Near-infrared Raman spectroscopy, an optical technique that is able to interrogate biological tissues, has been used to study bladder and prostate tissues, with the objective being to provide a first approximation of gross biochemical changes associated with the process of carcinogenesis. Prostate samples for this study were obtained by taking a chip at TURP, and bladder samples from a biopsy taken at TURBT and TURP, following ethical approval. Spectra were taken from purchased biochemical constituents and different pathologies within the bladder and the prostate. We were then able to determine the biochemical basis for these pathologies by utilising an ordinary least-squares fit. We have shown for the first time that we are able to utilise Raman spectroscopy in determining the biochemical basis for the different pathologies within the bladder and prostate gland. In this way we can achieve a better understanding of disease processes such as carcinogenesis. This could have major implications in the future of the diagnosis of disease within the bladder and the prostate gland.

The first analysis of the MRC RE01 trial in metastatic renal carcinoma identified a 28% reduction in the hazard of death for patients treated with interferon-a compared with medroxyprogesterone acetate (MPA). No subgroup was identified in which treatment with interferon-a was more or less effective than MPA. We used a new approach based on fractional polynomials to investigate the updated data from this trial for the possible interaction of treatment with prognostic factors. In the spirit of hypothesis generation, we considered 10 possible prognostic variables, of which white cell count (WCC) was found to influence the effectiveness of interferon treatment. In patients treated with MPA, there was no prognostic effect of WCC, whereas, in patients treated with interferon, the risk of dying increased significantly with WCC level. We defined subgroups of patients based on WCC levels and estimated a hazard ratio of 0.53 in favour of interferon in patients with WCC o6.5 Â 10 9 , whereas for patients with WCC 410 Â 10 9 the risk appears to be similar between the treatment groups, or even slightly raised in the interferon group. Since our results are derived from flexible statistical models, they may be interpreted as a new hypothesis and require validation in independent data. British Journal of Cancer (2004) Between 1992 and 1997, 350 patients with metastatic renal carcinoma were randomised to enter the MRC RE01 trial comparing interferon-a with medroxyprogesterone acetate (MPA) at 31 centres in the UK. In the first paper based on 335 patients and 236 deaths, a 28% reduction in the risk of death in the interferon-a group was reported (MRCRCC, 1999). The trial was stopped early, because the treatment effect crossed the effectiveness boundary in a triangular sequential design. Owing to the side effects of the interferon-a regimen, it is important to investigate whether the clear overall survival advantage is present in all patients. In the initial report (MRCRCC, 1999), there was no evidence from w 2 tests of heterogeneity that any prognostic factor had an influence on the effectiveness of interferon-a. Thus, no subgroup was identified in which the treatment was more or less effective.Updated data with 322 deaths were analysed by using a new approach to modelling interactions between treatment and continuous covariates (Royston and Sauerbrei, 2003). We systematically investigated whether any of the potential prognostic factors recorded at randomisation exhibits any predictive value, meaning that the effect of treatment depends on such a factor.Details of results on further end points such as progression-free survival may be found in the first paper (MRCRCC, 1999). Here we will consider only the primary end point of the trial, overall survival. In this investigation, we considered age, WHO performance status and other clinical and laboratory features listed in Table 2. With the exception of weight loss, erythrocyte sedimentation rate (ESR) and nuclear grade, this list includes the 'standard' prognostic factors for advan...

Raman spectroscopy is an optical technique able to interrogate biological tissues, giving us an understanding of the changes in molecular structure that are associated with disease development. The Kerr-gated Raman spectroscopy technique uses a picosecond pulsed laser as well as fast temporal gating of collected Raman scattered light. Prostate samples for this study were obtained by taking a chip at the transurethral resection of the prostate (TURP), and bladder samples from a biopsy taken at transurethral resection of bladder tumor (TURBT) and TURP. Spectra obtained through the bladder and prostate gland tissue, at different time delays after the laser pulse, clearly show change in the spectra as depth profiling occurs, eventually showing signals from the uric acid cell and urea cell, respectively. We show for the first time, using this novel technique, that we are able to obtain spectra from different depths through both the prostate gland and the bladder. This has major implications in the future of Raman spectroscopy as a tool for diagnosis. With the help of Raman spectroscopy and Kerr gating, it may be possible to pick up the spectral differences from a small focus of adenocarcinoma of the prostate gland in an otherwise benign gland, and also stage the bladder cancers by assessing the base of the tumor post resection.

Although a prospective randomized trial is needed to establish definite benefit from the use of interferon in advanced renal cell cancer, this analysis supports the rationale for performing such a trial, particularly in patients with relatively good prognostic features. Patients should be entered into the Medical Research Council study comparing interferon with medroxyprogesterone acetate.

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