New approaches for effective and safe pelvic radiotherapy in high-risk prostate cancer

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Abstract

Radical radiotherapy for prostate cancer offers excellent long-term outcomes for patients with high-risk disease. The increased risk of pelvic nodal involvement in this cohort has led to the development of whole-pelvis radiotherapy (WPRT) with a prostate boost. However, the use of WPRT remains controversial. Data are mixed, but advanced radiotherapy techniques enable delivery of increased radiation to pelvic nodes with acceptable levels of toxicity. Contemporary imaging modalities with increased sensitivity for detecting subclinical lymph node disease will facilitate selection of patients most likely to benefit from WPRT. Using such modalities for image guidance of advanced radiotherapy techniques could also permit high-dose delivery to nodes outside the conventional Radiation Therapy Oncology Group volumes, where magnetic resonance lymphography and single-photon-emission CT imaging have mapped a high frequency of microscopic disease. With increased toxicity a concern, an alternative to WPRT would be selective irradiation of target nodal groups most likely to harbour occult disease. New image-based ‘big data’ mining techniques enable the large-scale comparison of incidental dose distributions of thousands of patients treated in the past. By using novel computing methods and artificial intelligence, high-risk regions can be identified and used to optimize WPRT through refined knowledge of the likely location of subclinical disease.

Key points

  • Prophylactic pelvic nodal irradiation in patients with high-risk prostate cancer might improve clinical outcomes.

  • Negative results in clinical trials to date might be attributable to subtherapeutic radiation doses, inappropriate patient selection and suboptimal field size delineation.

  • Conformal radiotherapy techniques reduce incidental pelvic lymph node dose, increasing the potential utility of whole pelvis radiotherapy (WPRT) in the modern intensity-modulated radiotherapy era.

  • Contemporary imaging modalities with high sensitivity for the detection of occult lymph node metastases will improve patient selection for WPRT and guide appropriate target volume definition.

  • Advanced radiotherapy techniques will permit dose escalation to minimally positive nodal regions, both inside and outside of the standard Radiation Therapy Oncology Group target volumes.

  • Large-scale image-based data mining raises the possibility of selective irradiation of statistically identified high-risk nodal groups to improve the therapeutic ratio in WPRT.

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Fig. 1: Patterns of lymph node failure after prostate-only radiotherapy.
Fig. 2: Kaplan–Meier bPFS curves of intermediate and high-risk prostate cancer patients treated with EBRT and HDR brachytherapy.
Fig. 3: Potential radiotherapy clinical target volumes in high-risk prostate cancer.
Fig. 4: Image-based data mining infrastructure.

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Acknowledgements

H.T. is part funded by Prostate Cancer UK grant RIA-ST2-031. A.C. and M.V.H. are supported by the National Institute for Health Research (NIHR) Manchester Biomedical Research Centre.

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H.T. researched data for the article and wrote the manuscript. All authors made substantial contributions to discussions of content and reviewed and edited the manuscript before submission.

Correspondence to Hannah Tharmalingam.

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Nature Reviews Urology thanks C. Cozzarini and M. Roach III for their contribution to the peer review of this work.

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Glossary

Intensity-modulated radiotherapy

An advanced form of 3D radiotherapy that uses multiple narrow radiation beams of differing intensities aimed at the tumour from many angles to enable precise conformation of dose to the target.

Image-guided radiotherapy

The process of imaging during radiotherapy to ensure accuracy of treatment delivery and adherence to the actual radiation plan.

Propensity-score matched analyses

A statistical matching technique that estimates treatment effect by accounting for covariates that predict receipt of it, thereby attempting to reduce bias due to confounding factors.

High-dose rate (HDR) brachytherapy

A type of brachytherapy used in prostate cancer whereby a radioactive source is dispensed via a number of temporary catheters placed transperineally into the prostate to deliver radiation at a rapid rate of >12 Gy/h.

3D conformal radiotherapy

A type of radiotherapy that uses special imaging modalities to define the 3D shape of the tumour and computer-controlled planning techniques to conform the radiation beams to the target.

D33%

Mean radiation dose delivered to 33% of a defined target volume typically derived from a dose–volume histogram.

α/β ratio

A parameter derived from linear quadratic dose–response curves that determines the sensitivity of different types of tissue to radiation doses.

International Prostate Symptom Score

A validated self-assessment tool developed to measure lower urinary tract symptoms and health-related quality of life in patients with prostate disease.

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