Brian J. Davis

American Brachytherapy Society consensus guidelines for transrectal ultrasound-guided permanent prostate brachytherapy

PURPOSE To provide updated American Brachytherapy Society (ABS) guidelines for transrectal ultrasound-guided transperineal interstitial permanent prostate brachytherapy (PPB). METHODS AND MATERIALS The ABS formed a committee of brachytherapists and researchers experienced in the clinical practice of PPB to formulate updated guidelines for this technique. Sources of input for these guidelines included prior published guidelines, clinical trials, published literature, and experience of the committee. The recommendations of the committee were reviewed and approved by the Board of Directors of the ABS. RESULTS Patients with high probability of organ-confined disease or limited extraprostatic extension are considered appropriate candidates for PPB monotherapy. Low-risk patients may be treated with PPB alone without the need for supplemental external beam radiotherapy. High-risk patients should receive supplemental external beam radiotherapy if PPB is used. Intermediate-risk patients should be considered on an individual case basis. Intermediate-risk patients with favorable features may appropriately be treated with PPB monotherapy but results from confirmatory clinical trials are pending. Computed tomography-based postimplant dosimetry performed within 60 days of the implant is considered essential for maintenance of a satisfactory quality assurance program. Postimplant computed tomography-magnetic resonance image fusion is viewed as useful, but not mandatory. CONCLUSIONS Updated guidelines for patient selection, workup, treatment, postimplant dosimetry, and followup are provided. These recommendations are intended to be advisory in nature with the ultimate responsibility for the care of the patients resting with the treating physicians.

Adjuvant and salvage radiotherapy after prostatectomy: AUA/ASTRO guideline

PURPOSE The purpose of this guideline is to provide a clinical framework for the use of radiotherapy after radical prostatectomy as adjuvant or salvage therapy. MATERIALS AND METHODS A systematic literature review using the PubMed®, Embase, and Cochrane databases was conducted to identify peer-reviewed publications relevant to the use of radiotherapy after prostatectomy. The review yielded 294 articles; these publications were used to create the evidence-based guideline statements. Additional guidance is provided as Clinical Principles when insufficient evidence existed. RESULTS Guideline statements are provided for patient counseling, the use of radiotherapy in the adjuvant and salvage contexts, defining biochemical recurrence, and conducting a re-staging evaluation. CONCLUSIONS Physicians should offer adjuvant radiotherapy to patients with adverse pathologic findings at prostatectomy (i.e., seminal vesicle invasion, positive surgical margins, extraprostatic extension) and should offer salvage radiotherapy to patients with prostatic specific antigen or local recurrence after prostatectomy in whom there is no evidence of distant metastatic disease. The offer of radiotherapy should be made in the context of a thoughtful discussion of possible short- and long-term side effects of radiotherapy as well as the potential benefits of preventing recurrence. The decision to administer radiotherapy should be made by the patient and the multi-disciplinary treatment team with full consideration of the patients history, values, preferences, quality of life, and functional status. Please visit the ASTRO and AUA websites (http://www.redjournal.org/webfiles/images/journals/rob/RAP%20Guideline.pdf and http://www.auanet.org/education/guidelines/radiation-after-prostatectomy.cfm) to view this guideline in its entirety, including the full literature review.

The radial distance of extraprostatic extension of prostate carcinoma : Implications for prostate brachytherapy

Extraprostatic extension (EPE) is an unfavorable prognostic factor in patients with prostate carcinoma. Prior studies have reported the linear extent of EPE measured circumferentially along the edge of the prostate. In this study, the authors defined and evaluated a novel measure of EPE in a large series of radical prostatectomy specimens. These results have important clinical implications in the management of localized prostate carcinoma by brachytherapy and other modalities.

A Tissue Biomarker Panel Predicting Systemic Progression after PSA Recurrence Post-Definitive Prostate Cancer Therapy

Background Many men develop a rising PSA after initial therapy for prostate cancer. While some of these men will develop a local or metastatic recurrence that warrants further therapy, others will have no evidence of disease progression. We hypothesized that an expression biomarker panel can predict which men with a rising PSA would benefit from further therapy. Methodology/Principal Findings A case-control design was used to test the association of gene expression with outcome. Systemic (SYS) progression cases were men post-prostatectomy who developed systemic progression within 5 years after PSA recurrence. PSA progression controls were matched men post-prostatectomy with PSA recurrence but no evidence of clinical progression within 5 years. Using expression arrays optimized for paraffin-embedded tissue RNA, 1021 cancer-related genes were evaluated–including 570 genes implicated in prostate cancer progression. Genes from 8 previously reported marker panels were included. A systemic progression model containing 17 genes was developed. This model generated an AUC of 0.88 (95% CI: 0.84–0.92). Similar AUCs were generated using 3 previously reported panels. In secondary analyses, the model predicted the endpoints of prostate cancer death (in SYS cases) and systemic progression beyond 5 years (in PSA controls) with hazard ratios 2.5 and 4.7, respectively (log-rank p-values of 0.0007 and 0.0005). Genes mapped to 8q24 were significantly enriched in the model. Conclusions/Significance Specific gene expression patterns are significantly associated with systemic progression after PSA recurrence. The measurement of gene expression pattern may be useful for determining which men may benefit from additional therapy after PSA recurrence.

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.

PURPOSE To investigate the biochemical control rates and survival for Gleason score 7-10 prostate cancer patients undergoing permanent prostate brachytherapy as a function of the biologic effective dose (BED). METHODS AND MATERIALS Six centers provided data on 5,889 permanent prostate brachytherapy patients, of whom 1,078 had Gleason score 7 (n = 845) or Gleason score 8-10 (n = 233) prostate cancer and postimplant dosimetry results available. The median prostate-specific antigen level was 7.5 ng/mL (range, 0.4-300). The median follow-up for censored patients was 46 months (range, 5-130). Short-term hormonal therapy (median duration, 3.9 months) was used in 666 patients (61.8%) and supplemental external beam radiotherapy (EBRT) in 620 (57.5%). The patients were stratified into three BED groups: <200 Gy (n = 645), 200-220 Gy (n = 199), and >220 Gy (n = 234). Biochemical freedom from failure (bFFF) was determined using the Phoenix definition. RESULTS The 5-year bFFF rate was 80%. The bFFF rate stratified by the three BED groups was 76.4%, 83.5%, and 88.3% (p < 0.001), respectively. Cox regression analysis revealed Gleason score, prostate-specific antigen level, use of hormonal therapy, EBRT, and BED were associated with bFFF (p < 0.001). Freedom from metastasis improved from 92% to 99% with the greatest doses. The overall survival rate at 5 years for the three BED groups for Gleason score 8-10 cancer was 86.6%, 89.4%, and 94.6%, respectively (p = 0.048). CONCLUSION These data suggest that permanent prostate brachytherapy combined with EBRT and hormonal therapy yields excellent bFFF and survival results in Gleason score 7-10 patients when the delivered BEDs are >220 Gy. These doses can be achieved by a combination of 45-Gy EBRT with a minimal dose received by 90% of the target volume of 120 Gy of (103)Pd or 130 Gy of (125)I.

Metastatic prostate carcinoma to bone: Clinical and pathologic features associated with cancer-specific survival

The objective of this study was to examine the clinical and pathologic features of metastatic prostate carcinoma to bone in a large cohort of men, and the associations of these features with outcome.

Adjuvant and salvage radiation therapy after prostatectomy: American society for radiation oncology/american urological association guidelines

PURPOSE The purpose of this guideline was to provide a clinical framework for the use of radiation therapy after radical prostatectomy as adjuvant or salvage therapy. METHODS AND MATERIALS A systematic literature review using PubMed, Embase, and Cochrane database was conducted to identify peer-reviewed publications relevant to the use of radiation therapy after prostatectomy. The review yielded 294 articles; these publications were used to create the evidence-based guideline statements. Additional guidance is provided as Clinical Principles when insufficient evidence existed. RESULTS Guideline statements are provided for patient counseling, use of radiation therapy in the adjuvant and salvage contexts, defining biochemical recurrence, and conducting a restaging evaluation. CONCLUSIONS Physicians should offer adjuvant radiation therapy to patients with adverse pathologic findings at prostatectomy (ie, seminal vesicle invastion, positive surgical margins, extraprostatic extension) and salvage radiation therapy to patients with prostate-specific antigen (PSA) or local recurrence after prostatectomy in whom there is no evidence of distant metastatic disease. The offer of radiation therapy should be made in the context of a thoughtful discussion of possible short- and long-term side effects of radiation therapy as well as the potential benefits of preventing recurrence. The decision to administer radiation therapy should be made by the patient and the multidisciplinary treatment team with full consideration of the patients history, values, preferences, quality of life, and functional status. The American Society for Radiation Oncology and American Urological Association websites show this guideline in its entirety, including the full literature review.

Renal Mass and Localized Renal Cancer: AUA Guideline

Purpose: This AUA Guideline focuses on evaluation/counseling and management of adult patients with clinically localized renal masses suspicious for cancer, including solid‐enhancing tumors and Bosniak 3/4 complex‐cystic lesions. Materials and Methods: Systematic review utilized research from the Agency for Healthcare Research and Quality and additional supplementation by the authors and consultant methodologists. Evidence‐based statements were based on body of evidence strength Grade A/B/C (Strong/Moderate/Conditional Recommendations, respectively) with additional statements presented as Clinical Principles or Expert Opinions. Results: Great progress has been made since the previous guidelines on management of localized renal masses were released (2009). The current guidelines provide updated, evidence‐based recommendations regarding evaluation/counseling of patients with clinically localized renal masses, including the evolving role of renal mass biopsy. Given great variability of clinical, oncologic and functional characteristics, index patients are not utilized and the panel advocates individualized counseling/management. Management options (partial nephrectomy/radical nephrectomy/thermal ablation/active surveillance) are reviewed including recent data about comparative effectiveness and potential morbidities. Oncologic issues are prioritized while recognizing that functional outcomes are of great importance for survivorship for most patients with localized kidney cancer. A more restricted role for radical nephrectomy is recommended following well‐defined selection criteria. Priority for partial nephrectomy is recommended for clinical T1a lesions, along with selective use of thermal ablation, particularly for tumors ≤3.0 cm. Important considerations for shared decision‐making about active surveillance are explicitly defined. Conclusions: Several factors should be considered during counseling/management of patients with clinically localized renal masses, including general health/comorbidities, oncologic potential of the mass, pertinent functional issues and relative efficacy/potential morbidities of various management strategies.

TECHNICAL ASPECTS OF DAILY ONLINE POSITIONING OF THE PROSTATE FOR THREE-DIMENSIONAL CONFORMAL RADIOTHERAPY USING AN ELECTRONIC PORTAL IMAGING DEVICE

PURPOSE To develop a real-time electronic portal imaging device (EPID) procedure to identify intraprostatic gold markers and correct daily variations in target position during external beam radiotherapy for prostate cancer. METHODS AND MATERIALS Pretherapy electronic portal images (EPIs) were acquired with a small portion of the therapeutic 18-MV dose from an orthogonal pair of treatment fields. The position of the intraprostatic gold markers on the EPIs was aligned with that on the simulation digitally reconstructed radiographs. If the initial three-dimensional target displacement (3DI) exceeded 5 mm or rotations exceeded 3 degrees, the beam was realigned before the remainder of the dose was delivered. Field-only EPIs were then acquired for all fields and offline analysis was performed to determine the final 3D target placement (3DF). RESULTS Twenty patients completed protocol-specified treatment, and all markers were identified on 99.6% of the pretherapy EPIs. Overall, 53% of treatment fractions were realigned. The mean 3DI was 5.6 mm in all patients (range 3.7-9.3), and the mean 3DF was 2.8 mm (range 1.6-4.0), which was statistically significant (p < 0.001). Rotational corrections were made on 15% of treatments. Mean treatment duration was 1.4 min greater for protocol patients than for similar patients in whom localization was not performed. CONCLUSIONS Frequent field misalignment occurs when external fiducial marks are used for patient alignment. Misalignments can be readily and rapidly identified and corrected with an EPID-based online correction procedure that integrates commercially available equipment and software.

Stereotactic body radiation therapy in the treatment of oligometastatic prostate cancer

Purpose/objective(s): To report outcomes and toxicity for patients with oligometastatic (≤5 lesions) prostate cancer (PCa) treated with stereotactic body radiation therapy (SBRT). Materials/methods: Seventeen men with 21 PCa lesions were treated with SBRT between February 2009 and November 2011. All patients had a detectable prostate-specific antigen (PSA) at the time of SBRT, and 11 patients (65%) had hormone-refractory (HR) disease. Treatment sites included bone (n = 19), lymph nodes (n = 1), and liver (n = 1). For patients with bone lesions, the median dose was 20 Gy (range, 8–24 Gy) in a single fraction (range, 1–3). All but two patients received some form of anti-androgen therapy after completing SBRT. Results: Local control (LC) was 100%, and the PSA nadir was undetectable in nine patients (53%). The first post-SBRT PSA was lower than pre-treatment levels in 15 patients (88%), and continued to decline or remain undetectable in 12 patients (71%) at a median follow-up of 6 months (range, 2–24 months). Median PSA measurements before SBRT and at last follow-up were 2.1 ng/dl (range, 0.13–36.4) and 0.17 ng/dl (range, <0.1–140), respectively. Six (55%) of the 11 patients with HR PCa achieved either undetectable or declining PSA at a median follow-up of 4.8 months (range, 2.2–6.0 months). Reported toxicities included one case each of grade 2 dyspnea and back pain, there were no cases of grade ≥3 toxicity following treatment. Conclusion: We report excellent LC with SBRT in oligometastatic PCa. More importantly, over half the patients achieved an undetectable PSA after SBRT. Further follow-up is necessary to assess the long-term impact of SBRT on LC, toxicity, PSA response, and clinical outcomes.