Bladder CancerNCT01224665
S1011 Standard or Extended Pelvic Lymphadenectomy in Treating Patients Undergoing Surgery for Invasive Bladder Cancer
A study testing therapeutic conventional surgery, therapeutic standard lymphadenectomy and therapeutic extended lymphadenectomy in people with Bladder Cancer, run by SWOG Cancer Research Network at 35 sites in 2 countries.
Trial summary
RATIONALE: Lymphadenectomy may remove tumor cells that have spread to nearby lymph nodes in patients with invasive bladder cancer. It is not yet known whether extended pelvic lymphadenectomy is more effective than standard pelvic lymphadenectomy during surgery. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Bladder Cancer
- What is being tested?
- therapeutic conventional surgery, therapeutic standard lymphadenectomy and therapeutic extended lymphadenectomy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 658 participants
- Where
- 35 sitesin 2 countries
- Study dates
- 25 Nov 2011to May 2024
- Phase
- Interventional
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
DISEASE CHARACTERISTICS:
- Histologically confirmed urothelial carcinoma of the bladder
- Stage T2, T3, or T4a disease
- No clinical stage consistent with a low-risk of node metastasis (CIS only, T1)
- No T4b disease (fixed lesion)
- Disease that requires primary radical cystectomy and lymph node dissection for definitive treatment
- No laparoscopic surgery
- Predominant urothelial carcinoma with any of the following elements allowed:
- Adenocarcinoma
- Squamous cell carcinoma
- Micropapillary or minor components of other rare phenotype
- No pure squamous cell carcinoma or adenocarcinoma
- No visceral or nodal metastatic disease proximal to the common iliac bifurcation by 2-view chest x-ray and abdominal-pelvic imaging by computerized tomography or MRI of the abdomen and pelvis
- No intra-operative pelvic lymph node involvement (confirmed by frozen section) at or above the bifurcation of the common iliac vessels in any of the extended template
PATIENT CHARACTERISTICS:
- Zubrod performance status 0-2
- ALT and AST ≤ upper limit of normal (ULN)*
- Alkaline phosphatase ≤ ULN*
- Not pregnant or nursing
- Fertile patients must use an effective contraception
- No other prior malignancy except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or stage I or II cancer from which the patient is in complete remission for the past 5 years
- Medically suitable to undergo cystectomy, in the physician's opinion NOTE: *Levels may be ≥ ULN provided metastatic disease is excluded using dedicated liver imaging, bone scan, or biopsy.
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- No prior partial cystectomy for invasive bladder cancer
- No prior pelvic surgery that would obviate a complete extended lymphadenectomy (e.g., aorto-femoral/iliac bypass)
- Prior neoadjuvant chemotherapy for this cancer allowed provided it has been completed and patient has recovered
- No prior pelvic irradiation
Trial locations and contacts
35 sites in 2 countries.
35 sites in 2 countries
United States29 sites
University of Colorado Cancer Center - Anschutz Cancer Pavilion
Aurora, Colorado, 80045
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287
Brigham and Women's Hospital
Boston, Massachusetts, 02115
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
Parkland Memorial Hospital
Dallas, Texas, 75235
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, 75390
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, 77030
Baylor Saint Luke's Medical Center
Houston, Texas, 77030
M D Anderson Cancer Center
Houston, Texas, 77030
Los Angeles County-USC Medical Center
Los Angeles, California, 90033
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033
Loyola University Medical Center
Maywood, Illinois, 60153
Yale University
New Haven, Connecticut, 06520
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065
Stanford Cancer Institute
Palo Alto, California, 94304
Oregon Health and Science University
Portland, Oregon, 97239
Portland Veterans Administration Medical Center
Portland, Oregon, 97239
Mayo Clinic
Rochester, Minnesota, 55905
University of Rochester
Rochester, New York, 14642
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817
Audie L Murphy Veterans Affairs Hospital
San Antonio, Texas, 78209
University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229
UCSF Medical Center-Mount Zion
San Francisco, California, 94115
UCSF Medical Center-Mission Bay
San Francisco, California, 94158
Louisiana State University Health Sciences Center Shreveport
Shreveport, Louisiana, 71103
Washington University School of Medicine
St Louis, Missouri, 63110
Moffitt Cancer Center
Tampa, Florida, 33612
Canada6 sites
QEII Health Sciences Centre/Capital District Health Authority
Halifax, Nova Scotia, B3H 1V8
London Regional Cancer Program
London, Ontario, N6A 4L6
McGill University Department of Oncology
Montreal, Quebec, H2W 1S6
The Research Institute of the McGill University Health Centre (MUHC)
Montreal, Quebec, H3H 2R9
University Health Network-Princess Margaret Hospital
Toronto, Ontario, M5G 2M9
BCCA-Vancouver Cancer Centre
Vancouver, British Columbia, V5Z 4E6
About this study
Official title: A Phase III Surgical Trial to Evaluate the Benefit of a Standard Versus an Extended Pelvic Lymphadenectomy Performed at Time of Radical Cystectomy for Muscle Invasive Urothelial Cancer
RATIONALE: Lymphadenectomy may remove tumor cells that have spread to nearby lymph nodes in patients with invasive bladder cancer. It is not yet known whether extended pelvic lymphadenectomy is more effective than standard pelvic lymphadenectomy during surgery.
PURPOSE: This randomized phase II trial is studying standard pelvic lymphadenectomy to see how well it works compared to extended pelvic lymphadenectomy in treating patients undergoing surgery for invasive bladder cancer.
Read the detailed description
OBJECTIVES:
Primary
- To compare disease-free survival (DFS) of patients with muscle-invasive urothelial carcinoma of the bladder undergoing radical cystectomy with extended pelvic lymph node dissection (PLND) or standard pelvic lymphadenectomy.
Secondary
- To compare overall survival (OS) of patients randomized to extended PLND versus those randomized to standard pelvic lymphadenectomy.
- To evaluate operative time; whether or not nerve sparing was performed, intraoperative, peri-operative and 90-day morbidity and mortality; length of hospital stay; histology (pure urothelial versus mixed); lymph node counts and lymph node density; adjuvant chemotherapy received; and local and retroperitoneal soft tissue recurrence in patients randomized to extended PLND versus those randomized to standard pelvic lymphadenectomy.
- To collect peripheral blood and two paraffin-embedded blocks of the primary tumor for translational medicine studies, including circulating tumor cells (CTCs) and markers of epithelial and mesenchymal transition, and correlate these findings with pathologic T stage and node metastasis as well as DFS and OS.
OUTLINE: This is a multicenter study. Patients are stratified according to prior neoadjuvant therapy (yes vs no), clinical stage (T2 vs T3 vs T4a), and Zubrod performance status (0-1 vs 2). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients undergo radical cystectomy and standard pelvic lymphadenectomy.
- Arm II: Patients undergo radical cystectomy and extended pelvic lymphadenectomy.
Blood and tumor specimens may be collected periodically for translational studies.
After completion of study therapy, patients are followed up periodically for 6 years.
- Conditions
- Bladder Cancer
- Being tested
- therapeutic conventional surgery, therapeutic standard lymphadenectomy, therapeutic extended lymphadenectomy
- Keywords
- stage II bladder cancer, stage III bladder cancer, transitional cell carcinoma of the bladder
- Medical subject headings
- Urinary Bladder Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
therapeutic conventional surgeryProcedure or surgery
Patients undergo radical cystectomy
therapeutic standard lymphadenectomyProcedure or surgery
Patients undergo standard pelvic lymphadenectomy.
therapeutic extended lymphadenectomyProcedure or surgery
Patients undergo extended pelvic lymphadenectomy
| Study group | Role | What they receive |
|---|---|---|
| Arm I | Active comparator | therapeutic conventional surgery therapeutic standard lymphadenectomy Receives: Procedure: therapeutic conventional surgery; Procedure: therapeutic standard lymphadenectomy |
| Arm II | Experimental | therapeutic conventional surgery therapeutic extended lymphadenectomy Receives: Procedure: therapeutic conventional surgery; Procedure: therapeutic extended lymphadenectomy |
What is being measured
The primary outcome is the main question the study is designed to answer.
5-year Disease-free Survival (DFS)
Comparing 5-year disease-free survival (DFS) in participants undergoing radical cystectomy for muscle-invasive urothelial carcinoma of the bladder (UCB) treated with radical cystectomy and extended pelvic lymph node dissection (PLND) compared to radical cystectomy and standard pelvic lymphadenectomy. Disease-free survival is defined as the time from the date of randomization to date of first documentation of relapse/recurrence or death due to any cause. Participants last known to be alive without report of relapse/recurrence are censored at date of last contact. Criteria for recurrence included measurable disease on cross-sectional imaging or plain radiography targeting lung, liver, and bone. If local pelvic recurrence was identified on digital rectal examination, biopsy was required for confirmation. Second primary tumors of the upper urinary tract or retained urethra were not considered to be recurrence.
Measured: Duration of treatment and follow-up until death or 6 years after randomization
Secondary outcomes (8)
5-year Overall Survival (OS)
Comparing 5-year overall survival (OS) in participants randomized to extended PLND versus those randomized to standard pelvic lymphadenectomy. Overall survival is defined as the time from date of randomization to date of death from any cause. Participants known to be alive are censored at date of last contact.
Measured: Duration of treatment and follow-up until death or 6 years after randomization
Median Operative Time
Evaluating duration of surgery in participants randomized to extended lymphadenectomy versus those randomized to standard lymphadenectomy.
Measured: Duration of surgery
Median Days in Hospital
Evaluating duration of post-operative hospital stay in participants randomized to extended lymphadenectomy versus those randomized to standard lymphadenectomy.
Measured: From date of operation to 90 days post-operation
Use of Nerve Preservation
Evaluating the frequency of nerve sparing surgery in participants randomized to extended lymphadenectomy versus those randomized to standard lymphadenectomy.
Measured: Duration of surgery
Lymph Node Counts
Evaluating the number of positive lymph nodes removed during surgery as well as the total number of lymph nodes removed in participants randomized to extended lymphadenectomy versus those randomized to standard lymphadenectomy.
Measured: Duration of surgery
Receipt of Adjuvant Chemotherapy
Evaluating the receipt of adjuvant chemotherapy in participants randomized to extended lymphadenectomy versus those randomized to standard lymphadenectomy. Participants that reported plans to start adjuvant chemotherapy are included in these counts.
Measured: From date of operation to 90 days post-operation
Frequency of Post-Operative Local Recurrence
Evaluating the frequency of post-operative local and retroperitoneal soft-tissue recurrence in participants randomized to extended lymphadenectomy versus those randomized to standard lymphadenectomy.
Measured: From date of operation to 90 days post-operation
Post-Operative Morbidity
Evaluating perioperative morbidity (death within 30 days of surgery) and post-operative morbidity (death within 90 days of surgery) in participants randomized to extended lymphadenectomy versus those randomized to standard lymphadenectomy.
Measured: From date of operation to 90 days post-operation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Oct 2010 (estimated)
- Study start25 Nov 2011
- Primary completionMay 2024
- Study completionMay 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Bladder CancerStudies of the same condition, open and under way.
- More trials run by SWOG Cancer Research NetworkThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 658 participants (actual)
Sponsor and investigators
- Lead sponsor
- SWOG Cancer Research Network
- Sponsor type
- Research network
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Seth P. Lerner, MD, Principal investigator, Baylor College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01224665
- Sponsor's protocol ID
- S1011
- Other IDs
- SWOG-S1011, NCI-2011-02604
- Status last verified
- Nov 2024
- First submitted
- 19 Oct 2010
- Last updated
- 29 Nov 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Lerner SP, Tangen C, Svatek RS, Daneshmand S, Pohar KS, Skinner E, Schuckman A, Sagalowsky AI, Smith ND, Kamat AM, Kassouf W, Plets M, Bangs R, Koppie TM, Alva A, La Rosa FG, Pal SK, Kibel AS, Canter DJ, Thompson IM Jr; SWOG S1011 Trial Investigators. Standard or Extended Lymphadenectomy for Muscle-Invasive Bladder Cancer. N Engl J Med. 2024 Oct 3;391(13):1206-1216. doi: 10.1056/NEJMoa2401497.
PubMed 39589370Kamat AM, Hahn NM, Efstathiou JA, Lerner SP, Malmstrom PU, Choi W, Guo CC, Lotan Y, Kassouf W. Bladder cancer. Lancet. 2016 Dec 3;388(10061):2796-2810. doi: 10.1016/S0140-6736(16)30512-8. Epub 2016 Jun 23.
PubMed 27345655Froehner M, Novotny V, Heberling U, Rutsch L, Litz RJ, Hubler M, Koch R, Baretton GB, Wirth MP. Relationship of the number of removed lymph nodes to bladder cancer and competing mortality after radical cystectomy. Eur Urol. 2014 Dec;66(6):987-90. doi: 10.1016/j.eururo.2014.07.046. Epub 2014 Aug 19.
PubMed 25150172