Henk G. van der Poel

Systematic Review and Meta-analysis of Studies Reporting Urinary Continence Recovery After Robot-assisted Radical Prostatectomy

CONTEXT Robot-assisted radical prostatectomy (RARP) was proposed to improve functional outcomes in comparison with retropubic radical prostatectomy (RRP) or laparoscopic radical prostatectomy (LRP). In the initial RARP series, 12-mo urinary continence recovery rates ranged from 84% to 97%. However, the few available studies comparing RARP with RRP or LRP published before 2008 did not permit any definitive conclusions about the superiority of any one of these techniques in terms of urinary continence recovery. OBJECTIVE The aims of this systematic review were (1) to evaluate the prevalence and risk factors for urinary incontinence after RARP, (2) to identify surgical techniques able to improve urinary continence recovery after RARP, and (3) to perform a cumulative analysis of all available studies comparing RARP versus RRP or LRP in terms of the urinary continence recovery rate. EVIDENCE ACQUISITION A literature search was performed in August 2011 using the Medline, Embase, and Web of Science databases. The Medline search included only a free-text protocol using the term radical prostatectomy across the title and abstract fields of the records. The following limits were used: humans; gender (male); and publication date from January 1, 2008. Searches of the Embase and Web of Science databases used the same free-text protocol, keywords, and search period. Only comparative studies or clinical series including >100 cases reporting urinary continence outcomes were included in this review. Cumulative analysis was conducted using the Review Manager v.4.2 software designed for composing Cochrane Reviews (Cochrane Collaboration, Oxford, UK). EVIDENCE SYNTHESIS We analyzed 51 articles reporting urinary continence rates after RARP: 17 case series, 17 studies comparing different techniques in the context of RARP, 9 studies comparing RARP with RRP, and 8 studies comparing RARP with LRP. The 12-mo urinary incontinence rates ranged from 4% to 31%, with a mean value of 16% using a no pad definition. Considering a no pad or safety pad definition, the incidence ranged from 8% to 11%, with a mean value of 9%. Age, body mass index, comorbidity index, lower urinary tract symptoms, and prostate volume were the most relevant preoperative predictors of urinary incontinence after RARP. Only a few comparative studies evaluated the impact of different surgical techniques on urinary continence recovery after RARP. Posterior musculofascial reconstruction with or without anterior reconstruction was associated with a small advantage in urinary continence recovery 1 mo after RARP. Only complete reconstruction was associated with a significant advantage in urinary continence 3 mo after RARP (odds ratio [OR]: 0.76; p=0.04). Cumulative analyses showed a better 12-mo urinary continence recovery after RARP in comparison with RRP (OR: 1.53; p=0.03) or LRP (OR: 2.39; p=0.006). CONCLUSIONS The prevalence of urinary incontinence after RARP is influenced by preoperative patient characteristics, surgeon experience, surgical technique, and methods used to collect and report data. Posterior musculofascial reconstruction seems to offer a slight advantage in terms of 1-mo urinary continence recovery. Update of a previous systematic review of literature shows, for the first time, a statistically significant advantage in favor of RARP in comparison with both RRP and LRP in terms of 12-mo urinary continence recovery.

EAU–ESTRO–SIOG Guidelines on Prostate Cancer. Part 1: Screening, Diagnosis, and Local Treatment with Curative Intent

OBJECTIVE To present a summary of the 2016 version of the European Association of Urology (EAU) - European Society for Radiotherapy & Oncology (ESTRO) - International Society of Geriatric Oncology (SIOG) Guidelines on screening, diagnosis, and local treatment with curative intent of clinically localised prostate cancer (PCa). EVIDENCE ACQUISITION The working panel performed a literature review of the new data (2013-2015). The guidelines were updated and the levels of evidence and/or grades of recommendation were added based on a systematic review of the evidence. EVIDENCE SYNTHESIS BRCA2 mutations have been added as risk factors for early and aggressive disease. In addition to the Gleason score, the five-tier 2014 International Society of Urological Pathology grading system should now be provided. Systematic screening is still not recommended. Instead, an individual risk-adapted strategy following a detailed discussion and taking into account the patients wishes and life expectancy must be considered. An early prostate-specific antigen test, the use of a risk calculator, or one of the promising biomarker tools are being investigated and might be able to limit the overdetection of insignificant PCa. Breaking the link between diagnosis and treatment may lower the overtreatment risk. Multiparametric magnetic resonance imaging using standardised reporting cannot replace systematic biopsy, but robustly nested within the diagnostic work-up, it has a key role in local staging. Active surveillance always needs to be discussed with very low-risk patients. The place of surgery in high-risk disease and the role of lymph node dissection have been clarified, as well as the management of node-positive patients. Radiation therapy using dose-escalated intensity-modulated technology is a key treatment modality with recent improvement in the outcome based on increased doses as well as combination with hormonal treatment. Moderate hypofractionation is safe and effective, but longer-term data are still lacking. Brachytherapy represents an effective way to increase the delivered dose. Focal therapy remains experimental while cryosurgery and HIFU are still lacking long-term convincing results. CONCLUSIONS The knowledge in the field of diagnosis, staging, and treatment of localised PCa is evolving rapidly. The 2016 EAU-ESTRO-SIOG Guidelines on PCa summarise the most recent findings and advice for the use in clinical practice. These are the first PCa guidelines endorsed by the European Society for Radiotherapy and Oncology and the International Society of Geriatric Oncology and reflect the multidisciplinary nature of PCa management. A full version is available from the EAU office and online (http://uroweb.org/guideline/prostate-cancer/). PATIENT SUMMARY The 2016 EAU-STRO-IOG Prostate Cancer (PCa) Guidelines present updated information on the diagnosis, and treatment of clinically localised prostate cancer. In Northern and Western Europe, the number of men diagnosed with PCa has been on the rise. This may be due to an increase in opportunistic screening, but other factors may also be involved (eg, diet, sexual behaviour, low exposure to ultraviolet radiation). We propose that men who are potential candidates for screening should be engaged in a discussion with their clinician (also involving their families and caregivers) so that an informed decision may be made as part of an individualised risk-adapted approach.

Systematic Review and Meta-analysis of Studies Reporting Potency Rates After Robot-assisted Radical Prostatectomy

BACKGROUND Although the initial robot-assisted radical prostatectomy (RARP) series showed 12-mo potency rates ranging from 70% to 80%, the few available comparative studies did not permit any definitive conclusion about the superiority of this technique when compared with retropubic radical prostatectomy (RRP) and laparoscopic radical prostatectomy (LRP). OBJECTIVES The aims of this systematic review were (1) to evaluate the current prevalence and the potential risk factors of erectile dysfunction after RARP, (2) to identify surgical techniques able to improve the rate of potency recovery after RARP, and (3) to perform a cumulative analysis of all available studies comparing RARP versus RRP or LRP. EVIDENCE ACQUISITION A literature search was performed in August 2011 using the Medline, Embase, and Web of Science databases. Only comparative studies or clinical series including >100 cases reporting potency recovery outcomes were included in this review. Cumulative analysis was conducted using Review Manager v.4.2 software designed for composing Cochrane Reviews (Cochrane Collaboration, Oxford, UK). EVIDENCE SYNTHESIS We analyzed 15 case series, 6 studies comparing different techniques in the context of RARP, 6 studies comparing RARP with RRP, and 4 studies comparing RARP with LRP. The 12- and 24-mo potency rates ranged from 54% to 90% and from 63% to 94%, respectively. Age, baseline potency status, comorbidities index, and extension of the nerve-sparing procedure represent the most relevant preoperative and intraoperative predictors of potency recovery after RARP. Available data seem to support the use of cautery-free dissection or the use of pinpointed low-energy cauterization. Cumulative analyses showed better 12-mo potency rates after RARP in comparison with RRP (odds ratio [OR]: 2.84; 95% confidence interval [CI]: 1.46-5.43; p=0.002). Only a nonstatistically significant trend in favor of RARP was reported after comparison with LRP (OR: 1.89; p=0.21). CONCLUSIONS The incidence of potency recovery after RARP is influenced by numerous factors. Data coming from the present systematic review support the use of a cautery-free technique. This update of previous systematic reviews of the literature showed, for the first time, a significant advantage in favor of RARP in comparison with RRP in terms of 12-mo potency rates.

Intraoperative Laparoscopic Fluorescence Guidance to the Sentinel Lymph Node in Prostate Cancer Patients: Clinical Proof of Concept of an Integrated Functional Imaging Approach Using a Multimodal Tracer

BACKGROUND Integration of molecular imaging and in particular intraoperative image guidance is expected to improve the surgical accuracy of laparoscopic lymph node (LN) dissection. OBJECTIVE To show the applicability of combining preoperative, intraoperative, and postoperative sentinel node imaging using an integrated diagnostic approach based on an imaging agent that is both radioactive and fluorescent. DESIGN, SETTING, AND PARTICIPANTS Before surgery, multimodal indocyanine green (ICG)-(99m)Tc-NanoColl was injected into the prostate. Subsequent lymphoscintigraphy and single-photon emission computed tomography/computed tomography (SPECT/CT) imaging of pelvic nodes was performed to determine the location of the sentinel lymph nodes (SLNs) preoperatively. During the surgical procedure a fluorescence laparoscope, optimized for detection in the near infrared range, was used to visualize the nodes identified on SPECT/CT. Eleven patients scheduled for robot-assisted laparoscopic prostatectomy (RALP) with an increased risk of nodal metastasis, based on Memorial Sloan-Kettering Cancer Center/Kattan nomogram estimation, participated in a pilot assessment (N09IGF). SURGICAL PROCEDURE Patients underwent RALP with LN dissection for prostate cancer. MEASUREMENTS Radioactive and fluorescent signals were monitored using different modalities, and the correlation between the two types of signals was studied. The location of preoperatively detected SLNs was documented. RESULTS AND LIMITATIONS Preoperatively, SLNs were identified by SPECT/CT, and the multimodal nature of the imaging agent also enabled intraoperative detection via fluorescence imaging. Fluorescence particularly improved surgical guidance in areas with a high radioactive background signal such as the injection site. Ex vivo analysis revealed a strong correlation between the radioactive and fluorescent content in the excised LNs. Fluorescence detection is limited by the severe tissue attenuation of the signal. Therefore, radio guidance to the areas of interest is still desirable. CONCLUSIONS Initial data indicate that multimodal ICG-(99m)Tc-NanoColloid, in combination with a laparoscopic fluorescence laparoscope, can be used to facilitate and optimize dissection of SLNs during RALP procedures.

Best Practices in Robot-assisted Radical Prostatectomy: Recommendations of the Pasadena Consensus Panel

CONTEXT Radical retropubic prostatectomy (RRP) has long been the most common surgical technique used to treat clinically localized prostate cancer (PCa). More recently, robot-assisted radical prostatectomy (RARP) has been gaining increasing acceptance among patients and urologists, and it has become the dominant technique in the United States despite a paucity of prospective studies or randomized trials supporting its superiority over RRP. OBJECTIVE A 2-d consensus conference of 17 world leaders in prostate cancer and radical prostatectomy was organized in Pasadena, California, and at the City of Hope Cancer Center, Duarte, California, under the auspices of the European Association of Urology Robotic Urology Section to systematically review the currently available data on RARP, to critically assess current surgical techniques, and to generate best practice recommendations to guide clinicians and related medical personnel. No commercial support was obtained for the conference. EVIDENCE ACQUISITION A systematic review of the literature was performed in agreement with the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement. EVIDENCE SYNTHESIS The results of the systematic literature review were reviewed, discussed, and refined over the 2-d conference. Key recommendations were generated using a Delphi consensus approach. RARP is associated with less blood loss and transfusion rates compared with RRP, and there appear to be minimal differences between the two approaches in terms of overall postoperative complications. Positive surgical margin rates are at least equivalent with RARP, but firm conclusions about biochemical recurrence and other oncologic end points are difficult to draw because the follow-up in existing studies is relatively short and the overall experience with RARP in locally advanced PCa is still limited. RARP may offer advantages in postoperative recovery of urinary continence and erectile function, although there are methodological limitations in most studies to date and a need for well-controlled comparative outcomes studies of radical prostatectomy surgery following best practice guidelines. Surgeon experience and institutional volume of procedures strongly predict better outcomes in all relevant domains. CONCLUSIONS Available evidence suggests that RARP is a valuable therapeutic option for clinically localized PCa. Further research is needed to clarify the actual role of RARP in patients with locally advanced disease.

Short-term outcomes of the prospective multicentre ‘Prostate Cancer Research International: Active Surveillance’ study

Study Type – Therapy (prospective cohort)
Level of Evidence 2b

Comparing the Hybrid Fluorescent–Radioactive Tracer Indocyanine Green–99mTc-Nanocolloid with 99mTc-Nanocolloid for Sentinel Node Identification: A Validation Study Using Lymphoscintigraphy and SPECT/CT

The purpose of this study was to compare the lymphoscintigraphic drainage patterns of a hybrid sentinel node tracer consisting of the fluorescent dye indocyanine green (ICG) and 99mTc-nanocolloid with the drainage pattern of 99mTc-nanocolloid alone, the current standard tracer in many European countries. Methods: Twenty-five patients with a melanoma in the head and neck region (n = 10), a melanoma on the trunk (n = 6), or penile carcinoma (n = 9) who were scheduled for sentinel node biopsy were prospectively included. First, the standard 99mTc-nanocolloid procedure was performed. After injection at the lesion site, lymphoscintigraphy was performed with a 10-min dynamic study and static planar images at 10 min and 2 h after injection, followed by SPECT/CT. The same scintigraphic procedure was repeated after injection of hybrid ICG–99mTc-nanocolloid the same afternoon in 10 patients or the next morning in 15 patients. The paired images of both injections were evaluated, and count rates in the sentinel nodes were calculated and compared. Sentinel nodes were surgically localized using blue dye, a γ-ray detection probe, a portable γ-camera, and a fluorescence camera. Results: Lymphatic drainage was visualized in all 25 patients using 99mTc-nanocolloid, leading to the identification of 66 sentinel nodes in total. These same sentinel nodes were also identified during the second scintigraphic procedure with ICG–99mTc-nanocolloid. Moreover, a high correlation between the radioactive counting rates in the sentinel nodes of both scintigraphic studies was observed (mean R2 = 0.83). Intraoperatively (4–23 h after the second injection), all preoperatively identified sentinel nodes could be localized using radio- and fluorescence guidance combined. In total, 95% of the sentinel nodes could be intraoperatively visualized by means of fluorescence imaging, whereas merely 54% stained blue. Ex vivo, all radioactive sentinel nodes were fluorescent and vice versa. No adverse reactions were observed. Conclusion: The lymphatic drainage pattern of ICG–99mTc-nanocolloid is identical to that of 99mTc-nanocolloid. This observation, together with the added value of intraoperative fluorescence guidance, warrants wider evaluation of hybrid ICG–99mTc-nanocolloid as a tracer for sentinel node procedures.

Replication-selective oncolytic viruses in the treatment of cancer

In the search for novel strategies, oncolytic virotherapy has recently emerged as a viable approach to specifically kill tumor cells. Unlike conventional gene therapy, it uses replication competent viruses that are able to spread through tumor tissue by virtue of viral replication and concomitant cell lysis. Recent advances in molecular biology have allowed the design of several genetically modified viruses, such as adenovirus and herpes simplex virus that specifically replicate in, and kill tumor cells. On the other hand, viruses with intrinsic oncolytic capacity are also being evaluated for therapeutic purposes. In this review, an overview is given of the general mechanisms and genetic modifications by which these viruses achieve tumor cell-specific replication and antitumor efficacy. However, although generally the oncolytic efficacy of these approaches has been demonstrated in preclinical studies the therapeutic efficacy in clinical trails is still not optimal. Therefore, strategies are evaluated that could further enhance the oncolytic potential of conditionally replicating viruses. In this respect, the use of tumor-selective viruses in conjunction with other standard therapies seems most promising. However, still several hurdles regarding clinical limitations and safety issues should be overcome before this mode of therapy can become of clinical relevance.

Downsides of Robot-assisted Laparoscopic Radical Prostatectomy: Limitations and Complications

CONTEXT Robot-assisted laparoscopic radical prostatectomy (RALP) using the da Vinci Surgical System (Intuitive Surgical, Sunnyvale, CA, USA) is now in widespread use for the management of localised prostate cancer (PCa). Many reports of the safety and efficacy of this procedure have been published. However, there are few specific reports of the limitations and complications of RALP. OBJECTIVE The primary purpose of this review is to ascertain the downsides of RALP by focusing on complications and limitations of this approach. EVIDENCE ACQUISITION A Medline search of the English-language literature was performed to identify all papers published since 2001 relating to RALP. Papers providing data on technical failures, complications, learning curve, or other downsides of RALP were considered. Of 412 papers identified, 68 were selected for review based on their relevance to the objective of this paper. EVIDENCE SYNTHESIS RALP has the following principal downsides: (1) device failure occurs in 0.2-0.4% of cases; (2) assessment of functional outcome is unsatisfactory because of nonstandardised assessment techniques; (3) overall complication rates of RALP are low, although higher rates are noted when complications are reported using a standardised system; (4) long-term oncologic data and data on high-risk PCa are limited; (5) a steep learning curve exists, and although acceptable operative times can be achieved in <20 cases, positive surgical margin (PSM) rates may require experience with >80 cases before a plateau is achieved; (6) robotic assistance does not reduce the difficulty associated with obese patients and those with large prostates, middle lobes, or previous surgery, in whom outcomes are less satisfactory than in patients without such factors; (7) economic barriers prevent uniform dissemination of robotic technology. CONCLUSIONS Many of the downsides of RALP identified in this paper can be addressed with longer-term data and more widespread adoption of standardised reporting measures. The significant learning curve should not be understated, and the expense of this technology continues to restrict access for many patients.

Salvage Radical Prostatectomy for Radiation-recurrent Prostate Cancer: A Multi-institutional Collaboration

BACKGROUND Oncologic outcomes in men with radiation-recurrent prostate cancer (PCa) treated with salvage radical prostatectomy (SRP) are poorly defined. OBJECTIVE To identify predictors of biochemical recurrence (BCR), metastasis, and death following SRP to help select patients who may benefit from SRP. DESIGN, SETTING, AND PARTICIPANTS This is a retrospective, international, multi-institutional cohort analysis. There was a median follow-up of 4.4 yr following SRP performed on 404 men with radiation-recurrent PCa from 1985 to 2009 in tertiary centers. INTERVENTION Open SRP. MEASUREMENTS BCR after SRP was defined as a serum prostate-specific antigen (PSA) ≥ 0.1 or ≥ 0.2 ng/ml (depending on the institution). Secondary end points included progression to metastasis and cancer-specific death. RESULTS AND LIMITATIONS Median age at SRP was 65 yr of age, and median pre-SRP PSA was 4.5 ng/ml. Following SRP, 195 patients experienced BCR, 64 developed metastases, and 40 died from PCa. At 10 yr after SRP, BCR-free survival, metastasis-free survival, and cancer-specific survival (CSS) probabilities were 37% (95% confidence interval [CI], 31-43), 77% (95% CI, 71-82), and 83% (95% CI, 76-88), respectively. On preoperative multivariable analysis, pre-SRP PSA and Gleason score at postradiation prostate biopsy predicted BCR (p = 0.022; global p < 0.001) and metastasis (p = 0.022; global p < 0.001). On postoperative multivariable analysis, pre-SRP PSA and pathologic Gleason score at SRP predicted BCR (p = 0.014; global p < 0.001) and metastasis (p < 0.001; global p < 0.001). Lymph node involvement (LNI) also predicted metastasis (p = 0.017). The main limitations of this study are its retrospective design and the follow-up period. CONCLUSIONS In a select group of patients who underwent SRP for radiation-recurrent PCa, freedom from clinical metastasis was observed in >75% of patients 10 yr after surgery. Patients with lower pre-SRP PSA levels and lower postradiation prostate biopsy Gleason score have the highest probability of cure from SRP.