M1a prostate cancer:Results of a Dutch multidisciplinary consensus meeting

ObjectivesTo determine the consensus of a Dutch multidisciplinary expert panel on the diagnostic evaluation and treatment of de novo and recurrent metastatic prostate cancer (PCa) limited to non-regional lymph nodes (M1a) in daily clinical practice.Materials and methodsThe panel consisted of 37 Dutch specialists from disciplines involved in the management of M1a PCa (urology, medical and radiation oncology, radiology, and nuclear medicine). We used a modified Delphi method consisting of two voting rounds and a consensus meeting (video conference). Consensus (good agreement) was defined as the situation in which ≥ 75% of the panelists chose the same option.ResultsConsensus existed for 57% of the items. The panel agreed that prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA-PET/CT) is the most appropriate standard imaging modality to identify de novo (100%) and recurrent (97%) M1a PCa. Androgen deprivation therapy (ADT) combined with radiotherapy to the prostate ± the M1a lesion(s) was most frequently considered an option for de novo M1a PCa. For M1a as recurrent disease, ADT alone, deferring treatment, or local radiotherapy to the M1a lesion(s) were judged to be the most important treatment options. However, no specific indications for treatment choice in relation to disease characteristics could be formulated.ConclusionsThe Dutch consensus panel preferred PSMA-PET/CT as the standard diagnostic modality to detect M1a PCa. Although potential treatment options were identified, explicit recommendations could not be formulated. This might (partly) be explained by the absence of high-level clinical evidence in this subset of patients. Further research is, therefore, strongly encouraged

PSMA, EpCAM, VEGF and GRPR as Imaging Targets in Locally Recurrent Prostate Cancer after Radiotherapy

In this retrospective pilot study, the expression of the prostate-specific membrane antigen (PSMA), the epithelial cell adhesion molecule (EpCAM), the vascular endothelial growth factor (VEGF) and the gastrin-releasing peptide receptor (GRPR) in locally recurrent prostate cancer after brachytherapy or external beam radiotherapy (EBRT) was investigated, and their adequacy for targeted imaging was analyzed. Prostate cancer specimens were collected of 17 patients who underwent salvage prostatectomy because of locally recurrent prostate cancer after brachytherapy or EBRT. Immunohistochemistry was performed. A pathologist scored the immunoreactivity in prostate cancer and stroma. Staining for PSMA was seen in 100% (17/17), EpCAM in 82.3% (14/17), VEGF in 82.3% (14/17) and GRPR in 100% (17/17) of prostate cancer specimens. Staining for PSMA, EpCAM and VEGF was seen in 0% (0/17) and for GRPR in 100% (17/17) of the specimens’ stromal compartments. In 11.8% (2/17) of cases, the GRPR staining intensity of prostate cancer was higher than stroma, while in 88.2% (15/17), the staining was equal. Based on the absence of stromal staining, PSMA, EpCAM and VEGF show high tumor distinctiveness. Therefore, PSMA, EpCAM and VEGF can be used as targets for the bioimaging of recurrent prostate cancer after EBRT to exclude metastatic disease and/or to plan local salvage therapy

Current training on the basics of robotic surgery in the Netherlands: Time for a multidisciplinary approach?

Introduction: The following research questions were answered: (1) What are the training pathways followed by the current robot professionals? (2) Are there any differences between the surgical specialties in robot training and robot use? (3) What is their opinion about multidisciplinary basic skills training? Methods: An online questionnaire was sent to 91 robot professionals in The Netherlands. The questionnaire contained 21 multiple-choice questions focusing on demographics, received robot training, and their opinion on basic skills training in robotic surgery. Results: The response rate was 62 % (n = 56): 13 general surgeons, 16 gynecologists, and 27 urologists. The urologists performed significantly more robotic procedures than surgeons and gynecologists. The kind of training of all professionals varied from a training program by Intuitive Surgical, master-apprenticeship with or without duo console, fellowship, and self-designed training programs. The training did neither differ significantly among the different specialties nor the year of starting robotic surgery. Majority of respondents favor an obliged training program including an examination for the basics of robot skills training. Conclusion: Training of the current robot professionals is mostly dependent on local circumstances and the manufacturer of the robot system. Training is independent of the year of start with robotic surgery and speciality. To guarantee the quality of future training of residents and fellows in robot-assisted surgery, clear training goals should be formulated and implemented. Since this study shows that current training of different specialities does not differ, training in robotic surgery could be started by a multidisciplinary basic skills training and assessment

Membranous urethral length measurement on preoperative MRI to predict incontinence after radical prostatectomy:a literature review towards a proposal for measurement standardization

Objectives: To investigate the membranous urethral length (MUL) measurement and its interobserver agreement, and propose literature-based recommendations to standardize MUL measurement for increasing interobserver agreement. MUL measurements based on prostate MRI scans, for urinary incontinence risk assessment before radical prostatectomy (RP), may influence treatment decision-making in men with localised prostate cancer. Before implementation in clinical practise, MRI-based MUL measurements need standardization to improve observer agreement. Methods: Online libraries were searched up to August 5, 2022, on MUL measurements. Two reviewers performed article selection and critical appraisal. Papers reporting on preoperative MUL measurements and urinary continence correlation were selected. Extracted information included measuring procedures, MRI sequences, population mean/median values, and observer agreement. Results: Fifty papers were included. Studies that specified the MRI sequence used T2-weighted images and used either coronal images (n = 13), sagittal images (n = 18), or both (n = 12) for MUL measurements. ‘Prostatic apex’ was the most common description of the proximal membranous urethra landmark and ‘level/entry of the urethra into the penile bulb’ was the most common description of the distal landmark. Population mean (median) MUL value range was 10.4–17.1 mm (7.3–17.3 mm), suggesting either population or measurement differences. Detailed measurement technique descriptions for reproducibility were lacking. Recommendations on MRI-based MUL measurement were formulated by using anatomical landmarks and detailed descriptions and illustrations. Conclusions: In order to improve on measurement variability, a literature-based measuring method of the MUL was proposed, supported by several illustrative case studies, in an attempt to standardize MRI-based MUL measurements for appropriate urinary incontinence risk preoperatively. Clinical relevance statement: Implementation of MUL measurements into clinical practise for personalized post-prostatectomy continence prediction is hampered by lack of standardization and suboptimal interobserver agreement. Our proposed standardized MUL measurement aims to facilitate standardization and to improve the interobserver agreement. Key Points: • Variable approaches for membranous urethral length measurement are being used, without detailed description and with substantial differences in length of the membranous urethra, hampering standardization. • Limited interobserver agreement for membranous urethral length measurement was observed in several studies, while preoperative incontinence risk assessment necessitates high interobserver agreement. • Literature-based recommendations are proposed to standardize MRI-based membranous urethral length measurement for increasing interobserver agreement and improving preoperative incontinence risk assessment, using anatomical landmarks on sagittal T2-weighted images.</p

Specialist versus primary care prostate cancer follow-up:A process evaluation of a randomized controlled trial

Background: A randomized controlled trial (RCT) is currently comparing the effectiveness of specialist- versus primary care-based prostate cancer follow-up. This process evaluation assesses the reach and identified constructs for the implementation of primary care-based follow-up. Methods: A mixed-methods approach is used to assess the reach and the implementation through the Consolidated Framework for Implementation Research. We use quantitative data to evaluate the reach of the RCT and qualitative data (interviews) to indicate the perspectives of patients (n = 15), general practitioners (GPs) (n = 10), and specialists (n = 8). Thematic analysis is used to analyze the interview transcripts. Results: In total, we reached 402 (67%) patients from 12 hospitals and randomized them to specialist- (n = 201) or to primary care-based (n = 201) follow-up. From the interviews, we identify several advantages of primary care- versus specialist-based follow-up: it is closer to home, more accessible, and the relationship is more personal. Nevertheless, participants also identified challenges: guidelines should be implemented, communication and collaboration between primary and secondary care should be improved, quality indicators should be collected, and GPs should be compensated. Conclusion: Within an RCT context, 402 (67%) patients and their GPs were willing to receive/provide primary care-based follow-up. If the RCT shows that primary care is equally as effective as specialist-based follow-up, the challenges identified in this study need to be addressed to enable a smooth transition of prostate cancer follow-up to primary care. Netherlands Trial Registry, Trial NL7068 (NTR7266)

Can active surveillance really reduce the harms of overdiagnosing prostate cancer? A reflection of real life clinical practice in the PRIAS study

Background: Active surveillance (AS) for low-risk prostate cancer (PCa) appears to provide excellent long-term PCa-specific and overall survival. The choice for AS as initial treatment is mainly based on avoiding side effects from invasive treatment; but AS entails regular check-ups and the possibility of still having to switch or deciding to switch to invasive treatment. Here, we assessed the long-term follow-up data from AS in real life clinical practices. Methods: Data from the first 500 men, enrolled in PRIAS before July 2008 by 30 centers across 8 countries, were analyzed to provide long-term follow-up results. Men were advised to be regularly examined with prostate-specific antigen (PSA) tests, digital rectal examinations, and prostate biopsies. Men were advised to switch to invasive treatment if they had disease reclassification [Gleason score (GS) >= 3+ 4 on biopsy, more than two positive biopsy cores, a stage higher than cT2] or a PSA-doubling time of 0-3 years. We assessed time on AS, outcomes and reasons for discontinuing AS, and rates of potential unnecessary biopsies and treatments. Results: The median follow-up time was 6.5 years. During this period, 325 (65%) men discontinued after a median of 2.3 years and 121 (24%) men had no recent (> 1 year) data-update after a median of 7.3 years. The remaining 54 (11%) men were confirmed to be still on AS. Most men discontinued based on protocol advice; 38% had other reasons. During follow-up, 838 biopsy sessions were performed of which 79% to 90% did not lead to reclassification, depending on the criteria. Of the 325 discontinued men, 112 subsequently underwent radical prostatectomy (RP), 126 underwent radiotherapy, 57 switched to watchful waiting (WW) or died, and 30 had another or unknown treatment. RP results were available of 99 men: 34% to 68%, depending on definition, had favorable outcomes; 50% of unfavorable the outcomes occurred in the first 2 years. Of the 30 (6%) men who died, 1 man died due to PCa. Conclusions: These data, reflecting real life clinical practice, show that more than half of men switched to invasive treatment within 2.3 years, indicating limitations to the extent in which AS is able to reduce the adverse effects of overdiagnosis. Therefore, despite guidelines stating that PCa diagnosis must be uncoupled from treatment, it remains important to avoid overdiagnosing PCa as much as possible.Peer reviewe

Role of Local and/or Metastasis-directed Therapy in Patients with Hormone-sensitive M1a Prostate Cancer:A Systematic Review

CONTEXT: It remains unclear whether men with hormone-sensitive prostate cancer (PCa) metastasized to nonregional lymph nodes (M1a) benefit from prostate-directed therapy (PDT) and/or metastasis-directed therapy (MDT). OBJECTIVE: To systematically summarize the literature regarding oncological outcomes of de novo and recurrent M1a PCa patients treated with PDT and/or MDT. EVIDENCE ACQUISITION: We searched Medline (Ovid), Embase, and Scopus according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines for reports on oncological outcomes of de novo or recurrent hormone-sensitive M1a PCa patients treated with PDT (radical prostatectomy or radiotherapy) and/or MDT (nodal radiotherapy or salvage lymph node dissection) with or without androgen deprivation therapy. A descriptive data synthesis and a methodological quality assessment were performed to evaluate the impact of PDT and/or MDT on survival in M1a PCa patients. EVIDENCE SYNTHESIS: A total of 6136 articles were screened and 24 studies were included in this systematic review. In de novo M1a PCa patients, PDT was associated with improved oncological outcomes compared with no PDT. In recurrent M1a PCa, MDT could delay the need for systemic treatment in a selection of patients, but high-level evidence from prospective phase III randomized controlled trials is still awaited. CONCLUSIONS: This systematic review summarized the limited literature data on the management of M1a PCa. Subgroup analyses suggest a role for PDT plus systemic therapy in de novo M1a PCa. MDT to distant nodal metastases delayed the need for systemic therapy in recurrent disease, but robust data are lacking. The predominantly retrospective nature of the included studies and significant heterogeneity in study designs limit the strength of evidence. PATIENT SUMMARY: We reviewed the treatment of patients with prostate cancer that has spread to lymph nodes outside the pelvis without metastases in other organ systems. There is evidence that treatment of the primary prostate tumor improves outcomes in well-selected patients and that treatment targeting distant lymph node metastases can delay the start of systemic treatment.</p

Precision surgery:the role of intra-operative real-time image guidance - outcomes from a multidisciplinary European consensus conference

Developments within the field of image-guided surgery are ever expanding, driven by collective involvement of clinicians, researchers, and industry. While the general conception of the potential of image-guided surgery is to improve surgical outcome, the specific motives and goals that drive can differ between the different expert groups. To establish the current and future role of intra-operative image guidance within the field of image-guided surgery a Delphi consensus survey was conducted during the 2(nd) European Congress on Image-guided surgery. This multidisciplinary survey included questions on the conceptual potential and clinical value of image-guided surgery and was aimed at defining specific areas of research and development in the field in order to stimulate further advances towards precision surgery. Obtained results based on questionnaires filled in by 56 panel experts (clinicians: N=30, researchers: N=20 and industry: N=6) were discussed during a dedicated expert discussion session during the conference. The outcome of this Delphi consensus is indicative of the potential improvements offered by image-guided surgery and of the need for further research in this emerging field, that can be enriched by the identification of reliable molecular targets