From radiobiology to technology: what is changing in radiotherapy for prostate cancer

Abstract

In the last decades, new technologies have been introduced in the daily clinical practice of the radiation oncologist: 3D-Conformal radiotherapy (RT) became almost universally available, thereafter, intensity modulated RT (IMRT) gained large diffusion, due to its potential impact in improving the clinical outcomes, and more recently, helical and volumetric arc IMRT with image-guided RT are becoming more and more diffused and used for prostate cancer patients. The conventional dose-fractionation results to be the best compromise between the efficacy and the safety of the treatment, but combining new techniques, modern RT allows to overcame one of the major limits of the ‘older’ RT: the impossibility of delivering higher total doses and/or high dose/fraction. The evidences regarding radiobiology, clinical and technological evolution of RT in prostate cancer have been reported and discussed.

Keywords::

• outcome
• prostate cancer
• radiobiology
• radiotherapy
• technique
• technology

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• External beam radiation therapy is now considered a standard of care and a curative therapeutic modality for prostate cancer patients, but in the last decades, new technologies have been introduced in daily clinical practice: intensity modulated radiation therapy; image-guided radiation therapy; stereotactic body radiation therapy (SBRT).

• Presently, intensity modulated radiation therapy is recommended over 3D-Conformal radiation therapy for the treatment of localized prostate cancer with radical intent whenever dose escalation is considered suitable. In this context, image-guided radiation therapy systems are extremely helpful.

• The α/β ratio represents the radiobiological parameter explaining how normal and cancer tissues would respond to different radiation schedules. Several reviews estimated an average α/β ratio of 1.5–2 Gy for prostate cancer versus 3 Gy for rectal late effects, suggesting that prostate cancer cells have high sensitivity to dose per fraction respect to rectal tissue.

• Hypofractionation (from mild to extreme) could improve the therapeutic index of radiotherapy in prostate cancer, with optimal local control rates without higher side effects to surrounding late-responding healthy tissues.

• All trials confirmed that moderate hypofractionation for prostate cancer does not increase treatment-related toxic effects or decrease efficacy.

• SBRT is a novel treatment modality to deliver an ‘extreme hypofractionation’ (few fractions, usually 4–5, of very large dose/fraction, usually 7–8 Gy), allowing a reduction in the overall treatment time and, potentially, an increase of the favorable therapeutic ratio offered by the low α/β ratio of prostate cancer.

• The premature results of SBRT trials, although associated with good treatment tolerance, excellent early biochemical outcomes and low late toxicity rates, do not lead to any definitive conclusions.

• To date, although several technical, clinical and anatomical issues, studies on reirradiation for intraprostatic recurrent prostate cancer have been reported using brachytherapy or SBRT.