The rising incidence of and mortality from prostate cancer has generated great interest in improving the results of current methods of treatment. It is well-established that large tumour volumes and positive surgical margins are correlated with higher rates of local failure and distant metastasis. Significant decreases in both tumour volume and the rates of positive surgical margins are seen with NHT. Follow-up data from one randomized trial of hormonal therapy before RT have shown significantly improved disease-free survival, but so far there has been no benefit in overall survival. However, the addition of adjuvant hormonal therapy has been reported to improve survival. The results suggest that neoadjuvant and adjuvant hormonal therapy may be a viable option in men with locally advanced prostate cancer in whom cure is probably impossible, but disease progression can potentially be slowed. What remains to be determined is whether hormonal therapy alone can produce the same results. For younger men with clinically localized prostate cancer, radical prostatectomy is increasingly the treatment of choice. Prospective randomized trials of NHT have produced impressive statistics for decreasing the incidence of positive surgical margins, but the potential to down-stage tumours remains controversial. Follow-up serum PSA measurements have thus far shown no benefit from neoadjuvant therapy. The possibility that patients who fail biochemically, whether they are from the pretreated or control group, may simply represent a subgroup with aggressive tumours that may not respond to androgen withdrawal, has yet to be proved. As more follow-up data are analysed within the next several years, there must be a clear survival advantage if NHT is to be offered as a treatment option. Despite the potential of neoadjuvant therapy, the use of androgen withdrawal before definitive surgical treatment should be limited to clinical trials until a clearer picture emerges. Some may argue that although there is no evidence of a true advantage for NHT, neither is there evidence of harm. However, it must be recognized that androgen withdrawal therapy has side-effects and adds significantly to the overall cost of treatment. Furthermore, NHT delays definitive treatment; clearly, this can be a source of anxiety for the patient and the impact on survival is unknown. Currently, the rates of pathologically organ-confined disease are high in some subsets of patients (e.g. low-stage, low-grade and low PSA) so that NHT is unlikely to have great additional benefit. Although the influence of hormones on prostate growth has been known for many decades, we are only now elucidating the biological mechanisms of hormonal therapy. Although androgen ablation therapy has been used in men with metastatic prostate cancer for more than 50 years, further research at the cellular and molecular level is essential if we are to refine treatment modalities for both localized and advanced disease. Furthermore, until we have more follow-up data from randomized clinical trials ...

Objective  To study the rate of change in prostate specific antigen (PSA velocity) in patients with prostate cancer initially managed by ‘watchful waiting’. Patients and methods  Serial PSA levels were determined in 141 patients with prostate cancer confirmed by biopsy, who were initially managed expectantly and enrolled between May 1990 and December 1995. Sixty‐seven patients eventually underwent surgery (mean age 59 years) because they chose it (the decision for surgery was not based on PSA velocity). A cohort of 74 patients remained on ‘watchful waiting’ (mean age 69 years). Linear regression and logarithmic transformations were used to segregate those patients who showed a rapid rise, defined as a>50% rise in PSA per year (or a doubling time of <2 years) and designated ‘rapid risers’. Results  An initial analysis based on a minimum of two PSA values showed that 31% were rapid risers. Only 15% of patients with more than three serial PSA determinations over ≥6 months showed a rapid rise in PSA level. There was no advantage of log‐linear analysis over linear regression models. Conclusion  Three serial PSA determinations over ≥6 months in patients with clinically localized prostate cancer identifies a subset (15%) of patients with a rapidly rising PSA level. Shorter PSA surveillance with fewer PSA values may falsely identify patients with rapid rises in PSA level. However, further follow‐up is required to determine if a rapid rise in PSA level identifies a subset of patients with an aggressive biological phenotype who are either still curable or who have already progressed to incurability through metastatic disease.

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