European Urology

50th Volume Editorials

Geoffrey Chisholm was a far-sighted urologist and his innovation and forward-thinking is exemplified in this seminal paper. The predilection of radionuclides for the bony skeleton had been known since 1929, when Martland and Humphries, in a classical paper, described the development of osteosarcomata in painters of luminous watch dials. It had also been known for some years that scintigraphic imaging was a better discriminator of metastatic disease in bone, something which Chisholm and his co-workers had helped to establish during investigations while he was a Urologist in London [1], and [2]. It was also known that bisphosphonate-labelled technetium was the most accurate and reliable isotope [3]. There were, however, several unresolved questions related to bone scanning at that time:

• •How accurate was a scan, particularly in relation to an x-ray skeletal survey?

• •Which scanner type should be used in the scanning process?

• •Was bone scanning useful in staging and serial testing as a “tumour marker”?

Following his move to Edinburgh, Chisholm, with his co-workers, approached this problem systematically and prospectively, studying patients according to strict proforma based evaluation and data collection in an innovative, dedicated prostate cancer research and treatment clinic, something that in itself was unusual at that time in urology. The results produced and subsequently published in this paper went some way to answering a number of questions related to skeletal scintigraphy in the field of prostate cancer diagnosis, staging and treatment monitoring, and as a consequence, this publication made a significant contribution to urologic oncology, helping to set the pattern for prostate cancer management in the era before prostate-specific antigen (PSA) measurement.

At the time of publication, the paper facilitated significant improvements in the staging and diagnosis and follow-up of prostate cancer. It confirmed that scintigraphy was much more accurate than a conventional radiologic skeletal survey and that many men at that time had the stage of their disease raised, thus enabling more accurate treatment planning and avoidance of inappropriate local therapy. It is interesting to note the proportion of patients with metastatic disease at presentation at the time of this study (48% of the total) and to compare this with the current rate in the PSA era, a sobering reminder of the demographic changes that we have seen in this disease in the last 25 year. The paper also established that in the absence of a reliable tumour marker, serial skeletal scintigraphy was a useful way to assess the progression or regression of prostate cancer following treatment. This was a controversial issue at the time [2] and PSA testing was not widely available in the clinic for a number of years.

How have the data stood the test of time? By modern standards the study is relatively small and has flaws, such as the lack of definitive validation about whether hot spots revealed on a bone scan only were truly metastatic deposits, the fact that it was a single-site study, and that scans were not subjected to independent central review. There were, of course, mitigating circumstances for these flaws, particularly in relation to the hot spot validation; access to computed tomography was limited and magnetic resonance (MR) scanning was not available then. Notwithstanding these problems, and considering the fact that bone scanning has assumed a much reduced role in current practice as a consequence of PSA, skeletal scintigraphy is still an important adjunct to diagnostic staging and monitoring in this disease, albeit in a more focused manner. The positive detection rate of a bone scan in a patient with a PSA level <10 ng/ml is in the region of 1% [4], and its routine nonstratified use is neither accurate nor cost effective. Serial PSA monitoring has also supplanted serial bone scanning. However, scintigraphy is still helpful and widely used in cases where the PSA is rising, where the PSA is relatively high at first diagnosis, and where the tumour has a high Gleason grade. In addition, the skeletal overview available from a bone scan can also be used to direct the clinician to specific areas of the skeleton where the bone may be examined by other imaging techniques such as MR scanning. Thus, a multimodality approach to diagnostics, which involves skeletal scintigraphy is, in some ways, as relevant today as it was when Chisholm and his co-workers produced this seminal work.

Despite the enduring value of this study and the advances that have been made since its publication, Urologists do need something better than the current imaging, including standard isotope scintigraphy, for the diagnosis, staging, and management of prostate cancer. It is therefore worthwhile to study the approach taken by Chisholm et al. in this work as a model for clinical research in urology in the modern era because it is likely that a similarly innovative, systematic, and thorough clinical research-based approach will be needed to study men undergoing treatment for prostate cancer in the future.