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Comparative Evaluation of Radiation Treatments for Clinically Localized Prostate Cancer: An Updated Systematic Review FREE

Raveendhara R. Bannuru, MD; Tomas Dvorak, MD; Ndidiamaka Obadan, MD, MSc; Winifred W. Yu, MS, RD; Kamal Patel, MPH, MBA; Mei Chung, PhD, MPH; and Stanley Ip, MD
[+] Article and Author Information

From the Institute of Clinical Research and Health Policy Studies, Tufts University School of Medicine, Tufts Medical Center, and Tufts Clinical and Translational Science Institute, Boston, Massachusetts.


Disclaimer: The authors of this report are responsible for its content. Statements in the report should not be constituted as endorsement by the AHRQ or the U.S. Department of Health and Human Services.

Grant Support: By AHRQ, U.S. Department of Health and Human Services (contract 290 2007 10055 I). Dr. Bannuru is supported by a grant (T32 HS0000060) from AHRQ.

Potential Conflicts of Interest: Drs. Bannuru and Ip: Support for travel to meetings for the study or other purposes: AHRQ; Support for travel to meetings for the study or other purposes (money to institution): AHRQ; Fees for participation in review activities such as data monitoring boards, statistical analysis, end point committees, and the like (money to institution): AHRQ; Other (money to institution): AHRQ (reimbursement for preparation of the evidence report). Dr. Dvorak: Consulting fee or honorarium: AHRQ; Support for travel to meetings for the study or other purposes: AHRQ; Fees for participation in review activities such as data monitoring boards, statistical analysis, end point committees, and the like (money to institution): AHRQ. Dr. Obadan: Support for travel to meetings for the study or other purposes: AHRQ; Support for travel to meetings for the study or other purposes (money to institution): AHRQ. Ms. Yu, Mr. Patel, and Dr. Chung: Support for travel to meetings for the study or other purposes (money to institution): AHRQ; Fees for participation in review activities such as data monitoring boards, statistical analysis, end point committees, and the like (money to institution): AHRQ; Other (money to institution): AHRQ (reimbursement for preparation of the evidence report). Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M11-0178.

Corresponding Author: Stanley Ip, MD, Institute of Clinical Research and Health Policy Studies, Tufts Clinical and Translational Science Institute, Tufts Medical Center, Box 63, 800 Washington Street, Boston, MA 02111; e-mail, sip@tuftsmedicalcenter.org.

Current Author Addresses: Drs. Bannuru, Obadan, Chung, and Ip and Ms. Yu and Mr. Patel: Institute of Clinical Research and Health Policy Studies, Tufts Clinical and Translational Science Institute, Tufts Medical Center, Box 63, 800 Washington Street, Boston, MA 02111.

Dr. Dvorak: M.D. Anderson Cancer Center Orlando, 1400 South Orange Avenue, Orlando, FL 32086.

Author Contributions: Conception and design: R.R. Bannuru, T. Dvorak, N. Obadan, W.W. Yu, M. Chung, S. Ip.

Analysis and interpretation of the data: R.R. Bannuru, T. Dvorak, N. Obadan, W.W. Yu, K. Patel, M. Chung, S. Ip.

Drafting of the article: R.R. Bannuru, T. Dvorak, N. Obadan, K. Patel, S. Ip.

Critical revision of the article for important intellectual content: R.R. Bannuru, T. Dvorak, N. Obadan, W.W. Yu, M. Chung, S. Ip.

Final approval of the article: R.R. Bannuru, T. Dvorak, W.W. Yu, M. Chung, S. Ip.

Provision of study materials or patients: R.R. Bannuru, N. Obadan.

Statistical expertise: R.R. Bannuru, N. Obadan, M. Chung, S. Ip.

Administrative, technical, or logistic support: R.R. Bannuru, N. Obadan, W.W. Yu.

Collection and assembly of data: R.R. Bannuru, N. Obadan, W.W. Yu, K. Patel, M. Chung, S. Ip.


Ann Intern Med. 2011;155(3):171-178. doi:10.7326/0003-4819-155-3-201108020-00347
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Background: Radiation therapy is one of many treatment options for patients with prostate cancer.

Purpose: To update findings on the clinical and biochemical outcomes of radiation therapies for localized prostate cancer.

Data Sources: MEDLINE (2007 through March 2011) and the Cochrane Central Register of Controlled Trials (2007 through March 2011).

Study Selection: Published English-language comparative studies involving adults with localized prostate cancer who either had first-line radiation therapy or received no initial treatment.

Data Extraction: 6 researchers extracted information on study design, potential bias, sample characteristics, interventions, and outcomes and rated the strength of overall evidence. Data for each study were extracted by 1 reviewer and confirmed by another.

Data Synthesis: 75 studies (10 randomized, controlled trials [RCTs] and 65 nonrandomized studies) met the inclusion criteria. No RCTs compared radiation therapy with no treatment or no initial treatment. Among the 10 RCTs, 2 compared combinations of radiation therapies, 7 compared doses and fraction sizes of external-beam radiation therapy (EBRT), and 1 compared forms of low-dose rate radiation therapy. Heterogeneous outcomes were analyzed. Overall, moderate-strength evidence consistently showed that a higher EBRT dose was associated with increased rates of long-term biochemical control compared with lower EBRT dose. The body of evidence was rated as insufficient for all other comparisons.

Limitations: Studies inconsistently defined and reported outcomes. Much of the available evidence comes from observational studies with treatment selection biases.

Conclusion: A lack of high-quality comparative evidence precludes conclusions about the efficacy of radiation treatments compared with no treatments for localized prostate cancer.

Primary Funding Source: Agency for Healthcare Research and Quality.

Editors' Notes
Context

  • Is radiation therapy an effective treatment for localized prostate cancer?

Contribution

  • This review found inadequate evidence on survival benefits for radiation therapy compared with no treatment for localized prostate cancer. Data on the comparative effectiveness of different radiotherapies was also insufficient, except that higher external-beam radiation therapy (EBRT) dose was associated with better long-term biochemical control than was lower EBRT dose. Radiation therapies sometimes caused urinary or bowel problems, and brachytherapy seemed to be associated with more urinary toxicity than EBRT.

Implication

  • Whether or which radiation treatments improve clinical outcomes for men with localized prostate cancer is unknown.

—The Editors

Prostate cancer is the most common noncutaneous cancer diagnosed in men in the United States. The American Cancer Society estimates that in 2009, approximately 192 000 men received a prostate cancer diagnosis and approximately 27 000 men died of the disease (1). Widespread prostate-specific antigen (PSA) testing has doubled the incidence of prostate cancer and the lifetime risk for prostate cancer to approximately 16% (2). Prostate cancer is also diagnosed earlier, and the incidence of clinically “silent” T1 tumors has increased from 17% in 1989 to 48% in 2001 (3) since the advent of PSA screening. Overall, most patients with prostate cancer diagnoses today have clinically localized prostate cancer (T1-T2N0).

Depending on a patient's risk profile, many treatment options are available, including active surveillance or watchful waiting, surgery, radiation therapy, cryotherapy, high-intensity focused ultrasonography, and androgen-deprivation therapy (ADT). In 2008, the Agency for Healthcare Research and Quality (AHRQ) published a systematic review comparing all of the treatment options (4), which concluded that no one therapy can be considered the preferred treatment because of limitations in the available evidence and tradeoffs between effectiveness and adverse effects. Recently, the Coverage and Analysis Group at the Centers for Medicare & Medicaid Services commissioned AHRQ to update the report. AHRQ requested the Tufts Evidence-based Practice Center to conduct an update specifically reviewing the comparative effectiveness of radiation treatments for patients with localized prostate cancer.

We used methods adapted from the Methods Reference Guide for Effectiveness and Comparative Effectiveness Reviews, version 1.0, published by AHRQ (5). A full technical report that describes methods in detail, including literature search strategies, and results, including evidence tables, is available elsewhere (6).

Key Questions

We focused this report on 2 key questions:

1. What are the benefits and harms of radiation therapy for clinically localized prostate cancer compared with no treatment or no initial treatment (watchful waiting, active surveillance, or observation)?

2. What are the benefits and harms of different forms of radiation therapy for clinically localized prostate cancer?

Data Sources and Searches

We searched MEDLINE and the Cochrane Central Register of Controlled Trials from January 2007 to 11 March 2011 for studies in adults with clinically localized prostate cancer who had radiation treatments. We combined search terms or Medical Subject Heading terms for prostate neoplasm and terms relevant to radiation therapy (for example, proton beam, particle beam, external beam, radiotherapy, intensity-modulated radiotherapy, brachytherapy), and we limited our search to English-language reports of primary studies in adults that were published in peer-reviewed journals. We also used the previous review to identify randomized, controlled trials (RCTs) published before 2007 (4).

Study Selection

We included only RCTs and nonrandomized comparative studies. We excluded single-cohort studies, case reports, and conference abstracts.

Patient Populations of Interest

We included studies of men with clinically localized prostate cancer (T1-T2, N0-X, M0-X) regardless of age, histologic grade, or PSA level. We excluded studies in which more than 20% of patients had locally advanced (T3-T4) cancer; adjuvant, salvage, or postprostatectomy radiation therapy studies; and studies specifically evaluating ADT in conjunction with radiation therapy.

Interventions and Comparators of Interest

The intervention of interest was radiation treatment used as first-line treatment of prostate cancer, including external-beam radiation therapy (EBRT) (conformal radiation, intensity-modulated radiotherapy, or proton therapy), stereotactic body radiation therapy (SBRT), and brachytherapy (low-dose rate [permanent seed implantation] brachytherapy [LDRBT] and high-dose rate temporary brachytherapy [HDRBT]). We also included combination radiation therapies, such as EBRT with brachytherapy boost.

Comparators of interest were no treatment or no initial treatment or different forms of radiation therapy.

Outcomes of Interest

We included studies that reported either clinical or biochemical outcomes. Outcomes of interest included overall survival, prostate cancer–specific survival, metastases- and/or clinical progression–free survival, biochemical failure, health status, and quality of life.

Data Extraction and Quality Assessment

Six researchers participated in abstracting the studies. Data from each study were extracted by 1 of the reviewers and confirmed by another. The extracted data included information on patient samples, radiation treatment characteristics, clinical and biochemical outcomes, adverse events, and study design. For most outcomes, data from 5 years, 10 years, and/or the last reported time point were included. We also evaluated study quality and potential sources of bias with respect to adequate power, randomization, blinding, allocation concealment, intention-to-treat analysis, adequate length of follow-up, number of dropouts, and loss to follow-up. We rated the strength of the overall body of evidence for each comparison as high, moderate, or insufficient (5). The strength of the overall body of evidence was rated by the entire group of reviewers, and disagreements were resolved by consensus.

Data Synthesis and Analysis

For clinical outcomes, we calculated the risk or rate difference to quantify the effect size. For adverse events, most studies used the Radiation Therapy Oncology Group adverse event classification scheme (78) in reporting urinary and bowel toxicities. We enumerated only grade 3 or greater events.

Role of the Funding Source

AHRQ provided funding for this work. The funding source helped formulate the initial study questions but did not participate in the literature search; determination of study eligibility criteria; data analysis or interpretation; or preparation, review, or approval of the manuscript for publication.

We screened 1756 abstracts and evaluated 222 full-text articles (Appendix Figure); 66 studies from the searches met eligibility criteria. Including 9 RCTs from the earlier 2008 review, a total of 75 articles were analyzed: 10 RCTs and 65 nonrandomized comparative studies. Table 1 summarizes the characteristics of the included RCTs (in 14 publications [922]).

Grahic Jump Location
Appendix Figure.
Summary of evidence search and selection.

CENTRAL = Cochrane Central Register of Controlled Trials; RCT = randomized, controlled trial.

Grahic Jump Location
Table Jump PlaceholderTable 1.  Characteristics of Randomized, Controlled Trials Comparing Radiation Treatments for Clinically Localized Prostate Cancer
Radiation Therapy Versus No Treatment or No Initial Treatment

No RCT compared effectiveness between any form of radiation therapy and no treatment or no initial treatment (Table 2). One prospective study compared EBRT with no treatment or no initial treatment by using modeling and reported significantly worse sexual function in the former over 6 to 24 months of follow-up (P < 0.05); no statistically significant difference was found between brachytherapy and no treatment or no initial treatment (23). Four of 8 retrospective studies that compared some form of radiation therapy with no treatment or no initial treatment (2431) reported on disease-specific survival. One found a statistically significant improvement in patients who received brachytherapy compared with no treatment or no initial treatment (adjusted hazard ratio [HR], 0.45 [95% CI, 0.23 to 0.87]) (28). Of the 3 studies reporting on urinary and bowel function after radiation therapy compared with no treatment or no initial treatment (26, 29, 31), 1 found a higher rate of urethral strictures in patients treated with combined EBRT and brachytherapy (adjusted HR, 4.56 [CI, 1.23 to 16.88]) (26), 1 provided indirect data suggesting that patients treated with EBRT might have worse bowel function (29), and 1 reported significantly worse bowel function in patients who received radiation therapy (transformed Expanded Prostate Cancer Index Composite score, 87.1 vs. 92.8, respectively; P < 0.001) (31). One other study found statistically significantly higher rates of second primary cancer in patients treated with EBRT compared with no treatment (adjusted HR, 1.14 [CI, 1.09 to 1.19]) (24).

Table Jump PlaceholderTable 2.  Summary of Evidence on Outcomes of Therapies for Clinically Localized Prostate Cancer
Comparisons Between Radiation Treatments

Six prospective studies (7 publications [23, 3237]) and 9 retrospective studies (28, 3845) compared LDRBT with EBRT (Table 2). Among the prospective studies, none evaluated disease control, and outcomes for urinary and bowel toxicities and sexual dysfunction were mostly inconclusive. The 1 retrospective study that reported on disease-specific survival did not find a statistically significant difference between groups at 7 years (28). Results of retrospective studies were inconclusive regarding freedom from biochemical failure (38, 4145), urinary toxicities (4243, 45), and bowel toxicities (40, 4243, 45).

One retrospective study compared HDRBT (38 Gy or 42 Gy) with LDRBT (46) and reported no statistically significant differences in freedom from biochemical failure at 5 years, bowel and urinary toxicities, and sexual dysfunction. No studies compared SBRT with any other radiation method or HDRBT with EBRT.

Comparisons of Combinations of Radiation Therapies

Fifteen studies, including 2 RCTs, compared combinations of EBRT and brachytherapy (910, 24, 26, 45, 4756) (Tables 1 and 2 and Appendix Tables 1 and 2). One small trial reported that EBRT plus brachytherapy had lower biochemical or clinical failure rates at 5 years (adjusted HR, 0.37 [CI, 0.16 to 0.85]) than EBRT alone (9). The other trial did not find statistically significant differences in biochemical failure rates when comparing LDRBT plus EBRT in 2 different doses (10).

Table Jump PlaceholderAppendix Table 1.  Randomized, Controlled Trials Comparing Radiation Treatments for Clinically Localized Prostate Cancer and Reporting Freedom From Biochemical Failure
Table Jump PlaceholderAppendix Table 2.  Results for Comparisons of Combination Therapies

Several cohort studies reported results related to freedom from biochemical failure or urinary or bowel toxicities (24, 26, 45, 4756). For freedom from biochemical failure, 1 study favored LDRBT plus EBRT over LDRBT at 8 years (96% vs. 72%; P = 0.015) (53); 1 study favored high-dose HDRBT plus EBRT over low-dose HDRBT plus EBRT at 10 years (81% vs. 57%; P < 0.001) (56); and 1 study reported prostate cancer relapse–free survival at 5 years and favored HDRBT plus EBRT over EBRT (98% vs. 82%; P < 0.001) (54). Concerning urinary toxicity, 1 study found an increase in late urinary toxicity for LDRBT plus EBRT compared with EBRT (18% vs. 5%; P < 0.05) (45), and 1 study found an increase in urethral strictures for brachytherapy plus EBRT compared with EBRT (5.2% vs. 1.7%; P < 0.05) (26). Finally, 1 study that compared EBRT alone with EBRT plus brachytherapy showed an increase in cases of second primary cancer (10.3% vs. 5.7%; P < 0.001) and late (≥5 years) second primary cancer (4.2% vs. 1.4%; P < 0.001) for the former versus the latter therapy (24).

Comparisons Within a Given Radiation Treatment
Intra-SBRT Comparisons

One retrospective study compared SBRT of 35 Gy in 5 fractions with 36.25 Gy in 5 fractions and found no statistically significant difference in late bowel and urinary toxicities at 30 months (57).

Intra-EBRT Comparisons

Three RCTs (7 publications [1115, 5859]), 2 prospective studies (6061), and 9 retrospective studies (45, 6270) compared conventional-dose with high-dose EBRT (maximum, 86 Gy) (Tables 1 and 2 and Appendix Table 1). One trial used a proton therapy boost after initial photon therapy (1314, 59). All studies reported that higher-dose EBRT was associated with increased rates of freedom from biochemical failure at 5 to 10 years compared with lower-dose EBRT. No differences in urinary or bowel toxicities between higher- and lower-dose EBRT were found.

Four RCTs (5 publications [1619, 71]) and 2 retrospective analyses (7273) compared standard fractionation with hypofractionation. No statistically significant differences in freedom from biochemical failure or urinary and bowel toxicities were found between groups. A retrospective study comparing doses of hypofractionated EBRT also did not find statistically significant differences in urinary or bowel toxicities during and after treatment (74).

Intra-LDRBT Comparisons

One RCT (3 publications [2022]) and 2 retrospective studies (3 publications [7577]) examined LDRBT dose or radionuclide comparisons (Table 2 and Appendix Table 1). The RCT compared iodine-125 (144 Gy) with palladium-103 (125 Gy) and found little or no difference between groups in freedom from biochemical failure at 3 and 6 years and in urinary or bowel toxicities (2022). One retrospective study showed that a higher biological effective dose (>220 Gy) using either iodine-125 or palladium-103 improved the overall survival rate and the 5-year rate of freedom from biochemical failure compared with a lower dose (≤220 Gy) in patients at higher risk for progression of prostate cancer (7576). The second retrospective study comparing high- versus low-dose LDRBT found no significant differences in bowel or urinary toxicities or erectile dysfunction between groups (77).

Strength of Evidence for the Comparisons

We rated the strength of the body of evidence for intra-EBRT comparisons as moderate (Appendix Table 3). We rated evidence for all of the other comparisons as insufficient.

Table Jump PlaceholderAppendix Table 3.  Strength of Evidence for Radiation Treatments of Clinically Localized Prostate Cancer

This updated review showed unclear effectiveness of radiation treatments compared with no treatment or no initial treatment of localized prostate cancer on patient survival. Similarly, evidence was insufficient to determine whether certain forms of radiation treatment were more effective than others. Retrospective data suggested that radiation treatments were associated with increased urinary or bowel problems compared with no treatment or no initial treatment. Studies suggested that brachytherapy might be associated with more urinary toxicity than EBRT. For dose comparisons, moderate-strength evidence showed that higher EBRT doses were associated with increased rates of long-term biochemical control than were lower EBRT doses.

Summarizing and interpreting this body of evidence was challenging for several reasons. First, cross-study comparisons were difficult because studies inconsistently defined and reported many of the outcomes of interest. Second, most of the evidence came from observational studies in which patients probably had treatments tailored to their individual risk profiles. For instance, low-risk patients may have been selectively treated with brachytherapy, whereas intermediate-risk patients may have been treated with EBRT. Comparative treatment efficacies are difficult to determine from such selection biases (even among patients with T1 or T2 prostate cancer, the underlying risk for progression of prostate cancer varies widely, because this risk is also dependent on the Gleason score, pretreatment PSA concentration, and other factors). Third, while our focus was clinically localized prostate cancer (stages T1 and T2), approximately one third of the studies reviewed included up to 20% of patients with stage T3 or higher disease. Similarly, approximately one half of the studies had some patients who received ADT. Many of these studies did not report results stratified by tumor stage or ADT use.

An RCT not included in our review that compared radiation therapy plus concurrent ADT with ADT alone in patients with predominately stage T3 prostate cancer reported a survival benefit for the concurrent radiation therapy group (78). Although these results indirectly suggest a beneficial effect of radiation therapy over no initial treatment, a direct comparative study in appropriately selected patients with clinically localized prostate cancer is needed to confirm or refute this conjecture. Two ongoing RCTs are comparing active surveillance with radical prostatectomy and radiation therapy: the Canadian START trial (phase III Study of Active Surveillance Therapy Against Radical Treatment in Patients Diagnosed With Favourable Risk Prostate Cancer; ClinicalTrials.gov registration number: NCT00499174) and the British ProtecT trial (Prostate Testing for Cancer and Treatment; ClinicalTrials.gov registration number: NCT00632983). Results from these trials should help clarify which men can be safely observed and which men need therapy and how radiation therapy and radical prostatectomy compare as the primary treatment approach. Much research remains to be done to evaluate EBRT versus brachytherapy and the various dose and fractionation schedules.

In summary, currently available evidence is insufficient to draw definitive conclusions about the effectiveness of radiation treatments for localized prostate cancer compared with no treatment or no initial treatment. Despite the addition of new studies, these conclusions remain largely similar to those from the 2008 review (4).

Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ.  Cancer statistics, 2009. CA Cancer J Clin. 2009; 59:225-49.
PubMed
CrossRef
 
SEER stat fact sheets:  prostate. In: Howlader N, Noone AM, Krapcho M, Neyman N, Aminou R, Waldron W, eds, et al. SEER Cancer Statistics Review, 1975-2008. Bethesda, MD: National Cancer Institute; 2010. Accessed atwww.seer.cancer.gov/statfacts/html/prost.htmlon 15 November 2010.
 
Cooperberg MR, Lubeck DP, Mehta SS, Carroll PR, CaPSURE.  Time trends in clinical risk stratification for prostate cancer: implications for outcomes (data from CaPSURE). J Urol. 2003; 170:S21-5.
PubMed
 
Wilt TJ, MacDonald R, Rutks I, Shamliyan TA, Taylor BC, Kane RL.  Systematic review: comparative effectiveness and harms of treatments for clinically localized prostate cancer. Ann Intern Med. 2008; 148:435-48.
PubMed
 
Agency for Healthcare Research and Quality.  Methods Guide for Effectiveness and Comparative Effectiveness Reviews. AHRQ publication no. 10(11)-EHC063-EF. Rockville, MD: Agency for Healthcare Research and Quality; 2011.
 
Ip S, Dvorak T, Yu WW, Patel K, Obadan NO, Chung M, et al.  Comparative Evaluation of Radiation Treatments for Clinically Localized Prostate Cancer: An Update. (Prepared by the Tufts Evidence-based Practice Center under contract no. 209 2007 10055 I.) Technology Assessment report. Rockville, MD: Agency for Healthcare Research and Quality; 2010. Accessed atwww.cmms.hhs.gov/coveragegeninfo/downloads/id69ta.pdfon 6 May 2011.
 
Cooperative Group Common Toxicity Criteria.  Philadelphia: Radiation Therapy Oncology Group; 2010. Accessed atwww.rtog.org/ResearchAssociates/AdverseEventReporting/CooperativeGroupCommonToxicityCriteria.aspxon 20 May 2011.
 
Common Toxicity Criteria Manual. Bethesda, MD : National Cancer Institute Cancer Therapy Evaluation Program; 1999. Accessed athttp://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/ctcmanual_v4_10-4-99.pdfon 20 May 2011.
 
Sathya JR, Davis IR, Julian JA, Guo Q, Daya D, Dayes IS. et al.  Randomized trial comparing iridium implant plus external-beam radiation therapy with external-beam radiation therapy alone in node-negative locally advanced cancer of the prostate. J Clin Oncol. 2005; 23:1192-9.
PubMed
 
Wallner K, Merrick G, True L, Sherertz T, Sutlief S, Cavanagh W. et al.  20 Gy versus 44 Gy supplemental beam radiation with Pd-103 prostate brachytherapy: preliminary biochemical outcomes from a prospective randomized multi-center trial. Radiother Oncol. 2005; 75:307-10.
PubMed
 
Kuban DA, Tucker SL, Dong L, Starkschall G, Huang EH, Cheung MR. et al.  Long-term results of the M. D. Anderson randomized dose-escalation trial for prostate cancer. Int J Radiat Oncol Biol Phys. 2008; 70:67-74.
PubMed
 
Pollack A, Zagars GK, Starkschall G, Antolak JA, Lee JJ, Huang E. et al.  Prostate cancer radiation dose response: results of the M.D. Anderson phase III randomized trial. Int J Radiat Oncol Biol Phys. 2002; 53:1097-105.
PubMed
 
Zietman AL, DeSilvio ML, Slater JD, Rossi CJ Jr, Miller DW, Adams JA. et al.  Comparison of conventional-dose vs high-dose conformal radiation therapy in clinically localized adenocarcinoma of the prostate: a randomized controlled trial. JAMA. 2005; 294:1233-9.
PubMed
 
Zietman AL, Bae K, Slater JD, Shipley WU, Efstathiou JA, Coen JJ. et al.  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. 2010; 28:1106-11.
PubMed
 
Peeters ST, Heemsbergen WD, Koper PC, van Putten WL, Slot A, Dielwart MF. et al.  Dose-response in radiotherapy for localized prostate cancer: results of the Dutch multicenter randomized phase III trial comparing 68 Gy of radiotherapy with 78 Gy. J Clin Oncol. 2006; 24:1990-6.
PubMed
 
Lukka H, Hayter C, Julian JA, Warde P, Morris WJ, Gospodarowicz M. et al.  Randomized trial comparing two fractionation schedules for patients with localized prostate cancer. J Clin Oncol. 2005; 23:6132-8.
PubMed
 
Yeoh EE, Holloway RH, Fraser RJ, Botten RJ, Di Matteo AC, Butters J. et al.  Hypofractionated versus conventionally fractionated radiation therapy for prostate carcinoma: updated results of a phase III randomized trial. Int J Radiat Oncol Biol Phys. 2006; 66:1072-83.
PubMed
 
Norkus D, Miller A, Plieskiene A, Janulionis E, Valuckas KP.  A randomized trial comparing hypofractionated and conventionally fractionated three-dimensional conformal external-beam radiotherapy for localized prostate adenocarcinoma: a report on the first-year biochemical response. Medicina (Kaunas). 2009; 45:469-75.
PubMed
 
Pollack A, Hanlon AL, Horwitz EM, Feigenberg SJ, Konski AA, Movsas B. et al.  Dosimetry and preliminary acute toxicity in the first 100 men treated for prostate cancer on a randomized hypofractionation dose escalation trial. Int J Radiat Oncol Biol Phys. 2006; 64:518-26.
PubMed
 
Merrick GS, Butler WM, Wallner KE, Allen ZA, Kurko B, Anderson RL. et al.  Dosimetry of an extracapsular anulus following permanent prostate brachytherapy. Am J Clin Oncol. 2007; 30:228-33.
PubMed
 
Herstein A, Wallner K, Merrick G, Mitsuyama H, Armstrong J, True L. et al.  I-125 versus Pd-103 for low-risk prostate cancer: long-term morbidity outcomes from a prospective randomized multicenter controlled trial. Cancer J. 2005; 11:385-9.
PubMed
 
Wallner K, Merrick G, True L, Sutlief S, Cavanagh W, Butler W.  125I versus 103Pd for low-risk prostate cancer: preliminary PSA outcomes from a prospective randomized multicenter trial. Int J Radiat Oncol Biol Phys. 2003; 57:1297-303.
PubMed
 
Choo R, Long J, Gray R, Morton G, Gardner S, Danjoux C.  Prospective survey of sexual function among patients with clinically localized prostate cancer referred for definitive radiotherapy and the impact of radiotherapy on sexual function. Support Care Cancer. 2010; 18:715-22.
PubMed
 
Abdel-Wahab M, Reis IM, Hamilton K.  Second primary cancer after radiotherapy for prostate cancer—a SEER analysis of brachytherapy versus external beam radiotherapy. Int J Radiat Oncol Biol Phys. 2008; 72:58-68.
PubMed
 
Albertsen PC, Hanley JA, Penson DF, Barrows G, Fine J.  13-year outcomes following treatment for clinically localized prostate cancer in a population based cohort. J Urol. 2007; 177:932-6.
PubMed
 
Elliott SP, Meng MV, Elkin EP, McAninch JW, Duchane J, Carroll PR, CaPSURE Investigators.  Incidence of urethral stricture after primary treatment for prostate cancer: data From CaPSURE. J Urol. 2007; 178:529-34.
PubMed
 
Tewari A, Divine G, Chang P, Shemtov MM, Milowsky M, Nanus D. et al.  Long-term survival in men with high grade prostate cancer: a comparison between conservative treatment, radiation therapy and radical prostatectomy—a propensity scoring approach. J Urol. 2007; 177:911-5.
PubMed
 
Zhou EH, Ellis RJ, Cherullo E, Colussi V, Xu F, Chen WD. et al.  Radiotherapy and survival in prostate cancer patients: a population-based study. Int J Radiat Oncol Biol Phys. 2009; 73:15-23.
PubMed
 
Smith DP, King MT, Egger S, Berry MP, Stricker PD, Cozzi P. et al.  Quality of life three years after diagnosis of localised prostate cancer: population based cohort study. BMJ. 2009; 339:b4817.
PubMed
 
Stattin P, Holmberg E, Johansson JE, Holmberg L, Adolfsson J, Hugosson J, National Prostate Cancer Register (NPCR) of Sweden.  Outcomes in localized prostate cancer: National Prostate Cancer Register of Sweden follow-up study. J Natl Cancer Inst. 2010; 102:950-8.
PubMed
 
Thong MS, Mols F, Kil PJ, Korfage IJ, van de Poll-Franse LV.  Prostate cancer survivors who would be eligible for active surveillance but were either treated with radiotherapy or managed expectantly: comparisons on long-term quality of life and symptom burden. BJU Int. 2010; 105:652-8.
PubMed
 
Gore JL, Kwan L, Lee SP, Reiter RE, Litwin MS.  Survivorship beyond convalescence: 48-month quality-of-life outcomes after treatment for localized prostate cancer. J Natl Cancer Inst. 2009; 101:888-92.
PubMed
 
Litwin MS, Gore JL, Kwan L, Brandeis JM, Lee SP, Withers HR. et al.  Quality of life after surgery, external beam irradiation, or brachytherapy for early-stage prostate cancer. Cancer. 2007; 109:2239-47.
PubMed
 
Sanda MG, Dunn RL, Michalski J, Sandler HM, Northouse L, Hembroff L. et al.  Quality of life and satisfaction with outcome among prostate-cancer survivors. N Engl J Med. 2008; 358:1250-61.
PubMed
 
Chen RC, Clark JA, Talcott JA.  Individualizing quality-of-life outcomes reporting: how localized prostate cancer treatments affect patients with different levels of baseline urinary, bowel, and sexual function. J Clin Oncol. 2009; 27:3916-22.
PubMed
 
Ferrer M, Suárez JF, Guedea F, Fernández P, Macías V, Mariño A, et al. Multicentric Spanish Group of Clinically Localized Prostate Cancer.  Health-related quality of life 2 years after treatment with radical prostatectomy, prostate brachytherapy, or external beam radiotherapy in patients with clinically localized prostate cancer. Int J Radiat Oncol Biol Phys. 2008; 72:421-32.
PubMed
 
Pardo Y, Guedea F, Aguiló F, Fernández P, Macías V, Mariño A. et al.  Quality-of-life impact of primary treatments for localized prostate cancer in patients without hormonal treatment. J Clin Oncol. 2010; 28:4687-96.
PubMed
 
Pe ML, Trabulsi EJ, Kedika R, Pequignot E, Dicker AP, Gomella LG. et al.  Effect of percentage of positive prostate biopsy cores on biochemical outcome in low-risk PCa treated with brachytherapy or 3D-CRT. Urology. 2009; 73:1328-34.
PubMed
 
Nieder AM, Porter MP, Soloway MS.  Radiation therapy for prostate cancer increases subsequent risk of bladder and rectal cancer: a population based cohort study. J Urol. 2008; 180:2005-9.
PubMed
 
Lesperance RN, Kjorstadt RJ, Halligan JB, Steele SR.  Colorectal complications of external beam radiation versus brachytherapy for prostate cancer. Am J Surg. 2008;195:616-20; discussion 620. [PMID: 18374892]
 
Gondi V, Deutsch I, Mansukhani M, O'Toole KM, Shah JN, Schiff PB. et al.  Intermediate-risk localized prostate cancer in the PSA era: radiotherapeutic alternatives. Urology. 2007; 69:541-6.
PubMed
 
Eade TN, Horwitz EM, Ruth K, Buyyounouski MK, D'Ambrosio DJ, Feigenberg SJ. et al.  A comparison of acute and chronic toxicity for men with low-risk prostate cancer treated with intensity-modulated radiation therapy or (125)I permanent implant. Int J Radiat Oncol Biol Phys. 2008; 71:338-45.
PubMed
 
Pickles T, Keyes M, Morris WJ.  Brachytherapy or conformal external radiotherapy for prostate cancer: a single-institution matched-pair analysis. Int J Radiat Oncol Biol Phys. 2010; 76:43-9.
PubMed
 
Jabbari S, Weinberg VK, Shinohara K, Speight JL, Gottschalk AR, Hsu IC. et al.  Equivalent biochemical control and improved prostate-specific antigen nadir after permanent prostate seed implant brachytherapy versus high-dose three-dimensional conformal radiotherapy and high-dose conformal proton beam radiotherapy boost. Int J Radiat Oncol Biol Phys. 2010; 76:36-42.
PubMed
 
Wong WW, Vora SA, Schild SE, Ezzell GA, Andrews PE, Ferrigni RG. et al.  Radiation dose escalation for localized prostate cancer: intensity-modulated radiotherapy versus permanent transperineal brachytherapy. Cancer. 2009; 115:5596-606.
PubMed
 
Martinez AA, Demanes J, Vargas C, Schour L, Ghilezan M, Gustafson GS.  High-dose-rate prostate brachytherapy: an excellent accelerated-hypofractionated treatment for favorable prostate cancer. Am J Clin Oncol. 2010; 33:481-8.
PubMed
 
Lev EL, Eller LS, Gejerman G, Kolassa J, Colella J, Pezzino J. et al.  Quality of life of men treated for localized prostate cancer: outcomes at 6 and 12 months. Support Care Cancer. 2009; 17:509-17.
PubMed
 
Soumarová R, Homola L, Perková H, Stursa M.  Three-dimensional conformal external beam radiotherapy versus the combination of external radiotherapy with high-dose rate brachytherapy in localized carcinoma of the prostate: comparison of acute toxicity. Tumori. 2007; 93:37-44.
PubMed
 
Joseph KJ, Alvi R, Skarsgard D, Tonita J, Pervez N, Small C. et al.  Analysis of health related quality of life (HRQoL) of patients with clinically localized prostate cancer, one year after treatment with external beam radiotherapy (EBRT) alone versus EBRT and high dose rate brachytherapy (HDRBT). Radiat Oncol. 2008; 3:20.
PubMed
 
Song Y, Chan MF, Burman C, Cann D.  Comparison of two treatment approaches for prostate cancer: intensity-modulated radiation therapy combined with 125I seed-implant brachytherapy or 125I seed-implant brachytherapy alone. J Appl Clin Med Phys. 2008; 9:2283.
PubMed
 
Zelefsky MJ, Nedelka MA, Arican ZL, Yamada Y, Cohen GN, Shippy AM. et al.  Combined brachytherapy with external beam radiotherapy for localized prostate cancer: reduced morbidity with an intraoperative brachytherapy planning technique and supplemental intensity-modulated radiation therapy. Brachytherapy. 2008; 7:1-6.
PubMed
 
Aoki M, Miki K, Sasaki H, Kido M, Shirahama J, Takagi S. et al.  Evaluation of rectal bleeding factors associated with prostate brachytherapy. Jpn J Radiol. 2009; 27:444-9.
PubMed
 
da Silva Franca CA, Vieira SL, Carvalho AC, Bernabé AJ, Penna AB.  Localized prostate cancer with intermediate- or high-risk features treated with combined external beam radiotherapy and iodine-125 seed brachytherapy. Brachytherapy. 2010; 9:307-12.
PubMed
 
Deutsch I, Zelefsky MJ, Zhang Z, Mo Q, Zaider M, Cohen G. et al.  Comparison of PSA relapse-free survival in patients treated with ultra-high-dose IMRT versus combination HDR brachytherapy and IMRT. Brachytherapy. 2010; 9:313-8.
PubMed
 
Kalakota K, Rakhno E, Pelizzari CA, Jani AB, Liauw SL.  Late rectal toxicity after prostate brachytherapy: influence of supplemental external beam radiation on dose-volume histogram analysis. Brachytherapy. 2010; 9:131-6.
PubMed
 
Martinez AA, Gonzalez J, Ye H, Ghilezan M, Shetty S, Kernen K. 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. 2011; 79:363-70.
PubMed
 
Katz AJ, Santoro M, Ashley R, Diblasio F, Witten M.  Stereotactic body radiotherapy for organ-confined prostate cancer. BMC Urol. 2010; 10:1.
PubMed
 
Al-Mamgani A, Heemsbergen WD, Levendag PC, Lebesque JV.  Subgroup analysis of patients with localized prostate cancer treated within the Dutch-randomized dose escalation trial. Radiother Oncol. 2010; 96:13-8.
PubMed
 
Talcott JA, Rossi C, Shipley WU, Clark JA, Slater JD, Niemierko A. et al.  Patient-reported long-term outcomes after conventional and high-dose combined proton and photon radiation for early prostate cancer. JAMA. 2010; 303:1046-53.
PubMed
 
Lin C, Turner S, Mai T, Kneebone A, Gebski V.  Late rectal and urinary toxicity from conformal, dose-escalated radiation therapy for prostate cancer: a prospective study of 402 patients. Australas Radiol. 2007; 51:578-83.
PubMed
 
Michalski JM, Bae K, Roach M, Markoe AM, Sandler HM, Ryu J. et al.  Long-term toxicity following 3D conformal radiation therapy for prostate cancer from the RTOG 9406 phase I/II dose escalation study. Int J Radiat Oncol Biol Phys. 2010; 76:14-22.
PubMed
 
Eade TN, Hanlon AL, Horwitz EM, Buyyounouski MK, Hanks GE, Pollack A.  What dose of external-beam radiation is high enough for prostate cancer? Int J Radiat Oncol Biol Phys. 2007; 68:682-9.
PubMed
 
Goldner G, Bombosch V, Geinitz H, Becker G, Wachter S, Glocker S. et al.  Moderate risk-adapted dose escalation with three-dimensional conformal radiotherapy of localized prostate cancer from 70 to 74 Gy. First report on 5-year morbidity and biochemical control from a prospective Austrian-German multicenter phase II trial. Strahlenther Onkol. 2009; 185:94-100.
PubMed
 
Hanssen S, Norum J.  Bladder and rectal toxicity of BeamCath application in radiotherapy of prostate cancer. Anticancer Res. 2008; 28:2865-8.
PubMed
 
Jani AB, Su A, Correa D, Gratzle J.  Comparison of late gastrointestinal and genitourinary toxicity of prostate cancer patients undergoing intensity-modulated versus conventional radiotherapy using localized fields. Prostate Cancer Prostatic Dis. 2007; 10:82-6.
PubMed
 
Jani AB, Gratzle J, Correa D.  Influence of intensity-modulated radiotherapy on acute genitourinary and gastrointestinal toxicity in the treatment of localized prostate cancer. Technol Cancer Res Treat. 2007; 6:11-5.
PubMed
 
Kupelian PA, Ciezki J, Reddy CA, Klein EA, Mahadevan A.  Effect of increasing radiation doses on local and distant failures in patients with localized prostate cancer. Int J Radiat Oncol Biol Phys. 2008; 71:16-22.
PubMed
 
Vora SA, Wong WW, Schild SE, Ezzell GA, Halyard MY.  Analysis of biochemical control and prognostic factors in patients treated with either low-dose three-dimensional conformal radiation therapy or high-dose intensity-modulated radiotherapy for localized prostate cancer. Int J Radiat Oncol Biol Phys. 2007; 68:1053-8.
PubMed
 
Zelefsky MJ, Yamada Y, Fuks Z, Zhang Z, Hunt M, Cahlon O. et al.  Long-term results of conformal radiotherapy for prostate cancer: impact of dose escalation on biochemical tumor control and distant metastases-free survival outcomes. Int J Radiat Oncol Biol Phys. 2008; 71:1028-33.
PubMed
 
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.
PubMed
 
Yeoh EK, Bartholomeusz DL, Holloway RH, Fraser RJ, Botten R, Di Matteo A. et al.  Disturbed colonic motility contributes to anorectal symptoms and dysfunction after radiotherapy for carcinoma of the prostate. Int J Radiat Oncol Biol Phys. 2010; 78:773-80.
PubMed
 
Leborgne F, Fowler J.  Acute toxicity after hypofractionated conformal radiotherapy for localized prostate cancer: nonrandomized contemporary comparison with standard fractionation. Int J Radiat Oncol Biol Phys. 2008; 72:770-6.
PubMed
 
Leborgne F, Fowler J.  Late outcomes following hypofractionated conformal radiotherapy vs. standard fractionation for localized prostate cancer: a nonrandomized contemporary comparison. Int J Radiat Oncol Biol Phys. 2009; 74:1441-6.
PubMed
 
Zilli T, Rouzaud M, Jorcano S, Dipasquale G, Nouet P, Toscas JI. et al.  Dose escalation study with two different hypofractionated intensity modulated radiotherapy techniques for localized prostate cancer: acute toxicity. Technol Cancer Res Treat. 2010; 9:263-70.
PubMed
 
Stone NN, Potters L, Davis BJ, Ciezki JP, Zelefsky MJ, Roach M. et al.  Customized dose prescription for permanent prostate brachytherapy: insights from a multicenter analysis of dosimetry outcomes. Int J Radiat Oncol Biol Phys. 2007; 69:1472-7.
PubMed
 
Stone NN, Potters L, Davis BJ, Ciezki JP, Zelefsky MJ, Roach M. et al.  Multicenter analysis of effect of high biologic effective dose on biochemical failure and survival outcomes in patients with Gleason score 7-10 prostate cancer treated with permanent prostate brachytherapy. Int J Radiat Oncol Biol Phys. 2009; 73:341-6.
PubMed
 
Gaudet M, Vigneault E, Aubin S, Varfalvy N, Harel F, Beaulieu L. et al.  Dose escalation to the dominant intraprostatic lesion defined by sextant biopsy in a permanent prostate I-125 implant: a prospective comparative toxicity analysis. Int J Radiat Oncol Biol Phys. 2010; 77:153-9.
PubMed
 
Widmark A, Klepp O, Solberg A, Damber JE, Angelsen A, Fransson P, et al. Scandinavian Prostate Cancer Group Study 7.  Endocrine treatment, with or without radiotherapy, in locally advanced prostate cancer (SPCG-7/SFUO-3): an open randomised phase III trial. Lancet. 2009; 373:301-8.
PubMed
 

Figures

Grahic Jump Location
Appendix Figure.
Summary of evidence search and selection.

CENTRAL = Cochrane Central Register of Controlled Trials; RCT = randomized, controlled trial.

Grahic Jump Location

Tables

Table Jump PlaceholderTable 1.  Characteristics of Randomized, Controlled Trials Comparing Radiation Treatments for Clinically Localized Prostate Cancer
Table Jump PlaceholderTable 2.  Summary of Evidence on Outcomes of Therapies for Clinically Localized Prostate Cancer
Table Jump PlaceholderAppendix Table 1.  Randomized, Controlled Trials Comparing Radiation Treatments for Clinically Localized Prostate Cancer and Reporting Freedom From Biochemical Failure
Table Jump PlaceholderAppendix Table 2.  Results for Comparisons of Combination Therapies
Table Jump PlaceholderAppendix Table 3.  Strength of Evidence for Radiation Treatments of Clinically Localized Prostate Cancer

References

Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ.  Cancer statistics, 2009. CA Cancer J Clin. 2009; 59:225-49.
PubMed
CrossRef
 
SEER stat fact sheets:  prostate. In: Howlader N, Noone AM, Krapcho M, Neyman N, Aminou R, Waldron W, eds, et al. SEER Cancer Statistics Review, 1975-2008. Bethesda, MD: National Cancer Institute; 2010. Accessed atwww.seer.cancer.gov/statfacts/html/prost.htmlon 15 November 2010.
 
Cooperberg MR, Lubeck DP, Mehta SS, Carroll PR, CaPSURE.  Time trends in clinical risk stratification for prostate cancer: implications for outcomes (data from CaPSURE). J Urol. 2003; 170:S21-5.
PubMed
 
Wilt TJ, MacDonald R, Rutks I, Shamliyan TA, Taylor BC, Kane RL.  Systematic review: comparative effectiveness and harms of treatments for clinically localized prostate cancer. Ann Intern Med. 2008; 148:435-48.
PubMed
 
Agency for Healthcare Research and Quality.  Methods Guide for Effectiveness and Comparative Effectiveness Reviews. AHRQ publication no. 10(11)-EHC063-EF. Rockville, MD: Agency for Healthcare Research and Quality; 2011.
 
Ip S, Dvorak T, Yu WW, Patel K, Obadan NO, Chung M, et al.  Comparative Evaluation of Radiation Treatments for Clinically Localized Prostate Cancer: An Update. (Prepared by the Tufts Evidence-based Practice Center under contract no. 209 2007 10055 I.) Technology Assessment report. Rockville, MD: Agency for Healthcare Research and Quality; 2010. Accessed atwww.cmms.hhs.gov/coveragegeninfo/downloads/id69ta.pdfon 6 May 2011.
 
Cooperative Group Common Toxicity Criteria.  Philadelphia: Radiation Therapy Oncology Group; 2010. Accessed atwww.rtog.org/ResearchAssociates/AdverseEventReporting/CooperativeGroupCommonToxicityCriteria.aspxon 20 May 2011.
 
Common Toxicity Criteria Manual. Bethesda, MD : National Cancer Institute Cancer Therapy Evaluation Program; 1999. Accessed athttp://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/ctcmanual_v4_10-4-99.pdfon 20 May 2011.
 
Sathya JR, Davis IR, Julian JA, Guo Q, Daya D, Dayes IS. et al.  Randomized trial comparing iridium implant plus external-beam radiation therapy with external-beam radiation therapy alone in node-negative locally advanced cancer of the prostate. J Clin Oncol. 2005; 23:1192-9.
PubMed
 
Wallner K, Merrick G, True L, Sherertz T, Sutlief S, Cavanagh W. et al.  20 Gy versus 44 Gy supplemental beam radiation with Pd-103 prostate brachytherapy: preliminary biochemical outcomes from a prospective randomized multi-center trial. Radiother Oncol. 2005; 75:307-10.
PubMed
 
Kuban DA, Tucker SL, Dong L, Starkschall G, Huang EH, Cheung MR. et al.  Long-term results of the M. D. Anderson randomized dose-escalation trial for prostate cancer. Int J Radiat Oncol Biol Phys. 2008; 70:67-74.
PubMed
 
Pollack A, Zagars GK, Starkschall G, Antolak JA, Lee JJ, Huang E. et al.  Prostate cancer radiation dose response: results of the M.D. Anderson phase III randomized trial. Int J Radiat Oncol Biol Phys. 2002; 53:1097-105.
PubMed
 
Zietman AL, DeSilvio ML, Slater JD, Rossi CJ Jr, Miller DW, Adams JA. et al.  Comparison of conventional-dose vs high-dose conformal radiation therapy in clinically localized adenocarcinoma of the prostate: a randomized controlled trial. JAMA. 2005; 294:1233-9.
PubMed
 
Zietman AL, Bae K, Slater JD, Shipley WU, Efstathiou JA, Coen JJ. et al.  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. 2010; 28:1106-11.
PubMed
 
Peeters ST, Heemsbergen WD, Koper PC, van Putten WL, Slot A, Dielwart MF. et al.  Dose-response in radiotherapy for localized prostate cancer: results of the Dutch multicenter randomized phase III trial comparing 68 Gy of radiotherapy with 78 Gy. J Clin Oncol. 2006; 24:1990-6.
PubMed
 
Lukka H, Hayter C, Julian JA, Warde P, Morris WJ, Gospodarowicz M. et al.  Randomized trial comparing two fractionation schedules for patients with localized prostate cancer. J Clin Oncol. 2005; 23:6132-8.
PubMed
 
Yeoh EE, Holloway RH, Fraser RJ, Botten RJ, Di Matteo AC, Butters J. et al.  Hypofractionated versus conventionally fractionated radiation therapy for prostate carcinoma: updated results of a phase III randomized trial. Int J Radiat Oncol Biol Phys. 2006; 66:1072-83.
PubMed
 
Norkus D, Miller A, Plieskiene A, Janulionis E, Valuckas KP.  A randomized trial comparing hypofractionated and conventionally fractionated three-dimensional conformal external-beam radiotherapy for localized prostate adenocarcinoma: a report on the first-year biochemical response. Medicina (Kaunas). 2009; 45:469-75.
PubMed
 
Pollack A, Hanlon AL, Horwitz EM, Feigenberg SJ, Konski AA, Movsas B. et al.  Dosimetry and preliminary acute toxicity in the first 100 men treated for prostate cancer on a randomized hypofractionation dose escalation trial. Int J Radiat Oncol Biol Phys. 2006; 64:518-26.
PubMed
 
Merrick GS, Butler WM, Wallner KE, Allen ZA, Kurko B, Anderson RL. et al.  Dosimetry of an extracapsular anulus following permanent prostate brachytherapy. Am J Clin Oncol. 2007; 30:228-33.
PubMed
 
Herstein A, Wallner K, Merrick G, Mitsuyama H, Armstrong J, True L. et al.  I-125 versus Pd-103 for low-risk prostate cancer: long-term morbidity outcomes from a prospective randomized multicenter controlled trial. Cancer J. 2005; 11:385-9.
PubMed
 
Wallner K, Merrick G, True L, Sutlief S, Cavanagh W, Butler W.  125I versus 103Pd for low-risk prostate cancer: preliminary PSA outcomes from a prospective randomized multicenter trial. Int J Radiat Oncol Biol Phys. 2003; 57:1297-303.
PubMed
 
Choo R, Long J, Gray R, Morton G, Gardner S, Danjoux C.  Prospective survey of sexual function among patients with clinically localized prostate cancer referred for definitive radiotherapy and the impact of radiotherapy on sexual function. Support Care Cancer. 2010; 18:715-22.
PubMed
 
Abdel-Wahab M, Reis IM, Hamilton K.  Second primary cancer after radiotherapy for prostate cancer—a SEER analysis of brachytherapy versus external beam radiotherapy. Int J Radiat Oncol Biol Phys. 2008; 72:58-68.
PubMed
 
Albertsen PC, Hanley JA, Penson DF, Barrows G, Fine J.  13-year outcomes following treatment for clinically localized prostate cancer in a population based cohort. J Urol. 2007; 177:932-6.
PubMed
 
Elliott SP, Meng MV, Elkin EP, McAninch JW, Duchane J, Carroll PR, CaPSURE Investigators.  Incidence of urethral stricture after primary treatment for prostate cancer: data From CaPSURE. J Urol. 2007; 178:529-34.
PubMed
 
Tewari A, Divine G, Chang P, Shemtov MM, Milowsky M, Nanus D. et al.  Long-term survival in men with high grade prostate cancer: a comparison between conservative treatment, radiation therapy and radical prostatectomy—a propensity scoring approach. J Urol. 2007; 177:911-5.
PubMed
 
Zhou EH, Ellis RJ, Cherullo E, Colussi V, Xu F, Chen WD. et al.  Radiotherapy and survival in prostate cancer patients: a population-based study. Int J Radiat Oncol Biol Phys. 2009; 73:15-23.
PubMed
 
Smith DP, King MT, Egger S, Berry MP, Stricker PD, Cozzi P. et al.  Quality of life three years after diagnosis of localised prostate cancer: population based cohort study. BMJ. 2009; 339:b4817.
PubMed
 
Stattin P, Holmberg E, Johansson JE, Holmberg L, Adolfsson J, Hugosson J, National Prostate Cancer Register (NPCR) of Sweden.  Outcomes in localized prostate cancer: National Prostate Cancer Register of Sweden follow-up study. J Natl Cancer Inst. 2010; 102:950-8.
PubMed
 
Thong MS, Mols F, Kil PJ, Korfage IJ, van de Poll-Franse LV.  Prostate cancer survivors who would be eligible for active surveillance but were either treated with radiotherapy or managed expectantly: comparisons on long-term quality of life and symptom burden. BJU Int. 2010; 105:652-8.
PubMed
 
Gore JL, Kwan L, Lee SP, Reiter RE, Litwin MS.  Survivorship beyond convalescence: 48-month quality-of-life outcomes after treatment for localized prostate cancer. J Natl Cancer Inst. 2009; 101:888-92.
PubMed
 
Litwin MS, Gore JL, Kwan L, Brandeis JM, Lee SP, Withers HR. et al.  Quality of life after surgery, external beam irradiation, or brachytherapy for early-stage prostate cancer. Cancer. 2007; 109:2239-47.
PubMed
 
Sanda MG, Dunn RL, Michalski J, Sandler HM, Northouse L, Hembroff L. et al.  Quality of life and satisfaction with outcome among prostate-cancer survivors. N Engl J Med. 2008; 358:1250-61.
PubMed
 
Chen RC, Clark JA, Talcott JA.  Individualizing quality-of-life outcomes reporting: how localized prostate cancer treatments affect patients with different levels of baseline urinary, bowel, and sexual function. J Clin Oncol. 2009; 27:3916-22.
PubMed
 
Ferrer M, Suárez JF, Guedea F, Fernández P, Macías V, Mariño A, et al. Multicentric Spanish Group of Clinically Localized Prostate Cancer.  Health-related quality of life 2 years after treatment with radical prostatectomy, prostate brachytherapy, or external beam radiotherapy in patients with clinically localized prostate cancer. Int J Radiat Oncol Biol Phys. 2008; 72:421-32.
PubMed
 
Pardo Y, Guedea F, Aguiló F, Fernández P, Macías V, Mariño A. et al.  Quality-of-life impact of primary treatments for localized prostate cancer in patients without hormonal treatment. J Clin Oncol. 2010; 28:4687-96.
PubMed
 
Pe ML, Trabulsi EJ, Kedika R, Pequignot E, Dicker AP, Gomella LG. et al.  Effect of percentage of positive prostate biopsy cores on biochemical outcome in low-risk PCa treated with brachytherapy or 3D-CRT. Urology. 2009; 73:1328-34.
PubMed
 
Nieder AM, Porter MP, Soloway MS.  Radiation therapy for prostate cancer increases subsequent risk of bladder and rectal cancer: a population based cohort study. J Urol. 2008; 180:2005-9.
PubMed
 
Lesperance RN, Kjorstadt RJ, Halligan JB, Steele SR.  Colorectal complications of external beam radiation versus brachytherapy for prostate cancer. Am J Surg. 2008;195:616-20; discussion 620. [PMID: 18374892]
 
Gondi V, Deutsch I, Mansukhani M, O'Toole KM, Shah JN, Schiff PB. et al.  Intermediate-risk localized prostate cancer in the PSA era: radiotherapeutic alternatives. Urology. 2007; 69:541-6.
PubMed
 
Eade TN, Horwitz EM, Ruth K, Buyyounouski MK, D'Ambrosio DJ, Feigenberg SJ. et al.  A comparison of acute and chronic toxicity for men with low-risk prostate cancer treated with intensity-modulated radiation therapy or (125)I permanent implant. Int J Radiat Oncol Biol Phys. 2008; 71:338-45.
PubMed
 
Pickles T, Keyes M, Morris WJ.  Brachytherapy or conformal external radiotherapy for prostate cancer: a single-institution matched-pair analysis. Int J Radiat Oncol Biol Phys. 2010; 76:43-9.
PubMed
 
Jabbari S, Weinberg VK, Shinohara K, Speight JL, Gottschalk AR, Hsu IC. et al.  Equivalent biochemical control and improved prostate-specific antigen nadir after permanent prostate seed implant brachytherapy versus high-dose three-dimensional conformal radiotherapy and high-dose conformal proton beam radiotherapy boost. Int J Radiat Oncol Biol Phys. 2010; 76:36-42.
PubMed
 
Wong WW, Vora SA, Schild SE, Ezzell GA, Andrews PE, Ferrigni RG. et al.  Radiation dose escalation for localized prostate cancer: intensity-modulated radiotherapy versus permanent transperineal brachytherapy. Cancer. 2009; 115:5596-606.
PubMed
 
Martinez AA, Demanes J, Vargas C, Schour L, Ghilezan M, Gustafson GS.  High-dose-rate prostate brachytherapy: an excellent accelerated-hypofractionated treatment for favorable prostate cancer. Am J Clin Oncol. 2010; 33:481-8.
PubMed
 
Lev EL, Eller LS, Gejerman G, Kolassa J, Colella J, Pezzino J. et al.  Quality of life of men treated for localized prostate cancer: outcomes at 6 and 12 months. Support Care Cancer. 2009; 17:509-17.
PubMed
 
Soumarová R, Homola L, Perková H, Stursa M.  Three-dimensional conformal external beam radiotherapy versus the combination of external radiotherapy with high-dose rate brachytherapy in localized carcinoma of the prostate: comparison of acute toxicity. Tumori. 2007; 93:37-44.
PubMed
 
Joseph KJ, Alvi R, Skarsgard D, Tonita J, Pervez N, Small C. et al.  Analysis of health related quality of life (HRQoL) of patients with clinically localized prostate cancer, one year after treatment with external beam radiotherapy (EBRT) alone versus EBRT and high dose rate brachytherapy (HDRBT). Radiat Oncol. 2008; 3:20.
PubMed
 
Song Y, Chan MF, Burman C, Cann D.  Comparison of two treatment approaches for prostate cancer: intensity-modulated radiation therapy combined with 125I seed-implant brachytherapy or 125I seed-implant brachytherapy alone. J Appl Clin Med Phys. 2008; 9:2283.
PubMed
 
Zelefsky MJ, Nedelka MA, Arican ZL, Yamada Y, Cohen GN, Shippy AM. et al.  Combined brachytherapy with external beam radiotherapy for localized prostate cancer: reduced morbidity with an intraoperative brachytherapy planning technique and supplemental intensity-modulated radiation therapy. Brachytherapy. 2008; 7:1-6.
PubMed
 
Aoki M, Miki K, Sasaki H, Kido M, Shirahama J, Takagi S. et al.  Evaluation of rectal bleeding factors associated with prostate brachytherapy. Jpn J Radiol. 2009; 27:444-9.
PubMed
 
da Silva Franca CA, Vieira SL, Carvalho AC, Bernabé AJ, Penna AB.  Localized prostate cancer with intermediate- or high-risk features treated with combined external beam radiotherapy and iodine-125 seed brachytherapy. Brachytherapy. 2010; 9:307-12.
PubMed
 
Deutsch I, Zelefsky MJ, Zhang Z, Mo Q, Zaider M, Cohen G. et al.  Comparison of PSA relapse-free survival in patients treated with ultra-high-dose IMRT versus combination HDR brachytherapy and IMRT. Brachytherapy. 2010; 9:313-8.
PubMed
 
Kalakota K, Rakhno E, Pelizzari CA, Jani AB, Liauw SL.  Late rectal toxicity after prostate brachytherapy: influence of supplemental external beam radiation on dose-volume histogram analysis. Brachytherapy. 2010; 9:131-6.
PubMed
 
Martinez AA, Gonzalez J, Ye H, Ghilezan M, Shetty S, Kernen K. 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. 2011; 79:363-70.
PubMed
 
Katz AJ, Santoro M, Ashley R, Diblasio F, Witten M.  Stereotactic body radiotherapy for organ-confined prostate cancer. BMC Urol. 2010; 10:1.
PubMed
 
Al-Mamgani A, Heemsbergen WD, Levendag PC, Lebesque JV.  Subgroup analysis of patients with localized prostate cancer treated within the Dutch-randomized dose escalation trial. Radiother Oncol. 2010; 96:13-8.
PubMed
 
Talcott JA, Rossi C, Shipley WU, Clark JA, Slater JD, Niemierko A. et al.  Patient-reported long-term outcomes after conventional and high-dose combined proton and photon radiation for early prostate cancer. JAMA. 2010; 303:1046-53.
PubMed
 
Lin C, Turner S, Mai T, Kneebone A, Gebski V.  Late rectal and urinary toxicity from conformal, dose-escalated radiation therapy for prostate cancer: a prospective study of 402 patients. Australas Radiol. 2007; 51:578-83.
PubMed
 
Michalski JM, Bae K, Roach M, Markoe AM, Sandler HM, Ryu J. et al.  Long-term toxicity following 3D conformal radiation therapy for prostate cancer from the RTOG 9406 phase I/II dose escalation study. Int J Radiat Oncol Biol Phys. 2010; 76:14-22.
PubMed
 
Eade TN, Hanlon AL, Horwitz EM, Buyyounouski MK, Hanks GE, Pollack A.  What dose of external-beam radiation is high enough for prostate cancer? Int J Radiat Oncol Biol Phys. 2007; 68:682-9.
PubMed
 
Goldner G, Bombosch V, Geinitz H, Becker G, Wachter S, Glocker S. et al.  Moderate risk-adapted dose escalation with three-dimensional conformal radiotherapy of localized prostate cancer from 70 to 74 Gy. First report on 5-year morbidity and biochemical control from a prospective Austrian-German multicenter phase II trial. Strahlenther Onkol. 2009; 185:94-100.
PubMed
 
Hanssen S, Norum J.  Bladder and rectal toxicity of BeamCath application in radiotherapy of prostate cancer. Anticancer Res. 2008; 28:2865-8.
PubMed
 
Jani AB, Su A, Correa D, Gratzle J.  Comparison of late gastrointestinal and genitourinary toxicity of prostate cancer patients undergoing intensity-modulated versus conventional radiotherapy using localized fields. Prostate Cancer Prostatic Dis. 2007; 10:82-6.
PubMed
 
Jani AB, Gratzle J, Correa D.  Influence of intensity-modulated radiotherapy on acute genitourinary and gastrointestinal toxicity in the treatment of localized prostate cancer. Technol Cancer Res Treat. 2007; 6:11-5.
PubMed
 
Kupelian PA, Ciezki J, Reddy CA, Klein EA, Mahadevan A.  Effect of increasing radiation doses on local and distant failures in patients with localized prostate cancer. Int J Radiat Oncol Biol Phys. 2008; 71:16-22.
PubMed
 
Vora SA, Wong WW, Schild SE, Ezzell GA, Halyard MY.  Analysis of biochemical control and prognostic factors in patients treated with either low-dose three-dimensional conformal radiation therapy or high-dose intensity-modulated radiotherapy for localized prostate cancer. Int J Radiat Oncol Biol Phys. 2007; 68:1053-8.
PubMed
 
Zelefsky MJ, Yamada Y, Fuks Z, Zhang Z, Hunt M, Cahlon O. et al.  Long-term results of conformal radiotherapy for prostate cancer: impact of dose escalation on biochemical tumor control and distant metastases-free survival outcomes. Int J Radiat Oncol Biol Phys. 2008; 71:1028-33.
PubMed
 
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.
PubMed
 
Yeoh EK, Bartholomeusz DL, Holloway RH, Fraser RJ, Botten R, Di Matteo A. et al.  Disturbed colonic motility contributes to anorectal symptoms and dysfunction after radiotherapy for carcinoma of the prostate. Int J Radiat Oncol Biol Phys. 2010; 78:773-80.
PubMed
 
Leborgne F, Fowler J.  Acute toxicity after hypofractionated conformal radiotherapy for localized prostate cancer: nonrandomized contemporary comparison with standard fractionation. Int J Radiat Oncol Biol Phys. 2008; 72:770-6.
PubMed
 
Leborgne F, Fowler J.  Late outcomes following hypofractionated conformal radiotherapy vs. standard fractionation for localized prostate cancer: a nonrandomized contemporary comparison. Int J Radiat Oncol Biol Phys. 2009; 74:1441-6.
PubMed
 
Zilli T, Rouzaud M, Jorcano S, Dipasquale G, Nouet P, Toscas JI. et al.  Dose escalation study with two different hypofractionated intensity modulated radiotherapy techniques for localized prostate cancer: acute toxicity. Technol Cancer Res Treat. 2010; 9:263-70.
PubMed
 
Stone NN, Potters L, Davis BJ, Ciezki JP, Zelefsky MJ, Roach M. et al.  Customized dose prescription for permanent prostate brachytherapy: insights from a multicenter analysis of dosimetry outcomes. Int J Radiat Oncol Biol Phys. 2007; 69:1472-7.
PubMed
 
Stone NN, Potters L, Davis BJ, Ciezki JP, Zelefsky MJ, Roach M. et al.  Multicenter analysis of effect of high biologic effective dose on biochemical failure and survival outcomes in patients with Gleason score 7-10 prostate cancer treated with permanent prostate brachytherapy. Int J Radiat Oncol Biol Phys. 2009; 73:341-6.
PubMed
 
Gaudet M, Vigneault E, Aubin S, Varfalvy N, Harel F, Beaulieu L. et al.  Dose escalation to the dominant intraprostatic lesion defined by sextant biopsy in a permanent prostate I-125 implant: a prospective comparative toxicity analysis. Int J Radiat Oncol Biol Phys. 2010; 77:153-9.
PubMed
 
Widmark A, Klepp O, Solberg A, Damber JE, Angelsen A, Fransson P, et al. Scandinavian Prostate Cancer Group Study 7.  Endocrine treatment, with or without radiotherapy, in locally advanced prostate cancer (SPCG-7/SFUO-3): an open randomised phase III trial. Lancet. 2009; 373:301-8.
PubMed
 

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