Apoptosis, p53, bcl-2, and Ki-67 in invasive bladder carcinoma: possible predictors for response to radiochemotherapy and successful bladder preservation.
OBJECTIVE
Several groups have reported the value of bladder preservation by a combined treatment protocol, including transurethral resection (TUR-B) and radiochemotherapy (RCT). As more experience is acquired with organ-sparing treatment, patient selection should be optimized. The purpose of this study was to investigate the role of several biologic markers that may predict response to RCT in muscle-invasive bladder carcinoma.


METHODS
The apoptotic index (AI), Ki-67, p53, and bcl-2 were evaluated by immunohistochemistry on pretreatment biopsies from 70 patients treated for invasive bladder cancer by TUR-B and RCT. Expression of each marker was correlated with initial response, local control, and cancer-specific survival with preserved bladder. An exploratory multivariate analysis was also performed that included clinical and immunohistochemical variables.


RESULTS
A high AI (> median = 1.6%) and a high Ki-67 index (> median = 8.8%), but not the p53- and bcl-2 expression, were significantly related to initial complete response (CR) and local control with preserved bladder after 5 years. When the AI and Ki-67 expression were considered simultaneously, the association with initial CR (p < 0. 001), local control (p = 0.0002), and cancer-specific survival with preserved bladder (p = 0.008) was highly significant. In an exploratory multivariate analysis (final model), only AI, Ki-67, and the combined AI/Ki-67 variable retained significance for local control with preserved bladder at 5 years.


CONCLUSIONS
Patients with a high spontaneous AI and a high pretreatment Ki-67 index should be considered preferentially for treatment with RCT, whereas tumors with low proliferation and low levels of apoptosis are less likely to respond to RCT.
Rödel
C
C
Department of Radiation Oncology, University of Erlangen-Nürnberg, Erlangen, Germany. claus.roedel@strahlen.med.uni-erlangen.de
Grabenbauer
G G
GG
Rödel
F
F
Birkenhake
S
S
Kühn
R
R
Martus
P
P
Zörcher
T
T
Fürsich
D
D
Papadopoulos
T
T
Dunst
J
J
Schrott
K M
KM
Sauer
R
R
D000368:Aged; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000032:analysis*; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis*; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*; D001743:Urinary Bladder; D001749:Urinary Bladder Neoplasms / Q000737:chemistry* / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy
D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53