Dose-Escalated Radiation Alone or in Combination With Short-Term Total Androgen Suppression for Intermediate-Risk Prostate Cancer: Patient-Reported Outcomes From NRG/Radiation Therapy Oncology Group 0815 Randomized Trial.

PURPOSE: To report patient-reported outcomes (PROs) of a phase III trial evaluating total androgen suppression (TAS) combined with dose-escalated radiation therapy (RT) for patients with intermediate-risk prostate cancer. METHODS: Patients with intermediate-risk prostate cancer were randomly assigned to dose-escalated RT alone (arm 1) or RT plus TAS (arm 2) consisting of luteinizing hormone-releasing hormone agonist/antagonist with oral antiandrogen for 6 months. The primary PRO was the validated Expanded Prostate Cancer Index Composite (EPIC-50). Secondary PROs included Patient-Reported Outcome Measurement Information System (PROMIS)-fatigue and EuroQOL five-dimensions scale questionnaire (EQ-5D). PRO change scores, calculated for each patient as the follow-up score minus baseline score (at the end of RT and at 6, 12, and 60 months), were compared between treatment arms using a two-sample t test. An effect size of 0.50 standard deviation was considered clinically meaningful. RESULTS: For the primary PRO instrument (EPIC), the completion rates were ≥86% through the first year of follow-up and 70%-75% at 5 years. For the EPIC hormonal and sexual domains, there were clinically meaningful (P < .0001) deficits in the RT + TAS arm. However, there were no clinically meaningful differences by 1 year between arms. There were also no clinically meaningful differences at any time points between arms for PROMIS-fatigue, EQ-5D, and EPIC bowel/urinary scores. CONCLUSION: Compared with dose-escalated RT alone, adding TAS demonstrated clinically meaningful declines only in EPIC hormonal and sexual domains. However, even these PRO differences were transient, and there were no clinically meaningful differences between arms by 1 year.

Normal Tissue Integral Dose as a Result of Prostate Radiation Therapy: A Quantitative Comparison Between High-Dose-Rate Brachytherapy and Modern External Beam Radiation Therapy Techniques.

Purpose: Quantification of integral radiation dose delivered during treatment for prostate cancer is lacking. We performed a comparative quantification of dose to nontarget body tissues delivered via 4 common radiation techniques: conventional volumetric modulated arc therapy, stereotactic body radiation therapy, pencil-beam scanning proton therapy, and high-dose-rate brachytherapy. Methods and Materials: Plans for each radiation technique were generated for 10 patients with typical anatomy. For brachytherapy plans, virtual needles were placed to achieve standard dosimetry. Standard planning target volume margins or robustness margins were applied as appropriate. A "normal tissue" structure (entire computed tomography simulation volume minus planning target volume) was generated for integral dose computation. Dose-volume histogram parameters for targets and normal structures were tabulated. Normal tissue integral dose was calculated by multiplying normal tissue volume by mean dose. Results: Normal tissue integral dose was lowest for brachytherapy. Pencil-beam scanning protons, stereotactic body radiation therapy, and brachytherapy resulted in 17%, 57%, and 91% absolute reductions compared with standard volumetric modulated arc therapy, respectively. Mean nontarget tissues receiving 25%, 50%, and 75% of the prescription dose were reduced by 85%, 76%, and 83% for brachytherapy relative to volumetric modulated arc therapy, by 79%, 64%, and 74% relative to stereotactic body radiation therapy, and 73%, 60%, and 81% relative to proton therapy. All reductions observed using brachytherapy were statistically significant. Conclusions: High-dose-rate brachytherapy is an effective technique for reducing dose to nontarget body tissues relative to volumetric modulated arc therapy, stereotactic body radiation therapy, and pencil-beam scanning proton therapy.

Quality of Life Implications of Dose-Escalated External Beam Radiation for Localized Prostate Cancer: Results of a Prospective Randomized Phase 3 Clinical Trial, NRG/RTOG 0126.

PURPOSE: External beam radiation therapy (EBRT) dose escalation has been tested in multiple prospective trials. However, the impact on patient reported outcomes (PROs) associated with higher doses of EBRT remain poorly understood. We sought to assess the differences in PROs between men treated with a dose of 70.2 Gy versus 79.2 Gy of EBRT for prostate cancer. METHODS AND MATERIALS: The phase 3 clinical trial RTOG 0126 randomized 1532 patients with prostate cancer between March 2002 and August 2008 to 79.2 Gy over 44 fractions versus 70.2 Gy over 39 fractions. Eligible patients participated in the PRO data collection. PROs completed included the International Index of Erectile Function Questionnaire (IIEF), Functional Alterations due to Changes in Elimination (FACE), and the Spitzer Quality of Life Index (SQLI). The timepoints for the IIEF were collected pre-entry and at 6, 12, and 24 months. The FACE and SQLI were collected pre-entry and at 3, 6, 12, 18, and 24 months. The impact of EBRT dose to normal structures (penile bulb, rectum, and bladder) on PROs was also examined. Mixed effects models were used to analyze trends across time. RESULTS: In total, 1144 patients completed baseline IIEF forms and of these, 56%, 64%, and 61% completed the IIEF at 6, 12, and 24 months, respectively; 1123 patients completed the FACE score at baseline and 50%, 61%, 73%, 61%, and 65% completed all 15 items for the FACE metric at timepoints of 3, 6, 12, 18, and 24 months, respectively. Erectile dysfunction at 12 months based on the single question was not significantly different between arms (38.1% for the standard dose radiation therapy arm vs 49.7% for the dose escalated radiation therapy arm; P = .051). Treatment arm (70.2 vs 79.2) had no significant impact on any PRO metrics measured across all collected domains. Comprehensive dosimetric analyses are presented and reveal multiple significant differences to regional organs at risk. CONCLUSIONS: Compliance with PRO data collection was lower than anticipated in this phase 3 trial. Examining the available data, dose escalated EBRT did not appear to be associated with any detriment to PROs across numerous prospectively collected domains. These data, notwithstanding limitations, add to our understanding of the implications of EBRT dose escalation in prostate cancer. Furthermore, these results illustrate challenges associated with PRO data collection.

Long-Term Results of NRG Oncology/RTOG 0321: A Phase II Trial of Combined High Dose Rate Brachytherapy and External Beam Radiation Therapy for Adenocarcinoma of the Prostate.

PURPOSE: To report the long-term outcome of patients with prostate cancer treated with external beam radiation therapy and high dose rate (HDR) brachytherapy from a prospective multi-institutional trial conducted by NRG Oncology/RTOG. METHODS AND MATERIALS: Patients with clinically localized (T1c-T3b) prostate cancer without prior history of transurethral resection of prostate or hip prosthesis were eligible for this study. All patients were treated with a combination of 45 Gy in 25 fractions from external beam radiation therapy and one HDR implant delivering 19 Gy in 2 fractions. Adverse events (AE) were collected using Common Toxicity Criteria for Adverse Events, version 3. Cumulative incidence was used to estimate time to severe late gastrointestinal (GI)/genitourinary (GU) toxicity, biochemical failure, disease-specific mortality, local failure, and distant failure. Overall survival was estimated using the Kaplan-Meier method. RESULTS: One hundred and twenty-nine patients were enrolled from July 2004 to May 2006. AE data was available for 115 patients. Patients were National Comprehensive Cancer Network (NCCN) intermediate to very high risk. The median age was 68, T1c-T2c 91%, T3a-T3b 9%, PSA ≤10 70%, PSA >10 to ≤20 30%, GS 6 10%, GS 7 72%, and GS 8 to 10 18%. Forty-three percent of patients received hormonal therapy. At a median follow-up time of 10 years, there were 6 (5%) patients with grade 3 GI and GU treatment-related AEs, and no late grade 4 to 5 GI and GU AEs. At 5 and 10 years, the rate of late grade 3 gastrointestinal and genitourinary AEs was 4% and 5%, respectively. Five- and 10-year overall survival rates were 95% and 76%. Biochemical failure rates per Phoenix definition at 5 and 10 years were 14% and 23%. The 10-year rate of disease-specific mortality was 6%. At 5 and 10 years, the rates of distant failure were 4% and 8%, respectively. The rates of local failure at 5 and 10 years were 2% at both time points. CONCLUSIONS: Combined modality treatment using HDR prostate brachytherapy leads to excellent long-term clinical outcomes in this prospective multi-institutional trial.

Five-Year Outcomes of a Single-Institution Prospective Trial of 19-Gy Single-Fraction High-Dose-Rate Brachytherapy for Low- and Intermediate-Risk Prostate Cancer.

PURPOSE: To update outcome and toxicity results of a prospective trial of 19-Gy single-fraction high-dose-rate (HDR) brachytherapy for men with low- and intermediate-risk prostate cancer. METHODS AND MATERIALS: Patients were treated on a prospective study of single-fraction HDR brachytherapy. All patients had low- or intermediate-risk prostate cancer. Patients with prostate volumes >50 cm3, taking alpha-blockers for urinary symptoms, or with baseline American Urologic Association symptom scores >12 were ineligible. Patients underwent transrectal ultrasound-guided interstitial implant of the prostate followed by single-fraction HDR brachytherapy to a prescription dose of 19 Gy. RESULTS: Sixty-eight patients were enrolled with a median follow-up of 3.9 years. Median age was 62 years. Median gland volume at the time of treatment was 35 cm3, 92.6% of patients had T1 disease, 63.2% had a Gleason score of 6, and median pretreatment prostate-specific antigen was 5.0 ng/mL. Chronic grade 2 genitourinary toxicity was 14.7%. No grade 3 urinary toxicity occurred. A single patient experienced grade 2+ rectal toxicity (grade 3 diarrhea) that was transient and resolved with medical management. The 5-year estimated disease-free survival was 77.2% with no significant difference between low- and intermediate-risk patients. A single patient developed distant metastases during the follow-up period. Biopsy-proven local failure at 5 years was 18.8%, occurring at a median interval of 4.0 years posttreatment. No deaths occurred during follow-up. CONCLUSIONS: With extended follow-up, toxicity rates after single-fraction 19-Gy HDR brachytherapy remain low. Higher-than-expected rates of biochemical and local failure, however, raise concerns regarding the adequacy of this dose. Additional investigation to define the optimal single-fraction HDR brachytherapy dose is warranted, and single-fraction treatment currently should not be offered outside the context of a clinical trial.

Cost-effectiveness of prostate boost with high-dose-rate brachytherapy versus intensity-modulated radiation therapy in the treatment of intermediate-high risk prostate cancer.

PURPOSE: The recently published ASCENDE-RT randomized clinical trial demonstrated improved biochemical control, albeit with increased toxicity, for a prostate boost with brachytherapy versus external beam radiation therapy alone in patients with intermediate-high risk prostate cancer. In this study, we investigated the cost-effectiveness of these two modalities in the treatment of intermediate-high risk prostate cancer. METHODS AND MATERIALS: A multistate Markov model was created to model a patient with intermediate-high risk prostate cancer. The two treatment options modeled were (1) 23 fractions of intensity-modulated radiation therapy (IMRT) and two fractions of high-dose-rate prostate brachytherapy (brachytherapy boost) and (2) 44 fractions of IMRT (IMRT alone). Each patient received 1 year of hormone therapy, per the ASCENDE-RT protocol. Model assumptions, including clinical outcomes, toxicity, and utilities were derived from the medical literature. Costs of radiation therapy were estimated using Medicare reimbursement data. RESULTS: The estimated expected lifetime cost of brachytherapy boost was $68,696, compared to $114,944 for IMRT alone. Brachytherapy boost significantly lowered expected lifetime treatment costs because it decreased the incidence of metastatic castration-resistant prostate cancer, cutting the use of expensive targeted therapy for metastatic castration-resistant prostate cancer. Brachytherapy boost had an expected quality-adjusted life years of 10.8 years, compared to 9.3 years for IMRT alone. One-way sensitivity analyses of our results found brachytherapy boost to be cost-effective over a wide range of cost, utility, and cancer progression rate assumptions. CONCLUSIONS: IMRT with high-dose-rate brachytherapy boost is a cost-effective treatment for intermediate-high risk prostate cancer compared to IMRT alone.

ACR Appropriateness Criteria for external beam radiation therapy treatment planning for clinically localized prostate cancer, part II of II.

PURPOSE: To present the most updated American College of Radiology (ACR) Appropriateness Criteria formed by an expert panel on the appropriate delivery of external beam radiation to manage stage T1 and T2 prostate cancer (in the definitive setting and post-prostatectomy) and to provide clinical variants with expert recommendations based on accompanying Appropriateness Criteria for target volumes and treatment planning. METHODS AND MATERIALS: The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a panel of multidisciplinary experts. The guideline development and revision process includes an extensive analysis of current medical literature from peer-reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In instances in which evidence is lacking or equivocal, expert opinion may supplement available evidence to recommend imaging or treatment. RESULTS: The panel summarizes the most recent and relevant literature on the topic, including organ motion and localization methods, image guidance, and delivery techniques (eg, 3-dimensional conformal intensity modulation). The panel presents 7 clinical variants, including (1) a standard case and cases with (2) a distended rectum, (3) a large-volume prostate, (4) bilateral hip implants, (5) inflammatory bowel disease, (6) prior prostatectomy, and (7) a pannus extending into the radiation field. Each case outlines the appropriate techniques for simulation, treatment planning, image guidance, dose, and fractionation. Numerical rating and commentary is given for each treatment approach in each variant. CONCLUSIONS: External beam radiation is a key component of the curative management of T1 and T2 prostate cancer. By combining the most recent medical literature, these Appropriateness Criteria can aid clinicians in determining the appropriate treatment delivery and personalized approaches for individual patients.

Increasing Fractional Doses Increases the Probability of Benign PSA Bounce in Patients Undergoing Definitive HDR Brachytherapy for Prostate Cancer.

PURPOSE: Prostate-specific antigen (PSA) bounce is a temporary elevation of the PSA level above a prior nadir. The purpose of this study was to determine whether the frequency of a PSA bounce following high-dose-rate (HDR) interstitial brachytherapy for the treatment of prostate cancer is associated with individual treatment fraction size. METHODS AND MATERIALS: Between 1999 and 2014, 554 patients underwent treatment of low- or intermediate-risk prostate cancer with definitive HDR brachytherapy as monotherapy and had ≥3 subsequent PSA measurements. Four different fraction sizes were used: 950 cGy × 4 fractions, 1200 cGy × 2 fractions, 1350 cGy × 2 fractions, 1900 cGy × 1 fraction. Four definitions of PSA bounce were applied: ≥0.2, ≥0.5, ≥1.0, and ≥2.0 ng/mL above the prior nadir with a subsequent return to the nadir. RESULTS: The median follow-up period was 3.7 years. The actuarial 3-year rate of PSA bounce for the entire cohort was 41.3%, 28.4%, 17.4%, and 6.8% for nadir +0.2, +0.5, +1.0, and +2.0 ng/mL, respectively. The 3-year rate of PSA bounce >0.2 ng/mL was 42.2%, 32.1%, 41.0%, and 59.1% for the 950-, 1200-, 1350-, and 1900-cGy/fraction levels, respectively (P=.002). The hazard ratio for bounce >0.2 ng/mL for patients receiving a single fraction of 1900 cGy compared with those receiving treatment in multiple fractions was 1.786 (P=.024). For patients treated with a single 1900-cGy fraction, the 1-, 2-, and 3-year rates of PSA bounce exceeding the Phoenix biochemical failure definition (nadir +2 ng/mL) were 4.5%, 18.7%, and 18.7%, respectively, higher than the rates for all other administered dose levels (P=.025). CONCLUSIONS: The incidence of PSA bounce increases with single-fraction HDR treatment. Knowledge of posttreatment PSA kinetics may aid in decision making regarding management of potential biochemical failures.

ACR Appropriateness Criteria® Locally Advanced, High-Risk Prostate Cancer.

PURPOSE: To present the most updated American College of Radiology consensus guidelines formed from an expert panel on treatment of locally advanced, high-risk prostate cancer METHODS:: The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer-reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. RESULTS: The panel summarized the most recent and relevant literature on the topic and voted on 4 clinical variants illustrating the appropriate management of locally advanced, high-risk cancer. Numerical rating and commentary reflecting the panel consensus was given for each treatment approach in each variant. CONCLUSIONS: Aggressive local approaches including surgery followed by adjuvant XRT, beam combined with androgen deprivation therapy, and beam combined with brachytherapy have resulted in unpresented success in locally advanced, high-risk prostate cancer. By combining most recent medical literature and expert opinion, this guideline can aid clinicians in the appropriate integration of available therapeutic modalities.

ACR appropriateness criteria: Permanent source brachytherapy for prostate cancer.

PURPOSE: To provide updated American College of Radiology (ACR) appropriateness criteria for transrectal ultrasound-guided transperineal interstitial permanent source brachytherapy. METHODS AND MATERIALS: The ACR appropriateness criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. RESULTS: Permanent prostate brachytherapy (PPB) is a treatment option for appropriately selected patients with localized prostate cancer with low to very high risk disease. PPB monotherapy remains an appropriate and effective curative treatment for low-risk prostate cancer patients demonstrating excellent long-term cancer control and acceptable morbidity. PPB monotherapy can be considered for select intermediate-risk patients with multiparametric MRI useful in evaluation of such patients. High-risk patients treated with PPB should receive supplemental external beam radiotherapy (EBRT) along with androgen deprivation. Similarly, patients with involved pelvic lymph nodes may also be considered for such combined treatment but reported long-term outcomes are limited. Computed tomography-based postimplant dosimetry completed within 60 days of PPB is essential for quality assurance. PPB may be considered for treatment of local recurrence after EBRT but is associated with an increased risk of toxicity. CONCLUSIONS: Updated appropriateness criteria for patient evaluation, selection, treatment, and postimplant dosimetry are given. These criteria are intended to be advisory only with the final responsibility for patient care residing with the treating clinicians.

Favorable Preliminary Outcomes for Men With Low- and Intermediate-risk Prostate Cancer Treated With 19-Gy Single-fraction High-dose-rate Brachytherapy.

PURPOSE: To report the toxicity and preliminary clinical outcomes of a prospective trial evaluating 19-Gy, single-fraction high-dose-rate (HDR) brachytherapy for men with low- and intermediate-risk prostate cancer. METHODS AND MATERIALS: A total of 63 patients were treated according to an institutional review board-approved prospective study of single-fraction HDR brachytherapy. Eligible patients had tumor stage ≤T2a, prostate-specific antigen level ≤15 ng/mL, and Gleason score ≤7. Patients with a prostate gland volume >50 cm3 and baseline American Urologic Association symptom score >12 were ineligible. Patients underwent transrectal ultrasound-guided transperineal implantation of the prostate, followed by single-fraction HDR brachytherapy. Treatment was delivered using 192Ir to a dose of 19 Gy prescribed to the prostate, with no additional margin applied. RESULTS: Of the 63 patients, 58 had data available for analysis. Five patients had withdrawn consent during the follow-up period. The median follow-up period was 2.9 years (range 0.3-5.2). The median age was 61.4 years. The median gland volume at treatment was 34.8 cm3. Of the 58 patients, 91% had T1 disease, 71% had Gleason score ≤6 (29% with Gleason score 7), and the median pretreatment prostate-specific antigen level was 5.1 ng/mL. The acute and chronic grade 2 genitourinary toxicity incidence was 12.1% and 10.3%, respectively. No grade 3 urinary toxicity occurred. No patients experienced acute rectal toxicity grade ≥2, and 2 experienced grade ≥2 chronic gastrointestinal toxicity. Three patients experienced biochemical failure, yielding a 3-year cumulative incidence estimate of 6.8%. CONCLUSIONS: Single-fraction HDR brachytherapy is well-tolerated, with favorable preliminary biochemical and clinical disease control rates.

Outcomes Associated With 3 Treatment Schedules of High-Dose-Rate Brachytherapy Monotherapy for Favorable-Risk Prostate Cancer.

PURPOSE: We report the outcomes associated with 3 high-dose-rate (HDR) brachytherapy regimens used as monotherapy for favorable-risk prostate cancer. METHODS AND MATERIALS: Four hundred ninety-four patients with stage ≤T2b prostate cancer, Gleason score ≤7, and prostate-specific antigen levels ≤15 ng/mL underwent HDR brachytherapy as monotherapy. Of those, 319 received 38 Gy in 4 fractions, 79 received 24 Gy in 2 fractions, and 96 received 27 Gy in 2 fractions. Acute and chronic genitourinary (GU) and gastrointestinal (GI) toxicities were defined as side effects occurring ≤6 and >6 months, respectively, after radiation therapy (RT) and were graded according to the Common Terminology Criteria for Adverse Events version 3.0. The time to toxicity was calculated from the date of RT completion. Variables were analyzed with χ(2) test. P values <.05 were considered significant. RESULTS: The median overall follow-up time was 4 years (range, 5.5, 3.5, and 2.5 years for 38 Gy, 24 Gy, and 27 Gy, respectively, P<.001). Acute and chronic grade ≥2 GU and GI toxicity profiles were similar among groups. Acceptable rates of grade 2 GU toxicities were seen with overall acute/chronic frequency/urgency, dysuria, retention, incontinence, and hematuria rates of 14%/20%, 6%/7%, 7%/4%, 1.5%/2%, and 1.5%/7%, respectively. Minimal grade 3 and no grade 4 or 5 toxicities were seen. Grade 1, 2, and 3 chronic urethral stricture rates were 0.3%, 2%, and 1%, respectively. All GI toxicities were similar between groups, with overall rates of acute/chronic grade 2 diarrhea, rectal pain/tenesmus, rectal bleeding, and proctitis of 1%/1%, <1%/0.5%, 0%/2%, and <1%/1%, respectively. No grade 3, 4, or 5 toxicities were seen. All comparisons were similar for hormone-naïve patients. The median time to maximal GU/GI toxicity was similar between groups, ranging from 1 to 1.6 to 0.9 to 1.2 years, respectively. There were no differences in clinical outcomes between the 3 groups at 5 years. CONCLUSIONS: The acute and chronic toxicity profiles associated with these 3 HDR brachytherapy schedules were similar and were well tolerated. Acceptable grade 2, minimal grade 3, and no grade 4 or 5 toxicities were seen. This, combined with the fact that the clinical outcomes were similar, leads to the conclusion that all 3 regimens may be acceptable options for the management of low-risk to intermediate-risk prostate cancer.

ACR appropriateness Criteria® Postradical prostatectomy irradiation in prostate cancer.

The purpose of this article is to present an updated set of American College of Radiology consensus guidelines formed from an expert panel on the appropriate use of radiation therapy in postprostatectomy prostate cancer. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. Recent and relevant literature reviewed by the panel led to establishment of criteria for appropriate use of radiation therapy in postprostatectomy prostate cancer. The discussion includes treatment technique, appropriate dose, field design, and the role of prostate-specific antigen (PSA). Ratings and commentary of the panel on multiple treatment parameters were used to reach consensus. Patients with high-risk pathologic features benefit from postprostatectomy radiation therapy.

ACR Appropriateness Criteria® Definitive External-Beam Irradiation in stage T1 and T2 prostate cancer.

PURPOSE: To present the most updated American College of Radiology consensus guidelines formed from an expert panel on the appropriate use of external-beam radiation to manage stage T1 and T2 prostate cancer. METHODS: The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. RESULTS: The panel summarized the most recent and relevant literature on the topic and voted on 3 clinical variants illustrating the appropriate dose, techniques, and use of adjuvant hormone therapy with external-beam radiation for low-risk, intermediate-risk, and high-risk prostate cancer. Numerical rating and commentary reflecting the panel consensus was given for each treatment approach in each variant. CONCLUSIONS: External-beam radiation is a key component of the curative management of T1 and T2 prostate cancer. By combining the most recent medical literature and expert opinion, this guideline can aid clinicians in the appropriate use of external-beam radiation for prostate cancer.

An age-corrected matched-pair study of erectile function in patients treated with dose-escalated adaptive image-guided intensity-modulated radiation therapy vs. high-dose-rate brachytherapy for prostate cancer.

PURPOSE: To compare erectile dysfunction (ED) after adaptive dose-escalated image-guided intensity-modulated radiotherapy (IG-IMRT) and high-dose-rate interstitial brachytherapy (HDR) monotherapy. METHODS AND MATERIALS: Low- and intermediate-risk prostate cancer patients treated with IG-IMRT or HDR were matched on pretreatment ED, age, Gleason score, T-stage, and prostate specific antigen. Patients who received androgen deprivation therapy were excluded. ED was graded by Common Terminology Criteria for Adverse Events v4. Actuarial rates of ED were computed by the Kaplan-Meier method. RESULTS: There were 384 patients with median followup of 2.0 years (0.5-6.1) for IG-IMRT and 2.0 years (0.5-8.7) for HDR. The median IG-IMRT dose was 75.6 Gy and HDR dose 38 Gy in four fractions. For patients with no pretreatment ED, actuarial rates of requiring intervention (Grade ≥2 ED) at 3 years were 31% for IG-IMRT and 19% for HDR (p=0.23), and impotence despite medical intervention (Grade 3) were 0% for IG-IMRT and 6% for HDR (p=0.06). For patients with Grade 1 pretreatment ED, Grade ≥2 ED at 3 years were 47% for IG-IMRT and 34% for HDR (p=0.79), and Grade 3 ED were 15% in both groups (p=0.59). For patients with Grade 2 pretreatment ED, Grade 3 ED at 3 years were 22% for IG-IMRT and 37% for HDR (p=0.70). No variables were predictive of Grade ≥2 ED following treatment. CONCLUSIONS: Rates of ED requiring medical intervention for both IG-IMRT and HDR are low and equivalent. Even patients with ED before treatment are likely to maintain potency with medication use at 3 years following treatment.

Comparison of dose-escalated, image-guided radiotherapy vs. dose-escalated, high-dose-rate brachytherapy boost in a modern cohort of intermediate-risk prostate cancer patients.

PURPOSE: We compared outcomes in intermediate-risk prostate cancer patients treated with dose-escalated adaptive image-guided radiation therapy (IGRT) or dose-escalated high-dose-rate brachytherapy boost (HDR-B). METHODS AND MATERIALS: Patients with intermediate-risk prostate cancer by National Comprehensive Cancer Network criteria were treated with either CT-based off-line adaptive IGRT (n = 734) or HDR-B (n = 282). IGRT was delivered with 3D-conformal or intensity-modulated radiation therapy with a median dose of 77.4 Gy. For HDR-B, the whole pelvis received a median 46 Gy, and the prostate 2 implants of 9.5 Gy (n = 71), 10.5 Gy (n = 155), or 11.5 Gy (n = 56). RESULTS: Median followup was 3.7 years for IGRT and 8.0 years for HDR-B (p < 0.001). Eight-year biochemical control was 86% for IGRT and 91% for HDR-B (p = 0.22), disease-free survival 67% for IGRT and 79% for HDR-B (p = 0.006), and overall survival 75% for IGRT and 86% for HDR-B (p = 0.009). Cause-specific survival (8-year, 100% vs. 99%), freedom from distant metastases (98% vs. 97%), and freedom from local recurrence (98% vs. 98%) did not differ (p > 0.50 each). A worse prognosis group was defined by percent positive prostate biopsy cores >50%, perineural invasion, or stage T2b-c, encompassing 260 (35%) IGRT and 171 (61%) HDR-B patients. These patients evidenced a 5-year biochemical control of 96% for HDR-B and 87% for IGRT (p = 0.002). CONCLUSIONS: Dose-escalated IGRT and HDR-B both yield excellent clinical outcomes for patients with intermediate-risk prostate cancer. Improved biochemical control with HDR-B for patients with worse pretreatment characteristics suggests that a subgroup of intermediate-risk prostate cancer patients may benefit from dual-modality treatment.

ACR Appropriateness Criteria high-dose-rate brachytherapy for prostate cancer.

PURPOSE: High-dose-rate (HDR) brachytherapy plays a potential curative role in the treatment of prostate cancer. An expert panel was convened to review the recent literature and reach a consensus on its appropriate clinical applications. METHODS AND MATERIALS: The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. RESULTS: A summary of HDR brachytherapy's clinical applications and recent literature review was completed. Three clinical variants were developed to address common HDR dose, fractionations, and indications for its use in definitive therapy for primary and local recurrent prostate cancer. The panel reached a consensus on the specific treatment approaches with numerical rating and commentary. CONCLUSIONS: In combining available medical literature and expert opinion, this manuscript may serve as an aid for other practitioners in the appropriate application of HDR brachytherapy for prostate cancer.

Brachytherapy provides comparable outcomes and improved cost-effectiveness in the treatment of low/intermediate prostate cancer.

PURPOSE: To evaluate the cost-effectiveness and outcomes of low-dose-rate (LDR) and high-dose-rate (HDR) brachytherapy compared with intensity-modulated radiation therapy (IMRT) in patients with low/intermediate risk of prostate cancer. METHODS AND MATERIALS: One thousand three hundred twenty-eight patients with low or intermediate risk of prostate cancer were treated with LDR (n=207), HDR with four fractions (n=252), or IMRT (n=869) between January 1992 and December 2008. LDR patients were treated with palladium seeds to a median dose of 120 Gy, whereas HDR patients were treated to a median dose 38.0 Gy (four fractions). IMRT patients received 42-44 fractions with a median dose of 75.6 Gy. Clinical outcomes were compared, including biochemical failure, cause-specific survival, and overall survival. RESULTS: Overall, no differences in 5-year biochemical control (BC) or cause-specific survival were noted among treatment modalities. The calculated reimbursement for LDR brachytherapy, HDR brachytherapy with four fractions, and IMRT was $9,938; $17,514; and $29,356, respectively. HDR and LDR brachytherapy were statistically less costly to Medicare and the institution than IMRT (p<0.001), and LDR brachytherapy was less costly than HDR brachytherapy (p=0.01 and p<0.001). Incremental cost-effectiveness ratios for cost to Medicare for BC with IMRT were $4045 and $2754 per percent of BC for LDR and HDR brachytherapy, respectively. Incremental cost-effectiveness ratio using institutional cost comparing IMRT with LDR and HDR brachytherapy was $4962 and $4824 per 1% improvement in BC. CONCLUSIONS: In this study of patients with low and intermediate risk of prostate cancer, comparable outcomes at 5 years were noted between modalities with increased costs associated with IMRT.