RADICAL EXTERNAL BEAM RADIOTHERAPY

Management of localized prostate cancer: radical external beam radiotherapy (EBRT)
Since the early 1980s advances in radiotherapy for localized prostate cancer have included the advent of linear accelerators conformal and intensity-modulated techniques to minimize toxicity to the rectum and bladder. EBRT is administered with curative intent, often accompanied by 3 months of neoadjuvant hormone therapy in high-risk cases. A small, randomized study has demonstrated benefit in terms of progression and survival for patients treated with 6 months  (2 months each of neoadjuvant, concurrent, and adjuvant) androgen ablation, in addition to radiotherapy, compared with radiotherapy alone.

Indication
clinically localized prostate cancer, life expectancy >5 years. Patients with Gleason score 2 - 4 disease appear to do as well with WW as with any other treatment with 15-year follow-up.

Contraindications
- Severe lower urinary tract symptoms
- Inflammatory bowel disease
- Previous pelvic irradiation

Protocol
a 6-week course of daily treatments amounting to a dose of 60 - 72Gy.

Side-effects
- Transient moderate/severe filling-type LUTS (common, rarely permanent)
- Haematuria, contracted bladder: 4 - 23%
- Moderate to severe gastrointestinal symptoms, bloody diarrhoea, pain, rectal stenosis: 3 - 32%
- Erectile dysfunction (ED) gradually develops in 30 - 50%
- The risk of a second solid pelvic malignancy is estimated to be 1 in 300, falling to 1 in 70 long-term survivors.

Outcomes of EBRT
Definition of treatment failure: the ASTRO (American Society of Therapeutic Radiation Oncologists) definition is 3 consecutive PSA increases measured 4 months apart for 2 years, thereafter 6-monthly. Time to failure is midway through the 3 PSA measurements.
Pre-treatment prognostic factors: PSA, Gleason score, clinical stage, percentage of positive biopsies.
5-year PSA failure-free survival is
- 85% for low risk (T1 - 2a or PSA <10ng/ml or Gleason <7)
- 50% for intermediate risk (T2b or PSA 10 - 20 or Gleason 7)
- 33% for high risk (T2c or PSA >20ng/ml or Gleason 8 - 10)

Treatment of PSA relapse post-EBRT
Hormone therapy, either with anti-androgens or androgen deprivation, is currently the mainstay of treatment in this setting. However, local salvage treatment appears attractive, potentially offering another chance of cure if metastases cannot be demonstrated at repeat staging. Salvage radical prostatectomy is seldom undertaken because it is technically demanding, highly morbid, and outcomes are poor. Other local salvage treatments include cryotherapy and high-intensity focused ultrasound (HIFU), but outcomes data and access to these treatments are currently limited. If salvage local treatment is under consideration, repeat prostatic biopsies should be taken to demonstrate viable tumour cells. This should be at least 30 months post-EBRT, because fatally damaged cells may survive a few cell divisions.