Intraoperative image-guidance during robotic surgery: is there clinical evidence of enhanced patient outcomes?

BACKGROUND: To date, the benefit of image guidance during robot-assisted surgery (IGS) is an object of debate. The current study aims to address the quality of the contemporary body of literature concerning IGS in robotic surgery throughout different surgical specialties. METHODS: A systematic review of all English-language articles on IGS, from January 2013 to March 2023, was conducted using PubMed, Cochrane library's Central, EMBASE, MEDLINE, and Scopus databases. Comparative studies that tested performance of IGS vs control were included for the quantitative synthesis, which addressed outcomes analyzed in at least three studies: operative time, length of stay, blood loss, surgical margins, complications, number of nodal retrievals, metastatic nodes, ischemia time, and renal function loss. Bias-corrected ratio of means (ROM) and bias-corrected odds ratio (OR) compared continuous and dichotomous variables, respectively. Subgroup analyses according to guidance type (i.e., 3D virtual reality vs ultrasound vs near-infrared fluoresce) were performed. RESULTS: Twenty-nine studies, based on 11 surgical procedures of three specialties (general surgery, gynecology, urology), were included in the quantitative synthesis. IGS was associated with 12% reduction in length of stay (ROM 0.88; p = 0.03) and 13% reduction in blood loss (ROM 0.87; p = 0.03) but did not affect operative time (ROM 1.00; p = 0.9), or complications (OR 0.93; p = 0.4). IGS was associated with an estimated 44% increase in mean number of removed nodes (ROM 1.44; p < 0.001), and a significantly higher rate of metastatic nodal disease (OR 1.82; p < 0.001), as well as a significantly lower rate of positive surgical margins (OR 0.62; p < 0.001). In nephron sparing surgery, IGS significantly decreased renal function loss (ROM 0.37; p = 0.002). CONCLUSIONS: Robot-assisted surgery benefits from image guidance, especially in terms of pathologic outcomes, namely higher detection of metastatic nodes and lower surgical margins. Moreover, IGS enhances renal function preservation and lowers surgical blood loss.

Use of 18F-fluoro-2-deoxy-d-glucose (18F-FDG) PET/CT for lymph node assessment before radical cystectomy in bladder cancer patients.

OBJECTIVE: To assess the diagnostic performance of 18F-fluoro-2-deoxy-d-glucose (18F-FDG) positron emission tomograpy (PET)/computed tomography (CT) in nodal staging before radical cystectomy (RC) and pelvic lymph node dissection (PLND) for bladder cancer (BCa). MATERIALS AND METHODS: This analysis was based on a cohort of 199 BCa patients undergoing RC and bilateral PLND between 2015 and 2022. Neoadjuvant chemotherapy (NAC) or immunotherapy (NAI) was administered after oncological evaluation. All patients received preoperative 18F-FDG PET/CT to assess extravesical disease. Point estimates for true negative, false negative, false positive, true positive, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of conventional imaging and PET/CT were calculated. Subgroup analysis in patients receiving neoadjuvant treatment was performed. RESULTS: At preoperative evaluation, 30 patients (15.1%) had 48 suspicious nodal spots on 18F-FDG PET/CT. At RC and bilateral PLND, a total of 4871 lymph nodes (LNs) were removed with 237 node metastases corresponding to 126 different regions. Pathological node metastases were found in 17/30 (57%) vs 39/169 patients (23%) with suspicious vs negative preoperative 18F-FDG PET/CT, respectively (sensitivity = 0.30, specificity = 0.91, PPV = 0.57, NPV = 0.77, accuracy = 0.74). On per-region analysis including 1367 nodal regions, LN involvement was found in 19/48 (39%) vs 105/1319 (8%) suspicious vs negative regions at PET/CT, respectively (sensitivity = 0.15, specificity = 0.98, PPV = 0.40, NPV = 0.92, ACC = 0.90). Similar results were observed for patients receiving NAC (n = 44, 32.1%) and NAI (n = 93, 67.9% [per-patient: sensitivity = 0.36, specificity = 0.91, PPV = 0.59, NPV = 0.80, accuracy = 0.77; per-region: sensitivity = 0.12, specificity = 0.98, PPV = 0.32, NPV = 0.93, ACC = 0.91]). Study limitations include its retrospective design and limited patient numbers. CONCLUSIONS: In eight out of 10 patients with negative preoperative 18F-FDG PET/CT, pN0 disease was confirmed at final pathology. No differences were found based on NAC vs NAI treatment. These findings suggest that 18F-FDG PET/CT could play a role in the preoperative evaluation of nodal metastases in BCa patients, although its cost-effectiveness is uncertain.

Peri- and post-operative outcomes of robot-assisted radical cystectomy after the implementation of the EAU guidelines recommendations for collecting and reporting complications at a high-volume referral center.

PURPOSE: No studies relied on a standardized methodology to collect postoperative complications after robot-assisted radical cystectomy (RARC). The aim of our study was to evaluate peri- and post-operative outcomes of patients undergoing RARC adhering to the European Association of Urology (EAU) recommendations for reporting surgical outcomes and using a long postoperative follow-up. MATERIALS AND METHODS: 246 patients who underwent RARC with intracorporal urinary diversion at a single tertiary referral center with a postoperative follow-up ≥ 1 year for survivors. Postoperative outcomes were collected prospectively by interviews done by medical doctors. Complications were scored using the Clavien-Dindo classification (CD), grouped by type and severity (severe: CD score ≥ 3). We described peri- and post-operative outcomes and complication chronological distribution. RESULTS: Overall, 16 (6.5%) and 225 patients (91%) experienced intraoperative and postoperative complications, respectively. Moreover, 139 (57%) experienced severe complications. The most common any-grade and severe complications were infectious (72%) and genitourinary (35%), respectively. Overall, 52% of complications (358/682) occurred within 10 days from surgery, and 51% of severe complications (106/207) occurred within 35 days. However, 13% of complications (90/682) and 28% of severe complications (59/207) occurred 3 months after surgery. The earliest complications were fever of unknown origins and paralytic ileus (median time-to-complication [mTTC]: 4 days), the latest complications were urinary tract infection (mTTC: 40 days) and hydronephrosis/ureteral obstruction (mTTC: 70 days). CONCLUSIONS: The rate of postoperative complications after RARC is > 90% when a standardized collection method and a long follow-up is implemented. These results should be used to identify potential areas of improvement and for preoperative patient counseling.

Impact of the extent of lymph node dissection on survival outcomes in clinically lymph node-positive bladder cancer.

OBJECTIVE: To determine the oncological impact of extended pelvic lymph node dissection (ePLND) vs standard PLND (sPLND) during radical cystectomy (RC) in clinically lymph node-positive (cN+) bladder cancer (BCa). PATIENTS AND METHODS: In this retrospective, multicentre study we included 969 patients who underwent RC with sPLND (internal/external iliac and obturator lymph nodes) or ePLND (sPLND plus common iliac and presacral nodes) with or without platin-based peri-operative chemotherapy for cTany N1-3 M0 BCa between 1991 and 2022. We assessed the impact of ePLND on recurrence-free survival (RFS) and the distribution of recurrences (locoregional and distant recurrences). The secondary endpoint was overall survival (OS). We performed propensity-score matching using covariates associated with the extent of PLND in univariable logistic regression analysis. The association of the extent of PLND with RFS and OS was investigated using Cox regression models. RESULTS: Of 969 cN+ patients, 510 were 1:1 matched on propensity scores. The median (interquartile range [IQR]) time to recurrence was 8 (4-16) months, and median (IQR) follow-up of alive patients was 30 (13-51) months. Disease recurrence was observed in 104 patients in the ePLND and 107 in the sPLND group. Of these, 136 (27%), 47 (9.2%) and 19 patients (3.7%) experienced distant, locoregional, or both distant and locoregional disease recurrence, respectively. When stratified by the extent of PLND, we did not find a difference in recurrence patterns (P > 0.05). ePLND improved neither RFS (hazard ratio [HR] 0.91, 95% confidence interval [CI] 0.70-1.19; P = 0.5) nor OS (HR 0.78, 95% CI 0.60-1.01; P = 0.06) compared to sPLND. Stratification by induction chemotherapy did not change outcomes. CONCLUSION: Performing an ePLND at the time of RC in cN+ patients improved neither RFS nor OS compared to sPLND, regardless of induction chemotherapy status. Pretreatment risk stratification is paramount to identify ideal candidates for RC with ePLND as part of a multimodal treatment approach.

Assessing the Performance of 18F-FDG PET/CT in Bladder Cancer: A Narrative Review of Current Evidence.

INTRODUCTION: Lymph node (LN) involvement is a crucial determinant of prognosis for patients with bladder cancer, and an accurate staging is of utmost importance to better identify timely and appropriate therapeutic strategies. To improve the accuracy of LN detection, as an alternative to traditional methods such as CT or MRI, 18F-FDG PET/CT has been increasingly used. 18F-FDG PET/CT is also used in post-treatment restaging after neoadjuvant chemotherapy. The aim of this narrative literature review is to provide an overview of the current evidence on the use of 18F-FDG PET/CT in the diagnosis, staging, and restaging of bladder cancer, with a particular focus on its sensitivity and specificity for the detection of LN metastasis. We aim to provide clinicians with a better understanding of 18F-FDG PET/CT's potential benefits and limitations in clinical practice. MATERIALS AND METHODS: We designed a narrative review starting from a wide search in the PubMed/MEDLINE and Embase databases, selecting full-text English articles that have examined the sensibility and specificity of PET/CT for nodal staging or restaging after neoadjuvant therapy in patients with bladder cancer. The extracted data were analyzed and synthesized using a narrative synthesis approach. The results are presented in a tabular format, with a summary of the main findings of each study. RESULTS: Twenty-three studies met the inclusion criteria: fourteen studies evaluated 18F-FDG PET/CT for nodal staging, six studies examined its accuracy for restaging after neoadjuvant therapy, and three studies evaluated both applications. To date, the use of F-18 FDG PET/TC for detection of LN metastasis in bladder cancer is controversial and uncertain: some studies showed low accuracy rates, but over the years other studies have reported evidence of high sensitivity and specificity. CONCLUSIONS: 18F-FDG PET/CT provides important incremental staging and restaging information that can potentially influence clinical management in MIBC patients. Standardization and development of a scoring system are necessary for its wider adoption. Well-designed randomized controlled trials in larger populations are necessary to provide consistent recommendations and consolidate the role of 18F-FDG PET/CT in the management of bladder cancer patients.

Holmium Laser Enucleation of the Prostate Is Associated with Complications and Sequelae Even in the Hands of an Experienced Surgeon Following Completion of the Learning Curve.

BACKGROUND: Holmium laser enucleation of the prostate (HoLEP) is considered a challenging procedure even for surgeons who have completed the learning curve. OBJECTIVES: To assess outcomes and complications following HoLEP performed by a highly experienced surgeon. DESIGN, SETTING, AND PARTICIPANTS: This was a single-institution prospective study (NCT03583034) performed at a tertiary referral centre that included 243 consecutive patients with lower urinary tract symptoms (LUTS) due to benign prostatic enlargement (BPE) treated with HoLEP by a single experienced surgeon (>1600 cases). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Patients were assessed using validated questionnaires and uroflowmetry at baseline and several follow-up dates. Intraoperative and postoperative complications were recorded. Kaplan-Meier analysis was used to estimate recovery rates for urinary continence and erectile function. Logistic regression models were constructed to assess predictors of postoperative complications. RESULTS AND LIMITATIONS: Of the 243 patients, 78 (32.1%) had an indwelling urethral catheter. The median prostate volume (PV) was 87 cm3 (interquartile range 60-115) and 146 patients (59.8%) had PV >80 cm3. At 3-mo follow-up, 219 patients (90.1%) had a peak flow rate >20 ml/s and 182 (74.9%) had no postvoid residual urine. The improvement in subjective symptoms was significant at 1-mo follow-up and was maintained until 12 mo after surgery. Urinary continence recovery was slow, with an estimated rate of 68% (95% confidence interval [CI] 62-74%) at 1 mo and 94% (95% CI 91-97%) at 12 mo after HoLEP. The recovery rate for erectile function was 53% (95% CI 46-61%) at 1 mo and 85% (95% CI 77-90%) at 12 mo. Postoperative complications occurred in 36 patients (14.8%) during their hospital stay, in 34 (14%) within 1 mo following discharge from hospital, and in ten (4.1%) at later follow-up dates. Clinically significant complications (Clavien-Dindo ≥2) were observed in 44 cases (18%) and were more common for patients with an indwelling catheter at baseline (odds ratio 5.05; p = 0.006). CONCLUSIONS: HoLEP is an effective procedure for treating LUTS due to BPE, although it is not devoid of complications and sequelae, even in the hands of a highly experienced surgeon. PATIENT SUMMARY: Holmium laser treatment of the prostate to reduce its size has positive results for urinary function when performed by an experienced surgeon, even in complex cases, although there can be complications.

Health-related quality of life in patients with metastatic hormone-sensitive prostate cancer treated with androgen receptor signaling inhibitors: the role of combination treatment therapy.

BACKGROUND: While the addition of androgen receptor signaling inhibitors (ARSIs) to androgen deprivation therapy (ADT) results in better of overall survival in patients with metastatic hormone-sensitive prostate cancer (mHSPC), information regarding health related quality of life (HR-QoL) is sparse. We aimed at summarizing current evidence on the impact of ARSIs on HR-QoL. METHODS: We performed a systematic review of the published literature on PubMed/EMBASE, Web of Science, SCOPUS, and the Cochrane libraries between January 2011 and April 2022. We included only phase III randomized controlled trials (RCT), which were selected according to the PRISMA guidelines. We aimed at evaluating differences in HR-QoL, assessed by validated patient reported outcomes instruments. We analyzed global scores and sub-domains such as sexual functioning, urinary symptoms, bowel symptoms, pain/fatigue, emotional and social/family wellbeing. We reported data descriptively. RESULTS: Six RCTs were included: two used enzalutamide with ADT as intervention arms (ARCHES, ENZAMET); one used apalutamide with ADT (TITAN); two abiraterone acetate and prednisone (AAP) with ADT (STAMPEDE, LATITUDE); and one darolutamide with ADT (ARASENS). Enzalutamide or AAP with ADT increase overall HR-QoL in comparison with ADT alone, ADT with first generation nonsteroideal anti-androgens or ADT with docetaxel, whereas apalutamide and darolutamide with ADT maintain HR-QoL similarly to ADT alone or ADT with docetaxel, respectively. Time to first deterioration of pain was longer with combination therapy with enzalutamide, AAP or darolutamide, but not with apalutamide. No worsening of emotional wellbeing was reported from the addition of ARSIs to ADT than ADT alone. CONCLUSIONS: The addition of ARSIs to ADT in mHSPC tends to increase overall HR-QoL and prolong time to first deterioration of pain/fatigue compared with ADT alone, ADT with first generation nonsteroideal anti-androgens, and ADT with docetaxel. ARSIs show a complex interaction with remaining HR-QoL domains. We advocate a standardization of HR-QoL measurement and reporting to allow further comparisons.

Retzius-sparing robot-assisted radical prostatectomy after previous trans-urethral resection of the prostate: Assessment of functional and oncological outcomes.

BACKGROUND: no data exist concerning functional and oncological outcomes of Retzius-sparing robot-assisted radical prostatectomy (RS-RARP), in patients previously treated with trans-urethral resection of the prostate (p-TURP), for benign prostate obstruction. Our study addressed the impact of p-TURP on immediate and 12-months urinary continence recovery (UCR), as well as peri-operative outcomes and surgical margins, after RS-RARP. METHODS: all patients treated with RS-RARP for prostate cancer at a single high-volume European institution, between 2010 and 2021, were identified and stratified according to p-TURP status. Logistic, Poisson and Cox regression models were performed. RESULTS: Of 1386 RS-RARP patients, 99 (7%) had history of p-TURP. Between p-TURP and no-TURP patients no differences were detected regarding both intra- and post-operative complications (p values = 0.9). The rates of immediate UCR were 40 vs 67% in p-TURP vs no-TURP patients (p < 0.001). At 12 months from RS-RARP, the rates of UCR were 68 vs 94% in p-TURP vs no-TURP patients (p < 0.001). At multivariable logistic and Cox regression models, p-TURP was independently associated, respectively, with lower immediate (odds ratio [OR]: 0.32, p < 0.001) and 12-months UCR (hazard ratio: 0.54, p < 0.001). At multivariable Poisson analyses, p-TURP predicted longer operative time (rate ratio: 1.08, p < 0.001) but not longer length of stay or time to catheter removal (p values > 0.05). Positive surgical margins rates were 23 vs 17% in p-TURP vs no-TURP patients (p = 0.1), which translated in a non-statistically significant multivariable OR of 1.14 (p = 0.6). CONCLUSIONS: p-TURP does not increase surgical morbidity but portends longer operative time and worse urinary continence after RS-RARP.

Implications for diagnosis and treatment strategies in non-muscle invasive bladder cancer with variant histology: a systematic review.

INTRODUCTION: The identification of variant histology (VH) has been recognized as a critical element in the diagnostic pathway of bladder cancer (BCa), both for prognostic and therapeutic implications. However, the current evidence on the oncological outcomes of patients harboring VH BCa mostly derives from studies including muscle-invasive disease. Consequently, the correct management of patients with non-muscle invasive bladder cancer (NMIBC) and VH is limited and conflicting, and the optimal therapeutic approach remains therefore controversial. EVIDENCE ACQUISITION: In this review, we aimed at reporting the current evidence on NMIBC with VH. EVIDENCE SYNTHESIS: Despite a constant increase in VH reporting at transurethral resection of bladder tumor (TURBT) specimens as compared to previous decades, we found that the incidence of VH is still sparse among studies. Furthermore, the agreement between TURBT and radical cystectomy (RC) specimens in VH identification is another matter of debate. Currently, most of the included studies report a poor overall concordance, especially for the micropapillary variant. Finally, while squamous and micropapillary variants are those associated with the worst survival outcomes, immediate RC is mostly considered for micropapillary tumors. Conversely, the survival benefit of immediate RC as compared to bladder-sparing approaches (i.e., BCG immunotherapy) for the other types of VH BCa is still an open question owing to the paucity of data available. CONCLUSIONS: Thus, in these patients, BCG treatment could be proposed considering the need for more intensive oncological surveillance.

Challenging cases in high-risk prostate cancer patients treated with Retzius-sparing robot-assisted radical prostatectomy.

OBJECTIVE: To evaluate the relationship between enlarged prostate, bulky median lobe (BML) or prior benign prostatic hyperplasia (BPH) surgery and perioperative functional, and oncological outcomes in high-risk (HR) prostate cancer (PCa) patients treated with Retzius-sparing robot-assisted radical prostatectomy (RS-RARP). METHODS: 320 HR-PCa patients treated with RS-RARP between 2011 and 2020 at a single high-volume center. The relationship between prostate volume, BML, prior BPH surgery and perioperative outcomes, Clavien-Dindo (CD) grade ≥ 2 90-day postoperative complications, positive surgical margins (PSMs), and urinary continence (UC) recovery was evaluated respectively in multivariable linear, logistic and Cox regression models. Complications were collected according to the standardized methodology proposed by EAU guidelines. UC recovery was defined as the use of zero or one safety pad. RESULTS: Overall, 5.9% and 5.6% had respectively a BML or prior BPH surgery. Median PV was 45 g (range: 14-300). The rate of focal and non-focal PSMs was 8.4% and 17.8%. 53% and 10.9% patients had immediate UC recovery and CD ≥ 2. The 1- and 2-yr UC recovery was 84 and 85%. PV (p = 0.03) and prior BPH surgery (p = 0.02) was associated with longer operative time. BML was independent predictor of time to bladder catheter removal (p = 0.001). PV was independent predictor of PSMs (OR: 1.02; p = 0.009). Prior BPH surgery was associated with lower UC recovery (HR: 0.5; p = 0.03). CONCLUSION: HR-PCa patients with enlarged prostate have higher risk of PSMs, while patients with prior BPH surgery have suboptimal UC recovery. These findings should help physicians for accurate preoperative counseling and to improve surgical planning in case of HR-PCa patients with challenging features.

Multicentric experience in Retzius-sparing robot-assisted radical prostatectomy performed by expert surgeons for high-risk prostate cancer.

BACKGROUND: The study aim was to report the results of Retzius-Sparing robot-assisted radical Prostatectomy (RSP) in high-risk prostate cancer (HR-PCa) patients in a multicentric setting of expert surgeons and to analyze predictors of positive surgical margins (PSMs) and urinary continence recovery. METHODS: We retrospectively evaluated all consecutive HR-PCa patients who underwent RSP by expert surgeons in 7 centers. Pre-, peri- and postoperative features were collected. Minimum surgical experience required was 100 RSP cases. The oncological outcomes evaluated were PSMs and biochemical relapse (BCR). Urinary continence was defined as no pad or safety pad. Erectile function was defined as erections sufficient for intercourse. RESULTS: We collected 579 patients operated by 9 surgeons. Median age was 66, median PSA was 9,6 ng/mL. ISUP biopsy was 1 in 3.8%, 2 in 23%, 3 in 32,6%, 4 in 19,9%, 5 in 20,7; median surgical time was 195 minutes. Pathological stage was pT2 in 40,1%, pT3a in 35,9%, pT3b in 23,1%, and pT4 in 0,9% of cases. PSMs were present in 31,3% of cases. Urinary continence was achieved in 66,8% of cases one week after catheter removal. At 22 months (median follow-up), 89,1% patients were continent, BCR occurred in 27,5% patients. In multivariate analysis, PSA, prostate volume, surgical time were independent predictors of PSMs; ASA score and PSMs predicted urinary continence. CONCLUSIONS: We report the first multicentric experience of RSP for HR-PCa. Considering HR cases as those with the worst functional results, 89% of continent patients confirms that RSP helps achieve good functional results.

Retzius-sparing Robot-assisted Radical Prostatectomy in High-risk Prostate Cancer Patients: Results from a Large Single-institution Series.

Background: Retzius-sparing (RS) robot-assisted radical prostatectomy represents a valid surgical treatment option for prostate cancer (PCa) patients. However, the available evidence on the role of RS in high-risk (HR) PCa setting is sparse. Objective: To describe our RS technique for HR-PCa patients and to evaluate intra-, peri-, and postoperative oncological and functional outcomes. Design setting and participants: A total of 340 D'Amico HR-PCa patients underwent RS at a single high-volume centre between 2011 and 2020. Surgical procedure: Surgical procedures were performed by five experienced robotic surgeons. Measurements: Complications were collected according to the standardised methodology proposed by the European Association of Urology guidelines. Postoperative outcomes were evaluated in patients with complete follow-up data (n = 320). Biochemical recurrence (BCR) was defined as two consecutive prostate-specific antigen values of ≥0.2 ng/ml. Urinary continence (UC) recovery was defined as the use of zero or one safety pad. Kaplan-Meier and multivariable logistic and Cox regression models were performed. Results and limitations: Fourteen patients (4%) experienced intraoperative complications and 52 90-d complications occurred in 44 patients (14%), of whom 24 had Clavien-Dindo 3a/b. Final pathology reported 49% International Society of Urological Pathology (ISUP) grade 4-5, 55% ≥pT3a, and 28.8% positive surgical margins (PSMs; 9.4% focal and 19.4% extended PSMs). The median follow-up was 47 mo. Overall, 35.3% and 1.3% harboured BCR and died from PCa. At 4 yr of follow-up, BCR-free survival and additional treatment-free survival were 63.6% and 56.6%, respectively. ISUP 4-5 at biopsy (odds ratio [OR]: 2.6), prostate volume (OR: 1.03), partial or full nerve sparing (OR: 1.9), and full bladder neck preservation (OR: 2.2) were independent predictors of PSMs. Pathological ISUP 4-5 (hazard ratio [HR]: 1.5) and PSMs (HR: 2.3) were independent predictors of BCR. Pathological ISUP 4-5 (HR: 1.5), PSMs (HR: 2.4), pT ≥3b (HR: 1.8), and pN ≥1 (HR: 1.8) were independent predictors of additional treatment. Immediate UC recovery was recorded in 53% patients. The 1- and 2-yr UC recovery and erectile function recovery were, respectively, 84% and 85%, and 43% and 50%. Conclusions: RS in HR-PCa patients allows optimal intra-, peri-, and postoperative outcomes. The RS approach should be considered a valid surgical treatment option for HR-PCa patients in expert hands. Patient summary: Relying on the largest cohort of high-risk prostate cancer patients treated with Retzius sparing (RS), we observed that the RS approach is safe and allows optimal cancer control, without significantly compromising functional outcomes.