Publications by authors named "Bradley J Stish"

35 Publications

In Reply to Onal et al.

Int J Radiat Oncol Biol Phys 2021 Aug;110(5):1547-1548

Departments of Radiation Oncology and Molecular Radiation Sciences, Oncology, and Urology, Johns Hopkins School of Medicine, Baltimore, Maryland.

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http://dx.doi.org/10.1016/j.ijrobp.2021.04.003DOI Listing
August 2021

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
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8251338PMC
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

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

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

Reirradiation for Locoregional Recurrent Breast Cancer.

Adv Radiat Oncol 2021 Jan-Feb;6(1):100640. Epub 2020 Dec 17.

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

Purpose: Reirradiation poses a distinct therapeutic challenge owing to risks associated with exceeding normal tissue tolerances and possibly more therapeutically resistant disease biology. We report our experience with reirradiation for locoregional recurrent or second primary breast cancer.

Methods And Materials: Between 1999 and 2019, all patients with breast cancer treated with repeat breast/chest wall radiation therapy (RT) at our institution were identified. Adverse events were assessed using the Common Terminology Criteria for Adverse Events v5.0. Fisher exact, Mann-Whitney rank-sum, and unpaired tests were used for statistical analysis. Freedom from locoregional recurrence and distant metastasis as well as overall survival were calculated using the Kaplan-Meier method.

Results: Seventy-two patients underwent reirradiation. Median prior RT dose, reirradiation dose, and cumulative dose were 60 Gy (interquartile range [IQR], 50-60.4 Gy), 45 Gy (IQR, 40-50 Gy), and 103.54 Gy (IQR, 95.04-109.62 Gy), respectively. Median time between RT courses was 73 months (IQR, 29-129 months). Thirty-four patients (47%) had gross residual disease at time of reirradiation. Course intent was described as curative in 44 patients (61%) and palliative in 28 (39%). Fifty-two patients (72%) were treated with photons ± electrons and 20 (28%) with protons. With a median follow-up of 22 months (IQR, 10-43 months), grade 3 adverse events were experienced by 13% of patients (10% acute skin toxicity and 3% late skin necrosis). Time between RT courses and reirradiation fields was significantly associated with the development of grade 3 toxicity at any point. Proton therapy conferred a dosimetric advantage without difference in toxicity. At 2 years, locoregional recurrence-free survival was 74.6% and overall survival was 65.5% among all patients, and 93.1% and 76.8%, respectively, among curative intent patients treated without gross disease. Distant metastasis-free survival was 59.0% among all curative intent patients.

Conclusions: Reirradiation for locoregional recurrent breast cancer is feasible with acceptable rates of toxicity. Disease control and survival are promising among curative intent reirradiation patients without gross disease.
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http://dx.doi.org/10.1016/j.adro.2020.100640DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7814100PMC
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

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

Androgen Deprivation Therapy Use and Risk of Mild Cognitive Impairment in Prostate Cancer Patients.

Alzheimer Dis Assoc Disord 2021 Jan-Mar 01;35(1):44-47

Health Sciences Research.

Introduction: We examined the association between androgen deprivation therapy (ADT) use and the risk of mild cognitive impairment (MCI) among prostate cancer patients.

Methods: We included 241 cognitively unimpaired men, aged 70 to 90, with a history of prostate cancer before enrollment in the population-based Mayo Clinic Study of Aging. Using the Rochester Epidemiology Project medical records-linkage system, ADT use and length of exposure were abstracted. Follow-up visits occurred every 15 months and MCI diagnoses were made based on clinical consensus. Cox proportional hazards models, with age as the timescale, were used to examine the association between ADT use (yes/no) and length of exposure with the risk of MCI adjusting for education, apolipoprotein E, depression, and the Charlson Index score.

Results: There was no association between any ADT use (27.8% of participants) and the risk of MCI in the multivariable model [hazard ratio (HR), 1.25; 95% confidence interval (CI), 0.75-2.10]. Although not significant, there was an ADT dose-response relationship for risk of MCI: <5 years versus no use (HR, 1.08; 95% CI, 0.60-1.96) and ≥5 years versus not use (HR, 1.89; 95% CI, 0.83-4.27).

Conclusion: ADT use among prostate cancer patients was not associated with an increased risk of developing MCI.
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http://dx.doi.org/10.1097/WAD.0000000000000415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904573PMC
June 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

Patterns of Recurrence and Modes of Progression After Metastasis-Directed Therapy in Oligometastatic Castration-Sensitive Prostate Cancer.

Int J Radiat Oncol Biol Phys 2021 02 14;109(2):387-395. Epub 2020 Aug 14.

Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland; James Buchanan Brady Urological Institute, Johns Hopkins School of Medicine, Baltimore, Maryland. Electronic address:

Purpose: Metastasis-directed therapy (MDT) is increasingly used in castration-sensitive oligometastatic prostate cancer because it prolongs progression-free survival (PFS) and androgen deprivation free survival. Here we describe patterns of recurrence and identify modes of progression after MDT using SABR.

Methods And Materials: Two hundred fifty-eight patients with castration-sensitive oligometastatic prostate cancer (≤5 lesions at staging) were retrospectively identified from a multi-institutional database. Descriptive patterns of recurrence and modes of progression were reported. Other outcomes including median time to prostate-specific antigen (PSA) recurrence, time to next intervention, distant metastasis-free survival, overall survival, and biochemical PFS (bPFS) were reported. Survival analysis was performed using the Kaplan-Meier method, and multivariable analysis was performed.

Results: Median follow-up was 25.2 months, and 50.4% of patients received concurrent androgen deprivation. Median time to PSA recurrence was 15.7 months, time to next intervention was 28.6 months, distant metastasis-free survival was 19.1 months, and bPFS was 16.1 months. Two-year overall survival was 96.8%. On multivariable analysis, factors associated with bPFS included age (hazard ratio [HR], 1.03; P = .04), N1 disease at diagnosis (HR, 2.00; P = .02), M1 disease at diagnosis (HR, 0.44; P = .01), initial PSA at diagnosis (HR, 1.002; P = <.001), use of androgen deprivation therapy (HR, 0.41; P < .001), pre-SABR PSA (HR, 1.02; P = .01), and use of enhanced imaging for staging (HR, 2.81; P = .001). Patterns of progression favored an osseous component at recurrence; in patients initially treated to a bone lesion alone, the vast majority (86.5%) experienced a recurrence that included an osseous site. Patients treated initially to a nodal site alone tended to recur in a node only (64.5%); however, there was also a significant minority with an osseous component of recurrence at progression (32.3%). Modes of progressors were class I (patients with long term control [no recurrence ≥18 months after therapy]) occurring in 40.9%, class II (oligoprogressors [≤3 lesions at recurrence]) occurring in 36% (including 7.9% of patients with PSA recurrence but no metastatic disease), and class III (polyprogressors [>3 lesions]) occurring in 23.1% of patients.

Conclusions: After MDT, the majority of patients have long-term control or oligoprogression (class I or II). Recurrence tended to occur in osseous sites. These findings, if validated, have implications for future integration of MDT and clinical trial design.
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http://dx.doi.org/10.1016/j.ijrobp.2020.08.030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856169PMC
February 2021

Low-Dose Hypofractionated Total Skin Electron Beam Therapy for Adult Cutaneous T-Cell Lymphoma.

Pract Radiat Oncol 2020 Nov - Dec;10(6):e529-e537. Epub 2020 Aug 8.

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

Purpose: Historically, the standard of care for total skin electron beam therapy (TSEBT) delivered 30 to 36 Gy over 5 to 10 weeks. Given the high risk of relapse, a majority of patients require additional treatments. Therefore, attempts to use a shortened course of TSEBT have been investigated.

Methods And Materials: We conducted a single-institution retrospective review to evaluate disease response, control, and toxicity using a low-dose, hypofractionated course of TSEBT (HTSEBT) in patients with mycosis fungoides.

Results: Forty patients received 57 courses of HTSEBT. Median dose (Gy)/fractionation was 12/3, spanning a median time of 2.4 weeks. Overall response rate of patients assessed (n = 54) was 100%. Thirty-one courses (57.4%) resulted in a complete response and 23 courses (42.6%) resulted in a partial response. Cumulative incidence of progressive skin disease at 3 months was 37.2%, at 6 months, 56.9%, and at 1 year, 81.5%. Of the 40 patients treated with a first course of HTSEBT, 31 received subsequent courses of radiotherapy. Cumulative incidence of subsequent treatment was 28.0% at 3 months, 46.8% at 6 months, and 70.0% at 1 year. Patients who underwent repeat courses of HTSEBT continued to have similar treatment responses to repeat courses without increased toxicities. Toxicities from all courses were acceptable with the exception of 1 patient, who experienced grade 4 skin toxicity (moist desquamation requiring hospitalization).

Conclusions: Low-dose HTSEBT provides good palliation in patients with cutaneous T-cell lymphoma with a satisfactory response and toxicity profile. HTSEBT allows therapy to be completed in far fewer treatments. Low-dose HTSEBT is an appropriate treatment option for patients unable to come for daily treatment. HTSEBT provides a way to decrease exposure to other patients and staff during public health emergencies such as the coronavirus disease 2019 (COVID-19) pandemic.
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http://dx.doi.org/10.1016/j.prro.2020.08.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7414776PMC
November 2020

Metastasis-directed Therapy Prolongs Efficacy of Systemic Therapy and Improves Clinical Outcomes in Oligoprogressive Castration-resistant Prostate Cancer.

Eur Urol Oncol 2021 Jun 11;4(3):447-455. Epub 2020 Jun 11.

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

Background: Available therapies for castrate-resistant prostate cancer (CRPC) confer minimal survival advantage; thus, there is interest in metastasis-directed therapy (MDT) for oligometastatic or oligoprogressive disease to improve outcomes. Here, we describe outcomes of oligoprogressive CRPC treated with stereotactic ablative radiotherapy (SABR).

Objective: To report outcomes of oligoprogressive CRPC treated with MDT using SABR.

Design, Setting, And Participants: Patients with oligoprogressive CRPC were retrospectively evaluated, and outcomes following MDT were reported. Outcomes were additionally compared with oligoprogressive CRPC treated with change in systemic therapy alone.

Intervention: SABR to oligoprogressive lesions.

Outcome Measurements And Statistical Analysis: Outcomes of interest were time to prostate-specific antigen (PSA) failure, time to next intervention (TTNI), distant metastasis-free survival (DMFS), and overall survival. Survival analysis was performed using the Kaplan-Meier method, and univariable analysis and multivariable analysis (MVA) were performed.

Results And Limitations: A total of 68 patients were included. After MDT, median time to PSA recurrence, TTNI, and DMFS were 9.7, 15.6, and 10.8 months, respectively. A total of 112 lesions were treated, and the cumulative incidences of local failure at 12 and 24 months were 2.1% and 13.8%, respectively. Factors associated with the risk of local recurrence on univariable analysis were age (hazard ratio [HR] 1.07, p =  0.03) and Gleason grade group (HR 2.20, p =  0.07). Compared with change in systemic therapy alone (n = 52), MDT (n = 31) was associated with improved median time to PSA failure (9.7 vs 4.2 months, p =  0.066)), TTNI (14.9 vs 8.8 months, p =  0.025), and DMFS (12.7 vs 8.9 months, p = 0.045), and remained associated with improved outcomes on MVA.

Conclusions: In a retrospective cohort of oligoprogressive CRPC patients, MDT was associated with favorable outcomes and improved cancer control as compared with change in systemic treatment alone. Future prospective trials are needed to confirm these findings.

Patient Summary: In this report, we retrospectively analyzed outcomes of patients with oligoprogressive castrate-resistant prostate cancer treated with radiation therapy to progressing lesions. Our results suggest that treatment of these lesions with radiation therapy can result in sustained periods of disease-free survival and might add benefit in addition to systemic therapy at the time of progression. These results need to be verified in a prospective trial to identify the optimal integration of radiation therapy into metastatic castrate-resistant prostate cancer.
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http://dx.doi.org/10.1016/j.euo.2020.05.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7788526PMC
June 2021

Association of Presalvage Radiotherapy PSA Levels After Prostatectomy With Outcomes of Long-term Antiandrogen Therapy in Men With Prostate Cancer.

JAMA Oncol 2020 05;6(5):735-743

Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts.

Importance: In men with recurrent prostate cancer, addition of long-term antiandrogen therapy to salvage radiotherapy (SRT) was associated with overall survival (OS) in the NRG/RTOG 9601 study. However, hormone therapy has associated morbidity, and there are no validated predictive biomarkers to identify which patients derive most benefit from treatment.

Objective: To examine the role of pre-SRT prostate-specific antigen (PSA) levels to personalize hormone therapy use with SRT.

Interventions: Men were randomized to SRT plus high-dose nonsteroidal antiandrogen (bicalutamide, 150 mg/d) or placebo for 2 years.

Design, Setting, And Participants: In this secondary analysis of the multicenter RTOG 9601 double-blind, placebo-controlled randomized clinical trial conducted from 1998 to 2003 by a multinational cooperative group, men with a positive surgical margin or pathologic T3 disease after radical prostatectomy with pre-SRT PSA of 0.2 to 4.0 ng/mL were included. Analysis was performed between March 4, 2019, and December 20, 2019.

Main Outcomes And Measures: The primary outcome was overall survival (OS). Secondary end points included distant metastasis (DM), other-cause mortality (OCM), and grades 3 to 5 cardiac and neurologic toxic effects. Subgroup analyses were performed using the protocol-specified PSA stratification variable (1.5 ng/mL) and additional PSA cut points, including test for interaction. Competing risk analyses were performed for DM and other-cause mortality (OCM).

Results: Overall, 760 men with PSA elevation after radical prostatectomy for prostate cancer were included. The median (range) age of particpants was 65 (40-83) years. Antiandrogen assignment was associated with an OS benefit in the PSA stratum greater than 1.5 ng/mL (n = 118) with a 25% 12-year absolute benefit (hazard ratio [HR], 0.45; 95% CI, 0.25-0.81), but not in the PSA of 1.5 ng/mL or less stratum (n = 642) (1% 12-year absolute difference; HR, 0.87; 95% CI, 0.66-1.16). In a subanalysis of men with PSA of 0.61 to 1.5 (n = 253), there was an OS benefit associated with antiandrogen assignment (HR, 0.61; 95% CI, 0.39-0.94). In those receiving early SRT (PSA ≤0.6 ng/mL, n = 389), there was no improvement in OS (HR, 1.16; 95% CI, 0.79-1.70), an increased OCM hazard (subdistribution HR, 1.94; 95% CI, 1.17-3.20; P = .01), and an increased odds of late grades 3 to 5 cardiac and neurologic toxic effects (odds ratio, 3.57; 95% CI, 1.09-15.97; P = .05).

Conclusions And Relevance: These results suggest that pre-SRT PSA level may be a prognostic biomarker for outcomes of antiandrogen treatment with SRT. In patients receiving late SRT (PSA >0.6 ng/mL, hormone therapy was associated with improved outcomes. In men receiving early SRT (PSA ≤0.6 ng/mL), long-term antiandrogen treatment was not associated with improved OS. Future randomized clinical trials are needed to determine hormonal therapy benefit in this population.

Trial Registration: ClinicalTrials.gov Identifier: NCT00002874.
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http://dx.doi.org/10.1001/jamaoncol.2020.0109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7189892PMC
May 2020

Stereotactic Body Radiation Therapy for Nonspine Bone Metastases: International Practice Patterns to Guide Treatment Planning.

Pract Radiat Oncol 2020 Nov - Dec;10(6):e452-e460. Epub 2020 Mar 11.

Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.

Purpose: Stereotactic body radiation therapy (SBRT) is increasingly used for nonspine bone metastases (NSBM); however, there are limited data informing treatment planning. We surveyed international experts to better understand worldwide practice patterns in delivering NSBM-SBRT.

Methods And Materials: Nine international radiation oncologists were invited to participate based on demonstrated expertise with NSBM-SBRT. Experts were sent gross tumor volume contours and planning computed tomography and magnetic resonance images for 11 NSBM cases that covered a range of bony sites, including metastases to long bones (femur, humerus), pelvic bones (ilium, ischium, acetabulum, pubic symphysis), and thoracic bones (rib, sternum, scapula, clavicle). Experts were surveyed regarding treatment planning decisions and dose-fractionation selection. Descriptive analysis was conducted on the survey data.

Results: All experts participated and completed the survey. Most (56%) routinely fused magnetic resonance imaging with planning computed tomography imaging for target delineation. Dose fractionation schedules included single-fraction (18-24 Gy/1), 2 fractions (24 Gy/2), 3 fractions (28-30 Gy/3), 5 fractions (30-50 Gy/5), and 10 fractions (42-50 Gy/10). Although doses varied considerably, all had a biological equivalent dose of ≤100 Gy. Five-fraction schedules were most common, specifically 35 Gy/5, with 56% opting for this dose-fractionation in at least 1 case. Other dose-fractionation schedules used by at least 3 experts were 20 Gy/1, 30 Gy/3, and 30 Gy/5. Three experts prescribed 2 dose volumes using a simultaneous integrated boost. The 2 dose volumes were either the gross tumor volume and clinical target volume (CTV) or a smaller CTV (CTV1) encompassed within a larger CTV (CTV2) (eg, 30 Gy/3 to gross tumor volume or CTV1 and 15-24 Gy/3 to CTV or CTV2). Dose de-escalation was recommended by all experts in the setting of previous SBRT and by most in the context of previous convevoltherapy or in weight-bearing bones, especially if moderate-to-severe cortical erosion was present.

Conclusions: Significant heterogeneity exists worldwide in radiation technique and dose-fractionation for NSBM-SBRT, which supports the need for consensus guidelines to inform practice and trial design. Nonetheless, these data demonstrate expert agreement on selecting dose schedules with a biologically effective dose ≤100 Gy, reasons for dose de-escalation, and in determining acceptable dose schedules based on bony site.
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http://dx.doi.org/10.1016/j.prro.2020.02.011DOI Listing
March 2020

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

Prostate Cancer, Use of Androgen Deprivation Therapy, and Cognitive Impairment: A Population-based Study.

Alzheimer Dis Assoc Disord 2020 Apr-Jun;34(2):118-121

Health Sciences Research.

Introduction: The association of prostate cancer and androgen deprivation therapy (ADT) use with the odds of developing mild cognitive impairment (MCI) was determined in men from the population-based Mayo Clinic Study of Aging (MCSA).

Methods: The study included 2513 men (mean age of 73.1 y) enrolled in the MCSA. A history of prostate cancer, ADT use, and length of ADT exposure before their first MCSA visit was abstracted using the Rochester Epidemiology Project medical records-linkage system. MCI was diagnosed at the baseline visit. Logistic regression was used to determine whether prostate cancer and ADT use was associated with odds of MCI.

Results: Of the 2513 participants, 349 (13.9%) had a history of prostate cancer; among whom 99 (28.3%) were treated with ADT before MCSA enrollment. There were 382 (15.2%) with a diagnosis of MCI. In the univariate logistic regression models, prostate cancer (odds ratio, 1.50; 95% confidence interval, 1.12-2.00), and ADT exposure (odds ratio, 1.57; 95% confidence interval, 0.96-2.58) were associated with higher odds of MCI. These associations were greatly attenuated and not significant in multivariable models.

Conclusions: Neither a diagnosis of prostate cancer nor ADT use was associated with odds of MCI in this cross-sectional population-based study.
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http://dx.doi.org/10.1097/WAD.0000000000000366DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7242115PMC
June 2021

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

The current state of randomized clinical trial evidence for prostate brachytherapy.

Urol Oncol 2019 09 3;37(9):599-610. Epub 2019 May 3.

Department of Radiation Oncology, University of Michigan, Ann Arbor, MI.

Interstitial brachytherapy is one of several curative therapeutic options for the treatment of localized prostate cancer. In this review, we summarize all available randomized data to support the optimal use of prostate brachytherapy. Evidence from completed randomized controlled trials is the focus of this review with a presentation also of important ongoing trials. Gaps in knowledge are identified where future investigation may be fruitful with intent to inspire well-designed prospective studies with standardized treatment that focuses on improving oncological outcomes, reducing morbidity, or maintaining quality of life.
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http://dx.doi.org/10.1016/j.urolonc.2019.04.009DOI Listing
September 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

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

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

Durable response of early-stage breast cancer to bilateral definitive SBRT in a medically inoperable patient.

Pract Radiat Oncol 2018 Nov - Dec;8(6):361-365. Epub 2018 Mar 18.

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

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http://dx.doi.org/10.1016/j.prro.2018.03.006DOI Listing
January 2019

Brachytherapy in the Management of Prostate Cancer.

Surg Oncol Clin N Am 2017 07 11;26(3):491-513. Epub 2017 May 11.

Department of Radiation Oncology, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA.

Brachytherapy is performed by directly inserting radioactive sources into the prostate gland and is an important treatment option for appropriately selected men with prostate adenocarcinoma. Brachytherapy provides highly conformal radiotherapy and delivers tumoricidal doses that exceed those administered with external beam radiation therapy. There is a significant body of literature supporting the excellent long-term oncologic and safety outcomes achieved when brachytherapy is used for men in all risk categories of nonmetastatic prostate cancer. This article highlights some important considerations and published outcomes that relate to brachytherapy and its role in the treatment of prostate cancer.
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http://dx.doi.org/10.1016/j.soc.2017.01.008DOI Listing
July 2017

Reply to N. Fossati et al.

J Clin Oncol 2017 02 7;35(4):470-471. Epub 2016 Nov 7.

Thomas M. Pisansky and Bradley J. Stish, Mayo Clinic, Rochester MN.

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http://dx.doi.org/10.1200/JCO.2016.70.6119DOI Listing
February 2017
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