The fourth issue of Vol. 6 of Prostate Cancer and Prostatic Diseases contains articles that will both stimulate and intrigue both clinicians and basic scientists with an interest in these important disease areas. Bok et al, using Normal Greenberg's now famous TRAMP model, implicate pericellular proteases as the initiators of major proteolytic cascades during tumour progression and suggest targets for maximal therapeutic effect. Griewe et al evaluate the incidence and distribution of p53 mutations in radical prostatectomy specimens. Since abnormal expression of this gene, which is so strongly correlated with so many tumours, has been shown to relate to the risk of recurrence after radical prostatectomy, this is a significant piece of work.

Obesity is becoming one of the major health hazards of the 21st century and may be a risk factor for prostate cancer. Myldo et al speculate that higher concentrations of VEGF and FGF-2 detected in obese rodents may account for some of the differences seen in obesity-related tumour growth in the humans, but more work will be needed to conform this.

Gene therapy holds considerable promise for the future for the treatment of many cancers, but problems still surround achieving sufficient DNA transfections rates. Michel et al in Germany have investigated the use of the acoustic energy and accomplished an increase of transfection rates for 0.3 to 4.6%. Perhaps such results imply therapeutic levels. Certainly, more work is warranted to evaluated the technique.

The critical role that androgens have in stimulating prostate cancer cell growth has been known for more than half a century. Abdel-Wahab et al conform that in those patients with higher androgen receptor densities the S-phase fraction was significantly higher. This, of course, provides another rationale for the use of androgen ablation therapy for patients with prostate cancer. Unfortunately, withdrawal of androgen stimulation has several unwanted effects, not least a negative impact on sexual function. As a consequence, other gentler treatments have been sought. Guess et al provide very early evidence that modified citrus pectin (MCP) may have a role. Of course, we will need much more solid data from adequately powered randomised controlled trials before we are convinced, but an intriguing possibility of efficacy is raised, which will excite the ever-strengthening complementary medicine lobby.

Most urologists accept that high-grade prostatic intraepithelial neoplasia (HGPIN) is a precursor lesion for prostate cancer. Much less convincing is the evidence that low-grade prostatic intraepithelial neoplasia (LGPIN) is also a risk factor. In fact, many pathologists do not even report this finding. In this issue, Goeman et al report that 30% of patients undergoing repeat biopsies for LGPIN had at least one core positive for adenocarcinoma. These findings suggest that we should re-evaluate the important and the reporting of LGPIN. Of course, to identify the abnormality a transrectal ultrasound-guided biopsy of the gland is required. Ozveri et al remind us that periprostatic and intraprostatic local anaesthetic is now best practice with excellent efficacy and minimal complications.

Finally, in this issue, we contribute to the debate concerning which medical therapy should be deployed for the management of benign prostatic hyperplasia (BPH). Rigatti et al conclude that the alpha-blocker tamsulosin is more effective than finasteride in a 1-year randomised study. Similar conclusions were drawn by the Veterans study in the US and the PREDICT study in Europe, using terazosin and doxazosin, respectively, as the alpha-blocker in each trial. Due to be published soon, however, by McConnell et al in the N Engl J Med is the medical treatment of prostate symptoms (MTOPS) study, which concluded that combination therapy of an alpha-blocker and a 5 alpha-reductase inhibitor provided the optimal outcome in terms of symptom relief and prevention of BPH progression.

Patients and unrolgists will need to be informed of all these developments before choosing which medical treatment is most likely to be effective in the individual case.