Prostate Cancer & CyberKnife

Professor Dr Eric Yeoh, Volunteer Clinical Oncologist

20th August 2018

Prof. Dr. Eric Yeoh

Radiotherapy and surgery (radical prostatectomy) are the only two treatments known to cure prostate cancer. Each treatment is associated with risks of long term side effects with the potential for impairing the quality of life of at least 50% of patients who can expect to survive 14 years after treatment (1).

Radiotherapy is the treatment of choice in older (≥ 70 years) patients and also in younger patients not fit for radical surgery (2). Despite technological advances including intensity modulated radiation therapy (IMRT), up to 65% of patients suffer chronic gastrointestinal symptoms such as urgency of defaecation and faecal incontinence (3). More recent advances in radiotherapy technology, involving image guidance by reducing the margins of uncertainty around the prostate target of irradiation between (inter-fractional) radiation treatment sessions have been reported to result in reduction of gastrointestinal symptoms following radiotherapy (4).

However, the prostate target of irradiation also moves during (intra-fractionally) each radiation treatment session and a margin of uncertainty has to factor into the radiation treatment plan, the size of which depends on the duration of each treatment session (5). With the increasing adoption of hypo-fractionated (larger, incremental radiation doses) radiotherapy based on clinical trial evidence that hypo-fractionated radiotherapy is comparable in efficacy if not superior to conventionally fractionated radiotherapy (6,7), management of intra-fractional movement of the prostate target becomes more important. This is because hypo-fractionated radiotherapy takes longer to deliver the prescribed dose at each treatment session compared with conventionally fractionated radiotherapy.

Real-time management of intra-fractional movement of the prostate involves implanting transponders or gold seed markers into the organ and imaging the prostate by ultrasound or kilo-voltage x-ray.

The CyberKnife solution installed at Mount Miriam Cancer Hospital, Penang comprises a computerized robotic arm with a 6 MV linear accelerator perpendicular to an x-ray system to track the prostate target in real-time. The continuous monitoring of the position of the prostate by the computer software maximizes radiation dose delivery to the prostate target whilst minimizing the radiation exposure of surrounding normal tissues such as the bowel and bladder.

Early results of a prospective clinical trial, based on observation of outcome measures of efficacy and toxicity of ~1800 patients in a multi-institutional registry for prostate cancer treated by  extreme hypo-fractionated (≤5 treatment sessions) radiotherapy (also known as stereotactic body radiation therapy,  SBRT or radiosurgery) are promising (8).

Figure 1. Actuarial biochemical relapse free survival stratified according to NCCN prostate cancer risk groups

At 2 years, overall biochemical relapse free survival was reported to be 92%. The data, stratified according to National Comprehensive Cancer Network (NCCN) prostate cancer risk groups (Figure 1), indicate a 2 year biochemical relapse free survival of 99%, 97% and 87% for low, intermediate and high risk groups respectively.

Patients experienced only mild (Grade1) acute (within 3 months of completion of treatment) urinary toxicity reflected in an increase of baseline mean International Prostate Symptom Score (IPSS) of 7 to 10 (Figure 2a) but no detectable acute bowel toxicity (Figure 2b).

Figure 2a. Median (blue) and mean (red) urinary quality of life based on the IPSS seven point scale as in legend below figure

There was no chronic (3 – 24 months of completion of treatment) Grade 3 urinary toxicity but one chronic Grade 3 bowel toxicity (rectal bleeding, Figure 2b)

No overall trend of reduction in sexual function (measured by International Index of Erectile Function IIEF-5 scores) was observed after treatment although only 55% of men >70 years of age were able to maintain erections sufficient for intercourse versus 80% of men < 70 years of age (Figure 2c).        

Figure 2b. Median (blue) and mean (red) bowel health inventory scores

Figure 2c. Sexual potency based on IIEF-5 five point scale in legend below figure for men < 70 (blue) and men >70 (red) years of age

Based on the promising data form this and other studies, the American Society for Radiation Oncology (ASTRO) released a policy statement supporting the use of SBRT or radiosurgery as an appropriate alternative to conventionally fractionated radiotherapy for low- to intermediate-risk prostate cancer.  Longer term (> median of 60 months) follow-up data to confirm the promising early results from observational studies supported by data from randomised trials are required before SBRT becomes the standard of care for external beam radiotherapy of prostate cancer.

References:

  1. Resnick MJ et al. Long term functional outcomes after treatment for localized prostate cancer. N Engl J Med 2013, 368:436-445.

  2. Jani AB & Hellman . Early prostate cancer: clinical decision making. Lancet 2003, 361:1045-1053.

  3. Smeenk RJ et al. Application of anorectal sparing devices in prostate radiotherapy. Radiother Oncol 2013, 106:155-156.

  4. Vargas C et al. Phase II dose escalation study of image-guided adaptive radiotherapy for prostate cancer: use of dose volume constraints to achieve rectal isotoxicity. Int J Radiat Oncol Biol Phys 2005, 63(1):141-149.

  5. Pang EPP et al. Analysis of intra-fraction prostate motion and derivation of duration dependent margins for radiotherapy using real time 4D ultrasound. Physics and Imaging in Radiation Oncology 2018, 5:102-107.

  6. Yeoh EE et al. Hypofractionated versus conventionally fractionated radiotherapy for prostate carcinoma: Final results of Phase III randomized trial. Int J Radiat Oncol Biol Phys 2011, 81:1271-1278.

  7. Dearnaley D et al. Conventional versus hypofractionated high-dose intensity-modulated radiotherapy for prostate carcinoma: 5 year outcomes of the randomized, non-inferiority phase 3 CHHiP trial. Lancet Oncol 2016, 17:1047-1060.

  8. Freeman D et al. Multi-institutional registry for prostate cancer radiosurgery: a prospective, observational clinical trial. Front Oncol 2015, Vol 4 Article 369:1-8.