Radical radiotherapy is a standard form of management of localised prostate cancer. Conformal treatment planning spares adjacent normal tissues reducing treatment-related side effects and may permit safe dose escalation. We have tested the effects on tumour control and side effects of escalating radiotherapy dose and investigated the appropriate target volume margin. After an initial 3 -6 month period of androgen suppression, 126 men were randomised and treated with radiotherapy using a 2 by 2 factorial trial design. The initial radiotherapy tumour target volume included the prostate and base of seminal vesicles (SV) or complete SV depending on SV involvement risk. Treatments were randomised to deliver a dose of 64 Gy with either a 1.0 or 1.5 cm margin around the tumour volume (1.0 and 1.5 cm margin groups) and also to treat either with or without a 10 Gy boost to the prostate alone with no additional margin (64 and 74 Gy groups). Tumour control was monitored by prostate-specific antigen (PSA) testing and clinical examination with additional tests as appropriate. Acute and late side effects of treatment were measured using the Radiation Treatment and Oncology Groups (RTOG) and LENT SOM systems. The results showed that freedom from PSA failure was higher in the 74 Gy group compared to the 64 Gy group, but this did not reach conventional levels of statistical significance with 5-year actuarial control rates of 71% (95% CI 58 -81%) in the 74 Gy group vs 59% (95% CI 45 -70%) in the 64 Gy group. There were 23 failures in the 74Gy group and 33 in the 64 Gy group (Hazard ratio 0.64, 95% CI 0.38 -1.10, P ¼ 0.10). No difference in disease control was seen between the 1.0 and 1.5 cm margin groups (5-year actuarial control rates 67%, 95% CI 53 -77% vs 63%, 95% CI 50 -74%) with 28 events in each group (Hazard ratio 0.97, 95% CI 0.50 -1.86, P ¼ 0.94). Acute side effects were generally mild and 18 weeks after treatment, only four and five of the 126 men had persistent XGrade 1 bowel or bladder side effects, respectively. Statistically significant increases in acute bladder side effects were seen after treatment in the men receiving 74 Gy (P ¼ 0.006), and increases in both acute bowel side effects during treatment (P ¼ 0.05) and acute bladder sequelae (P ¼ 0.002) were recorded for men in the 1.5 cm margin group. While statistically significant, these differences were of short duration and of doubtful clinical importance. Late bowel side effects (RTOGX2) were seen more commonly in the 74 Gy and 1.5 cm margin groups (P ¼ 0.02 and P ¼ 0.05, respectively) in the first 2 years after randomisation. Similar results were found using the LENT SOM assessments. No significant differences in late bladder side effects were seen between the randomised groups using the RTOG scoring system. Using the LENT SOM instrument, a higher proportion of men treated in the 74 Gy group had Grade X3 urinary frequency at 6 and 12 months. Compared to baseline scores, bladder symptoms improved after 6 months or more follow-up in all groups. Sexual function d...

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We tested the feasibility and toxicity of high activities Rhenium-186 hydroxyethylidene diphosphonate, with peripheral blood stem cell rescue in patients with progressive hormone refractory prostate cancer metastatic to bone. Twenty-five patients received between 2500 and 5000 MBq of Rhenium-186 hydroxyethylidene diphosphonate followed 14 days later by the return of peripheral blood peripheral blood stem cells. Activity limiting toxicity was defined as grade III haematological toxicity, lasting at least 7 days, or grade IV haematological toxicity of any duration or any serious unexpected toxicity. Activity limiting toxicity occurred in two of six who received activities of 5000 MBq and maximum tolerated activity was defined at this activity level. Prostate specific antigen reductions of 50% or more lasting at least 4 weeks were seen in five of the 25 patients (20%) all of whom received more than 3500 MBq of Rhenium-186 hydroxyethylidene diphosphonate. The actuarial survival at 1 year is 54%. Administered activities of 5000 MBq of Rhenium-186 hydroxyethylidene diphosphonate are feasible using autologous peripheral blood peripheral blood stem cell rescue in patients with progressive hormone refractory prostate cancer metastatic to bone. The main toxicity is thrombocytopaenia, which is short lasting. A statistically significant activity/prostate specific antigen response was seen. We have now commenced a Phase II trial to further evaluate response rates. Prostate cancer is becoming the most common cause of cancer death in males. Of patients who die from the condition, between 80 and 100% have bone metastases. Bone metastases frequently result in pain, pathological fracture, deformity and neurological deficit and have enormous social and economic implications. Most patients with bone metastases will initially respond to primary androgen deprivation therapy but the duration of this response is variable with a median of 18 months. Once this strategy has failed, second line treatments including corticosteroids, anti-androgens, diethylstilbesterol and cytotoxic chemotherapy including estramustine have only had limited success in preventing disease progression with short-lasting subjective responses in approximately 30% of cases (Dearnaley, 1994;Tannock et al, 1996;Pisters, 1999). The average survival in patients with hormone refractory prostate cancer metastatic to bone is in the order of 8 months (Fossa et al, 1992;Kelly et al, 1993;Sridhara et al, 1995;Small and Vogelzang, 1997). Radionuclides including strontium-89, rhenium-186 and samarium-153 have been used in the palliation of bone metastases in prostate cancer (Lewington et al, 1991;Porter et al, 1993;Quilty et al, 1994;Kolesnikov-Gauthier et al, 2000). Pain response occurs in about 70% of cases. A correlation between injected activity and rates of pain control in prostate cancer bone metastases have been demonstrated in radionuclide therapy with Strontium-89 (Mertens et al, 1993).Rhenium is a group VII metal with a similar labelling chemistry to Technetium. The ...

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