Comparative Effectiveness of Treatment Strategies for Bladder Cancer With Clinical Evidence of Regional Lymph Node Involvement.
Patients with bladder cancer with clinical lymph node involvement (cN+) are at high risk for distant metastases, but are potentially curable. Such patients are excluded from neoadjuvant chemotherapy trials and pooled with patients with distant metastases in first-line chemotherapy trials not suited to define the role of combined-modality therapy. To address this evidence void, we performed a comparative effectiveness analysis.



We included cTanyN1-3M0 bladder cancer patients from the National Cancer Data Base (2003-2012) treated with chemotherapy and/or cystectomy. We used multistate survival analysis, allowing for delayed entry, to assess overall survival (OS) according to various treatment strategies. Effectiveness was estimated with multivariable adjustment for tumor-, patient-, and facility-level characteristics.



Among 1,739 patients (cN1, 48%; cN2, 45%; cN3, 7%), 1,104 underwent cystectomy and 635 were treated with chemotherapy alone. Of the cystectomy patients, 363 received preoperative and 328 received adjuvant chemotherapy. The crude 5-year OS for chemotherapy alone, cystectomy alone, preoperative chemotherapy followed by cystectomy, and cystectomy followed by adjuvant chemotherapy was 14% (95% CI, 11% to 17%), 19% (95% CI, 15% to 24%), 31% (95% CI, 25% to 38%), and 26% (95% CI, 21% to 34%), respectively. Compared with cystectomy alone, preoperative chemotherapy was associated with a significant improvement in OS (hazard ratio, 0.80; 95% CI, 0.66 to 0.97). Adjuvant chemotherapy was also associated with a significant improvement in survival compared with cystectomy alone. The survival of patients treated with chemotherapy alone was worse than those treated with cystectomy alone.



A subset of patients with cN+ bladder cancer achieves long-term survival. Combined-modality therapy, with chemotherapy and cystectomy, is associated with the best outcomes.
Matthew D. Galsky, John P. Sfakianos, Reza Mehrazin, Nihal Mohamed, Che-Kai Tsao, Paolo Boffetta, Peter Wiklund, William K. Oh, Madhu Mazumdar, and Bart Ferket, Icahn School of Medicine at Mount Sinai, New York; and Michael Diefenbach, Northwell Health, Great Neck, NY; Kristian Stensland, Lahey Clinic, Burlington, MA; and Peter Wiklund, Karolinska Institute, Stockholm Sweden. matthew.galsky@mssm.edu.
Matthew D
MD
Galsky
Matthew D. Galsky, John P. Sfakianos, Reza Mehrazin, Nihal Mohamed, Che-Kai Tsao, Paolo Boffetta, Peter Wiklund, William K. Oh, Madhu Mazumdar, and Bart Ferket, Icahn School of Medicine at Mount Sinai, New York; and Michael Diefenbach, Northwell Health, Great Neck, NY; Kristian Stensland, Lahey Clinic, Burlington, MA; and Peter Wiklund, Karolinska Institute, Stockholm Sweden.
Kristian
K
Stensland
Matthew D. Galsky, John P. Sfakianos, Reza Mehrazin, Nihal Mohamed, Che-Kai Tsao, Paolo Boffetta, Peter Wiklund, William K. Oh, Madhu Mazumdar, and Bart Ferket, Icahn School of Medicine at Mount Sinai, New York; and Michael Diefenbach, Northwell Health, Great Neck, NY; Kristian Stensland, Lahey Clinic, Burlington, MA; and Peter Wiklund, Karolinska Institute, Stockholm Sweden.
John P
JP
Sfakianos
Matthew D. Galsky, John P. Sfakianos, Reza Mehrazin, Nihal Mohamed, Che-Kai Tsao, Paolo Boffetta, Peter Wiklund, William K. Oh, Madhu Mazumdar, and Bart Ferket, Icahn School of Medicine at Mount Sinai, New York; and Michael Diefenbach, Northwell Health, Great Neck, NY; Kristian Stensland, Lahey Clinic, Burlington, MA; and Peter Wiklund, Karolinska Institute, Stockholm Sweden.
Reza
R
Mehrazin
Matthew D. Galsky, John P. Sfakianos, Reza Mehrazin, Nihal Mohamed, Che-Kai Tsao, Paolo Boffetta, Peter Wiklund, William K. Oh, Madhu Mazumdar, and Bart Ferket, Icahn School of Medicine at Mount Sinai, New York; and Michael Diefenbach, Northwell Health, Great Neck, NY; Kristian Stensland, Lahey Clinic, Burlington, MA; and Peter Wiklund, Karolinska Institute, Stockholm Sweden.
Michael
M
Diefenbach
Matthew D. Galsky, John P. Sfakianos, Reza Mehrazin, Nihal Mohamed, Che-Kai Tsao, Paolo Boffetta, Peter Wiklund, William K. Oh, Madhu Mazumdar, and Bart Ferket, Icahn School of Medicine at Mount Sinai, New York; and Michael Diefenbach, Northwell Health, Great Neck, NY; Kristian Stensland, Lahey Clinic, Burlington, MA; and Peter Wiklund, Karolinska Institute, Stockholm Sweden.
Nihal
N
Mohamed
Matthew D. Galsky, John P. Sfakianos, Reza Mehrazin, Nihal Mohamed, Che-Kai Tsao, Paolo Boffetta, Peter Wiklund, William K. Oh, Madhu Mazumdar, and Bart Ferket, Icahn School of Medicine at Mount Sinai, New York; and Michael Diefenbach, Northwell Health, Great Neck, NY; Kristian Stensland, Lahey Clinic, Burlington, MA; and Peter Wiklund, Karolinska Institute, Stockholm Sweden.
Che-Kai
CK
Tsao
Matthew D. Galsky, John P. Sfakianos, Reza Mehrazin, Nihal Mohamed, Che-Kai Tsao, Paolo Boffetta, Peter Wiklund, William K. Oh, Madhu Mazumdar, and Bart Ferket, Icahn School of Medicine at Mount Sinai, New York; and Michael Diefenbach, Northwell Health, Great Neck, NY; Kristian Stensland, Lahey Clinic, Burlington, MA; and Peter Wiklund, Karolinska Institute, Stockholm Sweden.
Paolo
P
Boffetta
Matthew D. Galsky, John P. Sfakianos, Reza Mehrazin, Nihal Mohamed, Che-Kai Tsao, Paolo Boffetta, Peter Wiklund, William K. Oh, Madhu Mazumdar, and Bart Ferket, Icahn School of Medicine at Mount Sinai, New York; and Michael Diefenbach, Northwell Health, Great Neck, NY; Kristian Stensland, Lahey Clinic, Burlington, MA; and Peter Wiklund, Karolinska Institute, Stockholm Sweden.
Peter
P
Wiklund
Matthew D. Galsky, John P. Sfakianos, Reza Mehrazin, Nihal Mohamed, Che-Kai Tsao, Paolo Boffetta, Peter Wiklund, William K. Oh, Madhu Mazumdar, and Bart Ferket, Icahn School of Medicine at Mount Sinai, New York; and Michael Diefenbach, Northwell Health, Great Neck, NY; Kristian Stensland, Lahey Clinic, Burlington, MA; and Peter Wiklund, Karolinska Institute, Stockholm Sweden.
William K
WK
Oh
Matthew D. Galsky, John P. Sfakianos, Reza Mehrazin, Nihal Mohamed, Che-Kai Tsao, Paolo Boffetta, Peter Wiklund, William K. Oh, Madhu Mazumdar, and Bart Ferket, Icahn School of Medicine at Mount Sinai, New York; and Michael Diefenbach, Northwell Health, Great Neck, NY; Kristian Stensland, Lahey Clinic, Burlington, MA; and Peter Wiklund, Karolinska Institute, Stockholm Sweden.
Madhu
M
Mazumdar
Matthew D. Galsky, John P. Sfakianos, Reza Mehrazin, Nihal Mohamed, Che-Kai Tsao, Paolo Boffetta, Peter Wiklund, William K. Oh, Madhu Mazumdar, and Bart Ferket, Icahn School of Medicine at Mount Sinai, New York; and Michael Diefenbach, Northwell Health, Great Neck, NY; Kristian Stensland, Lahey Clinic, Burlington, MA; and Peter Wiklund, Karolinska Institute, Stockholm Sweden.
Bart
B
Ferket
D000368:Aged; D000369:Aged, 80 and over; D017024:Chemotherapy, Adjuvant; D015653:Cystectomy; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000401:mortality / Q000473:pathology* / Q000628:therapy*