Active treatment of prostate cancer

Prostate cancer is the second most common cancer worldwide and the most common cancer in Finland among men. While the prognosis of low-risk localised prostate cancer is excellent, a substantial proportion of prostate cancer patients experience disease progression after first-line treatment. This doctoral dissertation includes four studies that focused on active treatment options for prostate cancer patients with adverse pathologic features or risk factors associated with increased disease recurrence and/or mortality. Epidermal growth factor receptor (EGFR) overexpression is associated with poor prognosis in prostate cancer and resistance to radiotherapy in several solid tumours. In the first two non-randomised trials, the objective was to evaluate the safety and efficacy of 250 mg once daily gefitinib, an orally active EGFR inhibitor, in prostate cancer patients. In the first (phase I/II) trial, 42 patients with nonmetastatic prostate cancer received gefitinib in combination with radical radiotherapy as the first-line treatment. In the second (phase II) trial, 30 patients with biochemical recurrence following radical treatment received gefitinib monotherapy. The third study was a retrospective patient series of 46 patients with previously untreated metastatic prostate cancer—a diagnosis that continues to have poor overall survival. This study evaluated the safety and efficacy of multimodal treatment, including androgen deprivation and radical radiotherapy. In addition, the patients received various individually planned treatments. The fourth study was a multicentre trial that randomised 250 radical prostatectomy-treated patients into an adjuvant radiation (126 patients) or observation (124 patients) group. All patients had positive surgical margins or extracapsular extension, both of which have been associated with increased prostate cancer progression; however, it was unclear whether these patients benefit from adjuvant radiation after surgery. While most of the adverse events in the first study were mild to moderate, the toxicity of gefitinib in combination with radiation was unacceptable, considering that most patients had low-risk prostate cancer with a favourable prognosis even without any active treatments. In studies II–IV, the toxicity was acceptable. The efficacy of gefitinib in prostate cancer patients was modest, both in combination with radical radiotherapy and as a monotherapy. The multimodal treatment approach in metastatic prostate cancer was promising but requires further confirmation in randomised trials. Adjuvant radiotherapy following radical prostatectomy resulted in significant improvement in patients’ biochemical recurrence-free survival when compared to surgery alone. However, salvage radiation upon biochemical recurrence following surgery appeared equally effective in terms of overall survival. Prostate cancer patients with adverse pathologic features or risk factors form a heterogeneous group of patients with different prognoses. To balance the subjective experience of treatment toxicity and the treatment’s expected efficacy on survival, the patient must be adequately informed about the toxicity profiles of the treatments available as well as the risk for later disease progression. The aims of future research include more accurate risk-profiling for each prostate cancer patient, a better understanding of individual disease characteristics, and, thus, the identification of optimal treatments.