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Highlights • Recurrence patterns on PET/CT after RT for PCN+ were correlated with nodal fields. • In-field nodal recurrences were uncommon. • Out-field nodal recurrences occurred mostly just above the elective nodal field. • Expanding elective fields to the aorta bifurcation may prolong disease-free survival., Purpose Biochemical failure after external beam radiotherapy (RT) for node-positive prostate cancer (PCN+) frequently involves nodal recurrences, in most cases out of field. This raises the question if current RTOG-based elective nodal fields can still be considered optimal. Modern diagnostic tools like PSMA PET/CT and choline PET/CT can visualize nodal recurrences with unprecedented accuracy. We evaluated recurrence patterns on PET/CT after RT for PCN+, with the aim to explore options for improved nodal target definition. Methods and materials Data of all patients treated with curative intent EBRT for PCN+ in NKI-AVL from 2008 to 2018 were retrospectively reviewed. EBRT comprised 70 Gy to the prostate or 66–70 Gy to the prostate bed, 60 Gy to involved nodes, and 52,5–56 Gy (46 Gy EQD2) to RTOG-based elective nodal fields, in 35 fractions. Locations of recurrences on PET/CT were noted, and nodal locations were correlated with the applied EBRT fields. Results 42 patients received PSMA (28) or choline (14) PET/CT at biochemical recurrence. 35 patients (83%) had a positive scan. At their first positive scan 17 patients had nodal metastasis, in some cases together with a local recurrence or distant disease. In-field nodal recurrences were uncommon (n = 3). Out-field nodal recurrences occurred more frequently (n = 14), with the majority (n = 12) just above the elective nodal field. These nodes were the single area of detectable failure in 6 patients (14%). Conclusions Current RT with RTOG-based nodal fields for PCN+ provides good in-field tumour control, but frequent out-field nodal recurrences suggest missed microscopic locations. Expanding elective fields to include the aorta bifurcation may prolong recurrence-free survival. Future research must address whether the potential benefits of this strategy outbalance additional toxicity.

Pancreatic metastasis from prostate cancer (PC) is quite rare. Herein, we report the case of a 67-year-old man with pancreatic metastasis from a neuroendocrine differentiated PC (NEDPC), a local recurrence after radical prostatectomy and androgen deprivation therapy for 6 years. Chemoradiotherapy was initiated for the locally recurrent NEDPC, and it had almost disappeared after the therapy. However, rapidly enlarged pancreatic metastasis from the NEDPC was detected 6 months after therapy. There is no standard treatment available for pancreatic metastasis from NEDPC owing to its rarity; hence, further knowledge and clinical experience regarding it are crucial.

Decision-making in the management of organ-confined prostate cancer is complex as it is based on multi-factorial considerations. It is complicated by a multitude of issues, which are related to the patient, treatment, disease, availability of equipment(s), expertise, and physicians. Combination of all these factors play a major role in the decision-making process and provide for an interactive decision-making preferably in the multi-disciplinary team (MDT) meeting. MDT decisions are comprehensive and are often based on all factors including patients’ biological status, disease and its aggressiveness, and physician and centres’ expertise. However, one important and often under rated factor is patient-related factors. There is considerable evidence that patients and physicians have different goals for treatment and physicians’ understanding of their own patients’ preferences is not accurate. Several patient-related key factors have been identified such as age, religious beliefs, sexual health, educational background, and cognitive impairment. We have focused on these areas and highlight some key factors that need to be taken considered whilst counselling a patient and understanding his choice of treatment, which might not always be match with the clinicians’ recommendation. Keywords: Prostate cancer, Decision-making, Multi-disciplinary team (MDT), Patients’ preferences

The most recent revolution in our understanding and knowledge of the human body is the introduction of new technologies allowing direct magnified vision of internal organs, as in laparoscopy and robotics. The possibility of viewing an anatomical detail, until now not directly visible during open surgical operations and only partially during dissections of cadavers, has created a ‘new surgical anatomy’. Consequent refinements of operative techniques, combined with better views of the surgical field, have given rise to continual and significant decreases in complication rates and improved functional and oncological outcomes. The possibility of exploring new ways of approaching organs to be treated now allows us to reinforce our anatomical knowledge and plan novel surgical approaches. The present review aims to clarify some of these issues. Keywords: Robotic surgery, Anatomy, Laparoscopy, Prostatectomy

Robot-assisted radical prostatectomy (RP) has gained remarkable worldwide distribution and has become a standard procedure for localised prostate cancer, indeed a new ‘gold standard’. There are proven advantages in reduced blood loss and shorter recovery time. Whilst case series publications often report improved functional outcomes, systematic hospital and healthcare data analyses mostly do not support these findings. Robotic surgery remains more costly. Its use has also increased knowledge about the anatomy of RP. Keywords: Prostate cancer, Radical prostatectomy, Robot-assisted radical prostatectomy, Outcome, Cost, Learning curve

Introduction The use of current available treatment for male erectile dysfunction (ED) has some limitations that are related to efficacy and adverse effects. Nanotechnology has been used as a new tool in medicine to improve these limitations and new medications potentially to alleviate and cure ED. Aim To review the currently literature on new nano medications for ED based on scientific and clinical studies, efficacy, safety, mechanisms of action, and to identify gaps for future research. Methods A comprehensive literature review was conducted via Google Scholar, Science Direct, and PubMed on English publications using different keywords such as “erectile dysfunction”, “emerging treatments”, “nanotechnology”, and “herbal medicine”. The retrieved papers were organized into groups according to the sections covered in this review paper. Main Outcomes Measures We reviewed novel ED treatments such as nanotechnological phosphodiesterase inhibitors, papaverine hydrochloride, sialorphin, adipose tissue-derived stem cells, sonic hedgehog, and herbal medicine. Results Numerous preclinical studies have addressed novel phosphodiesterase 5 inhibitors nanoparticle, and their recent delivery systems. Nitric oxide, sialorphin, sonic hedgehog, and herbal medicine loaded nanoparticles and nano adipose tissue-derived stem cells as a potential new treatment for ED. In addition, papaverine-containing nanoparticles have been reported. A limited number of randomized clinical studies have determined the mechanism of these treatments. Conclusion A literature review on the application of nanotechnology in ED therapy was successfully conducted. New nano medications are promising to treat ED. However, further studies are warranted to further assess their efficacy and safety.

We investigate the association of MUC1 with castration-resistant prostate cancer (CRPC), bone metastasis, and PC recurrence. MUC1 expression was studied in patient-derived bone metastasis and CRPCs produced by prostate-specific PTEN−/− mice and LNCaP xenografts. Elevations in MUC1 expression occur in CRPC. Among nine patients with hormone-naïve bone metastasis, eight express MUC1 in 61% to 100% of PC cells. Utilizing cBioPortal PC genomic data, we organized a training (n = 300), testing (n = 185), and validation (n = 194) cohort. Using the Cox model, a nine-gene signature was derived, including eight genes from a MUC1-related network (APC, CTNNB1/β-catenin, GALNT10, GRB2, LYN, SIGLEC1, SOS1, and ZAP70) and FAM84B. Genomic alterations in these genes reduce disease-free survival (DFS) in the training (P = .00161), testing (P = .00699), entire (training + testing, P = 5.557e-5), and a validation cohort (P = 3.326e-5). The signature independently predicts PC recurrence [hazard ratio (HR) = 1.731; 95% confidence interval (CI): 1.104-2.712; P = .0167] after adjusting for known clinical factors and stratifies patients with high risk of PC recurrence using the median (HR 2.072; 95% CI: 1.245-3.450, P = .0051) and quartile 3 (HR 3.707, 95% CI: 1.949-7.052, P = 6.51e-5) scores. Several novel β-catenin mutants are identified in PCs leading to a rapid onset of death and recurrence. Genomic alterations in APC and CTNNB1/β-catenin reduce DFS in two independent PC cohorts (n = 485, P = .0369; n = 84, P = .0437). The nine-gene signature also associates with reductions in overall survival (P = .0458) and DFS (P = .0163) in melanoma patients (n = 367). MUC1 upregulation is associated with CRPC and bone metastasis. A nine-gene signature derived from a MUC1 network predicts PC recurrence.

Background: Tumor-associated macrophages (TAMs) and microvessel density (MVD) play an essential role for tumor progression in prostate cancer (PCa). In this study, we evaluated the association between TAMs, the infiltration with tumor angiogenesis and the response to androgen deprivation therapies (ADTs) in PCa to evaluate TAM infiltration as a predictive factor for PCa survival. Materials and methods: Fifty-four specimens were collected and stained with CD 68 antibody to investigated TAM infiltration in tumor. Von Willebrand factor was stained to evaluate MVD around the cancer foci. We assessed the association between patient's age, preoperative serum prostate-specific antigen, pathologic Gleason sum (GS), TAM infiltration, MVD, and the response to ADT for 5 years after PCa diagnosis. Results: The median TAM was observed in 28 (6-76)/high power field (x400). Increasing TAM correlated with increasing tumor angiogenesis (P < 0.001, r = 0.61), and the response to ADT was significantly better in patients with fewer TAMs (28) (P = 0.003). TAM infiltration was significantly higher in those with higher serum prostate-specific antigen, higher GS, and metastasis. Multivariate analysis showed that GS, ADT type, and MVD number were significant prognostic factors for response to ADT in PCa (P < 0.0001). An increased infiltration of TAM [hazards ratio (HR) = 4.47; 95% confidence interval (CI): 1.97–10.15], MVD (HR = 2.66; 95% CI: 1.27–5.61), metastatic status (HR = 2.29; 95% CI: 0.14-0.60), and prostate volume (HR = 2.19; 95% CI: 1.27–3.12) significantly correlated with shorter survival in PCa patients by univariate analysis (P < 0.05). Multivariate analyses revealed that TAM and metastatic status significantly correlated with poor overall survival. Conclusions: TAM infiltration is associated with response to ADT and increased tumor angiogenesis in PCa. GS, ADT type, and MVD in PCa specimens are useful predictive factors for poor response to ADT. Increasing TAM and positive metastatic status were prognostic factors for a poorer survival in PCa patients.

Objective To review contemporary knowledge concerning the innovative trends and perspectives in the treatment of erectile dysfunction (ED). Methods Medline was reviewed for English-language journal articles between January 2000 and March 2016, using the terms ‘erectile dysfunction treatments’, ‘new trends’ and ‘perspectives’. In all, 114 original articles and 16 review articles were found to be relevant. Of the 76 cited papers that met the inclusion criteria, 51 papers had level of evidence of 1a–2b, whilst 25 had level of evidence of 3–4. Criteria included all pertinent review articles, randomised controlled trials with tight methodological design, cohort studies, and retrospective analyses. We also manually reviewed references from selected articles. Results Several interesting studies have addressed novel phosphodiesterase type 5 inhibitors (PDE5Is), orodispersible tablets, their recent chronic use, and combination with other agents. A few controlled studies have addressed herbal medicine as a sole or additional treatment for ED. Experimental studies and exciting review papers have addressed stem cells as novel players in the field of ED treatment. Other recent articles have revised the current status of low-intensity extracorporeal shockwave therapy in the field of ED. A few articles without long-term data have addressed new technologies that included: external penile support devices, penile vibrators, tissue engineering, nanotechnology, and endovascular tools for ED treatment. Conclusions The current treatment of ED is still far from ideal. We expect to see new drugs and technologies that may revolutionise ED treatment, especially in complex cases.

We describe the case of a 54-year-old man with nodal recurrence prostate cancer after radical prostatectomy, salvage external-beam radiotherapy and salvage lymph node dissection. The patient was evaluated with a lymphotropic ultrasmall superparamagnetic particles of iron oxide (USPIO)-MRI and a 68Ga radiolabelled prostate specific membrane antigen (Ga68-PSMA) PET-CT scan which enhanced persistent localized nodal disease. The patient was then considered for a second robot-assisted extended S-LND. Differently from preoperative imaging, pathology report revealed a wide nodal involvement mirroring a metastatic disease. The current manuscript is an explanatory case on the limitations of lymph node imaging in prostate cancer recurrence.

With the aim of minimising the patient’s postoperative pain, expediting recovery and improving cosmesis, the idea of performing a laparoscopic procedure through a single abdominal incision was introduced. In the present report, we describe five different access routes to the prostate that may be at the surgeon’s disposal with the potential of decreasing patient’s perioperative morbidity. Robotic radical prostatectomy has been refined and became a standard of care in surgery for localised prostate cancer. The advent of single-port robotic surgery has prompted the re-discovery of different access routes to the prostate and ideally all of them are feasible. The potential for avoiding the abdominal cavity will decrease the surgical morbidity and minimise the surgical dissection. In the near future, each of the described approaches could be chosen on the basis of the patient’s preoperative comorbidities, body habitus, anatomy, and disease characteristics and location. Keywords: LESS, Prostatectomy, Robot, Single-port, Single-site, Surgical technique

Objectives: To review the main complications related to the robot-assisted laparoscopic (RAL) approach in urology and to suggest measures to avoid such issues. Methods: A systematic search for articles of the contemporary literature was performed in PubMed database for complications in RAL urological procedures focused on positioning, access, and operative technique considerations. Each complication topic is followed by recommendations about how to avoid it. Results: In all, 40 of 253 articles were included in this analysis. Several complications in RAL procedures can be avoided if the surgical team follows some key steps. Adequate patient positioning must avoid skin, peripheral nerve, and muscles injuries, and ocular and cognitive complications mainly related to steep Trendelenburg positioning in pelvic procedures. Port-site access and closure should not be neglected during minimally invasive procedures as these complications although rare can be troublesome. Technique-related complications depend on surgeon experience and the early learning curve should be monitored. Conclusions: Adequate patient selection, surgical positioning, mentorship training, and avoiding long-lasting procedures are essential to prevent RAL-related complications. The robotic surgical team must be careful and work together to avoid possible complications. This review offers several steps in surgical planning to reach this goal. Keywords: Surgical complications, Robotic surgery, Minimally invasive surgery, Radical prostatectomy

Objective To analyse the functional and oncological outcome of consecutive renal-transplant recipients (RTRs) with clinically localised prostate cancer who underwent radical retropubic (RRP) or perineal (RPP) prostatectomy. Patients and methods Between January 2000 and July 2011 16 patients underwent RRP (group 1) and seven RPP (group 2). In all, 200 consecutive non-RTRs served as the control group, of whom 100 each underwent RRP and RPP, respectively. The mean (range) interval between renal transplantation and RP was 95 (24–206) months, the PSA at the time of diagnosis was 4.5 (3.0–17.5) ng/mL, and the mean patient age was 64 (59–67) years. Results The mean follow-up was 39 (RRP) and 48 months (RPP). There was no deterioration in graft function. In group 1, 13 and three patients had pT2a-cpN0 and pT3a-bpN0 prostate cancer, respectively, with a Gleason score of 6, 7 and 8 in 11, three and one patients, respectively. In group 2, three and four patients had pT2a-c and pT3a-b disease, respectively, with a Gleason score of 6 and 7 in two and five, respectively. In both groups one patient had a positive surgical margin and was followed expectantly, and all patients have no evidence of disease. Wound infections developed more often in the RPP group (29% vs. 7%), but there were no Clavien grade III–V complications. All patients achieved good continence, and two need one pad/day. Conclusions RRP and RPP are suitable surgical treatments for prostate cancer in RTRs. RRP might be preferable, as it has the advantage of simultaneous pelvic lymphadenectomy and a lower risk of infectious complications.

Objectives To provide an analysis of the outcomes in patients who have a suburethral sling placed using the transobturator approach for the treatment of stress urinary incontinence after radical prostatectomy, because data in this specific area remain limited, and recent changes in male sling surgery might improve the efficacy in men with moderate or mild incontinence. Methods We evaluated the results of transobturator non-adjustable and re-adjustable sling systems after reviewing previous reports identified using the Medline and PubMed databases for original articles, from 2002 to 2012, using the terms ‘postoperative male incontinence’, ‘transobturator’ and ‘male sling’. Of a total of 31 articles, we reviewed the 22 related to the outcomes of the suburethral sling with positioning by the transobturator approach. Results Currently the only results of the transobturator approach are those relating to the AdVance™ device (American Medical Systems, Minnetonka, MN, USA), for which the cure rate is ≈ 60% at 20 months. The remaining devices, although innovative, were assessed in studies for which the follow-up was too short to make a judgement. Conclusions It would be advisable to reserve the transobturator approach for patients with mild and moderate incontinence, and refer those with severe incontinence, with or without adjuvant radiotherapy after radical prostatectomy, for treatment with an artificial urinary sphincter. More results and a long-term follow-up are needed to evaluate the effectiveness of these devices.

Introduction Erectile dysfunction (ED) is the most common sexual disorder that men report to healthcare providers, and is the male sexual dysfunction that has been most investigated. Current treatments for ED focus on relieving the symptoms of ED and therefore tend to provide a temporary solution rather than a cure or reversing the cause. Recently, therapies based on stem cells (SCs) have had an increasing attention for their potential to restore erectile function. Preclinical studies showed that these cells might reverse the pathophysiological changes leading to ED, rather than treating the symptoms of ED. This review is intended to provide an overview of contemporary reports on the use of SCs to treat ED. Methods We made an extensive search for reports on SC-based therapy for the management of ED, published in English between 1966 and 2013, using the search engines SciVerse-sciencedirect, SciVerse-scopus, Google Scholar and Pubmed, with the search terms ‘erectile dysfunction’, ‘stem cells’, ‘multipotent stromal cells’, ‘adipose (tissue) derived stem cells’, ‘bone-marrow derived stem cells’, ‘animal model’, ‘diabetes’, ‘ageing’, ‘Peyronie’s Disease’ and ‘cavernous nerve injury’. Results Fifty-four papers were identified and contributed, either as an original research report or review thereof, to this review. Several preclinical studies addressed SC-based therapies for the recovery of erectile function caused by a variety of both chronic and acute conditions. Overall, these studies showed beneficial effects of SC therapy, while evidence on the mechanisms of action of SC therapy varied between studies. One clinical trial investigated the short-term effects of SC therapy in diabetic patients with ED. Two more clinical trials are currently recruiting patients. Conclusions The rapidly expanding and highly promising body of preclinical work on SC-based medicine providing a potential cure for ED, rather than merely symptom relief, is indicative of the increasing interest in regenerative options for sexual medicine over the past decade. Clinical trials are currently recruiting patients to test the preclinical results in men with ED.

We review the current strategies used for penile rehabilitation (PR) after a radical prostatectomy, where PR is defined as the attempt to restore spontaneous erectile function so that the patient can generate erections with no need for erectile aids. We searched PubMed for relevant reports, using the keywords ‘radical prostatectomy’, ‘penile rehabilitation’, ‘phosphodiesterase inhibitors’, ‘vacuum erection device’, ‘injection therapy’, ‘urethral suppository’, and ‘erectile dysfunction’. In all, 155 articles were identified and reviewed, and had a level of evidence ranging from 1b-4. The use of PR strategies should be based on the patient’s goals after a thorough explanation of realistic expectations, and the risks and consequences of the various treatment options. While a multitude of studies suggest a benefit with PR strategies, there are no established, proven regimens. Further research is needed to establish the optimal approaches to PR.

Background As laparoscopy becomes a standard approach in many urological procedures, researchers strive to make minimally invasive surgery less invasive. Our objective was to apply recent innovations in equipment and surgical approaches to develop the technique and perform laparo-endoscopic single site radical prostatectomy (LESS-RP). Methods The technique for LESS-RP was derived by combining existing techniques of standard laparoscopic RP and developing techniques of urological LESS. This incorporated newly available low-profile trocars, flexible instruments and a flexible-tip laparoscope. The procedure was performed through a single 3-cm transverse infra-umbilical incision. LESS-RP was completed successfully via a single operative site without auxiliary needles or trocars. Perioperative variables and postoperative outcomes were recorded and measured. Results The operative time was 424 min and the hospital stay was 10 days because of a vesicourethral leak and ileus. The anastomotic leak resolved and the urethral catheter was removed at 4 weeks after surgery. The final pathology showed negative margins and Gleason 3 + 4 pT2c prostatic adenocarcinoma. Conclusions LESS-RP is feasible by replicating laparoscopic RP techniques and incorporating the LESS technique with the advent of flexible-tip laparoscopes and flexible instruments. After a learning curve has been overcome, this should be further tested prospectively to compare oncological and functional outcomes with laparoscopic and robotic-assisted RP.

Background Prostate cancer is the most common cancer in men, and radical prostatectomy (RP) often results in erectile dysfunction (ED) and a substantially reduced quality of life. The efficacy of current interventions, principal treatment with PDE-5 inhibitors, is not satisfactory and this condition presents an unmet medical need. Preclinical studies using adipose-derived stem cells to treat ED have shown promising results. Herein, we report the results of a human phase 1 trial with autologous adipose-derived regenerative cells (ADRCs) freshly isolated after a liposuction. Methods Seventeen men suffering from post RP ED, with no recovery using conventional therapy, were enrolled in a prospective phase 1 open-label and single-arm study. All subjects had RP performed 5–18 months before enrolment, and were followed for 6 months after intracavernosal transplantation. ADRCs were analyzed for the presence of stem cell surface markers, viability and ability to differentiate. Primary endpoint was the safety and tolerance of the cell therapy while the secondary outcome was improvement of erectile function. Any adverse events were reported and erectile function was assessed by IIEF-5 scores. The study is registered with ClinicalTrials.gov, NCT02240823. Findings Intracavernous injection of ADRCs was well-tolerated and only minor events related to the liposuction and cell injections were reported at the one-month evaluation, but none at later time points. Overall during the study period, 8 of 17 men recovered their erectile function and were able to accomplish sexual intercourse. Post-hoc stratification according to urinary continence status was performed. Accordingly, for continent men (median IIEFinclusion = 7 (95% CI 5–12), 8 out of 11 men recovered erectile function (IIEF6months = 17 (6–23)), corresponding to a mean difference of 0.57 (0.38–0.85; p = 0.0069), versus inclusion. In contrast, incontinent men did not regain erectile function (median IIEF1/3/6 months = 5 (95% CI 5–6); mean difference 1 (95% CI 0.85–1.18), p > 0.9999). Interpretation In this phase I trial a single intracavernosal injection of freshly isolated autologous ADRCs was a safe procedure. A potential efficacy is suggested by a significant improvement in IIEF-5 scores and erectile function. We suggest that ADRCs represent a promising interventional therapy of ED following prostatectomy. Funding Danish Medical Research Council, Odense University Hospital and the Danish Cancer Society., Highlights • In this phase I study a single intracavernous injection of adipose-derived regenerative cells was a safe and well-tolerated procedure • Seventeen men suffering from erectile dysfuncion after radical prostatectomy were enrolled • The adipose-derived regenerative cells were used directly after a abdominal liposuction • 8/11 continent men regained the ability to have sexual intercourse, suggesting potential efficacy of ADRC injections