Does Radical Local Treatment in Oligometastatic Prostate Cancer Improve Overall Survival: A Systematic Review and Meta-analysis.

OBJECTIVE: To determine the impact of radical local treatment (RLT) on overall survival (OS) and other survival outcomes in patients with OligoMetastatic Prostate Cancer (OMPC). METHODS: We performed a meta-analysis of randomized controlled trials (RCTs) published in the MEDLINE and CENTRAL databases until May 2023. We included RCTs that randomized patients to RLT (either radical prostatectomy [RP] or external beam radiotherapy [EBRT]) and standard of care and reported on OMPC. Our primary objective was to analyze OS with a minimum median follow-up of 4years (PROSPERO-CRD42023422736). RESULTS: We analyzed 3 RCTs, presenting data across 5 papers. OS was significantly higher in the RLT group (HR - 0.643, 95%CI 0.514-0.8, P-value <.001). The data on EBRT was drawn from 520 patients and that of RP was from 85. The post-hoc power analysis showed 81% power to detect a difference of 10% with an alpha error of 0.01. Pooled prevalence of grade 3-4 bowel and bladder toxicity was 4.5%. Health-Related Quality of Life was similar in both groups (mean difference - 1.54, 95%CI -0.625 -3.705, P-value .163). The risk of bias as per the RoB2 tool was low for all domains and overall bias. As per GRADE criteria, the certainty of evidence was high. CONCLUSION: Our meta-analysis underscores the evidence-based significance of RLT, particularly emphasizing the benefits of EBRT in patients with OMPC. However, the findings should be interpreted with caution due to the limited number of studies and the relatively small sample sizes, especially in the RP subgroup. Future investigations in OMPC should consider incorporating EBRT in their standard treatment approach.

Best practice considerations on the assessment of robotic assisted surgical systems: results from an international consensus expert panel.

BACKGROUND: Health technology assessments (HTAs) of robotic assisted surgery (RAS) face several challenges in assessing the value of robotic surgical platforms. As a result of using different assessment methods, previous HTAs have reached different conclusions when evaluating RAS. While the number of available systems and surgical procedures is rapidly growing, existing frameworks for assessing MedTech provide a starting point, but specific considerations are needed for HTAs of RAS to ensure consistent results. This work aimed to discuss different approaches and produce guidance on evaluating RAS. METHODS: A consensus conference research methodology was adopted. A panel of 14 experts was assembled with international experience and representing relevant stakeholders: clinicians, health economists, HTA practitioners, policy makers, and industry. A review of previous HTAs was performed and seven key themes were extracted from the literature for consideration. Over five meetings, the panel discussed the key themes and formulated consensus statements. RESULTS: A total of ninety-eight previous HTAs were identified from twenty-five total countries. The seven key themes were evidence inclusion and exclusion, patient- and clinician-reported outcomes, the learning curve, allocation of costs, appropriate time horizons, economic analysis methods, and robotic ecosystem/wider benefits. CONCLUSIONS: Robotic surgical platforms are tools, not therapies. Their value varies according to context and should be considered across therapeutic areas and stakeholders. The principles set out in this paper should help HTA bodies at all levels to evaluate RAS. This work may serve as a case study for rapidly developing areas in MedTech that require particular consideration for HTAs.

Current practises and the future of robotic surgical training.

INTRODUCTION: This study reviews the current state of robotic surgery training for surgeons, including the various curricula, training methods, and tools available, as well as the challenges and limitations of these. METHODS: The authors carried out a literature search across PubMed, MEDLINE, and Google Scholar using keywords related to 'robotic surgery', 'computer-assisted surgery', 'simulation', 'virtual reality', 'surgical training', and 'surgical education'. Full text analysis was performed on 112 articles. TRAINING PROGRAMMES: The training program for robotic surgery should focus on proficiency, deliberation, and distribution principles. The curricula can be broadly split up into pre-console and console-side training. Pre-Console and Console-Side Training: Simulation training is an important aspect of robotic surgery training to improve technical skill acquisition and reduce mental workload, which helps prepare trainees for live procedures. OPERATIVE PERFORMANCE ASSESSMENT: The study also discusses the various validated assessment tools used for operative performance assessments. FUTURE ADVANCES: Finally, the authors propose potential future directions for robotic surgery training, including the use of emerging technologies such as AI and machine learning for real-time feedback, remote mentoring, and augmented reality platforms like Proximie to reduce costs and overcome geographic limitations. CONCLUSION: Standardisation in trainee performance assessment is needed. Each of the robotic curricula and platforms has strengths and weaknesses. The ERUS Robotic Curriculum represents an evidence-based example of how to implement training from novice to expert. Remote mentoring and augmented reality platforms can overcome the challenges of high equipment costs and limited access to experts. Emerging technologies offer promising advancements for real-time feedback and immersive training environments, improving patient outcomes.

Nightmares in Salvage Robot-assisted Radical Prostatectomy After Primary Radiation Therapy for Prostate Cancer: A Step by Step Tutorial.

Salvage radical prostatectomy after primary radiotherapy (sRP) is considered a challenging procedure. We highlight the complications of sRP and detail critical surgical steps to help prevent them. A nonsystematic literature review in PubMed using the term "salvage radical prostatectomy" was performed on December 1, 2021. Salvage robot-assisted RP (sRARP) cases and imaging materials were used to create an educational video providing practical examples. Owing to radiation-induced changes in the prostate and surrounding tissues after radiotherapy, sRP is typically more challenging than primary RP. Among its critical steps are incision of the endopelvic fascia, bladder neck dissection with attempts at sparing the neck, development of posterior planes between the prostate and rectum, and dissection of the prostatic apex. Complication rates are significant, in particular for bladder neck contracture (0-16%) and anastomotic leakage (10-33%). Rectal injury is now rare (<2%) but still feared; careful adherence to surgical principles is required to avoid this complication. Functional outcomes are nonoptimal, with a high risk of urinary incontinence (severe incontinence in ∼25% of men). sRARP is a challenging urological procedure and should be performed by experienced surgeons. Thorough knowledge of the surgical anatomy and a meticulous technique for the most difficult surgical steps are crucial to minimise complications and to improve patient outcomes. Patient summary: In patients with prostate cancer, removal of the prostate because of cancer recurrence after primary treatment with radiotherapy can be difficult because of radiation-induced tissue damage. This challenging procedure should be performed by experienced surgeons to minimise the risk of complications.

Retzius-sparing technique independently predicts early recovery of urinary continence after robot-assisted radical prostatectomy.

Robot-assisted radical prostatectomy (RARP) is the conventional surgical treatment option for localised prostate cancer. We investigated factors which may be associated with recovery of early urinary continence (EUC), including the use of the Retzius-sparing technique (RS-RARP). From March 2018 to December 2018, 501 consecutive patients underwent RARP at our high-volume institution. Four hundred and thirty-one patients had complete follow-up data and were included in our analyses. EUC was defined as zero pad use and social urinary continence (SUC) was defined as ≤ 1 pad/24-h period at 3 months following surgery. Patient demographics and clinical factors such as age, body mass index (BMI), neurovascular bundle (NVB) sparing, RS-RARP operative technique and operating surgeon (consultant, trainee) were recorded. Median age was 64.0 years (IQR 57.0-69.0 years) with a median BMI of 27.0 (IQR 25.0-29.9). RS-RARP accounted for 59 of the 431 (13.7%) patients. 196 (45.5%), 142 (32.9%) and 86 (20.0%) received a bilateral, unilateral and nil NVB sparing, respectively. EUC was achieved by 241 patients (55.9%) and SUC was achieved in 339 (78.7%) patients. Multivariable logistic regression analysis suggests younger age (HR 1.04, 95% CI 1.01-1.07, p = 0.014) and RS-RARP technique (HR 2.19, 95% CI 1.15-4.16, p = 0.017) were independently associated with EUC at 3 months even after adjusting for BMI, external membranous urethral length and NVB sparing. Our results suggest that RS-RARP technique is independently predictive of EUC even after accounting for confounding factors. These findings should be further validated in a prospective or randomised trial.

Beyond Prostate Specific Antigen: New Prostate Cancer Screening Options.

Prostate specific antigen (PSA) is one of the best-known biomarkers for screening, diagnosis and follow-up of patients for prostate cancer. Owing to several inherent limitations with PSA, various newer blood and urinary based biomarkers have been evaluated in pursuit of better detection and risk stratification of prostate cancer cases. A combination of these different markers, in adjunct with clinical risk factors, and recent advances in imaging promises to offer better diagnostic performance with clearer risk stratification guiding therapeutics. We carried out an extensive literature search for the different biomarkers available for screening and diagnosis of prostate cancer, compared their performance with serum PSA to allow clinicians to draw meaningful conclusions to offer their patients a more personalized medical care.

Newly Diagnosed Oligometastatic Prostate Cancer: Current Controversies and Future Developments.

This report presents a 56-yr-old man in good general health status, newly diagnosed with a cT3b, cN1, cM1b, International Society of Urological Pathology grade group 3, low-volume (CHAARTED criteria), low-risk (LATITUDE criteria) metastatic prostate cancer. Staging was performed with conventional imaging: a computed tomography (CT) scan showed the presence of two enlarged lymph nodes on the left, close to the external iliac vessels. In addition, a suspicious 15-mm metastatic lesion was detected in the left pubic bone. This lesion was confirmed on the bone scan, without further metastatic lesions. In the context of a clinical trial, after an initial course of androgen deprivation therapy (ADT), the patient was treated with robot-assisted radical prostatectomy and extended pelvic lymph node dissection (histopathological examination: ypT3b pN1 R1). Postprostatectomy radiation therapy was delivered on prostatic bed (70Gy), pelvic lymph node area (54Gy), and pubic bone (51Gy). ADT was scheduled for a total period of 36 mo. Currently, the patient is still receiving ADT, which will be completed within 6 mo. The last prostate-specific antigen level was undetectable. The discussion is focused on the following three open questions: (1) Would molecular imaging (eg, prostate-specific membrane antigen positron emission tomography/CT) change the therapeutic approach to the patient? (2) Is there a role for local treatment in the metastatic setting? (iii) Should metastasis-directed therapy be considered for this patient? PATIENT SUMMARY: The optimal management of patients newly diagnosed with oligometastatic prostate cancer remains challenging. The fields of staging with modern imaging and therapy with novel treatment options are evolving rapidly. In particular, the role of a prostate-specific membrane antigen positron emission tomography/computed tomography scan for primary staging, the impact of a local treatment on the prostate, and the effect of direct therapies on the metastases represent important open questions in this intriguing field.

Society for Endocrinology guidelines for testosterone replacement therapy in male hypogonadism.

Male hypogonadism (MH) is a common endocrine disorder. However, uncertainties and variations in its diagnosis and management exist. There are several current guidelines on testosterone replacement therapy that have been driven predominantly by single disciplines. The Society for Endocrinology commissioned this new guideline to provide all care providers with a multidisciplinary approach to treating patients with MH. This guideline has been compiled using expertise from endocrine (medical and nursing), primary care, clinical biochemistry, urology and reproductive medicine practices. These guidelines also provide a patient perspective to help clinicians best manage MH.

Feasibility and safety of radical prostatectomy for oligo-metastatic prostate cancer: the Testing Radical prostatectomy in men with prostate cancer and oligo-Metastases to the bone (TRoMbone) trial.

OBJECTIVES: To test the feasibility of randomisation to radical prostatectomy (RP) plus pelvic lymphadenectomy in addition to standard-of-care (SOC) systemic therapy in men with newly diagnosed oligo-metastatic prostate cancer. PATIENTS AND METHODS: A prospective, randomised, non-blinded, feasibility clinical trial with an embedded QuinteT Recruitment Intervention (QRI) to optimise recruitment was conducted in nine nationwide tertiary care centres undertaking high-volume robotic surgery. We aimed to randomise 50 men with synchronous oligo-metastatic prostate cancer within an 18-month recruitment period to SOC systemic therapy vs SOC plus RP (intervention arm). The main outcome measures were: ability to randomise patients, optimised by a QRI; EuroQoL five Dimensions five Levels (EQ-5D-5L) questionnaires to capture quality-of-life (QoL) data at baseline and 3 months post-randomisation; routine clinicopathological assessment to capture adverse events and prostate-specific antigen in both arms, plus standard perioperative parameters in the surgical arm. RESULTS: A total of 51 men were randomised within 14 months (one was subsequently deemed ineligible), with 60-83% accrual rate in centres that recruited at least two patients. All patients completed the trial follow-up; one patient in the intervention arm subsequently did not undergo the surgical intervention and one in the SOC arm refused all therapies. The QRI positively impacted recruitment. QoL data showed similarly high functioning in both study arms. Surgery for men with oligo-metastatic prostate cancer was found to be safe and had similar impact on early functional outcomes as surgery for standard indication. CONCLUSION: It is feasible to randomise men with synchronous oligo-metastatic prostate cancer to a surgical intervention in addition to standard systemic therapies. While surgery appeared safe with no substantial impact on QoL in this feasibility study, a large randomised controlled trial is now warranted to examine treatment effectiveness of this additional component in the multimodality management of oligo-metastatic prostate cancer.

Centralisation of Care for Prevalent Urological Malignancies: The Case for Prostate Cancer.

Prostate cancer presents a significant challenge and burden for health care centres across the world. In the UK and other parts of Europe, as well as areas of the USA, centralisation of services has been implemented. In the UK and Europe, hospital centres are split into a hub-and-spoke system. High-volume centres carry out treatment as hubs and local hospitals carry out diagnostics and referrals as spokes. In this narrative mini-review we evaluate whether centralisation of services has improved patient outcomes, streamlined the use of resources, and reduced costs. We also discuss the positive and negative impacts of centralisation of prostate cancer services. PATIENT SUMMARY: This mini-review discusses the current use of centralisation of prostate cancer services. We assess the evidence in favour of centralisation as well as the issues it can present to both health care systems and patients.

Comparative Outcomes of Salvage Retzius-Sparing versus Standard Robotic Prostatectomy: An International, Multi-Surgeon Series.

PURPOSE: Salvage radical prostatectomy is rare due to the risk of postoperative complications. We compare salvage Retzius-sparing robotic assisted radical prostatectomy (SRS-RARP) with salvage standard robotic assisted radical prostatectomy (SS-RARP). MATERIALS AND METHODS: A total of 72 patients across 9 centers were identified (40 SRS-RARP vs 32 SS-RARP). Demographics, perioperative data, and pathological and functional outcomes were compared using Student's t-test and ANOVA. Cox proportional hazard models and Kaplan-Meier curves were constructed to assess risk of incontinence and time to continence. Linear regression models were constructed to investigate postoperative pad use and console time. RESULTS: Median followup was 23 vs 36 months for SRS-RARP vs SS-RARP. Console time and estimated blood loss favored SRS-RARP. There were no differences in complication rates or oncologic outcomes. SRS-RARP had improved continence (78.4% vs 43.8%, p <0.001 for 0-1 pad, 54.1% vs 6.3%, p <0.001 for 0 pad), lower pads per day (0.57 vs 2.03, p <0.001), and earlier return to continence (median 47 vs 180 days, p=0.008). SRS-RARP was associated with decreased incontinence defined as >0-1 pad (HR 0.28, 95% CI 0.10-0.79, p=0.016), although not when defined as >0 pad (HR 0.56, 95% CI 0.31-1.01, p=0.053). On adjusted analysis SRS-RARP was associated with decreased pads per day. Lymph node dissection and primary treatment with stereotactic body radiation therapy were associated with longer console time. CONCLUSIONS: SRS-RARP is a feasible salvage option with significantly improved urinary function outcomes. This may warrant increased utilization of SRS-RARP to manage men who fail nonsurgical primary treatment for prostate cancer.

Salvage Versus Primary Robot-assisted Radical Prostatectomy: A Propensity-matched Comparative Effectiveness Study from a High-volume Tertiary Centre.

BACKGROUND: Salvage robot-assisted radical prostatectomy (sRARP) is a potential treatment option for locally recurrent prostate cancer (PCa) after nonsurgical primary treatment. There are minimal data comparing outcomes between propensity-matched sRARP and primary robot-assisted radical prostatectomy (RARP). OBJECTIVE: The primary objective is to compare perioperative, oncological, and functional outcomes of sRARP with primary RARP, and the secondary is to compare outcomes between sRARP after whole and focal gland therapy. DESIGN SETTING AND PARTICIPANTS: A 1:1 propensity-matched comparison was carried out of 135 sRARP cases with primary RARP cases from a cohort of 3852 consecutive patients from a high-volume tertiary centre. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Perioperative, oncological, and functional outcomes including complication rates, positive surgical margins, biochemical recurrence (BCR), continence, and erectile dysfunction (ED) were retrospectively collected. RESULTS AND LIMITATIONS: There were no significant differences in patient characteristics between sRARP and primary RARP groups. In the salvage and primary groups, median (interquartile range) follow-up periods were 521 (304-951) and 638 (394-951) d, grade III-V Clavien-Dindo complication rates were 1.5% and 0% (p = 0.310), BCR rates were 31.9% and 14.1% (p < 0.001) at the last follow-up, pad-free continence rates were 78.8% and 84.3% at 2 yr (p = 0.337), and ED rates were 94.8% and 76.3% (p < 0.001), respectively. Comparing the whole and focal gland groups, BCR rates were 36.7% and 29.1% (p = 0.687) at follow-up, pad-free continence rates were 53.1% and 89.3% at 2 yr (p < 0.001), and ED rates were 98% and 93% (p = 0.214), respectively. CONCLUSIONS: Salvage RARP has similar perioperative outcomes to primary RARP with inferior potency rates. Post-focal therapy sRARP has similar recurrence and continence rates to primary RARP. Post-whole gland therapy, complication, and recurrence rates are higher, and there is a higher risk of urinary incontinence. PATIENT SUMMARY: We report the largest propensity-matched comparison of salvage robot-assisted radical prostatectomy (RARP) after focal and whole gland therapy. Salvage RARP is a feasible procedure for the treatment of locally recurrent prostate cancer in high-volume centres; however, patients should be counselled appropriately as to the different outcomes.

Outcomes of the RAFT trial: robotic surgery after focal therapy.

OBJECTIVES: To report toxicity of treatment observed in men participating in the Robotic surgery After Focal Therapy (RAFT) clinical trial. PATIENTS AND METHODS: Men were eligible for this prospective single group interventional study if they had histologically confirmed recurrent/residual prostate adenocarcinoma following primary FT. The short-form Expanded Prostate Cancer Index Composite (EPIC-26) measured prior to salvage robotic prostatectomy (S-RARP) and 3-monthly post-operatively together with Clavien-Dindo complications (I-IV). Secondary outcomes included biochemical recurrence-free survival (BCFS) following surgery and need for salvage treatment after surgery. This study is registered with ClinicalTrials.gov NCT03011606. RESULTS: Twenty-four men were recruited between February 2016 and September 2018. 1 patient withdrew from the trial after consenting and before S-RARP. 23 men completed 12-month post S-RARP follow-up. Median EPIC-26 urinary continence scores initially deteriorated after 3 months (82.4 vs 100) but there was no statistically significant difference from baseline at 12 months (100 vs 100, P = 0.31). Median lower urinary tract symptom scores improved after 12 months compared to baseline (93.8 vs 87.5, P = 0.01). At 12 months, 19/23 (83%) were pad-free and 22/23 (96%) required 0/1 pads. Median sexual function subscale scores deteriorated and remained low at 12 months (22.2 vs 58.3, P < 0.001). Utilising a minimally important difference of nine points, at 12 months after surgery 17/23 (74%) reported urinary continence to be 'better' or 'not different' to pre-operative baseline. The corresponding figure for sexual function (utilising a minimally important difference of 12 points) was 7/23 (30%). There was no statistically significant difference on median bowel/hormonal subscale scores. Only a single patient had a post-operative complication (Clavien-Dindo Grade I). BCFS at 12 months after surgery was 82.6% (95% confidence interval [CI]: 60.1-93.1%) while 4/23 (17%) received salvage radiation. CONCLUSIONS: The RAFT clinical trial suggests toxicity of surgery after FT is low, with good urinary function outcomes, albeit sexual function deteriorated overall. Oncological outcomes at 12 months appear acceptable.

High-intensity Focused Ultrasound for the Treatment of Prostate Cancer: A National Cohort Study Focusing on the Development of Stricture and Fistulae.

BACKGROUND: High-intensity focused ultrasound (HIFU) is a novel therapy for prostate cancer. Owing to a lack of long-term data, HIFU is recommended for use only in the context of research. OBJECTIVE: To examine the trend for HIFU use nationally and rates of strictures and fistulae. DESIGN, SETTING, AND PARTICIPANTS: Patients undergoing HIFU for prostate cancer between April 2007 and March 2018 were studied in an English national database (Hospital Episode Statistics). Data on complications were included for patients with a minimum of 1-yr follow-up. Analysis of complications was controlled for other interventions. OUTCOME MEASURES AND STATISTICAL ANALYSIS: Descriptive analyses of HIFU rates and the incidence of strictures and fistulae were carried out. Cox and logistic regression models were built for urethral stricture incidence. RESULTS AND LIMITATIONS: A total of 2320 HIFU treatments among 1990 patients were identified. The median age was 67yr (interquartile range 61-72). Some 1742 patients met the criteria for follow-up analysis. The highest-volume centre performed 1513 HIFU procedures, followed by 194 at the second highest. The number of HIFU procedures increased annually, rising from 196 to 283 per year. There were 208 patients (11.9%) who went on to have radiotherapy and 102 (5.9%) radical prostatectomy after HIFU. Following HIFU, stricture developed in 133/1290 patients (10.3%) and urinary fistula in 16/1240 (1.3%) before any further intervention. More recent years for HIFU were associated with a lower likelihood of stricture formation (2016/2017 vs 2007/2008: hazard ratio 0.30, 95% confidence interval 0.11-0.79; p=0.015). Limitations include the lack of staging information and unknown rates of HIFU outside of publicly funded health care. CONCLUSIONS: HIFU is performed at a large number of low-volume centres and complication rates do not differ from those for established therapies. PATIENT SUMMARY: This report highlights the trend for provision of high-intensity focused ultrasound treatment for prostate cancer in England. The results suggest that the rate of urethral structural complications may not be lower than that for established prostate cancer treatments.