Treatment planning and seed implantation for LDR brachytherapy is usually performed as a single day-case procedure. A general anaesthetic is preferred, although spinal anaesthesia is possible. Patients usually return to normal activities in a few days, but are advised to avoid close contact with pregnant women and young children for the first two months. Sexual intercourse may resume after a few weeks. Contraindications to radiotherapy are listed in Box 3 and side-effects and their management in Boxes 4,5, and 6.
Androgen deprivation therapy
ADT with neoadjuvant luteinising hormone releasing hormone (LHRH) agonists reduces the prostate volume and hence the volume of irradiated normal tissue. LHRH agonists reduce the non-cancerous gland size more than antiandrogen drugs such as bicalutamide.
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ADT also increases prostate cancer cell kill through the apoptotic effect of castration. Large meta-analyses have shown significant improvement in disease-free survival for intermediate- and high-risk patients treated with four months of neoadjuvant and concurrent ADT compared to EBRT alone.5,6 The benefit for low-risk patients was less clear. High-risk patients receiving a minimum two years of adjuvant ADT after radiotherapy gained a 20% increase in disease-free survival. This is the basis of the NICE recommendation of ADT with EBRT.1 There is no substantial evidence to support ADT/brachytherapy combinations.
Adjuvant and salvage treatment
Adjuvant radiotherapy is not recommended by NICE after prostatectomy, even when there are positive margins, but this remains controversial.7,8 Radical EBRT is recommended for a rising PSA after prostatectomy and early treatment seems to improve survival.9 The treatment of patients with a rising PSA following radiotherapy is individualised. Hormonal management is the mainstay of treatment because the disease is usually felt to be systemic, but in carefully selected cases there may be options for salvage surgery, brachytherapy, cryotherapy or high-intensity focused ultrasound. All salvage procedures carry a greater risk of complications.
Palliative radiotherapy
Approximately 70% to 80% of patients with painful bony metastases will obtain benefit from EBRT, generally without toxicity.10-12 A single fraction of 8Gy provides equal palliation to longer schedules, although the need for retreatment may be higher.13 Maximal pain relief may take several weeks to achieve. Retreatment is appropriate if good pain relief was achieved for a few months following initial treatment.
For patients experiencing widespread pain, a single fraction of hemibody radiotherapy can provide rapid palliation.14 Prostatic bony metastases are predominantly osteoblastic and systematic reviews of placebo-controlled trials have shown that a single radioisotope injection can provide pain relief.15,16 Strontium-89 is approved by NICE.1 The main side-effect is myelosuppression, so it should be avoided in patients likely to receive chemotherapy.
Compression of the spinal cord by expansion of vertebral metastases is commonly treated with EBRT. The neurological response is largely dictated by pretreatment muscle power. When compression results from fracture-related bony propulsion, a surgical approach is required.
EBRT to the prostate and bladder base can also successfully palliate haematuria and usually one to three fractions are given. Prophylactic irradiation of the breast buds may prevent gynaecomastia in patients starting long-term bicalutamide monotherapy or stilboestrol.17
For palliative treatments, a planning session is still required but is usually with conventional X-ray simulation and allows therapy to start within a week.
| Dr Jilly Maclean and Dr Daniel Smith are specialist registrars in clinical oncology and Dr P. Nicholas Plowman is consultant in clinical oncology, at St Bartholomew’s Hospital, London. Competing interests: None declared |
References
1. NICE. Guidance on prostate cancer: diagnosis and treatment. CG58. London, NICE, 2008 (accessed 30 July 2009).
2. Kupelian PA, Potters L, Khuntia D et al. Radical prostatectomy, external beam radiotherapy <72Gy, external beam radiotherapy > or =72Gy, permanent seed implantation, or combined seeds/external beam radiotherapy for stage T1-2 prostate cancer. Int J Radiat Oncol Biol Phys 2004;58:25-33.
3. Lawton CA, DeSilvio M, Roach IM et al. An update of the phase III trial comparing whole-pelvic (WP) to prostate only (PO) radiotherapy and neoadjuvant to adjuvant total androgen suppression (TAS): updated analysis of RTOG 94-13. 47th Annual ASTRO Meeting. Int J Radiat Oncol Biol Phys 2005;63:S19.
4. Dearnaley DP, Sydes MR, Graham JD et al. Escalated-dose versus standard-dose conformal radiotherapy in prostate cancer: first results from the MRC RT01 randomised controlled trial. Lancet Oncol 2007;8:475-87.
5. Roach M, Lu J, Pilepich MV et al. Predicting long-term survival, and the need for hormonal therapy: a meta-analysis of RTOG prostate cancer trials. Int J Radiat Oncol Biol Phys 2000;47:617.
6. Kumar S, Shelley M, Harrison C et al. Neo-adjuvant and adjuvant hormone therapy for localised and locally advanced prostate cancer. Cochrane Database Syst Rev 2006, Issue 4. Art No: CD006019. DOI: 10.1002/14651858.CD006019.pub2.
7. Bolla M, Van PH, Collette L et al. Postoperative radiotherapy after radical prostatectomy: a randomised controlled trial (EORTC trial 22911). Lancet 2005;366:572-8.
8. Thompson IM, Tangen CM, Paradelo J et al. Adjuvant radiotherapy for pathologically advanced prostate cancer: a randomized clinical trial. JAMA 2006;296:2329-35.
9. Macdonald OK, Schild SE, Vora S et al. Salvage radiotherapy for men with isolated rising PSA or locally palpable recurrence after radical prostatectomy: do outcomes differ? Urology 2004;64:760-4.
10. Nielsen OS. Palliative radiotherapy of bone metastases: there is now evidence for the use of single fractions. Radiother Oncol 1999;52:95.
11. Berk L. Prospective trials for the radiotherapeutic treatment of bone metastases. Am J Hosp Pall Care 1995;12:24-8.
12. Arcangeli G, Giovinazzo G, Saracino D et al. Radiation therapy in the management of symptomatic bone metastases: the effect of total dose and histology on pain relief and response duration. Int J Radiat Oncol Biol Phys 1998;42:1119-26.
13. Chow E, Harris K, Fan G et al. Palliative radiotherapy trials for bone metastases: a systematic review. J Clin Oncol 2007;25:1423-36.
14. Salazar OM, Sandhu T, da Motta NW et al. Fractionated half-body irradiation (HBI) for the rapid palliation of widespread, symptomatic metastatic bone disease: a randomised phase III trial of the International Atomic Energy Agency (IAEA). Int J Radiat Oncol Biol Phys 2001;50:765-75.
15. Roque i Figuls M, Martinez-Zapata MJ, Alonso-Coello P et al. Radioisotopes for metastatic bone pain. Cochrane Database Syst Rev 2003, Issue 4. Art No: CD003347. DOI: 10.1002/14651858.CD003347.
16. Finlay OG, Mason MD, Shelley M. Radioisotopes for the palliation of metastatic bone cancer: a systematic review. Lancet Oncol 2005;6:392-400.
17. Di Lorenzo G, Autorino R, Perdona S et al. Management of gynaecomastia in patients with prostate cancer: a systematic review. Lancet Oncol 2005;6:972-9.
18. Greene FL, Page DL, Fleming ID et al (editors). AJCC (American Joint Committee on Cancer) Cancer Staging Manual (sixth edition). New York, Springer-Verlag, 2002.
Originally published in the September 2009 edition of MIMS Oncology & Palliative Care.
