Prediction of Adverse Radiotherapeutic Effects in Prostate Cancer Patients Prior to Radiation
Received Date: Aug 29, 2012 / Accepted Date: Aug 30, 2012 / Published Date: Sep 03, 2012
It is estimated that there will be 241,740 new Prostate Cancer (PCa) cases diagnosed in the U.S. in 2012 . Radiotherapy is a widely used treatment modality for PCa. A recent review revealed that approximately 48% of patients diagnosed with prostate cancer received some form of radiotherapy for their initial treatment . This amounts to around 100,000 patients per year receiving radiotherapy for PCa in the United States alone with a risk of grade 2 or higher bladder or gastrointestinal toxicity of 7-38% [3-5]. This adds up to 7,000 to 38,000 moderate or worse toxicities and up to 2000 severe toxicities each year. Indeed, most PCa patients have mild to moderate side-effects from radiotherapy, but some patients do have severe Adverse Radiotherapeutic Effects (AREs), such as severe lower urinary tract irritation, erectile dysfunction, and rectal bleeding, ulceration or dysfunction, despite the fact that radiotherapy doses and techniques are generally uniform. These severe side effects cause significant morbidity and require costly intervention.
Increasing evidence indicates that there is significant variability in the response to radiation in the general population. It is estimated that approximately 80% to 90% of the variability is attributed to deterministic differences, possibly arising from potential individual genetic makeup, whereas only 10% to 20% of the variations result from stochastic events associated with the random nature of radiationinduced cell killing, in addition to random variations in dosimetry and dose delivery . Common manifestations of late injury include fibrosis, telangiectasia, and atrophy . Many patients may have bladder irritation, impotence, or rectal bleeding for the rest of their lives or even require surgical intervention [3-5]. If we can identify these patients at high risk for developing significant AREs prior to radiotherapy, then we can offer them alternative therapies that may lower their risk of developing severe side effects. For patients at low risk for AREs, radiation dose escalation may be implemented to increase cure rates without increasing toxicity. However, the best strategy to determine the risk of AREs is currently unknown.
Single Nucleotide Polymorphisms (SNPs) of a limited number of genes have been shown to be associated with variable AREs in general populations. For example, ATM 5557G>A is associated with radiotherapy-induced fibrosis in PCa patients [8,9]. Kerns et al.  performed a genome-wide association study on 27 cases and 52 controls and found that SNP rs2268363, located in the follicle-stimulating hormone receptor gene was associated with erectile dysfunction following external beam radiotherapy in African American PCa patients.
Besides the patient’s genetic predisposition, other factors including age, smoking history, androgen deprivation therapy, use of alphablockers, use of anticoagulants, prostate volume, comorbidities such as diabetes and hypertension, baseline toxicity/function scores, and different types of radiotherapy may contribute to radiation toxicity as well [11-20]. However, these clinical variables cannot fully explain the variability in AREs [21-24] .
To accurately predict the risk of AREs in PCa patient, more studies are needed to identify variables that significantly influence radiationinduced normal tissue injuries in PCa patients, determine the individual contribution of each genetic and non-genetic factor to AREs, and develop models to predict the risk of AREs. Using these models, we will be able to identify patients who are at a high risk of AREs. For those patients, other effective therapeutic modalities such as radical prostatectomy, hormonal therapy, cryotherapy, or active surveillance  may be offered instead of radiotherapy. Therefore, a great number of severe AREs may be avoided if we use alternative therapies with fewer side effects for these patients at high risk. Similarly, if patients are found to be at low risk for AREs, radiation dose escalation may be implemented to increase cure rates without increasing toxicity. In prostate cancer, dose escalation has been show to improve disease control in multiple studies [26-28]. If we can successfully predict the risk of AREs in prostate cancer patients, we will be able to develop similar models to predict AREs in patients with other cancers or other diseases treated with radiotherapy. These models may become important tools for individualizing cancer therapy.
- Siegel R, Naishadham D, Jemal A (2012) Cancer Statistics, 2012. CA Cancer J Clin 62: 10-29.
- Snyder CF, Frick KD, Blackford AL, Herbert RJ, Neville BA, et al. (2010) How does initial treatment choice affect short-term and long-term costs for clinically localized prostate cancer? Cancer 116: 5391-5399.
- Pollack A, Zagars GK, Starkschall G, Antolak JA, Lee JJ, et al. (2002) Prostate cancer radiation dose response: results of the M. D. Anderson phase III randomized trial. Int J Radiat Oncol Biol Phys 53: 1097-1105.
- Koper PC, Jansen P, van Putten W, van Os M, Wijnmaalen AJ, et al. (2004) Gastro-intestinal and genito-urinary morbidity after 3D conformal radiotherapy of prostate cancer: observations of a randomized trial. Radiother Oncol 73: 1-9.
- Chism DB, Horwitz EM, Hanlon AL, Pinover WH, Mitra RK, et al. (2003) Late morbidity profiles in prostate cancer patients treated to 79-84 Gy by a simple four-field coplanar beam arrangement. Int J Radiat Oncol Biol Phys 55: 71-77.
- Ho AY, Atencio DP, Peters S, Stock RG, Formenti SC, et al. (2006) Genetic predictors of adverse radiotherapy effects: the Gene-PARE project. Int J Radiat Oncol Biol Phys 65: 646-655.
- O'Sullivan B, Levin W (2003) Late radiation-related fibrosis: pathogenesis, manifestations, and current management. Semin Radiat Oncol 13: 274-289.
- Cesaretti JA, Stock RG, Atencio DP, Peters SA, Peters CA, et al. (2007) A genetically determined dose-volume histogram predicts for rectal bleeding among patients treated with prostate brachytherapy. Int J Radiat Oncol Biol Phys 68: 1410-1416.
- Cesaretti JA, Stock RG, Lehrer S, Atencio DA, Bernstein JL, et al. (2005) ATM sequence variants are predictive of adverse radiotherapy response among patients treated for prostate cancer. Int J Radiat Oncol Biol Phys 61: 196-202.
- Kerns SL, Ostrer H, Stock R, Li W, Moore J, et al. (2010) Genome-wide association study to identify single nucleotide polymorphisms (SNPs) associated with the development of erectile dysfunction in African-American men after radiotherapy for prostate cancer. Int J Radiat Oncol Biol Phys 78: 1292-1300.
- Locke J, Ellis W, Wallner K, Cavanagh W, Blasko J (2002) Risk factors for acute urinary retention requiring temporary intermittent catheterization after prostate brachytherapy: a prospective study. Int J Radiat Oncol Biol Phys 52: 712-719.
- Salem N, Simonian-Sauve M, Rosello R, Alzieu C, Gravis G, et al. (2003) Predictive factors of acute urinary morbidity after iodine-125 brachytherapy for localised prostate cancer: a phase 2 study. Radiother Oncol 66: 159-165.
- Bucci J, Morris WJ, Keyes M, Spadinger I, Sidhu S, et al. (2002) Predictive factors of urinary retention following prostate brachytherapy. Int J Radiat Oncol Biol Phys 53: 91-98.
- Penedo FJ, Dahn JR, Shen BJ, Schneiderman N, Antoni MH (2006) Ethnicity and determinants of quality of life after prostate cancer treatment. Urology 67: 1022-1027.
- Chen AB, D'Amico AV, Neville BA, Earle CC (2006) Patient and treatment factors associated with complications after prostate brachytherapy. J Clin Oncol 24: 5298-5304.
- Mayahara H, Murakami M, Kagawa K, Kawaguchi A, Oda Y, et al. (2007) Acute morbidity of proton therapy for prostate cancer: the Hyogo Ion Beam Medical Center experience. Int J Radiat Oncol Biol Phys 69: 434-443.
- Peschel RE, Chen Z, Roberts K, Nath R (1999) Long-term complications with prostate implants: iodine-125 vs. palladium-103. Radiat Oncol Investig 7: 278-288.
- Gelblum DY, Potters L, Ashley R, Waldbaum R, Wang XH, et al. (1999) Urinary morbidity following ultrasound-guided transperineal prostate seed implantation. Int J Radiat Oncol Biol Phys 45: 59-67.
- Thomas MD, Cormack R, Tempany CM, Kumar S, Manola J, et al. (2000) Identifying the predictors of acute urinary retention following magnetic-resonance-guided prostate brachytherapy. Int J Radiat Oncol Biol Phys 47: 905-908.
- Bentzen SM, Overgaard J (1994) Patient-to-Patient Variability in the Expression of Radiation-Induced Normal Tissue Injury. Semin Radiat Oncol 4: 68-80.
- Robinson JW, Moritz S, Fung T (2002) Meta-analysis of rates of erectile function after treatment of localized prostate carcinoma. Int J Radiat Oncol Biol Phys 54: 1063-1068.
- Talcott JA, Manola J, Clark JA, Kaplan I, Beard CJ, et al. (2003) Time course and predictors of symptoms after primary prostate cancer therapy. J Clin Oncol 21: 3979-3986.
- Pinkawa M, Fischedick K, Gagel B, Piroth MD, Asadpour B, et al. (2009) Impact of age and comorbidities on health-related quality of life for patients with prostate cancer: evaluation before a curative treatment. BMC Cancer 9: 296.
- Wilt TJ, MacDonald R, Rutks I, Shamliyan TA, Taylor BC, et al. (2008) Systematic review: comparative effectiveness and harms of treatments for clinically localized prostate cancer. Ann Intern Med 148: 435-448.
- Thompson I, Thrasher JB, Aus G, Burnett AL, Canby-Hagino ED, et al. (2007) Guideline for the management of clinically localized prostate cancer: 2007 update.
- Kuban DA, Tucker SL, Dong L, Starkschall G, Huang EH, et al. (2008) Long-term results of the M. D. Anderson randomized dose-escalation trial for prostate cancer. Int J Radiat Oncol Biol Phys 70: 67-74.
- Zietman AL, Bae K, Slater JD, Shipley WU, Efstathiou JA, et al. (2010) Randomized trial comparing conventional-dose with high-dose conformal radiation therapy 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.
- Al-Mamgani A, van Putten WL, Heemsbergen WD, van Leenders GJ, Slot A, et al. (2008) Update of Dutch multicenter dose-escalation trial of radiotherapy for localized prostate cancer. Int J Radiat Oncol Biol Phys 72: 980-988.
Citation: Zhu Y, Marshall DT (2012) Prediction of Adverse Radiotherapeutic Effects in Prostate Cancer Patients Prior to Radiation. J Clin Exp Pathol 2:e112. Doi: 10.4172/2161-0681.1000e112
Copyright: © 2012 Zhu Y, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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