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  • Review Article
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Evolution of advanced technologies in prostate cancer radiotherapy

Abstract

Conventional treatment options for clinically localized, low-risk prostate cancer include radical prostatectomy, external-beam radiotherapy (EBRT) and low-dose-rate brachytherapy. Advances in image-guided radiotherapy (IGRT) since the 1980s, the development of intensity-modulated radiotherapy (IMRT) during the 1990s and evidence from radiobiological models—which support the use of high doses per fraction—have developed alongside novel advanced radiotherapy modalities that include high-dose-rate brachytherapy (HDR-BT), stereotactic body radiotherapy (SBRT) and proton beam therapy. The relationship between the outcomes of and toxicities experienced by patients with prostate cancer treated with HDR-BT, SBRT and particle-beam therapy should provide urologists and oncologists an understanding of the continually evolving technology in prostate radiotherapy. On the basis of published evidence, conventionally fractionated EBRT with IMRT is considered the standard of care over conventional 3D conformal radiotherapy, whereas HDR-BT boost is an acceptable treatment option for selected patients with intermediate-risk and high-risk prostate cancer. SBRT and proton therapy should not be used for patients (regardless of disease risk group) outside the setting of a clinical trial. Finally, comparative effectiveness research should be conducted to provide a framework for evaluating advanced radiotherapy technologies by comparing the benefits and harms of available therapeutic options to optimize the risk:benefit ratio and improve cost effectiveness.

Key Points

  • Image-guided radiotherapy and intensity-modulated radiotherapy have been important in the development of novel radiotherapy modalities

  • Similarly, radiobiological models, which support high dose per fraction delivery, have been critical for the introduction and evolution of high-dose-rate brachytherapy (HDR-BT), stereotactic body radiotherapy (SBRT) and proton beam therapy

  • HDR-BT boost is a relatively well-established advanced radiotherapy modality that is suitable for certain patients with intermediate-risk and high-risk prostate cancer

  • Patients of all risk groups can be offered SBRT and proton beam therapy, but only in the setting of a clinical trial because, to date, high-level evidence of efficacy and safety are lacking

  • Comparative effectiveness research will provide a framework for evaluating advanced radiotherapy technologies by comparing the benefits and harms of the available options to optimize the risk:benefit ratio and improve cost effectiveness

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Figure 1: Dose fractionation in advanced radiotherapy techniques.
Figure 2: The timeline and cooperation of radiotherapy advances.
Figure 3: A plot of BED curves for α:β ratios of 1.5–10 for several radiotherapy schedules.

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References

  1. Center, M. M. et al. International variation in prostate cancer incidence and mortality rates. Eur. Urol. 61, 1079–1092 (2012).

    PubMed  Google Scholar 

  2. Cahlon, O. et al. Ultra-high dose (86.4 Gy) IMRT for localized prostate cancer: toxicity and biochemical outcomes. Int. J. Radiat. Oncol. Biol. Phys. 71, 330–337 (2008).

    Article  CAS  PubMed  Google Scholar 

  3. Budiharto, T., Haustermans, K. & Kovacs, G. External beam radiotherapy for prostate cancer. J. Endourol. 24, 781–789 (2010).

    Article  PubMed  Google Scholar 

  4. Kao, J., Cesaretti, J. A., Stone, N. N. & Stock, R. G. Update on prostate brachytherapy: long-term outcomes and treatment-related morbidity. Curr. Urol. Rep. 12, 237–242 (2011).

    Article  PubMed  Google Scholar 

  5. Button, M. R. & Staffurth, J. N. Clinical application of image-guided radiotherapy in bladder and prostate cancer. Clin. Oncol. (R. Coll. Radiol.) 22, 698–706 (2010).

    Article  CAS  Google Scholar 

  6. Stephans, K. L., Xia, P., Tendulkar, R. D. & Ciezki, J. P. The current status of image-guided external beam radiotherapy for prostate cancer. Curr. Opin. Urol. 20, 223–228 (2010).

    Article  PubMed  Google Scholar 

  7. van Herk, M. Different styles of image-guided radiotherapy. Semin. Radiat. Oncol. 17, 258–267 (2007).

    Article  PubMed  Google Scholar 

  8. Hartford, A. C. et al. American Society for Therapeutic Radiology and Oncology (ASTRO) and American College of Radiology (ACR) Practice Guidelines for Intensity-Modulated Radiation Therapy (IMRT). Int. J. Radiat. Oncol. Biol. Phys. 73, 9–14 (2009).

    Article  PubMed  Google Scholar 

  9. Hummel, S., Simpson, E. L., Hemingway, P., Stevenson, M. D. & Rees, A. Intensity-modulated radiotherapy for the treatment of prostate cancer: a systematic review and economic evaluation. Health Technol. Assess. 14, 1–108, iii–iv (2010).

    Article  CAS  PubMed  Google Scholar 

  10. Bauman, G., Rumble, R. B., Chen, J., Loblaw, A. & Warde, P. Intensity-modulated radiotherapy in the treatment of prostate cancer. Clin. Oncol. (R. Coll. Radiol.) 24, 461–473 (2012).

    Article  CAS  Google Scholar 

  11. Fowler, J., Chappell, R. & Ritter, M. Is α/β for prostate tumors really low? Int. J. Radiat. Oncol. Biol. Phys. 50, 1021–1031 (2001).

    Article  CAS  PubMed  Google Scholar 

  12. Mohler, J. L. The 2010 NCCN clinical practice guidelines in oncology on prostate cancer. J. Natl Compr. Canc. Netw. 8, 145 (2010).

    Article  PubMed  Google Scholar 

  13. Zaorsky, N. G., Trabulsi, E. J., Lin, J. & Den, R. B. Multimodality therapy for patients with high-risk prostate cancer: current status and future directions. Semin. Oncol. 40, 308–321 (2013).

    Article  PubMed  Google Scholar 

  14. Grimm, P. et al. Comparative analysis of prostate-specific antigen free survival outcomes for patients with low, intermediate and high risk prostate cancer treatment by radical therapy. Results from the Prostate Cancer Results Study Group. BJU Int. 109 (Suppl. 1), 22–29 (2012).

    Article  PubMed  Google Scholar 

  15. Dandapani, S. V. & Sanda, M. G. Measuring health-related quality of life consequences from primary treatment for early-stage prostate cancer. Semin. Radiat. Oncol. 18, 67–72 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  16. Graf, R., Boehmer, D., Budach, V. & Wust, P. Interfraction rotation of the prostate as evaluated by kilovoltage X-ray fiducial marker imaging in intensity-modulated radiotherapy of localized prostate cancer. Med. Dosim. 37, 396–400 (2012).

    Article  PubMed  Google Scholar 

  17. Owen, R. et al. Interfraction prostate rotation determined from in-room computerized tomography images. Med. Dosim. 36, 188–194 (2011).

    Article  PubMed  Google Scholar 

  18. Li, J. S. et al. Gains from real-time tracking of prostate motion during external beam radiation therapy. Int. J. Radiat. Oncol. Biol. Phys. 75, 1613–1620 (2009).

    Article  PubMed  Google Scholar 

  19. Litzenberg, D. W. et al. Prostate intrafraction translation margins for real-time monitoring and correction strategies. Prostate Cancer 2012, 130579 (2012).

    Article  PubMed  Google Scholar 

  20. Amro, H. et al. The dosimetric impact of prostate rotations during electromagnetically guided external-beam radiation therapy. Int. J. Radiat. Oncol. Biol. Phys. 85, 230–236 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  21. Peng, C. et al. Characterizing interfraction variations and their dosimetric effects in prostate cancer radiotherapy. Int. J. Radiat. Oncol. Biol. Phys. 79, 909–914 (2011).

    Article  PubMed  Google Scholar 

  22. Zelefsky, M. J. et al. Improved clinical outcomes with high-dose image guided radiotherapy compared with non-IGRT for the treatment of clinically localized prostate cancer. Int. J. Radiat. Oncol. Biol. Phys. 84, 125–129 (2012).

    Article  PubMed  Google Scholar 

  23. Heemsbergen, W. D. et al. Increased risk of biochemical and clinical failure for prostate patients with a large rectum at radiotherapy planning: results from the Dutch trial of 68 Gy versus 78 Gy. Int. J. Radiat. Oncol. Biol. Phys. 67, 1418–1424 (2007).

    Article  CAS  PubMed  Google Scholar 

  24. de Crevoisier, R. et al. Increased risk of biochemical and local failure in patients with distended rectum on the planning CT for prostate cancer radiotherapy. Int. J. Radiat. Oncol. Biol. Phys. 62, 965–973 (2005).

    Article  PubMed  Google Scholar 

  25. Song, W. Y., Schaly, B., Bauman, G., Battista, J. J. & Van Dyk, J. Evaluation of image-guided radiation therapy (IGRT) technologies and their impact on the outcomes of hypofractionated prostate cancer treatments: a radiobiologic analysis. Int. J. Radiat. Oncol. Biol. Phys. 64, 289–300 (2006).

    Article  PubMed  Google Scholar 

  26. Ost, P. et al. A comparison of the acute toxicity profile between two-dimensional and three-dimensional image-guided radiotherapy for postoperative prostate cancer. Clin. Oncol. (R. Coll. Radiol.) 23, 344–349 (2011).

    Article  CAS  Google Scholar 

  27. Albert, J. M. et al. Magnetic resonance imaging-based treatment planning for prostate brachytherapy. Brachytherapy 12, 30–37 (2013).

    Article  PubMed  Google Scholar 

  28. Hanks, G. E. External-beam radiation therapy for clinically localized prostate cancer: patterns of care studies in the United States. NCI Monogr. 7, 75–84 (1988).

    Google Scholar 

  29. Kuban, D. A. et al. Long-term results of the MD Anderson randomized dose-escalation trial for prostate cancer. Int. J. Radiat. Oncol. Biol. Phys. 70, 67–74 (2008).

    Article  PubMed  Google Scholar 

  30. Al-Mamgani, A. et al. Update of Dutch multicenter dose-escalation trial of radiotherapy for localized prostate cancer. Int. J. Radiat. Oncol. Biol. Phys. 72, 980–988 (2008).

    Article  PubMed  Google Scholar 

  31. Zietman, A. L. et al. Comparison of conventional-dose vs high-dose conformal radiation therapy in clinically localized adenocarcinoma of the prostate: a randomized controlled trial. JAMA 294, 1233–1239 (2005).

    Article  CAS  PubMed  Google Scholar 

  32. Zietman, A. L. et al. Randomized trial comparing conventional-dose with high-dose conformal radiation therpay in early-stage adenocarcinoma of the prostate: long-term results from Proton Radiation Oncology Group/American College of Radiology 95–09. J. Clin. Oncol. 28, 1106–1111 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  33. Dearnaley, D. P. et al. Escalated-dose versus standard-dose conformal radiotherapy in prostate cancer: first results from the MRC RT01 randomised controlled trial. Lancet Oncol. 8, 475–487 (2007).

    Article  PubMed  Google Scholar 

  34. Yoshimura, K. et al. Health-related quality-of-life after external beam radiation therapy for localized prostate cancer: intensity-modulated radiation therapy versus conformal radiation therapy. Prostate Cancer Prostatic Dis. 10, 288–292 (2007).

    Article  CAS  PubMed  Google Scholar 

  35. Namiki, S. et al. Five-year follow-up of health-related quality of life after intensity-modulated radiation therapy for prostate cancer. Jpn J. Clin. Oncol. 39, 732–738 (2009).

    Article  PubMed  Google Scholar 

  36. Galalae, R. M. et al. Health-related quality of life measurement in long-term survivors and outcome following radical radiotherapy for localized prostate cancer. Strahlenther. Onkol. 180, 582–589 (2004).

    Article  PubMed  Google Scholar 

  37. Kleinmann, N. et al. The effect of ethnicity and sexual preference on prostate-cancer-related quality of life. Nat. Rev. Urol. 9, 258–265 (2012).

    Article  PubMed  Google Scholar 

  38. Sheets, N. C. et al. Intensity-modulated radiation therapy, proton therapy, or conformal radiation therapy and morbidity and disease control in localized prostate cancer. JAMA 307, 1611–1620 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Bekelman, J. E. et al. Outcomes after intensity-modulated versus conformal radiotherapy in older men with nonmetastatic prostate cancer. Int. J. Radiat. Oncol. Biol. Phys. 81, e325–e334 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  40. Gray, P. J. et al. Patient-reported outcomes after 3-dimensional conformal, intensity-modulated, or proton beam radiotherapy for localized prostate cancer. Cancer 119, 1729–1735 (2013).

    Article  PubMed  Google Scholar 

  41. Fowler, J. F., Ritter, M. A., Chappell, R. J. & Brenner, D. J. What hypofractionated protocols should be tested for prostate cancer? Int. J. Radiat. Oncol. Biol. Phys. 56, 1093–1104 (2003).

    Article  PubMed  Google Scholar 

  42. Brenner, D. J. et al. Direct evidence that prostate tumors show high sensitivity to fractionation (low α/β ratio), similar to late-responding normal tissue. Int. J. Radiat. Oncol. Biol. Phys. 52, 6–13 (2002).

    Article  PubMed  Google Scholar 

  43. Park, C., Papiez, L., Zhang, S., Story, M. & Timmerman, R. D. Universal survival curve and single fraction equivalent dose: useful tools in understanding potency of ablative radiotherapy. Int. J. Radiat. Oncol. Biol. Phys. 70, 847–852 (2008).

    Article  PubMed  Google Scholar 

  44. Tree, A. C., Alexander, E. J., Van As, N. J., Dearnaley, D. P. & Khoo, V. Biological dose escalation and hypofractionation: what is there to be gained and how will it best be done? Clin. Oncol. (R. Coll. Radiol.) 25, 483–498 (2013).

    Article  CAS  Google Scholar 

  45. Viani, G. A., Stefano, E. J. & Afonso, S. L. Higher-than-conventional radiation doses in localized prostate cancer treatment: a meta-analysis of randomized, controlled trials. Int. J. Radiat. Oncol. Biol. Phys. 74, 1405–1418 (2009).

    Article  PubMed  Google Scholar 

  46. Zelefsky, M. J. et al. Dose escalation for prostate cancer radiotherapy: predictors of long-term biochemical tumor control and distant metastases-free survival outcomes. Eur. Urol. 60, 1133–1139 (2011).

    Article  PubMed  Google Scholar 

  47. Martinez, A. A. et al. Dose escalation improves cancer-related events at 10 years for intermediate- and high-risk prostate cancer patients treated with hypofractionated high-dose-rate boost and external beam radiotherapy. Int. J. Radiat. Oncol. Biol. Phys. 79, 363–370 (2011).

    Article  PubMed  Google Scholar 

  48. Heysek, R. V. Modern brachytherapy for treatment of prostate cancer. Cancer Control 14, 238–243 (2007).

    Article  PubMed  Google Scholar 

  49. Glasgow, G. P., Bourland, J. D., Grigsby, P. W., Meli, J. A. & Weaver, K. A. Remote Afterloading Technology 1–29 (American Association of Physicists in Medicine, 1993).

    Google Scholar 

  50. Yamada, Y. et al. American Brachytherapy Society consensus guidelines for high-dose-rate prostate brachytherapy. Brachytherapy 11, 20–32 (2012).

    Article  PubMed  Google Scholar 

  51. Knaup, C. et al. Investigating the dosimetric and tumor control consequences of prostate seed loss and migration. Med. Phys. 39, 3291–3298 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  52. Yoshioka, Y. Current status and perspectives of brachytherapy for prostate cancer. Int. J. Clin. Oncol. 14, 31–36 (2009).

    Article  PubMed  Google Scholar 

  53. Zaorsky, N. G., Doyle, L. A., Hurwitz, M. D., Dicker, A. P. & Den, R. B. Do theoretical potential and advanced technology justify the use of high dose rate brachytherapy as monotherapy for prostate cancer? Expert Rev. Anticancer Ther. (in press).

  54. Demanes, D. J., Rodriguez, R. R., Schour, L., Brandt, D. & Altieri, G. High-dose-rate intensity-modulated brachytherapy with external beam radiotherapy for prostate cancer: California endocurietherapy's 10-year results. Int. J. Radiat. Oncol. Biol. Phys. 61, 1306–1316 (2005).

    Article  PubMed  Google Scholar 

  55. Hoskin, P. J. et al. Randomised trial of external beam radiotherapy alone or combined with high-dose-rate brachytherapy boost for localised prostate cancer. Radiother. Oncol. 103, 217–222 (2012).

    Article  PubMed  Google Scholar 

  56. Duchesne, G. M., Williams, S. G., Das, R. & Tai, K. H. Patterns of toxicity following high-dose-rate brachytherapy boost for prostate cancer: mature prospective phase I/II study results. Radiother. Oncol. 84, 128–134 (2007).

    Article  PubMed  Google Scholar 

  57. Demanes, D. J., Brandt, D., Schour, L. & Hill, D. R. Excellent results from high dose rate brachytherapy and external beam for prostate cancer are not improved by androgen deprivation. Am. J. Clin. Oncol. 32, 342–347 (2009).

    Article  PubMed  Google Scholar 

  58. Kalkner, K. M. et al. Clinical outcome in patients with prostate cancer treated with external beam radiotherapy and high dose-rate iridium 192 brachytherapy boost: a 6-year follow-up. Acta Oncol. 46, 909–917 (2007).

    Article  PubMed  Google Scholar 

  59. Galalae, R. M. et al. Hypofractionated conformal HDR brachytherapy in hormone naive men with localized prostate cancer. Is escalation to very high biologically equivalent dose beneficial in all prognostic risk groups? Strahlenther. Onkol. 182, 135–141 (2006).

    Article  PubMed  Google Scholar 

  60. Demanes, D. J. et al. High-dose-rate monotherapy: safe and effective brachytherapy for patients with localized prostate cancer. Int. J. Radiat. Oncol. Biol. Phys. 81, 1286–1292 (2011).

    Article  PubMed  Google Scholar 

  61. Tang, J. I., Williams, S. G., Tai, K. H., Dean, J. & Duchesne, G. M. A prospective dose escalation trial of high-dose-rate brachytherapy boost for prostate cancer: evidence of hypofractionation efficacy? Brachytherapy 5, 256–261 (2006).

    Article  PubMed  Google Scholar 

  62. Vargas, C. E. et al. High-dose irradiation for prostate cancer via a high-dose-rate brachytherapy boost: results of a phase I to II study. Int. J. Radiat. Oncol. Biol. Phys. 66, 416–423 (2006).

    Article  PubMed  Google Scholar 

  63. Martinez, A. et al. Conformal high dose rate brachytherapy improves biochemical control and cause specific survival in patients with prostate cancer and poor prognostic factors. J. Urol. 169, 974–979; discussion 979–980 (2003).

    Article  PubMed  Google Scholar 

  64. Martinez, A. A. et al. High-dose-rate prostate brachytherapy: an excellent accelerated-hypofractionated treatment for favorable prostate cancer. Am. J. Clin. Oncol. 33, 481–488 (2010).

    Article  PubMed  Google Scholar 

  65. Yamoah, K., Stone, N. & Stock, R. Impact of race on biochemical disease recurrence after prostate brachytherapy. Cancer 117, 5589–5600 (2011).

    Article  PubMed  Google Scholar 

  66. Myers, M. A. et al. Phase I/II trial of single-fraction high-dose-rate brachytherapy-boosted hypofractionated intensity-modulated radiation therapy for localized adenocarcinoma of the prostate. Brachytherapy 11, 292–298 (2012).

    Article  PubMed  Google Scholar 

  67. Zwahlen, D. R. et al. The use of photon beams of a flattening filter-free linear accelerator for hypofractionated volumetric modulated arc therapy in localized prostate cancer. Int. J. Radiat. Oncol. Biol. Phys. 83, 1655–1660 (2012).

    Article  PubMed  Google Scholar 

  68. Klayton, T. et al. Prostate bed motion during intensity-modulated radiotherapy treatment. Int. J. Radiat. Oncol. Biol. Phys. 84, 130–136 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  69. Zaorsky, N. G., Ohri, N., Showalter, T. N., Dicker, A. P. & Den, R. B. Systematic review of hypofractionated radiation therapy for prostate cancer. Cancer Treat. Rev. 9, 728–736 (2013).

    Article  Google Scholar 

  70. Oliveira, S. M., Teixeira, N. J. & Fernandes, L. What do we know about the α/β for prostate cancer? Med. Phys. 39, 3189–3201 (2012).

    Article  CAS  PubMed  Google Scholar 

  71. Lee, W. R. Extreme hypofractionation for prostate cancer. Expert Rev. Anticancer Ther. 9, 61–65 (2009).

    Article  CAS  PubMed  Google Scholar 

  72. Zaorsky, N. G., Studenski, M. T., Dicker, A. P., Gomella, L. & Den, R. B. Stereotactic body radiation therapy for prostate cancer: is the technology ready to be the standard of care? Cancer Treat. Rev. 39, 212–218 (2013).

    Article  PubMed  Google Scholar 

  73. McBride, S. M. et al. Hypofractionated stereotactic body radiotherapy in low-risk prostate adenocarcinoma: preliminary results of a multi-institutional phase 1 feasibility trial. Cancer 118, 3681–3690 (2012).

    Article  PubMed  Google Scholar 

  74. Madsen, B. L. et al. Stereotactic hypofractionated accurate radiotherapy of the prostate (SHARP), 33.5 Gy in five fractions for localized disease: first clinical trial results. Int. J. Radiat. Oncol. Biol. Phys. 67, 1099–1105 (2007).

    Article  PubMed  Google Scholar 

  75. Katz, A. J., Santoro, M., DiBlasio, F. & Ashley, R. Stereotactic body radiation therapy for low, intermediate, and high-risk prostate cancer: disease control and quality of life. Int. J. Radiat. Oncol. 81, S100–S100 (2011).

    Article  Google Scholar 

  76. Katz, A. J., Santoro, M., Ashley, R., Diblasio, F. & Witten, M. Stereotactic body radiotherapy as boost for organ-confined prostate cancer. Technol. Cancer Res. Treat. 9, 575–582 (2010).

    Article  PubMed  Google Scholar 

  77. King, C. R., Brooks, J. D., Gill, H. & Presti, J. C. Jr. Long-term outcomes from a prospective trial of stereotactic body radiotherapy for low-risk prostate cancer. Int. J. Radiat. Oncol. Biol. Phys. 82, 877–882 (2012).

    Article  PubMed  Google Scholar 

  78. Mantz, C. A., Fernandez, E., Zucker, I. & Harrison, S. A Phase II trial of real-time target tracking SBRT for low-risk prostate cancer utilizing the Calypso 4D localization system: patient-reported quality of life and toxicity outcomes [abstract 199]. Int. J. Radiat. Oncol. Biol. Phys. 81 (Suppl.), S100 (2011).

    Article  Google Scholar 

  79. Boike, T. P. et al. Phase I dose-escalation study of stereotactic body radiation therapy for low- and intermediate-risk prostate cancer. J. Clin. Oncol. 29, 2020–2026 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  80. Tang, C. I. et al. Phase I/II study of a five-fraction hypofractionated accelerated radiotherapy treatment for low-risk localised prostate cancer: early results of pHART3. Clin. Oncol. (R. Coll. Radiol.) 20, 729–737 (2008).

    Article  CAS  Google Scholar 

  81. Quon, H. et al. Phase II study of a five-fraction hypofractionated accelerated radiotherapy treatment for low-risk localized prostate cancer: Toxicity results of pHART3 [abstract 48]. ASCO 2010 Genitourinary Cancers Symposium (San Francisco, CA, 2010).

  82. Ritter, M. Rationale, conduct, and outcome using hypofractionated radiotherapy in prostate cancer. Semin. Radiat. Oncol. 18, 249–256 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  83. Wennberg, B. & Lax, I. The impact of fractionation in SBRT: analysis with the linear quadratic model and the universal survival curve model. Acta Oncol. 52, 902–909 (2013).

    Article  PubMed  Google Scholar 

  84. Hossain, S. et al. Simulated real time image guided intrafraction tracking-delivery for hypofractionated prostate IMRT. Med. Phys. 35, 4041–4048 (2008).

    Article  PubMed  Google Scholar 

  85. Wilson, R. R. Radiological use of fast protons. Radiology 47, 487–491 (1946).

    Article  CAS  PubMed  Google Scholar 

  86. Coen, J. J. et al. Long-term quality of life outcome after proton beam monotherapy for localized prostate cancer. Int. J. Radiat. Oncol. Biol. Phys. 82, e201–e209 (2012).

    Article  PubMed  Google Scholar 

  87. Shipley, W. U. et al. Advanced prostate cancer: The results of a randomized comparative trial of high dose irradiation boosting with conformal protons compared with conventional dose irradiation using photons alone. Int. J. Radiat. Oncol. 32, 3–12 (1995).

    Article  CAS  Google Scholar 

  88. Mendenhall, N. P. et al. Early outcomes from three prospective trials of image-guided proton therapy for prostate cancer. Int. J. Radiat. Oncol. Biol. Phys. 82, 213–221 (2012).

    Article  PubMed  Google Scholar 

  89. Yonemoto, L. T. et al. Combined proton and photon conformal radiation therapy for locally advanced carcinoma of the prostate: preliminary results of a phase I/II study. Int. J. Radiat. Oncol. Biol. Phys. 37, 21–29 (1997).

    Article  CAS  PubMed  Google Scholar 

  90. Kim, S. et al. Late gastrointestinal toxicities following radiation therapy for prostate cancer. Eur. Urol. 60, 908–916 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  91. Forman, J. D. & Porter, A. T. The experience with neutron irradiation in locally advanced adenocarcinoma of the prostate. Semin. Urol. Oncol. 15, 239–243 (1997).

    CAS  PubMed  Google Scholar 

  92. Laramore, G. E. et al. Fast neutron radiotherapy for locally advanced prostate cancer. Final report of Radiation Therapy Oncology Group randomized clinical trial. Am. J. Clin. Oncol. 16, 164–167 (1993).

    Article  CAS  PubMed  Google Scholar 

  93. Akakura, K. et al. Phase I/II clinical trials of carbon ion therapy for prostate cancer. Prostate 58, 252–258 (2004).

    Article  CAS  PubMed  Google Scholar 

  94. Tsuji, H. et al. Hypofractionated radiotherapy with carbon ion beams for prostate cancer. Int. J. Radiat. Oncol. Biol. Phys. 63, 1153–1160 (2005).

    Article  PubMed  Google Scholar 

  95. Ishikawa, H. et al. Carbon ion radiation therapy for prostate cancer: results of a prospective phase II study. Radiother. Oncol. 81, 57–64 (2006).

    Article  PubMed  Google Scholar 

  96. Ishikawa, H. et al. Carbon-ion radiation therapy for prostate cancer. Int. J. Urol. 19, 296–305 (2012).

    Article  PubMed  Google Scholar 

  97. Efstathiou, J. A., Gray, P. J. & Zietman, A. L. Proton beam therapy and localised prostate cancer: current status and controversies. Br. J. Cancer 108, 1225–1230 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. MacDonald, S. M. et al. Proton radiotherapy for childhood ependymoma: initial clinical outcomes and dose comparisons. Int. J. Radiat. Oncol. Biol. Phys. 71, 979–986 (2008).

    Article  PubMed  Google Scholar 

  99. Childs, S. K. et al. Proton radiotherapy for parameningeal rhabdomyosarcoma: clinical outcomes and late effects. Int. J. Radiat. Oncol. Biol. Phys. 82, 635–642 (2012).

    Article  PubMed  Google Scholar 

  100. Miralbell, R., Lomax, A., Cella, L. & Schneider, U. Potential reduction of the incidence of radiation-induced second cancers by using proton beams in the treatment of pediatric tumors. Int. J. Radiat. Oncol. Biol. Phys. 54, 824–829 (2002).

    Article  PubMed  Google Scholar 

  101. Shah, A., Paly, J. J., Efstathiou, J. A. & Bekelman, J. E. Physician evaluation of internet health information on proton therapy for prostate cancer. Int. J. Radiat. Oncol. Biol. Phys. 85, e173–e177 (2013).

    Article  PubMed  Google Scholar 

  102. US National Library of Medicine. ClinicalTrials.gov [online], (2013).

  103. Zietman, A., Goitein, M. & Tepper, J. E. Technology evolution: is it survival of the fittest? J. Clin. Oncol. 28, 4275–4279 (2010).

    Article  PubMed  Google Scholar 

  104. Lawrence, T. S. & Feng, M. Protons for prostate cancer: the dream versus the reality. J. Natl Cancer Inst. 105, 7–8 (2013).

    Article  PubMed  Google Scholar 

  105. Widesott, L. et al. Helical tomotherapy vs. intensity-modulated proton therapy for whole pelvis irradiation in high-risk prostate cancer patients: dosimetric, normal tissue complication probability, and generalized equivalent uniform dose analysis. Int. J. Radiat. Oncol. Biol. Phys. 80, 1589–1600 (2011).

    Article  PubMed  Google Scholar 

  106. Schwarz, M. et al. Helical tomotherapy and intensity modulated proton therapy in the treatment of early stage prostate cancer: a treatment planning comparison. Radiother. Oncol. 98, 74–80 (2011).

    Article  PubMed  Google Scholar 

  107. Concato, J. et al. Observational methods in comparative effectiveness research. Am. J. Med. 123, e16–e23 (2010).

    Article  PubMed  Google Scholar 

  108. Epstein, R. S. & Teagarden, J. R. Comparative effectiveness research and personalized medicine: catalyzing or colliding? Pharmacoeconomics 28, 905–913 (2010).

    Article  PubMed  Google Scholar 

  109. Jagsi, R. et al. A research agenda for radiation oncology: results of the radiation oncology institute's comprehensive research needs assessment. Int. J. Radiat. Oncol. Biol. Phys. 84, 318–322 (2012).

    Article  PubMed  Google Scholar 

  110. Bekelman, J. E. & Hahn, S. M. The body of evidence for advanced technology in radiation oncology. J. Natl Cancer Inst. 105, 6–7 (2013).

    Article  PubMed  Google Scholar 

  111. Edge, S. B. et al. (eds) AJCC Cancer Staging Manual, 7th edn 457–468 (Springer, 2010).

    Google Scholar 

  112. Zaorsky, N. G., Li, T., Devarajan, K., Horwitz, E. M. & Buyyounouski, M. K. Assessment of the American Joint Committee on Cancer staging (sixth and seventh editions) for clinically localized prostate cancer treated with external beam radiotherapy and comparison with the National Comprehensive Cancer Network risk-stratification method. Cancer 118, 5535–5543 (2012).

    Article  PubMed  Google Scholar 

  113. Shen, X. et al. Comparative effectiveness research for prostate cancer radiation therapy: current status and future directions. Future Oncol. 8, 37–54 (2012).

    Article  PubMed  Google Scholar 

  114. Zumsteg, Z. S. et al. A new risk classification system for therapeutic decision making with intermediate-risk prostate cancer patients undergoing dose-escalated external-beam radiation therapy. Eur. Urol. http://dx.doi.org/10.1016/j.eururo.2013.03.033.

  115. Butler, W. M., Morris, M. N., Merrick, G. S., Kurko, B. S. & Murray, B. C. Effect of body mass index on intrafraction prostate displacement monitored by real-time electromagnetic tracking. Int. J. Radiat. Oncol. Biol. Phys. 84, e173–e179 (2012).

    Article  PubMed  Google Scholar 

  116. de Crevoisier, R. et al. Changes in the pelvic anatomy after an IMRT treatment fraction of prostate cancer. Int. J. Radiat. Oncol. Biol. Phys. 68, 1529–1536 (2007).

    Article  PubMed  Google Scholar 

  117. Wang, B., Tward, J. D. & Salter, B. J. An evaluation of interference of inflatable penile prostheses with electromagnetic localization and tracking system. Med. Phys. 39, 4807–4811 (2012).

    Article  PubMed  Google Scholar 

  118. Pinkawa, M., Eble, M. J. & Mottaghy, F. M. PET and PET/CT in radiation treatment planning for prostate cancer. Expert Rev. Anticancer Ther. 11, 1033–1039 (2011).

    Article  PubMed  Google Scholar 

  119. Bouchelouche, K. et al. PET/CT Imaging and radioimmunotherapy of prostate cancer. Semin. Nucl. Med. 41, 29–44 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  120. Seitz, M. et al. Functional magnetic resonance imaging in prostate cancer. Eur. Urol. 55, 801–814 (2009).

    Article  CAS  PubMed  Google Scholar 

  121. Sciarra, A. et al. Advances in magnetic resonance imaging: how they are changing the management of prostate cancer. Eur. Urol. 59, 962–977 (2011).

    Article  PubMed  Google Scholar 

  122. Lips, I. M. et al. Single blind randomized phase III trial to investigate the benefit of a focal lesion ablative microboost in prostate cancer (FLAME-trial): study protocol for a randomized controlled trial. Trials 12, 255 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  123. Engels, B., Soete, G., Verellen, D. & Storme, G. Conformal arc radiotherapy for prostate cancer: increased biochemical failure in patients with distended rectum on the planning computed tomogram despite image guidance by implanted markers. Int. J. Radiat. Oncol. Biol. Phys. 74, 388–391 (2009).

    Article  PubMed  Google Scholar 

  124. Song, D. Y. et al. A multi-institutional clinical trial of rectal dose reduction via injected polyethylene-glycol hydrogel during intensity modulated radiation therapy for prostate cancer: analysis of dosimetric outcomes. Int. J. Radiat. Oncol. Biol. Phys. 87, 81–87 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  125. Pinkawa, M. et al. Application of a spacer gel to optimize three-dimensional conformal and intensity modulated radiotherapy for prostate cancer. Radiother. Oncol. 100, 436–441 (2011).

    Article  CAS  PubMed  Google Scholar 

  126. Noel, C. E., Santanam, L., Olsen, J. R., Baker, K. W. & Parikh, P. J. An automated method for adaptive radiation therapy for prostate cancer patients using continuous fiducial-based tracking. Phys. Med. Biol. 55, 65–82 (2010).

    Article  CAS  PubMed  Google Scholar 

  127. Mohan, R. et al. Use of deformed intensity distributions for on-line modification of image-guided IMRT to account for interfractional anatomic changes. Int. J. Radiat. Oncol. Biol. Phys. 61, 1258–1266 (2005).

    Article  PubMed  Google Scholar 

  128. Thomsen, J. B., Arp, D. T. & Carl, J. Urethra sparing—potential of combined nickel-titanium stent and intensity modulated radiation therapy in prostate cancer. Radiother. Oncol. 103, 256–260 (2012).

    Article  PubMed  Google Scholar 

  129. Fellin, F. et al. Helical tomotherapy and intensity modulated proton therapy in the treatment of dominant intraprostatic lesion: a treament planning comparison. Radiother. Oncol. 107, 207–212 (2013).

    Article  PubMed  Google Scholar 

  130. Fachal, L. et al. Association of a XRCC3 polymorphism and rectum mean dose with the risk of acute radio-induced gastrointestinal toxicity in prostate cancer patients. Radiother. Oncol. 105, 321–328 (2012).

    Article  CAS  PubMed  Google Scholar 

  131. Fachal, L. et al. TGFβ1 SNPs and radio-induced toxicity in prostate cancer patients. Radiother. Oncol. 103, 206–209 (2012).

    Article  CAS  PubMed  Google Scholar 

  132. Goh, C. L. et al. Genetic variants associated with predisposition to prostate cancer and potential clinical implications. J. Intern. Med. 271, 353–365 (2012).

    Article  CAS  PubMed  Google Scholar 

  133. West, C. et al. Establishment of a radiogenomics consortium. Int. J. Radiat. Oncol. Biol. Phys. 76, 1295–1296 (2010).

    Article  PubMed  Google Scholar 

  134. Kerns, S. L. et al. Genome-wide association study identifies a region on chromosome 11q14.3 associated with late rectal bleeding following radiation therapy for prostate cancer. Radiother. Oncol. 107, 372–376 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Peeters, S. T. et al. Acute and late complications after radiotherapy for prostate cancer: results of a multicenter randomized trial comparing 68 Gy to 78 Gy. Int. J. Radiat. Oncol. Biol. Phys. 61, 1019–1034 (2005).

    Article  PubMed  Google Scholar 

  136. Yeoh, E. K. et al. Disturbed colonic motility contributes to anorectal symptoms and dysfunction after radiotherapy for carcinoma of the prostate. Int. J. Radiat. Oncol. Biol. Phys. 78, 773–780 (2010).

    Article  PubMed  Google Scholar 

  137. Fonteyne, V., Lumen, N., Villeirs, G., Ost, P. & De Meerleer, G. Clinical results after high-dose intensity-modulated radiotherapy for high-risk prostate cancer. Adv. Urol. 2012, 368528 (2012).

    Article  PubMed  Google Scholar 

  138. Fonteyne, V., De Neve, W., Villeirs, G., De Wagter, C. & De Meerleer, G. Late radiotherapy-induced lower intestinal toxicity (RILIT) of intensity-modulated radiotherapy for prostate cancer: the need for adapting toxicity scales and the appearance of the sigmoid colon as co-responsible organ for lower intestinal toxicity. Radiother. Oncol. 84, 156–163 (2007).

    Article  PubMed  Google Scholar 

  139. Denham, J. W. et al. Is there more than one late radiation proctitis syndrome? Radiother. Oncol. 51, 43–53 (1999).

    Article  CAS  PubMed  Google Scholar 

  140. Potters, L. et al. American Society for Therapeutic Radiology and Oncology (ASTRO) and American College of Radiology (ACR) practice guideline for the performance of stereotactic body radiation therapy. Int. J. Radiat. Oncol. Biol. Phys. 76, 326–332 (2010).

    Article  PubMed  Google Scholar 

  141. Yeoh, E. K. et al. Pathophysiology and natural history of anorectal sequelae following radiation therapy for carcinoma of the prostate. Int. J. Radiat. Oncol. Biol. Phys. 84, e593–e599 (2012).

    Article  PubMed  Google Scholar 

  142. Vordermark, D. et al. Prospective evaluation of quality of life after permanent prostate brachytherapy with I-125: importance of baseline symptoms and of prostate-V150. Radiother. Oncol. 91, 217–224 (2009).

    Article  PubMed  Google Scholar 

  143. Thompson, I. et al. Guideline for the management of clinically localized prostate cancer: 2007 update. J. Urol. 177, 2106–2131 (2007).

    Article  PubMed  Google Scholar 

  144. Haynes, B. Can it work? Does it work? Is it worth it? The testing of healthcare interventions is evolving. BMJ 319, 652–653 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Popiolek, M. et al. Natural history of early, localized prostate cancer: a final report from three decades of follow-up. Eur. Urol. 63, 428–435 (2013).

    Article  PubMed  Google Scholar 

  146. Johansson, J. E. et al. Natural history of early, localized prostate cancer. JAMA 291, 2713–2719 (2004).

    Article  CAS  PubMed  Google Scholar 

  147. Konski, A. Cost, quality, and value in healthcare: a new paradigm. Oncology (Willston Park) 24, 542–543 (2010).

    Google Scholar 

  148. Perez, C. A. et al. Cost accounting in radiation oncology: a computer-based model for reimbursement. Int. J. Radiat. Oncol. Biol. Phys. 25, 895–906 (1993).

    Article  CAS  PubMed  Google Scholar 

  149. Lievens, Y., van den Bogaert, W. & Kesteloot, K. Activity-based costing: a practical model for cost calculation in radiotherapy. Int. J. Radiat. Oncol. Biol. Phys. 57, 522–535 (2003).

    Article  PubMed  Google Scholar 

  150. Norlund, A. Costs of radiotherapy. Acta Oncol. 42, 411–415 (2003).

    Article  PubMed  Google Scholar 

  151. Kesteloot, K., Lievens, Y. & van der Schueren, E. Improved management of radiotherapy departments through accurate cost data. Radiother. Oncol. 55, 251–262 (2000).

    Article  CAS  PubMed  Google Scholar 

  152. Van de Werf, E., Lievens, Y., Verstraete, J., Pauwels, K. & Van den Bogaert, W. Time and motion study of radiotherapy delivery: economic burden of increased quality assurance and IMRT. Radiother. Oncol. 93, 137–140 (2009).

    Article  PubMed  Google Scholar 

  153. Shah, C. et al. Brachytherapy provides comparable outcomes and improved cost-effectiveness in the treatment of low/intermediate prostate cancer. Brachytherapy 11, 441–445 (2012).

    Article  PubMed  Google Scholar 

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N. G. Zaorsky researched the data for the article and wrote the manuscript. All authors discussed the article's content and edited the manuscript before submission.

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Zaorsky, N., Harrison, A., Trabulsi, E. et al. Evolution of advanced technologies in prostate cancer radiotherapy. Nat Rev Urol 10, 565–579 (2013). https://doi.org/10.1038/nrurol.2013.185

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