Abstract
Background/purpose
To evaluate the impact of intensity-modulated radiotherapy (IMRT) with intra-prostate fiducial markers image-guided radiotherapy (IGRT) on the incidence of late urinary toxicity compared to 3D conformal radiotherapy (3DCRT) for patients with prostate cancer (PC).
Methods and materials
We selected 733 consecutive patients with localized PC treated with dose-escalation radiotherapy between 2001 and 2014. Eligibility criteria were radiation dose >72.0 Gy, no pelvic RT and minimum follow-up 24 months. 438 patients were treated with 3DCRT and 295 with IMRT. Acute and late urinary complications were assessed using the EORTC/RTOG and CTCAEs v3.0 definition. The Cox regression model was used to compare grade ≥2 urinary toxicity between both techniques. The median follow-up was 75 months (range 24–204).
Results
The median isocenter radiation dose was 78.7 Gy for 3DCRT and 80.7 Gy for IMRT/IGRT (p < 0.001). The 5-year incidence of late grade ≥2 urinary toxicity was 6.4% for IMRT and 10.8% for 3DCRT [hazard ratio (HR) 0.575, p = 0.056]. The corresponding 5-year estimates of late grade ≥2 hematuria were 2% for IMRT and 5.3% for 3DCRT (HR 0.296, p = 0.024). On multivariate analysis, the antecedent of prior transurethral resection of the prostate was also a strong predictor of a higher risk of urinary complications (HR 2.464, p = 0.002) and of hematuria (HR 5.196, p < 0.001).
Conclusion
Compared with 3DCRT, high-dose IMRT/IGRT is associated with a lower rate of late urinary complications in spite of higher radiation dose.
Similar content being viewed by others
References
Sheets NC, Goldin GH, Meyer AM, Wu Y, Chang Y, Stürmer T, et al. Intensity-modulated radiation therapy, proton therapy, or conformal radiation therapy and morbidity and disease control in localized prostate cancer. JAMA. 2012;307:1611–20.
Al-Mamgani A, Heemsbergen WD, Peeters ST, Lebesque JV. Role of intensity-modulated radiotherapy in reducing toxicity in dose escalation for localized prostate cancer. IntJ Radiat Oncol Biol Phys. 2009;73:685–91.
Zelefsky MJ, Kollmeier M, Cox B, Fidaleo A, Pei X, Carver B, 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. 2012;84:125–9.
Singh J, Greer PB, White MA, Parker J, Patterson J, Tang CI, et al. Treatment-related morbidity in prostate cancer: a comparison of 3-dimensional conformal radiation therapy with and without image guidance using implanted fiducial markers. Int J Radiat Oncol Biol Phys. 2013;85:1018–23.
Fonteyne V, Ost P, Vanpachtenbeke F, Colman R, Sadeghi S, Villeirs G, et al. Rectal toxicity after intensity modulated radiotherapy for prostate cancer: which rectal dose volume constraints should we use? Radiother Oncol. 2014;113:398–403.
Michalski JM, Yan Y, Watkins-Bruner D, Bosch W, Winter K, Galvin JM, et al. Preliminary toxicity analysis of 3-dimensional conformal radiation therapy versus intensity modulated radiation therapy on the high-dose arm of the RTOG 0126 prostate cancer trial. Int J Radiat Oncol Biol Phys. 2013;87:932–8.
Zapatero A, Valcarcel F, Calvo FA, Algás R, Béjar A, Maldonado J, et al. Risk-adapted androgen deprivation and escalated three-dimensional conformal radiotherapy for prostate cancer: does radiation dose influence outcome of patients treated with adjuvant androgen deprivation? A GICOR study. J Clin Oncol. 2005;23:6561–8.
Zapatero A, Guerrero A, Maldonado X, Álvarez A, González-San Segundo C, Cabeza Rodríguez MA, et al. High-dose radiotherapy with short-term or long-term androgen deprivation in localized prostate cancer (DART 01/05 GICOR): a randomized, controlled, phase 3 trial. Lancet Oncol. 2015;16:320–7.
Zapatero A, García-Vicente F, Modolell I, Alcántara P, Floriano A, Cruz-Conde A, et al. Impact of mean rectal dose on late rectal bleeding after conformal radiotherapy for prostate cancer: dose-volume effect. Int J Radiat Oncol Biol Phys. 2004;59:1343–51.
Sevillano-Martínez D, García-Vicente F, Zapatero A, Ferrer-Gracia C, Gómez-Barrado A, Pérez-González L, et al. Study on the use of gold seeds in prostate cancer treatment verification. Rev Fis Med. 2008;93:105–12.
Zelefsky MJ, Levin EJ, Hunt M, Yamada Y, Shippy AM, Jackson A, et al. Incidence of late rectal and urinary toxicities after three-dimensional conformal radiotherapy and intensity-modulated radiotherapy for localized prostate cancer. Int J Radiat Oncol Biol Phys. 2008;70:1124–9.
Wortel RC, Incrocci L, Pos FJ, van der Heide UA, Lebesque JV, Aluwini S, et al. Late side effects after image guided intensity modulated radiation therapy compared to 3D-conformal radiation therapy for prostate cancer: results from 2 prospective cohorts. Int J Radiat Oncol Biol Phys. 2016;95:680–9.
Landoni V, Fiorino C, Cozzarini C, Sanquineti G, Valdagni R, Rancati T. Predicting toxicity in radiotherapy for prostate cancer. Physic aMedica. 2016;32:521–32.
Pinkawa M, Fischedick K, Asadpour B, Gagel B, Piroth MD, Eble MJ. Low-grade toxicity after conformal radiation therapy for prostate cancer—impact of bladder volume. Int J Radiat Oncol Biol Phys. 2006;64:835–41.
Ahmed AA, Egleston B, Alcantara P, Li L, Pollack A, Horwitz EM, et al. A novel method for predicting late genitourinary toxicity after prostate radiation therapy and the need for age-based risk-adapted dose constraints. Int J Radiat Oncol Biol Phys. 2013;86:709–15.
Harsolia A, Vargas C, Yan D, Brabbins D, Lockman D, Liang J, et al. Predictors for chronic urinary toxicity after the treatment of prostate cancer with adaptive three-dimensional conformal radiotherapy: dose–volume analysis of a phase II dose-escalation study. Int J Radiat Oncol Biol Phys. 2007;69:1100–9.
Rosewall T, Catton C, Currie G, Bayley A, Chung P, Wheat J, et al. The relationship between external beam radiotherapy dose and chronic urinary dysfunction. A methodological critique. Radiother Oncol. 2010;97:40–7.
Ghadjar P, Zelefsky MJ, Spratt DE, Munckaf Rosenschöld P, Oh JH, Hunt M, et al. The impact of dose to the bladder trigone on long-term urinary function after high-dose intensity-modulated radiation therapy for localized prostate cancer. Int J Radiat Oncol Biol Phys. 2014;88:339–44.
Peeters STH, Heemsbergen WD, Van Putten WL, Slot A, Tabak H, Mens JW, 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. 2005;61:1019–34.
Skala M, Rosewall T, Dawson L, Divanbeigi L, Lockwood G, Thomas C, et al. Patient-assessed late toxicity rates and principal component analysis after image-guided radiation therapy for prostate cancer. Int J Radiat Oncol Biol Phys. 2007;68:690–8.
Garcia-Vicente F, Zapatero A, Martin de Vidales C, Rodríguez G, Leaman O, Cruz-Conde A, et al. Predictors for late urinary toxicity after high-dose radiation therapy for localized prostate cancer. Int J Radiat Oncol Biol Phys. 2013;87(Suppl 2):S365–6.
Budaüs L, Bolla M, Bossi A, Cozzarini C, Crook J, Widmark A, et al. Functional outcomes and complications following radiation therapy for prostate cancer: a critical analysis of the literature. Eur Urol. 2012;61:112–27.
Zapatero A, García-Vicente F, Sevillano D, Martín de Vidales C, Ferrer C, Torres JJ, et al. Is hormone therapy a protective factor for late hematuria after high-dose radiotherapy in prostate cancer? Urology. 2008;72:1130–4.
Sandhu AS, Zelefsky MJ, Lee HJ, Lombardi D, Fuks Z, Leibel SA. Long-term GU toxicity after 3-dimensional conformal radiotherapy for prostate cancer in patients with prior history of transurethral resection. Int J Radiat Oncol Biol Phys. 2000;48:643–7.
Kim S, Moore DF, Shih W, Lin Y, Li H, Shao YH, et al. Severe genitourinary toxicity following radiation therapy for prostate cancer. How long does it last? J Urol. 2013;189:116–21.
De Langhe S, De Meerleer G, De Ruyck K, Ost P, Fonteyne V, De Neve W, et al. Integrated models for the prediction of late genitourinary complaints after high-dose intensity modulated radiotherapy for prostate cancer: making informed decisions. Radiother Oncol. 2014;112:95–9.
Hanks GE, Pajak TF, Porter A, Grignon D, Brereton H, Venkatesan V, et al. Phase III trial of long-term adjuvant androgen deprivation after neoadjuvant hormonal cytoreduction and radiotherapy in locally advanced carcinoma of the prostate: the Radiation Therapy Oncology Group Protocol 92-02. J Clin Oncol. 2003;21:3972–8.
Jani AB, Gratzle J. Late radiotherapy toxicity after prostate cancer treatment: influence of hormonal therapy. Urology. 2005;66:566–70.
Lawton C, Bae K, Pilepich M, Hanks G, Shipley W. Long-term treatment sequelae after external beam irradiation with or without hormonal manipulation for adenocarcinoma of the prostate: analysis of radiation therapy oncology group studies 85-31, 86-10, and 92-02. Int J Radiat Oncol Biol Phys. 2008;70:437–41.
Zapatero A, Guerrero A, Maldonado X, Álvarez A, González-San Segundo C, Cabeza Rodríguez MA, et al. Late radiation and cardiovascular adverse effects following androgen deprivation and high-dose radiotherapy in prostate cancer: results from the DART 01/05 randomized phase III trial. Int J Radiat Oncol Biol Phys. 2016;96:341–8.
Author information
Authors and Affiliations
Contributions
All the authors have contributed sufficiently to the scientific work and therefore share collective responsibility and accountability for the results. All the authors have read, approved and consented to submit the manuscript. The manuscript is not under consideration for publication elsewhere.
Corresponding author
Ethics declarations
Funding sources
This work has no specific funding.
Conflict of interest
The authors declare that they have no conflict of interest.
Ethical approval
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent
For this type of study formal consent is not required.
Rights and permissions
About this article
Cite this article
Zapatero, A., Roch, M., Büchser, D. et al. Reduced late urinary toxicity with high-dose intensity-modulated radiotherapy using intra-prostate fiducial markers for localized prostate cancer. Clin Transl Oncol 19, 1161–1167 (2017). https://doi.org/10.1007/s12094-017-1655-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12094-017-1655-9