pattern 3 (44.9%) was identified most common, followed by pattern 5 (26.6%), 1 (24.5%), and 2 and 4 (both 2%). BPH patterns were significant predictors of preoperative LUTS, with pedunculated with bilateral transition zone (TZ) and retrourethral enlargement (pattern 5) causing more severe symptoms compared with bilateral TZ and retrourethral enlargement (pattern 3) and bilateral TZ enlargement (pattern 1), whereas pattern 3 was additionally associated with more voiding symptoms compared with pattern 1. None of the BPH patterns was predictive of postoperative LUTS and continence. Independent predictors of continence at 12 months were lower preoperative PR25-LUTS score (P = .022) and longer membranous urethral length (P = .025). CONCLUSION MRI is useful for classifying patients in BPH patterns which are strongly associated with preoperative LUTS. However, BPH patterns did not predict remnant LUTS or postoperative incontinence. Postoperative continence status was only associated with preoperative LUTS and membranous urethra length.

Ultrasensitive prostate-specific antigen level as a predictor of biochemical progression after robot-assisted radical prostatectomy: Towards risk adapted follow-up

Ultrasensitive prostate‐specific antigen (USPSA) is useful for stratifying patients according to their USPSA‐based risk. Aim of our study was to determine the usefulness of USPSA as predictor of biochemical recurrence (BCR) after robot‐assisted radical prostatectomy (RARP).

European Oncology Nursing Society (EONS) at 30: much has been achieved, but there is still more to do.

2014 marked the 30th anniversary of the founding of the European Oncology Nursing Society. The origins of EONS can be traced to a meeting of like-minded people who were attending international cancer nursing conferences during the late 1970s and early 1980s. They saw the potential of a network of European cancer nursing societies that could grow alongside the expanding European Community. The European Community itself was founded on the political ideals of mutual benefit from trading alliances working together as well as promoting the ideals of peace; this was important after two wars had torn Europe apart in the 20th century. The founding goals of EONS were not so different as there was benefit to be gained from bringing cancer nurses together, learning from each other and sharing new knowledge from research and innovations in practice. Peace was not such a major problem in nursing but friendships and allegiances were also the outcomes of this venture in 1983/84 when the first steps were taken to establish the Society. Robert Tiffany, Director of Nursing at the Royal Marsden Hospital was a visionary person, who, together with nursing colleagues from across Europe, founded the new European Oncology Nursing Society. Looking at the vision and mission from 30 years ago and the EONS strategy today, we can conclude that some of the goals have been achieved but others remain to challenge us. We still believe that all people affected by cancer should benefit from well educated, informed and competent cancer nurses. As the leading European nursing organization we also recognize that working together in partnership with other professional organizations in Europe is becoming more and more important to develop the cancer nursing profession and improve patient outcomes. We are faced with real problems, such as a nursing shortage in Europe; especially in rural areas. Over the last decades we have also seen tremendous developments in the field of cancer nursing care, education and research, but unfortunately not across all of Europe. This is one of the reasons that EONS is keen to support activities together with colleagues from the lower-income countries or those where cancer nursing is still developing. EONS must be inclusive e in both attracting nurses from all parts of Europe e and by engaging them in the working groups and in all our different activities. We must also reflect on their feedback and seek their collaboration. We really need to know whether we are transparent and are meeting the needs of all