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Robot-assisted radical cystectomy versus open radical cystectomy in patients with bladder cancer (RAZOR): an open-label, randomised, phase 3, non-inferiority trial
2018
Radical cystectomy is the surgical standard for invasive bladder cancer. Robot-assisted cystectomy has been proposed to provide similar oncological outcomes with lower morbidity. We aimed to compare progression-free survival in patients with bladder cancer treated with open cystectomy and robot-assisted cystectomy.
The RAZOR study is a randomised, open-label, non-inferiority, phase 3 trial done in 15 medical centres in the USA. Eligible participants (aged ≥18 years) had biopsy-proven clinical stage T1–T4, N0–N1, M0 bladder cancer or refractory carcinoma in situ. Individuals who had previously had open abdominal or pelvic surgery, or who had any pre-existing health conditions that would preclude safe initiation or maintenance of pneumoperitoneum were excluded. Patients were centrally assigned (1:1) via a web-based system, with block randomisation by institution, stratified by type of urinary diversion, clinical T stage, and Eastern Cooperative Oncology Group performance status, to receive robot-assisted radical cystectomy or open radical cystectomy with extracorporeal urinary diversion. Treatment allocation was only masked from pathologists. The primary endpoint was 2-year progression-free survival, with non-inferiority established if the lower bound of the one-sided 97·5% CI for the treatment difference (robotic cystectomy minus open cystectomy) was greater than −15 percentage points. The primary analysis was done in the per-protocol population. Safety was assessed in the same population. This trial is registered with ClinicalTrials.gov, number NCT01157676.
Between July 1, 2011, and Nov 18, 2014, 350 participants were randomly assigned to treatment. The intended treatment was robotic cystectomy in 176 patients and open cystectomy in 174 patients. 17 (10%) of 176 patients in the robotic cystectomy group did not have surgery and nine (5%) patients had a different surgery to that they were assigned. 21 (12%) of 174 patients in the open cystectomy group did not have surgery and one (1%) patient had robotic cystectomy instead of open cystectomy. Thus, 302 patients (150 in the robotic cystectomy group and 152 in the open cystectomy group) were included in the per-protocol analysis set. 2-year progression-free survival was 72·3% (95% CI 64·3 to 78·8) in the robotic cystectomy group and 71·6% (95% CI 63·6 to 78·2) in the open cystectomy group (difference 0·7%, 95% CI −9·6% to 10·9%; pnon-inferiority=0·001), indicating non-inferiority of robotic cystectomy. Adverse events occurred in 101 (67%) of 150 patients in the robotic cystectomy group and 105 (69%) of 152 patients in the open cystectomy group. The most common adverse events were urinary tract infection (53 [35%] in the robotic cystectomy group vs 39 [26%] in the open cystectomy group) and postoperative ileus (33 [22%] in the robotic cystectomy group vs 31 [20%] in the open cystectomy group).
In patients with bladder cancer, robotic cystectomy was non-inferior to open cystectomy for 2-year progression-free survival. Increased adoption of robotic surgery in clinical practice should lead to future randomised trials to assess the true value of this surgical approach in patients with other cancer types.
National Institutes of Health National Cancer Institute.
Journal Article
Standard or Extended Lymphadenectomy for Muscle-Invasive Bladder Cancer
2024
In patients with muscle-invasive bladder cancer, extended lymphadenectomy did not improve disease-free or overall survival as compared with the standard procedure and was associated with higher morbidity and mortality.
Journal Article
Effects of an exercise intervention in primary care after robot-assisted radical cystectomy for urinary bladder cancer: a randomised controlled trial
by
Porserud, Andrea
,
Rydwik, Elisabeth
,
Henningsohn, Lars
in
Aged
,
Biomedical and Life Sciences
,
Biomedicine
2024
Introduction
After radical cystectomy physical activity is important to reduce risk of complications, but patients with urinary bladder cancer have difficulties in achieving general recommendations on physical activity and exercise. The aim of this randomised controlled trial was therefore to evaluate the effects of a physical exercise programme in primary care, following discharge from hospital after robot-assisted radical cystectomy for urinary bladder cancer.
Materials and Methods
Patients with urinary bladder cancer scheduled for robot-assisted radical cystectomy at Karolinska University Hospital, Sweden between September 2019 and October 2022 were invited to join the study. At discharge, they were randomised to intervention or active control group. The intervention group was planned to start exercise with physiotherapist in primary care during the third week; the programme included aerobic and strengthening exercises, twice a week for 12 weeks, and daily walks. The control group received unsupervised home-based exercise with daily walks and a sit-to-stand exercise. Assessments were conducted before surgery, at discharge and after four months regarding the primary outcome physical function (Six-minute walk test), and secondary outcomes physical activity, pain, health-related quality of life, fatigue, and psychological wellbeing.
Results
Ninety patients were included, mean (sd) age 71.5 (8.5) years. An intention-to-treat analysis showed no intervention effect on the primary outcome physical function, or on pain or psychological wellbeing, but effect on physical activity with a difference from discharge to four months with a median (IQR) of 4790 (3000) and 2670 (4340) daily steps in the intervention and control group, respectively (
p
= 0.046), and for fatigue, and health-related quality of life, in favour of the intervention group.
Conclusion
Both the intervention and control groups improved physical function, but the patients who exercised in primary care experienced additional positive effects on physical activity, fatigue, and health-related quality of life. Hence, exercise in primary care after discharge from hospital could be a promising method after radical cystectomy for urinary bladder cancer.
Trial registration
The study was registered in Clinical Trials with registration number NCT03998579, 20,190,607.
Journal Article
Patients´ experiences of an exercise intervention in primary care following robot-assisted radical cystectomy due to bladder cancer: a qualitative study
by
Porserud, Andrea
,
Rydwik, Elisabeth
,
Olsson, Christina B.
in
Abdominal surgery
,
Aged
,
Aged, 80 and over
2024
Background
Physical activity is thought to be a key component in reducing postoperative complications following major abdominal surgery. The available literature on exercise interventions following radical cystectomy in patients with bladder cancer is scarce but suggests that physical activity and exercise might improve physical function and health-related quality of life, thus calling for further investigation. The CanMoRe-trial is a single-blinded randomised controlled trial (Clinicals Trials NCT03998579 25/06/2019), aimed at evaluating the impact of an exercise intervention in primary care following robot-assisted radical cystectomy. This study seeks to explore patients’ experiences of the exercise intervention in the CanMoRe-trial to gain a better understanding of facilitating aspects and potential barriers.
Methods
A qualitative study was conducted involving 20 patients from the intervention group of the CanMoRe-trial who were interviewed individually between October 2020 and March 2023 using a semi-structured interview guide. The interviews were recorded and transcribed verbatim and reflexive thematic analysis was used to analyse the data.
Results
Four main themes were identified:
Having to adapt to new circumstances
, describing the challenges regarding physical activity patients face after discharge.
Optimising conditions for rehabilitation
, describing how practical conditions affect patients’ ability to exercise.
Motivated to get back to normal
, describing patients´ desire to get back to normal life and factors influencing motivation.
Importance of a supportive environment
, describing the impact of social support, support from physiotherapists, and how the environment where exercise takes place impacts patients’ ability to exercise.
Conclusion
This study found that patients participating in the CanMoRe-trial are positive towards physical exercise in PC following radical RARC. They are motivated to get back to normal life but face major challenges when arriving home following surgery, which affect their ability to perform physical activity and engage in exercise. Conditions need to be optimised to support patients’ ability to engage in exercise by providing an accessible PC location to perform exercise in. A supportive environment is also needed, including guidance from healthcare professionals regarding which type of exercise, intensity and amount of exercise that should be performed, enabling patients gradually to develop self-efficacy regarding exercise and focusing on goals related to patients’ normal lives before surgery.
Journal Article
Immediate versus deferred chemotherapy after radical cystectomy in patients with pT3–pT4 or N+ M0 urothelial carcinoma of the bladder (EORTC 30994): an intergroup, open-label, randomised phase 3 trial
by
Agerbaek, Mads
,
Symonds, Paul
,
Théodore, Christine
in
Antineoplastic Combined Chemotherapy Protocols - adverse effects
,
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
,
Bladder cancer
2015
Patients with muscle-invasive urothelial carcinoma of the bladder have poor survival after cystectomy. The EORTC 30994 trial aimed to compare immediate versus deferred cisplatin-based combination chemotherapy after radical cystectomy in patients with pT3–pT4 or N+ M0 urothelial carcinoma of the bladder.
This intergroup, open-label, randomised, phase 3 trial recruited patients from hospitals across Europe and Canada. Eligible patients had histologically proven urothelial carcinoma of the bladder, pT3–pT4 disease or node positive (pN1–3) M0 disease after radical cystectomy and bilateral lymphadenectomy, with no evidence of any microscopic residual disease. Within 90 days of cystectomy, patients were centrally randomly assigned (1:1) by minimisation to either immediate adjuvant chemotherapy (four cycles of gemcitabine plus cisplatin, high-dose methotrexate, vinblastine, doxorubicin, and cisplatin [high-dose MVAC], or MVAC) or six cycles of deferred chemotherapy at relapse, with stratification for institution, pT category, and lymph node status according to the number of nodes dissected. Neither patients nor investigators were masked. Overall survival was the primary endpoint; all analyses were by intention to treat. The trial was closed after recruitment of 284 of the planned 660 patients. This trial is registered with ClinicalTrials.gov, number NCT00028756.
From April 29, 2002, to Aug 14, 2008, 284 patients were randomly assigned (141 to immediate treatment and 143 to deferred treatment), and followed up until the data cutoff of Aug 21, 2013. After a median follow-up of 7·0 years (IQR 5·2–8·7), 66 (47%) of 141 patients in the immediate treatment group had died compared with 82 (57%) of 143 in the deferred treatment group. No significant improvement in overall survival was noted with immediate treatment when compared with deferred treatment (adjusted HR 0·78, 95% CI 0·56–1·08; p=0·13). Immediate treatment significantly prolonged progression-free survival compared with deferred treatment (HR 0·54, 95% CI 0·4–0·73, p<0·0001), with 5-year progression-free survival of 47·6% (95% CI 38·8–55·9) in the immediate treatment group and 31·8% (24·2–39·6) in the deferred treatment group. Grade 3–4 myelosuppression was reported in 33 (26%) of 128 patients who received treatment in the immediate chemotherapy group versus 24 (35%) of 68 patients who received treatment in the deferred chemotherapy group, neutropenia occurred in 49 (38%) versus 36 (53%) patients, respectively, and thrombocytopenia in 36 (28%) versus 26 (38%). Two patients died due to toxicity, one in each group.
Our data did not show a significant improvement in overall survival with immediate versus deferred chemotherapy after radical cystectomy and bilateral lymphadenectomy for patients with muscle-invasive urothelial carcinoma. However, the trial is limited in power, and it is possible that some subgroups of patients might still benefit from immediate chemotherapy. An updated individual patient data meta-analysis and biomarker research are needed to further elucidate the potential for survival benefit in subgroups of patients.
Lilly, Canadian Cancer Society Research.
Journal Article
Short-term outcomes comparison of KangDuo 2.0 and Da Vinci Xi in radical cystectomy
2025
In urological surgery, the Da Vinci Xi robotic system has many advantages, but it also has limitations such as high equipment costs and the need for professional training. Kangduo is a laparoscopic surgical robot developed in China, and SR2000 is its newly approved four-arm laparoscopic surgical robot. This study compares the short-term outcomes of the two in radical cystectomy. Data from a centre-based randomised non-inferiority trial were used and patients between March 2023 and June 2024 were enrolled and randomised according to criteria. The primary outcome was surgical success, and secondary outcomes included intraoperative variables, surgical outcomes, pathological outcomes, and postoperative outcomes. A total of 34 patients, 16 in the KD group and 18 in the DV group, had no intermediate open or conventional laparoscopic surgery, and the surgical success rate was 100%, with no significant differences between the two groups in many aspects. The effectiveness and safety of the KangDuo SR2000 system were demonstrated. Experienced surgeons confirmed that performing radical cystectomy using the KangDuo SR2000 system yielded results comparable to those achieved using the Da Vinci robotic system.
Journal Article
The CanMoRe trial – evaluating the effects of an exercise intervention after robotic-assisted radical cystectomy for urinary bladder cancer: the study protocol of a randomised controlled trial
by
Porserud, Andrea
,
Rydwik, Elisabeth
,
Henningsohn, Lars
in
Abdomen
,
Abdominal surgery
,
Adolescent
2020
Background
Patients who have undergone radical cystectomy for urinary bladder cancer are not sufficiently physically active and therefore may suffer complications leading to readmissions. A physical rehabilitation programme early postoperatively might prevent or at least alleviate these potential complications and improve physical function. The main aim of the CanMoRe trial is to evaluate the impact of a standardised and individually adapted exercise intervention in primary health care to improve physical function (primary outcome) and habitual physical activity, health-related quality of life, fatigue, psychological wellbeing and readmissions due to complications in patients undergoing robotic-assisted radical cystectomy for urinary bladder cancer.
Methods
In total, 120 patients will be included and assigned to either intervention or control arm of the study. All patients will receive preoperative information on the importance of early mobilisation and during the hospital stay they will follow a standard protocol for enhanced mobilisation. The intervention group will be given a referral to a physiotherapist in primary health care close to their home. Within the third week after discharge, the intervention group will begin 12 weeks of biweekly exercise. The exercise programme includes aerobic and strengthening exercises. The control group will receive oral and written information about a home-based exercise programme.
Physical function will serve as the primary outcome and will be measured using the Six-minute walk test. Secondary outcomes are gait speed, handgrip strength, leg strength, habitual physical activity, health-related quality of life, fatigue, psychological wellbeing and readmissions due to complications. The measurements will be conducted at discharge (i.e. baseline), post-intervention and 1 year after surgery. To evaluate the effects of the intervention mixed or linear regression models according to the intention to treat procedure will be used.
Discussion
This proposed randomised controlled trial has the potential to provide new knowledge within rehabilitation after radical cystectomy for urinary bladder cancer. The programme should be easy to apply to other patient groups undergoing abdominal surgery for cancer and has the potential to change the health care chain for these patients.
Trial registration
ClinicalTrials.gov. Clinical trial registration number
NCT03998579
. First posted June 26, 2019.
Journal Article
Retrospective study of systemic immune-inflammation index in muscle invasive bladder cancer: initial results of single centre
2020
PurposesWe aimed to evaluate the prognostic value of the preoperative systemic immune-inflammation index (SII) in patients who underwent radical cystectomy due to muscle invasive bladder cancer (MIBC).MethodsWe researched our cystectomy database between April 2006 and December 2018. Demographic data, operation and postoperative data were recorded. There were 191 MIBC patients who underwent radical cystectomy. After detailed analyses, preoperative SII was calculated by the formula as “(neutrophil) × (platelet)/(lymphocyte)”. Cancer-specific survival (CSS) and overall survival (OS) were examined. The prognostic value of SII was analysed with univariate and multivariate Cox proportional hazards regression models. Receiver operating characteristic (ROC) was used to determine the optimum SII. Significant P was P < 0.05.ResultsThe mean follow-up was 37 ± 6.7 months. The mean age of patients was 62.1 ± 9 years. The optimal cutoff value of SII was determined as 843 in ROC curve (area under the curve: 0.9; P < 0.001). The CSS and OS were significantly poor in patients with higher SII level (respectively; P < 0.001, P = 0.04). Gender, lymph node involvement, pathologic stage, grade and SII were statistically significant in multivariate Cox proportional hazards regression model for CSS.ConclusionsPreoperative elevated SII could be an independent prognostic factor in MIBC patients who underwent radical cystectomy. If SII > 843, CSS might be poor. Our results should be confirmed with randomised-controlled prospectively designed future studies with large cohorts.
Journal Article
Ileal conduit versus single stoma uretero-cutanoustomy after radical cystectomy in patients ≥ 75 years; which technique is better? a prospective randomized comparative study
by
Elbehairy, Ahmed A.
,
Behnsawy, Hosny M.
,
Moeen, Ahmed M.
in
Aged
,
Bladder cancer
,
Comorbidity
2023
Purpose
To compare the clinical results and patients’ health-related quality of life (HR-QoL) of ileal conduit (IC) versus single stoma uretero-cutanoustomy (SSUC) after radical cystectomy in two groups of randomly selected patients ≥ 75 years.
Methods
From January 2013 to March 2018, 100 patients ≥ 75 years with muscle invasive BCa underwent RCX and cutaneous diversion. Patients were divided in two groups; group I underwent IC (50 patients) and group II underwent SSUC (50 patients). Postoperative evaluation included clinical, laboratory, radiographic and HR-QoL. The latter was performed using the Functional Assessment of Cancer Therapy–Bladder Cancer (FACT-BL) after 12 months postoperatively.
Results
Patients’ characteristics were comparable between both groups. No intraoperative complications occurred. Early postoperative complications occurred in 27 patients [16 (35.5%) in group I and 11 (23.9%) in group II (p = 0.02)]. Delayed postoperative complications occurred in 26 patients [6 (13.3%) in group I and 20 (43.4%) in group II, (P = 0.002)]. No significant differences between both groups regarding the physical, social/family, emotional, functional and additional concerns scales of FACT-BL questionnaire were reported.
Conclusion
SSUC is a good alternative to IC in elderly frail patients ≥ 75 years and those with multiple comorbidities who require rapid surgery in terms of perioperative complications and HR-QoL. However, the stomal complications and the possibility of a frequent stent exchange are considered its drawbacks.
Journal Article
Comparative evaluation of reproductive organ-preserving versus standard radical cystectomy in female: a meta-analysis and systematic review of perioperative, oncological, and functional outcomes
2024
BackgroundTo evaluate the perioperative, oncological, and functional outcomes of reproductive organ-preserving radical cystectomy (ROPRC) compared to standard radical cystectomy (SRC) in the treatment of female bladder cancer.MethodsA systematic search was conducted in November 2023 across several scientific databases. We executed a systematic review and cumulative meta-analysis of the primary outcomes of interest, adhering to the PRISMA and AMSTAR guidelines. The study was registered in PROSPERO (CRD42024501522).ResultsThe meta-analysis included 10 studies with a total of 2015 participants. ROPRC showed a significant reduction in operative time and postoperative fasting period compared to SRC (MD − 45.69, 95% CI − 78.91 ~ − 12.47, p = 0.007, and MD − 0.69, 95% CI − 1.25 ~ − 0.13, p = 0.02, respectively). Functional outcomes, both daytime continence rate (OR 4.94, 95% CI 1.53 ~ 15.91, p = 0.008) and nighttime continence rate (OR 5.91, 95% CI 1.94 ~ 18.01, p = 0.002), and sexual function measured by the Female Sexual Function Index (MD 5.72, 95% CI 0.19 ~ 11.26, p = 0.04), were significantly improved in the ROPRC group. There were no significant differences between ROPRC and SRC in terms of estimated blood loss, length of hospital stay, overall postoperative complications, minor complications or major complications. Oncologically, both procedures showed comparable outcomes with no significant differences in positive surgical margins, tumor recurrence rates, overall survival, cancer-specific survival, recurrence-free survival, or progression-free survival.ConclusionsROPRC is a viable and effective alternative to SRC in female bladder cancer patients, offering enhanced functional outcomes and similar oncological safety. These findings suggest that ROPRC can improve the quality of life in female bladder cancer patients without compromising the efficacy of cancer treatment.
Journal Article