Publications by authors named "Brian J Davis"

122 Publications

Comparison of Multimodal Therapies and Outcomes Among Patients With High-Risk Prostate Cancer With Adverse Clinicopathologic Features.

JAMA Netw Open 2021 Jul 1;4(7):e2115312. Epub 2021 Jul 1.

Department of Urology, Brady Urological Institute, Johns Hopkins University, Baltimore, Maryland.

Importance: The optimal management strategy for high-risk prostate cancer and additional adverse clinicopathologic features remains unknown.

Objective: To compare clinical outcomes among patients with high-risk prostate cancer after definitive treatment.

Design, Setting, And Participants: This retrospective cohort study included patients with high-risk prostate cancer (as defined by the National Comprehensive Cancer Network [NCCN]) and at least 1 adverse clinicopathologic feature (defined as any primary Gleason pattern 5 on biopsy, clinical T3b-4 disease, ≥50% cores with biopsy results positive for prostate cancer, or NCCN ≥2 high-risk features) treated between 2000 and 2014 at 16 tertiary centers. Data were analyzed in November 2020.

Exposures: Radical prostatectomy (RP), external beam radiotherapy (EBRT) with androgen deprivation therapy (ADT), or EBRT plus brachytherapy boost (BT) with ADT. Guideline-concordant multimodal treatment was defined as RP with appropriate use of multimodal therapy (optimal RP), EBRT with at least 2 years of ADT (optimal EBRT), or EBRT with BT with at least 1 year ADT (optimal EBRT with BT).

Main Outcomes And Measures: The primary outcome was prostate cancer-specific mortality; distant metastasis was a secondary outcome. Differences were evaluated using inverse probability of treatment weight-adjusted Fine-Gray competing risk regression models.

Results: A total of 6004 men (median [interquartile range] age, 66.4 [60.9-71.8] years) with high-risk prostate cancer were analyzed, including 3175 patients (52.9%) who underwent RP, 1830 patients (30.5%) who underwent EBRT alone, and 999 patients (16.6%) who underwent EBRT with BT. Compared with RP, treatment with EBRT with BT (subdistribution hazard ratio [sHR] 0.78, [95% CI, 0.63-0.97]; P = .03) or with EBRT alone (sHR, 0.70 [95% CI, 0.53-0.92]; P = .01) was associated with significantly improved prostate cancer-specific mortality; there was no difference in prostate cancer-specific mortality between EBRT with BT and EBRT alone (sHR, 0.89 [95% CI, 0.67-1.18]; P = .43). No significant differences in prostate cancer-specific mortality were found across treatment cohorts among 2940 patients who received guideline-concordant multimodality treatment (eg, optimal EBRT alone vs optimal RP: sHR, 0.76 [95% CI, 0.52-1.09]; P = .14). However, treatment with EBRT alone or EBRT with BT was consistently associated with lower rates of distant metastasis compared with treatment with RP (eg, EBRT vs RP: sHR, 0.50 [95% CI, 0.44-0.58]; P < .001).

Conclusions And Relevance: These findings suggest that among patients with high-risk prostate cancer and additional unfavorable clinicopathologic features receiving guideline-concordant multimodal therapy, prostate cancer-specific mortality outcomes were equivalent among those treated with RP, EBRT, and EBRT with BT, although distant metastasis outcomes were more favorable among patients treated with EBRT and EBRT with BT. Optimal multimodality treatment is critical for improving outcomes in patients with high-risk prostate cancer.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.15312DOI Listing
July 2021

The prognostic value, sensitivity, and specificity of multiparametric magnetic resonance imaging before salvage radiotherapy for prostate cancer.

Radiother Oncol 2021 May 21;161:9-15. Epub 2021 May 21.

Department of Radiation Oncology, Mayo Clinic, Rochester, USA.

Aim: To determine the operational characteristics of pelvic magnetic resonance imaging (MRI) prior to salvage radiation therapy (SRT) for biochemically recurrent prostate cancer following radical prostatectomy.

Methods And Materials: We reviewed the medical records of 386 patients who underwent MRI prior to SRT. We assessed associations of pre-SRT MRI findings with biochemical recurrence (BCR), distant metastasis (DM), prostate cancer-specific mortality (PCSM), and salvage androgen deprivation therapy (ADT) use following SRT. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of MRI for detecting local recurrence were also calculated.

Results: Pre-SRT MRI was positive for local recurrence in 216 patients (56%), indeterminate in 46 (12%), and negative in 124 (32%). On univariate analysis, BCR following SRT was significantly less likely for patients with positive (HR: 0.58, 95% CI: 0.42-0.8) or indeterminate (HR: 0.6: 0.36-1) MRI findings, compared to patients with negative imaging (p = 0.003). These associations remained significant on multivariate analysis (p < 0.05) and across pre-SRT PSA groups. For the entire cohort, the sensitivity of MRI for local recurrence was 61.0% (53.5-68.1%), specificity 60.0% (44.3-73.0%), PPV 86.1% (78.9-91.5%) and NPV 27.6% (19.0-37.5%). Sensitivity of MRI was better in men with higher pre-SRT PSA (80.0% for PSA > 1.0), and specificity was improved with lower pre-SRT PSA (73.9% for PSA 0.1-0.5).

Conclusions: Positive or indeterminate MRI findings prior to SRT were associated with improved biochemical control following SRT, across PSA levels. The sensitivity and specificity of MRI for local recurrence were 61% and 58.7%, respectively.
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http://dx.doi.org/10.1016/j.radonc.2021.05.015DOI Listing
May 2021

Patterns of Clinical Progression in Radiorecurrent High-risk Prostate Cancer.

Eur Urol 2021 Aug 10;80(2):142-146. Epub 2021 May 10.

Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

The natural history of radiorecurrent high-risk prostate cancer (HRPCa) is not well-described. To better understand its clinical course, we evaluated rates of distant metastases (DM) and prostate cancer-specific mortality (PCSM) in a cohort of 978 men with radiorecurrent HRPCa who previously received either external beam radiation therapy (EBRT, n = 654, 67%) or EBRT + brachytherapy (EBRT + BT, n = 324, 33%) across 15 institutions from 1997 to 2015. In men who did not die, median follow-up after treatment was 8.9 yr and median follow-up after biochemical recurrence (BCR) was 3.7 yr. Local and systemic therapy salvage, respectively, were delivered to 21 and 390 men after EBRT, and eight and 103 men after EBRT + BT. Overall, 435 men developed DM, and 248 were detected within 1 yr of BCR. Measured from time of recurrence, 5-yr DM rates were 50% and 34% after EBRT and EBRT + BT, respectively. Measured from BCR, 5-yr PCSM rates were 27% and 29%, respectively. Interval to BCR was independently associated with DM (p < 0.001) and PCSM (p < 0.001). These data suggest that radiorecurrent HRPCa has an aggressive natural history and that DM is clinically evident early after BCR. These findings underscore the importance of further investigations into upfront risk assessment and prompt systemic evaluation upon recurrence in HRPCa. PATIENT SUMMARY: High-risk prostate cancer that recurs after radiation therapy is an aggressive disease entity and spreads to other parts of the body (metastases). Some 60% of metastases occur within 1 yr. Approximately 30% of these patients die from their prostate cancer.
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http://dx.doi.org/10.1016/j.eururo.2021.04.035DOI Listing
August 2021

Oligometastatic prostatic cancer recurrence: role of salvage lymph node dissection (sLND) and radiation therapy-stereotactic body radiation therapy (RT-SBRT).

Curr Opin Urol 2021 05;31(3):199-205

Department of Urology.

Purpose Of Review: Metastases directed therapy (MDT) is an increasingly utilized modality in patients with oligometastatic prostate cancer (OMPC) recurrence. The purpose of our review is to discuss the recent literature on the safety and oncologic outcomes of this treatment approach.

Recent Findings: Metastases directed therapy, in particular, stereotactic body radiation therapy (SBRT) and salvage lymph node dissection (sLND), has shown promising efficacy in patients with OMPC. Many case series report favorable outcomes with MDT as compared to hormonal deprivation therapy alone or surveillance. Of the few case series investigating the use of MDT as part of a multimodality approach in castrate-resistant OMPC, more favorable outcomes in comparison to the use of systemic treatment alone are reported.

Summary: With the recent advances in imaging techniques, particularly molecular imaging, management of OMPC has progressed rapidly in the last few years. The feasibility and benefits of MDT in OMPC have been demonstrated in prospective and retrospective series. Further prospective studies investigating the role of MDT to define optimal patient subgroups and management strategies are warranted.
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http://dx.doi.org/10.1097/MOU.0000000000000865DOI Listing
May 2021

Predictors of Locoregional Recurrence and Delineation of Adjuvant Radiation Therapy Fields for Patients With Upper Tract Urothelial Carcinoma Receiving Nephroureterectomy.

Pract Radiat Oncol 2021 Feb 23. Epub 2021 Feb 23.

Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota. Electronic address:

Purpose: To identify factors predictive of locoregional recurrence (LRR) in upper tract urothelial carcinoma (UTUC) treated with nephroureterectomy and to propose adjuvant radiation therapy (ART) fields.

Methods And Materials: Clinical and pathologic variables for patients receiving nephroureterectomy for UTUC between 1995 and 2009 were analyzed for associations with outcomes. Sites of LRR from all patients with available imaging (39) were contoured on computed tomography image sets of patients with representative anatomy, and ART fields were proposed based on these distributions.

Results: A total of 279 patients with a median follow-up of 13.0 years were analyzed. The 5-year cumulative incidence of LRR was 16.7% (95% CI, 12.2-21). Pathologic risk factors (PRFs) associated with increased risk of LRR included tumor in both the renal pelvis and ureter, T stage ≥2, lymph node involvement, grade 3 histology, and positive surgical margins (P < .05). Patients with an increased number of PRFs had a significantly greater risk of LRR. The 5-year cumulative incidence estimates of LRR were 5.3% (95% CI, 1.8%-16.0%), 15.6% (95% CI, 9.5%-25.7%), and 43.9% (95% CI, 31.1%-62.1%) for those with 1, 2, and ≥3 PRFs, respectively. ART fields covering the renal fossa and retroperitoneal lymph nodes from the superior border of L1 through the aortic bifurcation would encompass all sites of LRR for 33 of 46 patients (72%). Non-LRR bladder and distant failure occurred in 101 (36.2%) and 73 (26.2%) of the patients, respectively. The 5-year cumulative incidence estimate of distant failure was 22.5% (95% CI, 17.4%-27.3%).

Conclusions: In patients receiving nephroureterectomy for UTUC, LRR is significantly increased in patients with 2 or more PRFs. These data provide clinically valuable insight into the selection of candidates for ART and the design of ART fields.
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http://dx.doi.org/10.1016/j.prro.2021.02.005DOI Listing
February 2021

NCCN Guidelines Insights: Prostate Cancer, Version 1.2021.

J Natl Compr Canc Netw 2021 02 2;19(2):134-143. Epub 2021 Feb 2.

Huntsman Cancer Institute at the University of Utah; and.

The NCCN Guidelines for Prostate Cancer address staging and risk assessment after a prostate cancer diagnosis and include management options for localized, regional, and metastatic disease. Recommendations for disease monitoring and treatment of recurrent disease are also included. The NCCN Prostate Cancer Panel meets annually to reevaluate and update their recommendations based on new clinical data and input from within NCCN Member Institutions and from external entities. This article summarizes the panel's discussions for the 2021 update of the guidelines with regard to systemic therapy for metastatic castration-resistant prostate cancer.
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http://dx.doi.org/10.6004/jnccn.2021.0008DOI Listing
February 2021

A Pooled Toxicity Analysis of Moderately Hypofractionated Proton Beam Therapy and Intensity Modulated Radiation Therapy in Early-Stage Prostate Cancer Patients.

Int J Radiat Oncol Biol Phys 2021 Jul 1;110(4):1082-1089. Epub 2021 Feb 1.

Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania. Electronic address:

Purpose: Data comparing moderately hypofractionated intensity modulated radiation therapy (IMRT) and proton beam therapy (PBT) are lacking. We aim to compare late toxicity profiles of patients with early-stage prostate cancer treated with moderately hypofractionated PBT and IMRT.

Methods And Materials: This multi-institutional analysis included patients with low- or intermediate-risk biopsy-proven prostate adenocarcinoma from 7 tertiary referral centers treated from 1998 to 2018. All patients were treated with moderately hypofractionated radiation, defined as 250 to 300 cGy per daily fraction given for 4 to 6 weeks, and stratified by use of IMRT or PBT. Primary outcomes were late genitourinary (GU) and gastrointestinal (GI) toxicity. Adjusted toxicity rates were calculated using inverse probability of treatment weighting, accounting for race, National Comprehensive Cancer Network risk group, age, pretreatment International Prostate Symptom Score (GU only), and anticoagulant use (GI only).

Results: A total of 1850 patients were included: 1282 IMRT (median follow-up 80.0 months) and 568 PBT (median follow-up 43.9 months). Overall toxicity rates were low, with the majority of patients experiencing no late GU (56.6%, n = 1048) or late GI (74.4%, n = 1377) toxicity. No difference was seen in the rates of late toxicity between the groups, with late grade 3+ GU toxicity of 2.0% versus 3.9% (odds ratio [OR] 0.47; 95% confidence interval 0.17-1.28) and late grade 2+ GI toxicity of 14.6% versus 4.7% (OR 2.69; confidence interval 0.80-9.05) for the PBT and IMRT cohorts, respectively. On multivariable analysis, no factors were significantly predictive of GU toxicity, and only anticoagulant use was significantly predictive of GI toxicity (OR 1.90; P = .008).

Conclusions: In this large, multi-institutional analysis of 1850 patients with early-stage prostate cancer, treatment with moderately hypofractionated IMRT and PBT resulted in low rates of toxicity. No difference was seen in late GI and GU toxicity between the modalities during long-term follow-up. Both treatments are safe and well tolerated.
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http://dx.doi.org/10.1016/j.ijrobp.2021.01.043DOI Listing
July 2021

A Systematic Review and Meta-analysis of Local Salvage Therapies After Radiotherapy for Prostate Cancer (MASTER).

Eur Urol 2020 Dec 10. Epub 2020 Dec 10.

Department of Radiation Oncology, University of California, Los Angeles, CA, USA; Department of Urology, University of California, Los Angeles, CA, USA. Electronic address:

Context: Management of locally recurrent prostate cancer after definitive radiotherapy remains controversial due to the perceived high rates of severe genitourinary (GU) and gastrointestinal (GI) toxicity associated with any local salvage modality.

Objective: To quantitatively compare the efficacy and toxicity of salvage radical prostatectomy (RP), high-intensity focused ultrasound (HIFU), cryotherapy, stereotactic body radiotherapy (SBRT), low-dose-rate (LDR) brachytherapy, and high-dose-rate (HDR) brachytherapy.

Evidence Acquisition: We performed a systematic review of PubMed, EMBASE, and MEDLINE. Two- and 5-yr recurrence-free survival (RFS) rates and crude incidences of severe GU and GI toxicity were extracted as endpoints of interest. Random-effect meta-analyses were conducted to characterize summary effect sizes and quantify heterogeneity. Estimates for each modality were then compared with RP after adjusting for individual study-level covariates using mixed-effect regression models, while allowing for differences in between-study variance across treatment modalities.

Evidence Synthesis: A total of 150 studies were included for analysis. There was significant heterogeneity between studies within each modality, and covariates differed between modalities, necessitating adjustment. Adjusted 5-yr RFS ranged from 50% after cryotherapy to 60% after HDR brachytherapy and SBRT, with no significant differences between any modality and RP. Severe GU toxicity was significantly lower with all three forms of radiotherapeutic salvage than with RP (adjusted rates of 20% after RP vs 5.6%, 9.6%, and 9.1% after SBRT, HDR brachytherapy, and LDR brachytherapy, respectively; p ≤ 0.001 for all). Severe GI toxicity was significantly lower with HDR salvage than with RP (adjusted rates 1.8% vs 0.0%, p < 0.01), with no other differences identified.

Conclusions: Large differences in 5-yr outcomes were not uncovered when comparing all salvage treatment modalities against RP. Reirradiation with SBRT, HDR brachytherapy, or LDR brachytherapy appears to result in less severe GU toxicity than RP, and reirradiation with HDR brachytherapy yields less severe GI toxicity than RP. Prospective studies of local salvage for radiorecurrent disease are warranted.

Patient Summary: In a large study-level meta-analysis, we looked at treatment outcomes and toxicity for men treated with a number of salvage treatments for radiorecurrent prostate cancer. We conclude that relapse-free survival at 5 years is equivalent among salvage modalities, but reirradiation may lead to lower toxicity.
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http://dx.doi.org/10.1016/j.eururo.2020.11.010DOI Listing
December 2020

Oligorecurrent prostate cancer treated with metastases-directed therapy or standard of care: a single-center experience.

Prostate Cancer Prostatic Dis 2021 Jun 2;24(2):514-523. Epub 2020 Dec 2.

Department of Urology, Mayo Clinic, Rochester, MN, USA.

Background: The optimal treatment for oligorecurrent prostate cancer (PCa) is a matter of debate. We aimed to assess oncologic outcomes of patients treated with metastasis-directed therapy (MDT) vs. androgen deprivation therapy (ADT) for oligorecurrent PCa.

Methods: We analyzed data from patients with oligorecurrent PCa treated with ADT (n = 121), salvage lymph node dissection (sLND) (n = 191) or external beam RT (EBRT) (n = 178). Radiological recurrence (RAR) was defined as a positive positron emission tomography imaging after MDT or ADT. Second-line systemic therapies (SST) were defined as any systemic therapy administered for progression. Oncologic outcomes were evaluated separately for patients with node-only or bone metastases. Kaplan-Meier method was used to assess time to RAR, SST, and cancer-specific mortality (CSM). Predictors of RAR, SST, and castration-resistant PCa (CRPCa) were assessed with Cox regression analyses.

Results: Overall, 74 (22.6%), 63 (19.2%), and 191 (58.2%) patients were treated with ADT, EBRT, and sLND for lymph node-only recurrence. Both sLND (HR 0.56, 95% CI 0.33-0.94) and EBRT (HR 0.46, 95% CI 0.25-0.85) were associated with better RAR than ADT. Similarly, sLND (HR 0.25, 95% CI 0.13-0.50) and EBRT (HR 0.41, 95% CI 0.19-0.87) were associated with longer SST, as compared with ADT. Similar results were found for CRPCa status. Oncologic outcomes were similar between sLND and EBRT. MDT was not associated with survival benefit in patients with bone metastases as compared with ADT.

Conclusions: sLND and EBRT were associated with better RAR, SST, and CRPCa-free survival as compared with ADT in patients with oligometastatic PCa nodal recurrence. No difference in survival outcomes was observed between sLND and EBRT. MDT was not associated with survival benefit in patients with bone metastases, as compared with ADT.
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http://dx.doi.org/10.1038/s41391-020-00307-yDOI Listing
June 2021

Executive Summary of the American Radium Society Appropriate Use Criteria for Radiation Treatment of Node-Negative Muscle Invasive Bladder Cancer.

Int J Radiat Oncol Biol Phys 2021 03 27;109(4):953-963. Epub 2020 Oct 27.

Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota.

Purpose: Definitive radiation therapy (RT), with or without concurrent chemotherapy, is an alternative to radical cystectomy for patients with localized, muscle-invasive bladder cancer (MIBC) who are either not surgical candidates or prefer organ preservation. We aim to synthesize an evidence-based guideline regarding the appropriate use of RT.

Methods And Materials: We performed a Preferred Reporting Items for Systematic Reviews and Meta-analyses literature review using the PubMed and Embase databases. Based on the literature review, critical management topics were identified and reformulated into consensus questions. An expert panel was assembled to address key areas of both consensus and controversy using the modified Delphi framework.

Results: A total of 761 articles were screened, of which 61 were published between 1975 and 2019 and included for full review. There were 7 well-designed studies, 20 good quality studies, 28 quality studies with design limitations, and 6 references not suited as primary evidence. Adjuvant radiation therapy after cystectomy was not included owing to lack of high-quality data or clinical use. An expert panel consisting of 14 radiation oncologists, 1 medical oncologist, and 1 urologist was assembled. We identified 4 clinical variants of MIBC: surgically fit patients who wish to pursue organ preservation, patients surgically unfit for cystectomy, patients medically unfit for cisplatin-based chemotherapy, and borderline cystectomy candidates based on age with unilateral hydronephrosis and normal renal function. We identified key areas of controversy, including use of definitive radiation therapy for patients with negative prognostic factors, appropriate radiation therapy dose, fractionation, fields and technique when used, and chemotherapy sequencing and choice of agent.

Conclusions: There is limited level-one evidence to guide appropriate treatment of MIBC. Studies vary significantly with regards to patient selection, chemotherapy use, and radiation therapy technique. A consensus guideline on the appropriateness of RT for MIBC may aid practicing oncologists in bridging the gap between data and clinical practice.
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http://dx.doi.org/10.1016/j.ijrobp.2020.10.031DOI Listing
March 2021

Development and Validation of a Clinical Prognostic Stage Group System for Nonmetastatic Prostate Cancer Using Disease-Specific Mortality Results From the International Staging Collaboration for Cancer of the Prostate.

JAMA Oncol 2020 12;6(12):1912-1920

Department of Radiation Oncology, Penn State Cancer Institute, Hershey, Pennsylvania.

Importance: In 2016, the American Joint Committee on Cancer (AJCC) established criteria to evaluate prediction models for staging. No localized prostate cancer models were endorsed by the Precision Medicine Core committee, and 8th edition staging was based on expert consensus.

Objective: To develop and validate a pretreatment clinical prognostic stage group system for nonmetastatic prostate cancer.

Design, Setting, And Participants: This multinational cohort study included 7 centers from the United States, Canada, and Europe, the Shared Equal Access Regional Cancer Hospital (SEARCH) Veterans Affairs Medical Centers collaborative (5 centers), and the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry (43 centers) (the STAR-CAP cohort). Patients with cT1-4N0-1M0 prostate adenocarcinoma treated from January 1, 1992, to December 31, 2013 (follow-up completed December 31, 2017). The STAR-CAP cohort was randomly divided into training and validation data sets; statisticians were blinded to the validation data until the model was locked. A Surveillance, Epidemiology, and End Results (SEER) cohort was used as a second validation set. Analysis was performed from January 1, 2018, to November 30, 2019.

Exposures: Curative intent radical prostatectomy (RP) or radiotherapy with or without androgen deprivation therapy.

Main Outcomes And Measures: Prostate cancer-specific mortality (PCSM). Based on a competing-risk regression model, a points-based Score staging system was developed. Model discrimination (C index), calibration, and overall performance were assessed in the validation cohorts.

Results: Of 19 684 patients included in the analysis (median age, 64.0 [interquartile range (IQR), 59.0-70.0] years), 12 421 were treated with RP and 7263 with radiotherapy. Median follow-up was 71.8 (IQR, 34.3-124.3) months; 4078 (20.7%) were followed up for at least 10 years. Age, T category, N category, Gleason grade, pretreatment serum prostate-specific antigen level, and the percentage of positive core biopsy results among biopsies performed were included as variables. In the validation set, predicted 10-year PCSM for the 9 Score groups ranged from 0.3% to 40.0%. The 10-year C index (0.796; 95% CI, 0.760-0.828) exceeded that of the AJCC 8th edition (0.757; 95% CI, 0.719-0.792), which was improved across age, race, and treatment modality and within the SEER validation cohort. The Score system performed similarly to individualized random survival forest and interaction models and outperformed National Comprehensive Cancer Network (NCCN) and Cancer of the Prostate Risk Assessment (CAPRA) risk grouping 3- and 4-tier classification systems (10-year C index for NCCN 3-tier, 0.729; for NCCN 4-tier, 0.746; for Score, 0.794) as well as CAPRA (10-year C index for CAPRA, 0.760; for Score, 0.782).

Conclusions And Relevance: Using a large, diverse international cohort treated with standard curative treatment options, a proposed AJCC-compliant clinical prognostic stage group system for prostate cancer has been developed. This system may allow consistency of reporting and interpretation of results and clinical trial design.
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http://dx.doi.org/10.1001/jamaoncol.2020.4922DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7582232PMC
December 2020

C-choline positron emission tomography/computed tomography for detection of disease relapse in patients with history of biochemically recurrent prostate cancer and prostate-specific antigen ≤0.1 ng/ml.

J Cancer Res Ther 2021 Apr-Jun;17(2):358-365

Department of Radiology, Mayo Clinic, Rochester, MN, USA.

Objectives: The objective was to evaluate the diagnostic performance of surveillance C-choline positron emission tomography/computed tomography (PET/CT) for the detection of disease relapse in patients with a history of biochemically recurrent (BCR) prostate cancer (PCa) and prostate-specific antigen (PSA) ≤0.1 ng/ml.

Materials And Methods: We included patients who had been treated for BCR PCa and had a surveillance C-choline PET/CT at serum PSA ≤0.1 ng/ml. Positive surveillance PET/CT was defined as a study that identified a new tracer-avid lesion or new tracer uptake in a previously treated lesion or both. Findings were confirmed against a composite radiologic-pathologic gold standard. Time to recurrence association analyses were performed for disease relapse risk with the use of Cox proportional hazards regression.

Results: In total, 13 (12.1%) of the 107 patients had positive surveillance PET/CT scans, confirmed on pathologic assessment (n = 5) and subsequent imaging (n = 8). Among these 13 patients, ten had distant metastases, two had local recurrence, and one had both. Nine of the ten patients with metastases had oligometastatic disease defined as the presence of ≤3 metastases. Serum PSA became detectable again in only seven patients with positive surveillance PET/CT, after a mean interval from surveillance PET/CT of 292 days (range: 105-543 days). We identified an association of N stage with increased risk of recurrence (hazard ratio = 3.85; P = 0.036) although this was not significant after accounting for multiple testing.

Conclusions: Surveillance C-choline PET/CT can detect early disease relapse at serum PSA ≤0.1 ng/ml in patients with a history of BCR PCa.
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http://dx.doi.org/10.4103/jcrt.JCRT_373_19DOI Listing
October 2020

Comparing bowel and urinary domains of patient-reported quality of life at the end of and 3 months post radiotherapy between intensity-modulated radiotherapy and proton beam therapy for clinically localized prostate cancer.

Cancer Med 2020 11 15;9(21):7925-7934. Epub 2020 Sep 15.

Department of Radiation Oncology, Mayo Clinic, Rochester, MN, USA.

Purpose: To prospectively assess acute differences in patient-reported outcomes in bowel and urinary domains between intensity-modulated radiotherapy (IMRT) and proton beam therapy (PBT) for prostate cancer.

Methods And Materials: Bowel function (BF), urinary irritative/obstructive symptoms (UO), and urinary incontinence (UI) domains of EPIC-26 were collected in patients with T1-T2 prostate cancer receiving IMRT or PBT at a tertiary cancer center (2015-2018). Mean changes in domain scores were analyzed from pretreatment to the end of and 3 months post-radiotherapy for each modality. A clinically meaningful change was defined as a score change >50% of the baseline standard deviation.

Results: A total of 157 patients receiving IMRT and 105 receiving PBT were included. There were no baseline differences in domain scores between cohorts. At the end of radiotherapy, there was significant and clinically meaningful worsening of BF and UO scores for patients receiving either modality. In the BF domain, the IMRT cohort experienced greater decrement (-13.0 vs -6.7, P < .01), and had a higher proportion of patients with clinically meaningful reduction (58.4% vs 39.5%, P = .01), compared to PBT. At 3 months post-radiotherapy, the IMRT group had significant and clinically meaningful worsening of BF (-9.3, P < .001), whereas the change in BF score of the PBT cohort was no longer significant or clinically meaningful (-1.2, P = .25). There were no significant or clinically meaningful changes in UO or UI 3 months post-radiotherapy.

Conclusions: PBT had less acute decrement in BF than IMRT following radiotherapy. There was no difference between the two modalities in UO and UI.
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http://dx.doi.org/10.1002/cam4.3414DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7643652PMC
November 2020

NRG Oncology Updated International Consensus Atlas on Pelvic Lymph Node Volumes for Intact and Postoperative Prostate Cancer.

Int J Radiat Oncol Biol Phys 2021 01 27;109(1):174-185. Epub 2020 Aug 27.

Medical College of Wisconsin, Department of Radiation Oncology, Milwaukee, Wisconsin.

Purpose: In 2009, the Radiation Therapy Oncology Group (RTOG) genitourinary members published a consensus atlas for contouring prostate pelvic nodal clinical target volumes (CTVs). Data have emerged further informing nodal recurrence patterns. The objective of this study is to provide an updated prostate pelvic nodal consensus atlas.

Methods And Materials: A literature review was performed abstracting data on nodal recurrence patterns. Data were presented to a panel of international experts, including radiation oncologists, radiologists, and urologists. After data review, participants contoured nodal CTVs on 3 cases: postoperative, intact node positive, and intact node negative. Radiation oncologist contours were analyzed qualitatively using count maps, which provided a visual assessment of controversial regions, and quantitatively analyzed using Sorensen-Dice similarity coefficients and Hausdorff distances compared with the 2009 RTOG atlas. Diagnostic radiologists generated a reference table outlining considerations for determining clinical node positivity.

Results: Eighteen radiation oncologists' contours (54 CTVs) were included. Two urologists' volumes were examined in a separate analysis. The mean CTV for the postoperative case was 302 cm, intact node positive case was 409 cm, and intact node negative case was 342 cm. Compared with the original RTOG consensus, the mean Sorensen-Dice similarity coefficient for the postoperative case was 0.63 (standard deviation [SD] 0.13), the intact node positive case was 0.68 (SD 0.13), and the intact node negative case was 0.66 (SD 0.18). The mean Hausdorff distance (in cm) for the postoperative case was 0.24 (SD 0.13), the intact node positive case was 0.23 (SD 0.09), and intact node negative case was 0.33 (SD 0.24). Four regions of CTV controversy were identified, and consensus for each of these areas was reached.

Conclusions: Discordance with the 2009 RTOG consensus atlas was seen in a group of experienced NRG Oncology and international genitourinary radiation oncologists. To address areas of variability and account for new data, an updated NRG Oncology consensus contour atlas was developed.
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http://dx.doi.org/10.1016/j.ijrobp.2020.08.034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7736505PMC
January 2021

Outcomes and Profiles of Older Patients Receiving Definitive Radiation Therapy for Muscle-Invasive Bladder Cancer at a Tertiary Medical Center.

Pract Radiat Oncol 2020 Sep - Oct;10(5):e378-e387. Epub 2020 Feb 26.

Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota. Electronic address:

Purpose: Our purpose was to evaluate the outcomes and profiles of older patients with muscle-invasive bladder cancer (MIBC) treated with definitive radiation therapy (RT) with or without chemotherapy (CHT) at a tertiary medical center.

Methods And Materials: A retrospective study was conducted for older patients with MIBC who were ≥70 years old and underwent RT with or without CHT between 2000 and 2016. Overall survival (OS) was estimated using the Kaplan-Meier method. Disease-specific survival (DSS), cumulative incidence of progression, patterns of recurrence, and toxicities were examined. Univariate analyses were performed to identify variables associated with OS, DSS, and cumulative incidence of progression, using the Cox proportional hazards model.

Results: A total of 84 patients underwent definitive RT with or without CHT. Of these, only 29% were deemed medically fit to undergo radical cystectomy, and the remainder were medically unfit or had surgically unresectable disease. Median age was 81 years. Sixty-one percent, 29%, and 11% had clinical stage II, III, and IV disease, respectively. Eighty-six percent had maximal transurethral resection of bladder tumor before RT. Seventy-three percent received CHT with RT, and 27% had RT alone. Median follow-up was 5.7 years. Median OS was 1.9 years. OS was 42% and 25%, and DSS was 64% and 54% at 3 and 5 years, respectively. On univariate analysis, medical fitness to undergo radical cystectomy, receipt of CHT, lower T stage, and maximal transurethral resection of bladder tumor were associated with better OS; lower T stage was associated with better DSS. The cumulative incidence of progression was 44% and 49% at 3 and 5 years, respectively. Late grade 3 genitourinary and gastrointestinal toxicity were 15% and 4%, respectively. None had grade 4 or 5 toxicity.

Conclusions: Older patients with MIBC referred for RT were often medically unfit or had a surgically unresectable tumor. In these medically compromised patients, definitive RT with or without CHT was well tolerated and yielded encouraging treatment outcomes.
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http://dx.doi.org/10.1016/j.prro.2020.02.008DOI Listing
February 2020

c-Jun N terminal kinase signaling pathways mediate cannabinoid tolerance in an agonist-specific manner.

Neuropharmacology 2020 03 20;164:107847. Epub 2019 Nov 20.

Department of Anesthesiology and Perioperative Medicine, Penn State University College of Medicine, Hershey, PA, 17033, USA. Electronic address:

Tolerance to the antinociceptive effects of cannabinoids represents a significant limitation to their clinical use in managing chronic pain. Tolerance likely results from desensitization and down-regulation of the cannabinoid type 1 receptor (CBR), with CBR desensitization occurring via phosphorylation of CBRs by a G protein-coupled receptor kinase and subsequent association with an arrestin protein. Previous studies have shown that (1) desensitization-resistant S426A/S430A mice exhibit a modest delay in tolerance for Δ-THC and (-)-CP55,940 but a more pronounced disruption in tolerance for WIN 55,212-2 and (2) that c-Jun N-terminal kinase (JNK) signaling may selectively mediate antinociceptive tolerance to morphine compared to other opioid analgesics. In the current study, we found that pretreatment with the JNK inhibitor SP600125 (3 mg/kg) attenuates tolerance to the antinociceptive in the formalin test and to the anti-allodynic effects of Δ-THC (6 mg/kg) in cisplatin-evoked neuropathic pain using wild-type mice. We also find that SP600125 causes an especially robust reduction in tolerance to the antinociceptive effects of Δ-THC (30 mg/kg), but not WIN 55,212-2 (10 mg/kg) in the tail-flick assay using S426A/S430A mice. Interestingly, SP600125 pretreatment accelerated tolerance to the antinociceptive and anti-allodynic effects of (-)-CP55,940 (0.3 mg/kg) in mice with acute and neuropathic pain. These results demonstrate that inhibition of JNK signaling pathways delay tolerance to Δ-THC, but not to CP55,940 or WIN55,212-2, demonstrating that the mechanisms of cannabinoid tolerance are agonist-specific.
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http://dx.doi.org/10.1016/j.neuropharm.2019.107847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190707PMC
March 2020

C-Choline PET Guided Salvage Radiation Therapy for Isolated Pelvic and Paraortic Nodal Recurrence of Prostate Cancer After Radical Prostatectomy: Rationale and Early Genitourinary or Gastrointestinal Toxicities.

Adv Radiat Oncol 2019 Oct-Dec;4(4):659-667. Epub 2019 Jul 4.

Department of Radiation Oncology, Rochester, Minnesota.

Purpose: To assess gastrointestinal (GI) and genitourinary (GU) adverse events (AEs) of C-choline-positron emission tomography (CholPET) guided lymph node (LN) radiation therapy (RT) in patients who experience biochemical failure after radical prostatectomy.

Methods And Materials: From 2013 to 2016, 107 patients experienced biochemical failure of prostate cancer, had CholPET-detected pelvic and/or paraortic LN recurrence, and were referred for RT. Patients received androgen suppression and CholPET guided LN RT (median dose, 45 Gy) with a simultaneous integrated boost to CholPET-avid sites (median dose, 56.25 Gy), all in 25 fractions. RT-naïve patients had the prostatic fossa included in the initial treatment volumes followed by a sequential boost (median dose, 68 Gy). GI and GU AEs were reported per Common Terminology Criteria for Adverse Events (version 4.0) with data gathered retrospectively. Differences in maximum GI and GU AEs at baseline, immediately post-RT, and at early (median, 4 months) and late (median, 14 months) follow-up were assessed.

Results: Median follow-up was 16 months (interquartile range [IQR], 11-25). Median prostate-specific antigen at time of positive CholPET was 2.3 ng/mL (IQR, 1.3-4.8), with a median of 2 (IQR, 1-4) choline-avid LNs per patient. Most recurrences were within the pelvis (53%) or pelvis + paraortic (40%). Baseline rates of grade 1 to 2 GI AEs were 8.4% compared with 51.9% (4.7% grade 2) of patients post-RT ( < .01). These differences resolved by 4-month (12.2%,  = .65) and 14-month AE assessments (9.1%,  = .87). There was no significant change in grade 1 to 2 GU AEs post-RT (64.1%) relative to baseline (56.0%,  = .21), although differences did arise at 4-month (72.2%,  = .01) and 14-month (74.3%,  = .01) AE assessments.

Conclusions: Salvage CholPET guided nodal RT has acceptably low rates of acute GI and GU AEs and no significant detriment in 14-month GI AEs. These data are of value in counseling patients and designing prospective trials evaluating the oncologic efficacy of this treatment strategy.
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http://dx.doi.org/10.1016/j.adro.2019.06.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6817538PMC
July 2019

Radiotherapy for node-positive prostate cancer: 2019 Recommendations of the Australian and New Zealand Radiation Oncology Genito-Urinary group.

Radiother Oncol 2019 11 6;140:68-75. Epub 2019 Jun 6.

North Coast Cancer Institute, Coffs Harbour, Australia; University of New South Wales Rural Clinical School, Australia.

The management of node-positive prostate cancer is highly variable, with both locoregional and systemic treatment options available. With the increasing use of novel imaging techniques such as PSMA-PET and MRI, combined with the increasing use of surgery for high-risk prostate cancer, clinical and pathological regional nodal disease is being detected at a higher rate and at an earlier stage than previously. This creates a window for a potentially curative management approach. The role of radiotherapy including optimal radiation target volumes and dose, as well as the timing and duration of accompanying systemic therapy remains uncertain. At a workshop in 2017, the Australian and New Zealand Faculty of Radiation Oncology Genito-Urinary Group (FROGG) identified variations in the management of node-positive prostate cancer identified on primary staging or on histopathology at radical prostatectomy. FROGG reviewed the literature and developed a set of evidence-based recommendations on the appropriate investigation and management of clinically and pathologically node-positive prostate cancer. These recommendations encompass imaging techniques, radiation treatment target volumes and doses, as well as the use of androgen deprivation therapy.
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http://dx.doi.org/10.1016/j.radonc.2019.05.016DOI Listing
November 2019

Current Status of MRI and PET in the NCCN Guidelines for Prostate Cancer.

J Natl Compr Canc Netw 2019 05;17(5):506-513

Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri.

Prostate cancer (PCa) represents a significant source of morbidity and mortality for men in the United States, with approximately 1 in 9 being diagnosed with PCa in their lifetime. The role of imaging in the evaluation of men with PCa has evolved and currently plays a central role in diagnosis, treatment planning, and evaluation of recurrence. Appropriate use of multiparametric MRI (mpMRI) and MRI-guided transrectal ultrasound (MR-TRUS) biopsy increases the detection of clinically significant PCa while decreasing the detection of clinically insignificant PCa. This process may help patients with clinically insignificant PCa avoid the adverse effects of unnecessary therapy. In the setting of a known PCa, patients with low-grade disease can be observed using active surveillance, which often includes a combination of prostate-specific antigen (PSA) testing, serial mpMRI, and, if indicated, follow-up systematic and targeted TRUS-guided tissue sampling. mpMRI can provide important information in the posttreatment setting, but PET/CT is creating a paradigm shift in imaging standards for patients with locally recurrent and metastatic PCa. This article examines the strengths and limitations of mpMRI for initial PCa diagnosis, active surveillance, recurrent disease evaluation, and image-guided biopsies, and the use of PET/CT imaging in men with recurrent PCa. The goal of this review is to provide a rational basis for current NCCN Clinical Practice Guidelines in Oncology for PCa as they pertain to the use of these advanced imaging modalities.
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http://dx.doi.org/10.6004/jnccn.2019.7306DOI Listing
May 2019

Prostate Cancer, Version 2.2019, NCCN Clinical Practice Guidelines in Oncology.

J Natl Compr Canc Netw 2019 05;17(5):479-505

Stanford Cancer Institute.

The NCCN Guidelines for Prostate Cancer include recommendations regarding diagnosis, risk stratification and workup, treatment options for localized disease, and management of recurrent and advanced disease for clinicians who treat patients with prostate cancer. The portions of the guidelines included herein focus on the roles of germline and somatic genetic testing, risk stratification with nomograms and tumor multigene molecular testing, androgen deprivation therapy, secondary hormonal therapy, chemotherapy, and immunotherapy in patients with prostate cancer.
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http://dx.doi.org/10.6004/jnccn.2019.0023DOI Listing
May 2019

Single-fraction Stereotactic Body Radiation Therapy versus Conventionally Fractionated Radiation Therapy for the Treatment of Prostate Cancer Bone Metastases.

Adv Radiat Oncol 2019 Apr-Jun;4(2):314-322. Epub 2019 Feb 19.

Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota.

Purpose: This study aimed to compare outcomes of patients with prostate cancer with bone metastases treated with stereotactic body radiation therapy (SBRT) versus conventionally fractionated radiation therapy (CFRT).

Methods And Materials: An institutional, retrospective review was conducted of patients with prostate cancer receiving radiation therapy to bone metastases. In-field failure (IFF) was the primary outcome of the study, and distant failure (DF) and biochemical failure (BF) were secondary outcomes.

Results: A total of 249 metastases (191 SBRT; 58 CFRT) in 201 patients with a median follow-up of 2.2 years were analyzed. The SBRT prescription dose was predominantly 18 Gy (45.5%) or 20 Gy (46.6%) in a single fraction. CFRT was given either as 8 Gy in 1 fraction (56.9%) or 20 Gy in 5 fractions (41.4%). Imaging follow up was performed most frequently with C-choline positron emission tomography/computed tomography (79%) or bone scan (10%). The median time to IFF was 1.6 years for CFRT-treated lesions and not met (>4.4 years) for SBRT. The 1- and 3-year IFF estimates were 34.4% (95% confidence interval [CI], 19.9-46.2) and 53.3% (95% CI, 34.3-66.8) for lesions treated with CFRT compared with 4.5% (95% CI, 1.4-7.5) and 12.9% (95% CI, 6.6-18-8) for those treated with SBRT ( < .01). On multivariate regression, the hazard ratio (HR) for IFF with CFRT compared with SBRT was 6.8 (95% CI, 3.7-12.5;  < .01). There were nonsignificant reduced rates of BF (HR, 1.4; 95% CI, 1.0-2.1;  = .05) and DF (HR, 1.3; 95% CI, 1.0-1.8;  = .08) in patients who received SBRT. The 3-year BF and DF estimates in these patients were 88.6% (95% CI, 82.0-92.8) and 82.2% (95% CI, 74.5-87.6), respectively.

Conclusions: SBRT for the management of prostate cancer bone metastases significantly reduces radiographic IFF. However, the high rate of subsequent DF and BF highlights the challenges in selecting patients who may benefit from aggressive radiation therapy.
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http://dx.doi.org/10.1016/j.adro.2019.02.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6460234PMC
February 2019

Evaluating the Potential Role of Salvage Vesiculectomy for Prostate Cancer Recurrence.

Clin Genitourin Cancer 2019 06 6;17(3):e536-e540. Epub 2019 Feb 6.

Department of Urology, Mayo Clinic, Rochester, MN. Electronic address:

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http://dx.doi.org/10.1016/j.clgc.2019.01.019DOI Listing
June 2019

Reducing seed migration to near zero with stranded-seed implants: Comparison of seed migration rates to the chest in 1000 permanent prostate brachytherapy patients undergoing implants with loose or stranded seeds.

Brachytherapy 2019 May - Jun;18(3):306-312. Epub 2019 Mar 8.

Department of Radiation Oncology, Mayo Clinic, Rochester, MN.

Purpose: Pulmonary seed emboli to the chest may occur after permanent prostate brachytherapy (PPB). The purpose of this study is to analyze factors associated with seed migration to the chest in a large series of PPB patients from a single institution undergoing implant with either loose seeds (LS), mixed loose and stranded seeds (MS), or exclusively stranded seeds in an absorbable vicryl suture (VS).

Methods And Materials: Between May 1998 and July 2015, a total of 1000 consecutive PPB patients with postoperative diagnostic chest x-rays at 4 months after implant were analyzed for seed migration. Patients were grouped based on seed implant technique: LS = 391 (39.1%), MS = 43 (4.3%), or VS = 566 (56.6%). Univariate and multivariate analysis were performed using Cox proportional hazards regression models to determine predictors of seed migration.

Results: Overall, 18.8% of patients experienced seed migration to the chest. The incidence of seed migration per patient was 45.5%, 11.6%, and 0.9% (p < 0.0001), for patients receiving LS, MS, or VS PPB, respectively. The right and left lower lobes were the most frequent sites of pulmonary seed migration. On multivariable analysis, planimetry volume (p = 0.0002; HR = 0.7 per 10 cc [0.6-0.8]), number of seeds implanted (p < 0.0001, HR = 2.4 per 25 seeds [1.7-3.4]), LS implant (p < 0.0001, HR = 15.9 [5.9-42.1]), and MS implant (p = 0.001, HR = 7.9 [2.3-28.1]) were associated with seed migration to the chest.

Conclusions: In this large series, significantly higher rates of seed migration to the chest are observed in implants using any LS with observed hazard ratios of 15.9 and 7.9 for LS and MS respectively, as compared with implants using solely stranded seeds.
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http://dx.doi.org/10.1016/j.brachy.2019.01.007DOI Listing
December 2019

Percutaneous Image-Guided Nodal Biopsy After 11C-Choline PET/CT for Biochemically Recurrent Prostate Cancer: Imaging Predictors of Disease and Clinical Implications.

Adv Radiat Oncol 2019 Jan-Mar;4(1):79-89. Epub 2018 Sep 5.

Department of Radiology, Mayo Clinic, Rochester, Minnesota.

Purpose: Management of recurrent prostate cancer necessitates timely diagnosis and accurate localization of the sites of recurrent disease. The purpose of this study was to assess predictors of histologic outcomes after 11C-choline positron emission tomography/computed tomography (CholPET) to increase the positive predictive value and specificity of CholPET in identifying imaging predictors of malignant and benign nodal disease to better inform clinical decision making regarding local therapy planning.

Materials And Methods: Retrospective review of patients undergoing CholPET followed by percutaneous core needle biopsy between January 1, 2010 and January 1, 2016. A total of 153 patients were identified who underwent 166 biopsy procedures. Patient, CholPET, procedural, and pathologic characteristics were recorded.

Results: A total of 157 biopsies were technically successful, and 110 (70.1%; 95% confidence interval, 62.2-77.1) yielded histologic results abnormal for metastatic prostate cancer. Lesion location, lesion maximum standardized uptake value (SUVmax), SUV ratio (calculated as the ratio of SUVmax to SUV mean in the right atrium), prostate-specific antigen, lesion short axis length, total Gleason score, and castration resistance were all associated with abnormal biopsy results ( values <.001, <.001, <.001, .02, .02, .02, and .015, respectively). External iliac, common iliac, and inguinal sites were associated with much lower rates of histologic positivity (mean [95% confidence interval], 51.2% [35.1-67.1], 46.2% [19.2-74.9], and 33.3% [7.5-70.1]), respectively.

Conclusions: In a cohort of patients in whom core needle biopsy was performed after CholPET, characteristics of choline localization including node location, SUVmax, lesion-to-blood pool SUV ratio, prostate-specific antigen, total Gleason score, and castration resistance were significantly associated with abnormal biopsy results for metastatic disease on CholPET. Relatively high false positive rates were found in common iliac, external iliac, and inguinal lymph node locations. Histologic confirmation of these sites should be strongly considered in the appropriate clinical scenario before designing additional local therapy plans.
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http://dx.doi.org/10.1016/j.adro.2018.08.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6349661PMC
September 2018

Permanent prostate brachytherapy monotherapy with I-125 for low- and intermediate-risk prostate cancer: Outcomes in 974 patients.

Brachytherapy 2019 Jan - Feb;18(1):1-7. Epub 2018 Oct 4.

Department of Radiation Oncology, Mayo Clinic, Rochester, MN. Electronic address:

Purpose: To report outcomes of patients undergoing low-dose-rate (LDR) brachytherapy and investigate factors associated with biochemical failure and survival.

Methods: Consecutive patients undergoing LDR with I-125 at our institution between 1998 through 2013 for primary intact prostate cancer were examined. Those with low- and intermediate-risk disease receiving LDR with a minimum of 2 years followup and at least one post-LDR prostate-specific antigen (PSA) were included.

Results: About 974 patients satisfied inclusion criteria. With median followup of 72 months, biochemical failure occurred in 45 patients. Freedom from biochemical failure as defined by the Phoenix criterion was 96% and 88% at 5 and 10 years, worse for intermediate risk as compared with low risk, with 10-year freedom from biochemical failure of 76% versus 92% (hazard ratio [HR] = 3.7, p < 0.001), respectively. On multivariable analysis, increased prebiopsy PSA, Gleason 4 + 3, and no androgen deprivation therapy were associated with biochemical failure. Gleason 4 + 3 was the factor most strongly associated with biochemical failure (HR = 7.01, p < 0.001). No examined factors were associated with local failure. Gleason 4 + 3 disease increased the likelihood of distant metastasis (HR = 12.4, p = 0.003) and prostate cancer-specific death (HR = 13.2, p < 0.001). No difference in outcomes between patients with Gleason 3 + 3 versus 3 + 4 was observed.

Conclusions: LDR brachytherapy provided excellent outcomes in this large series of patients treated for localized organ-confined prostate cancer. Local recurrence at 10 years was low at 2.1%. Primary Gleason 4 + 3, higher pretreatment PSA, and no receipt of androgen deprivation therapy were the only factors associated with biochemical failure. Primary Gleason 4 disease was also predictive of distant metastases and decreased prostate cancer-specific survival.
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http://dx.doi.org/10.1016/j.brachy.2018.09.003DOI Listing
April 2019

The American Brachytherapy Society and the American Radium Society Appropriate Use Criteria Genitourinary Committee Endorse the American Society of Clinical Oncology/Cancer Care Ontario Guidelines.

J Clin Oncol 2018 Sep 13:JCO1800626. Epub 2018 Sep 13.

Albert J. Chang, University of California, Los Angeles, Los Angeles, CA; Sean McBride, Memorial Sloan Kettering Cancer Center, New York, NY; Mira Keyes, British Columbia Cancer Agency and University of British Columbia, Vancouver, British Colombia, Canada; Hans T. Chung, University of Toronto and Odette Cancer Centre, Toronto, Ontario, Canada; Brian J. Davis, Mayo Clinic, Rochester, MN; Brett W. Cox, Northwell Health and Hofstra Northwell School of Medicine, New York, NY; Juanita Crook, British Columbia Cancer Agency, Cancer Center for the Southern Interior, Kelowna, British Columbia, Canada; David J. Demanes, University of California, Los Angeles, Los Angeles, CA; I. Chow Hsu, University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA; Mitchell Kamrava, Cedars Sinai Medical Center, Los Angeles, CA; Daniel J. Krauss, Beaumont Health System, Royal Oak, MI; Gerard Morton, University of Toronto and Odette Cancer Centre, Toronto, Ontario, Canada; Peter F. Orio III, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Mack Roach III, University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA; Puja S. Venkat, University of California, Los Angeles, Los Angeles, CA; Eric Vigneault, Centre de Recherche sur le Cancer, CHU de Québec, Université Laval, Québec, Canada; and Michael J. Zelefsky, Memorial Sloan Kettering Cancer Center, New York, NY.

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http://dx.doi.org/10.1200/JCO.18.00626DOI Listing
September 2018

Prospective Immunophenotyping of CD8 T Cells and Associated Clinical Outcomes of Patients With Oligometastatic Prostate Cancer Treated With Metastasis-Directed SBRT.

Int J Radiat Oncol Biol Phys 2019 01 8;103(1):229-240. Epub 2018 Sep 8.

Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota. Electronic address:

Purpose: This study examined the effects of metastasis-directed stereotactic body radiation therapy (mdSBRT) on CD8 T-cell subpopulations and correlated post-mdSBRT immunophenotypic responses with clinical outcomes in patients with oligometastatic prostate cancer (OPCa).

Methods And Materials: Peripheral blood mononuclear cells were prospectively isolated from 37 patients with OPCa (≤3 metastases) who were treated with mdSBRT. Immunophenotyping identified circulating CD8 T-cell subpopulations, including tumor-reactive (T), effector memory, central memory (T), effector, and naïve T cells from samples collected before and after mdSBRT. Univariate Cox proportional hazards regression was used to assess whether changes in these T-cell subpopulations were potential risk factors for death and/or progression. The Kaplan-Meier method was used for survival. Cumulative incidence for progression and new distant metastasis weas estimated, considering death as a competing risk.

Results: Median follow-up was 39 months (interquartile range, 34-43). Overall survival at 3 years was 78.2%. Cumulative incidence for local progression and new distant metastasis at 3 years was 16.5% and 67.6%, respectively. Between baseline and day 14 after mdSBRT, an increase in the T cell subpopulation was associated with the risk of death (hazard ratio, 1.22 [95% confidence interval, 1.02-1.47]; P = .033), and an increase in the T cell subpopulation was protective against the risk of local progression (hazard ratio, 0.80 [95% confidence interval, 0.65-0.98]; P = .032).

Conclusions: An increase in the T cell subpopulation was protective against the risk of disease progression, and an increase in the T cell subpopulation was associated with the risk of death in patients with OPCa treated with mdSBRT. Disease control may be further improved by better understanding the CD8 T-cell subpopulations and by enhancing their antitumor effect.
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http://dx.doi.org/10.1016/j.ijrobp.2018.09.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6301146PMC
January 2019

Increased utilization of external beam radiotherapy relative to cystectomy for localized, muscle-invasive bladder cancer: a SEER analysis.

Bladder (San Franc) 2018 23;5(3):e34. Epub 2018 Aug 23.

Department of Radiation Oncology, Mayo Clinic, Rochester, MN, USA.

Objective: To assess recent utilization patterns of radiotherapy (RT) relative to cystectomy for muscle-invasive bladder cancer (MIBC) and evaluate survival trends over time in patients receiving RT.

Materials And Methods: The surveillance, epidemiology, and end results program (SEER) was used to identify patients diagnosed between 1992 and 2013 with localized MIBC. Patients with a prior history of non-bladder malignancy, who received no treatment, or did not have available treatment information, were excluded. Treatment utilization patterns were assessed using Cochran-Armitage tests for trend, and patient characteristics were compared using chi-square tests. Overall survival (OS) and cause-specific survival (CSS) were estimated using the Kaplan-Meier method. All-cause (ACM) and cause-specific mortality (CSM) were evaluated with multivariable Cox proportional hazards regression.

Results: Of 16175 patients analyzed, 11917 (74%) underwent cystectomy, and 4258 (26%) were treated with RT. Patients who received RT were older (median age 79 . 68, < 0.01). Over time, the proportion of patients receiving RT relative to cystectomy increased (24% 1992-2002 . 28% 2003-2013, < 0.01), despite median patient age throughout the study period remaining unchanged (71 for each 1992-2002 and 2003-2013, = 0.41). For RT, compared with patients diagnosed earlier, those diagnosed from 2010-2013 showed improved OS (64% . 60% at 1 year, < 0.01; 38% . 29% at 3 years, < 0.01) and CSS (71% . 67% at 1 year, = 0.01; 51% . 40% at 3 years, < 0.01). On multivariable analysis, diagnosis from 2010-2013 was associated with a lower estimated risk of ACM (hazard ratio 0.77; 95% confidence interval 0.66-0.89, < 0.001) and CSM (hazard ratio 0.81; 95% confidence interval 0.67-0.97, = 0.02).

Conclusion: Utilization of RT for localized MIBC increased relative to cystectomy from 1992 to 2013, despite the median age of treated patients remaining unchanged. More recent survival outcomes for patients receiving RT were improved, supporting continued use of bladder preservation strategies utilizing RT.
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http://dx.doi.org/10.14440/bladder.2018.639DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7401988PMC
August 2018

Low dose rate prostate brachytherapy.

Transl Androl Urol 2018 Jun;7(3):341-356

Department of Radiation Oncology, Mayo Clinic, Rochester, MN 55905, USA.

Low dose rate (LDR) prostate brachytherapy is an evidence based radiation technique with excellent oncologic outcomes. By utilizing direct image guidance for radioactive source placement, LDR brachytherapy provides superior radiation dose escalation and conformality compared to external beam radiation therapy (EBRT). With this level of precision, late grade 3 or 4 genitourinary or gastrointestinal toxicity rates are typically between 1% and 4%. Furthermore, when performed as a same day surgical procedure, this technique provides a cost effective and convenient strategy. A large body of literature with robust follow-up has led multiple expert consensus groups to endorse the use of LDR brachytherapy as an appropriate management option for all risk groups of non-metastatic prostate cancer. LDR brachytherapy is often effective when delivered as a monotherapy, although for some patients with intermediate or high-risk disease, optimal outcome are achieved in combination with supplemental EBRT and/or androgen deprivation therapy (ADT). In addition to reviewing technical aspects and reported clinical outcomes of LDR prostate brachytherapy, this article will focus on the considerations related to appropriate patient selection and other aspects of its use in the treatment of prostate cancer.
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http://dx.doi.org/10.21037/tau.2017.12.15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6043740PMC
June 2018