Studies of the response of muscle invasive bladder cancer to radiotherapy
The purpose of this study was to investigate several biological markers that may predict the response of muscle invasive transitional cell carcinoma TCC of the bladder to radical radiotherapy. The specific markers chosen were tumour angiogenesis (CD31 &CD34), tumour cell proliferation (Ki-67) and apoptosis (bcl-2), intratumour macrophage infiltration (CD68) and p53. Archival formalin fixed paraffin embedded pre treatment bladder biopsies from 101 patients with muscle invasive TCC were obtained. All patients subsequently received radical radiotherapy as their only treatment for the disease. 4µm sections were graded according to the WHO grading system and staged by the TNM classification. Angiogenesis (CD31&CD34) counts were obtained using a 25-point Chalkley eyepiece graticule. Bcl-2 scored as positive and negative, while p53, Ki-67 and CD68 were estimated using an eyepiece graticule. The medical records were examined to assess the response of the tumour at the 3-month post radiotherapy cystoscopy and the long-term outcome. Patients were classified into two groups in two sections: the first section includes (1) those free of disease (no tumour detected in the bladder at the 3-month cystoscopy), (2) those with resistant disease (tumour present at 3 months). The second section includes (1) those with persistent or recurrent cancer in the bladder (tumour recurred after an initial 3 months negative check cystoscopy together with patients with resistant disease at 3 months), (2) those free of disease at all subsequent cystoscopies. Detailed statistical analysis revealed that there were no association between any of the markers examined and the response to radiotherapy. MVD using CD34 was lower in higher stage tumours (p=0.050). Females, whilst representing only a small fraction (16) of the total of patients studied showed an inferior response to radiotherapy when compared to that of male patients (p=0.048). Higher median haemoglobin levels for the response group (p=0.031) was observed as well as a positive significant correlation between p53 (L1) expression and MIB-1 (LI) (r=0.332, p=0.001). The Kaplan-Meier survival analysis shows that the survival time is significantly better for those who were exposed longer to radiotherapy (> 33 days) (Log Rank, p=0.0246). There was a significantly higher survival time for patients who have CD68 higher than 42.4 (log rank, p=D.036). The study concluded that none of the selected markers could be used as prognostic value in determining patients most suitable for radiotherapy as primary treatment with curative intent for their bladder cancer. The finding of a poorer response in females is worthy of further study since, hormonal and anatomical influences may be important.