p53 expression in patients with advanced urothelial cancer of the urinary bladder.
OBJECTIVE
To test whether assessing p53 expression could improve the ability to predict disease recurrence and disease-specific survival in a multi-institutional cohort of patients with advanced urothelial carcinoma of the urinary bladder (UCB).


METHODS
The study comprised 692 patients with pT3-4 N0 or pTany N+ UCB treated with radical cystectomy and lymphadenectomy. The predictive accuracy (PA) was quantified using the 200 bootstrap-corrected concordance index. The base model comprised age, gender, stage, grade, lymphovascular invasion, number of lymph nodes removed, number of lymph nodes positive, concomitant carcinoma in situ, and adjuvant chemotherapy.


RESULTS
p53 expression was altered in 341 (49.3%) patients. In multivariable analyses, p53 expression was independently associated with disease recurrence (hazard ratio, 1.66; P < 0.001) and cancer-specific mortality (hazard ratio 1.65, P < 0.001). Overall, adding p53 did not significantly improve the PA of the base model (recurrence +0.7%, P = 0.085, and cancer-specific mortality +1.2%, P = 0.050). In the subgroups of pT3N0 (280) and pT4N0 (83) patients, p53 slightly improved the PA of the base model by a statistically significant degree (recurrence +1.7% and +3.6%, respectively; cancer-specific mortality +1.9% and +3.5%, respectively; all P < 0.001). In 329 patients with pTany N+ disease p53 status did not improve the PA of the base model.


CONCLUSIONS
While assessing p53 expression has limited utility in patients with lymph node-positive UCB, it marginally improves prognostication in patients with advanced non-metastatic UCB. Integration of p53 into a panel of biomarkers might be necessary to capture a more accurate picture of the biological potential of advanced UCB.
Shariat
Shahrokh F
SF
Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA. sfshariat@gmail.com
Bolenz
Christian
C
Karakiewicz
Pierre I
PI
Fradet
Yves
Y
Ashfaq
Raheela
R
Bastian
Patrick J
PJ
Nielsen
Matthew E
ME
Capitanio
Umberto
U
Jeldres
Claudio
C
Rigaud
Jérôme
J
Müller
Stefan C
SC
Lerner
Seth P
SP
Montorsi
Francesco
F
Sagalowsky
Arthur I
AI
Cote
Richard J
RJ
Lotan
Yair
Y
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002278:Carcinoma in Situ / Q000378:metabolism / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D015653:Cystectomy; D004812:Epidemiologic Methods; D005260:Female; D006801:Humans; D008197:Lymph Node Excision; D008198:Lymph Nodes / Q000473:pathology* / Q000601:surgery; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D011379:Prognosis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D001743:Urinary Bladder / Q000473:pathology* / Q000601:surgery; D001749:Urinary Bladder Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D019459:Urothelium / Q000473:pathology
D016159:Tumor Suppressor Protein p53