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Importance: Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) can detect low-volume, nonlocalized (ie, regional or metastatic) prostate cancer that was occult on conventional imaging. However, the long-term clinical implications of PSMA PET/CT upstaging remain unclear., Objectives: To evaluate the prognostic significance of a nomogram that models an individual's risk of nonlocalized upstaging on PSMA PET/CT and to compare its performance with existing risk-stratification tools., Design, Setting, and Participants: This cohort study included patients diagnosed with high-risk or very high-risk prostate cancer (ie, prostate-specific antigen [PSA] level >20 ng/mL, Gleason score 8-10, and/or clinical stage T3-T4, without evidence of nodal or metastatic disease by conventional workup) from April 1995 to August 2018. This multinational study was conducted at 15 centers. Data were analyzed from December 2020 to March 2021., Exposures: Curative-intent radical prostatectomy (RP), external beam radiotherapy (EBRT), or EBRT plus brachytherapy (BT), with or without androgen deprivation therapy., Main Outcomes and Measures: PSMA upstage probability was calculated from a nomogram using the biopsy Gleason score, percentage positive systematic biopsy cores, clinical T category, and PSA level. Biochemical recurrence (BCR), distant metastasis (DM), prostate cancer-specific mortality (PCSM), and overall survival (OS) were analyzed using Fine-Gray and Cox regressions. Model performance was quantified with the concordance (C) index., Results: Of 5275 patients, the median (IQR) age was 66 (60-72) years; 2883 (55%) were treated with RP, 1669 (32%) with EBRT, and 723 (14%) with EBRT plus BT; median (IQR) PSA level was 10.5 (5.9-23.2) ng/mL; 3987 (76%) had Gleason grade 8 to 10 disease; and 750 (14%) had stage T3 to T4 disease. Median (IQR) follow-up was 5.1 (3.1-7.9) years; 1221 (23%) were followed up for at least 8 years. Overall, 1895 (36%) had BCR, 851 (16%) developed DM, and 242 (5%) died of prostate cancer. PSMA upstage probability was significantly prognostic of all clinical end points, with 8-year C indices of 0.63 (95% CI, 0.61-0.65) for BCR, 0.69 (95% CI, 0.66-0.71) for DM, 0.71 (95% CI, 0.67-0.75) for PCSM, and 0.60 (95% CI, 0.57-0.62) for PCSM (P < .001). The PSMA nomogram outperformed existing risk-stratification tools, except for similar performance to Staging Collaboration for Cancer of the Prostate (STAR-CAP) for PCSM (eg, DM: PSMA, 0.69 [95% CI, 0.66-0.71] vs STAR-CAP, 0.65 [95% CI, 0.62-0.68]; P < .001; Memorial Sloan Kettering Cancer Center nomogram, 0.57 [95% CI, 0.54-0.60]; P < .001; Cancer of the Prostate Risk Assessment groups, 0.53 [95% CI, 0.51-0.56]; P < .001). Results were validated in secondary cohorts from the Surveillance, Epidemiology, and End Results database and the National Cancer Database., Conclusions and Relevance: These findings suggest that PSMA upstage probability is associated with long-term, clinically meaningful end points. Furthermore, PSMA upstaging had superior risk discrimination compared with existing tools. Formerly occult, PSMA PET/CT-detectable nonlocalized disease may be the main driver of outcomes in high-risk patients.

Purpose: Outcomes for resistant metastatic castration-resistant prostate cancer (CRPC) are poor. Stereotactic ablative radiotherapy (SABR) induces antitumor immunity in clinical and preclinical studies, but immunologic biomarkers are lacking., Patients and Methods: Eighty-nine patients with oligometastatic CRPC were identified by 11 C-Choline-PET (Choline-PET) from August 2016 to December 2019 and treated with SABR. Prespecified coprimary endpoints were 2-year overall survival (OS) and PSA progression. Secondary endpoints included 2-year SABR-treated local failure and 6-month adverse events. Correlative studies included peripheral blood T-cell subpopulations before and after SABR., Results: 128 lesions in 89 patients were included in this analysis. Median OS was 29.3 months, and 1- and 2-year OS were 96% and 80%, respectively. PSA PFS was 40% at 1 year and 21% at 2 years. Local PFS was 84.4% and 75.3% at 1 and 2 years, respectively, and no grade ≥3 AEs were observed. Baseline high levels of tumor-reactive T cells (T TR ; CD8 + CD11a high ) predicted superior local, PSA, and distant PFS. Baseline high levels of effector memory T cells (T EM ; CCR7 - CD45RA - ) were associated with improved PSA PFS. An increase in T TR at day 14 from baseline was associated with superior OS., Conclusions: This is the first comprehensive effector T-cell immunophenotype analysis in a phase II trial before and after SABR in CRPC. Results are favorable and support the incorporation of immune-based markers in the design of future randomized trials in patients with oligometastatic CRPC treated with SABR., (©2021 American Association for Cancer Research.)

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., (Copyright © 2021 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2021 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

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.

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., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: The objective was to evaluate the diagnostic performance of surveillance 11 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 11 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 11 C-choline PET/CT can detect early disease relapse at serum PSA ≤0.1 ng/ml in patients with a history of BCR PCa., Competing Interests: None

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.

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.

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., (Copyright © 2020 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Purpose: To assess gastrointestinal (GI) and genitourinary (GU) adverse events (AEs) of 11 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 ( P  < .01). These differences resolved by 4-month (12.2%, P  = .65) and 14-month AE assessments (9.1%, P  = .87). There was no significant change in grade 1 to 2 GU AEs post-RT (64.1%) relative to baseline (56.0%, P  = .21), although differences did arise at 4-month (72.2%, P  = .01) and 14-month (74.3%, P  = .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., (© 2019 The Authors.)

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., (Copyright © 2019 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

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 TR ), effector memory, central memory (T CM ), 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 CM 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 TR 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 TR cell subpopulation was protective against the risk of disease progression, and an increase in the T CM 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., (Copyright © 2018 Elsevier Inc. All rights reserved.)

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 ( P 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.

Prostate cancer-specific positron emission tomography (pcPET) has been shown to detect sites of disease recurrence at serum prostate-specific antigen (PSA) levels that are lower than those levels detected by conventional imaging. Commonly used pcPET radiotracers in the setting of biochemical recurrence are reviewed including carbon 11/fludeoxyglucose 18 (F-18) choline, gallium 68/F-18 prostate-specific membrane antigen (PSMA), and F-18 fluciclovine. Review of the literature generally favors PSMA-based agents for the detection of recurrence as a function of low PSA levels. Positive gallium 68/F-18 PSMA positron emission tomography/computed tomography scans detected potential sites of recurrence in a median 51.5% of patients when PSA level is <1.0 ng/mL, 74% of patients when PSA level is 1.0 to 2.0 ng/mL, and 90.5% of patients when PSA level is >2.0 ng/mL. Review of carbon 11/fludeoxyglucose 18 (F-18) choline and F-18 fluciclovine data commonly demonstrated lower detection rates for each respective PSA cohort, although with some important caveats, despite having similar operational characteristics to PSMA-based imaging. Sensitive pcPET imaging has provided new insight into the early patterns of disease spread, which has prompted judicious reconsideration of additional local therapy after either prostatectomy, definitive radiation therapy, or postprostatectomy radiation therapy. This review discusses the literature, clinical utility, availability, and fundamental understanding of pcPET imaging needed to improve clinical practice., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: This AUA Guideline focuses on evaluation/counseling and management of adult patients with clinically localized renal masses suspicious for cancer, including solid-enhancing tumors and Bosniak 3/4 complex-cystic lesions., Materials and Methods: Systematic review utilized research from the Agency for Healthcare Research and Quality and additional supplementation by the authors and consultant methodologists. Evidence-based statements were based on body of evidence strength Grade A/B/C (Strong/Moderate/Conditional Recommendations, respectively) with additional statements presented as Clinical Principles or Expert Opinions., Results: Great progress has been made since the previous guidelines on management of localized renal masses were released (2009). The current guidelines provide updated, evidence-based recommendations regarding evaluation/counseling of patients with clinically localized renal masses, including the evolving role of renal mass biopsy. Given great variability of clinical, oncologic and functional characteristics, index patients are not utilized and the panel advocates individualized counseling/management. Management options (partial nephrectomy/radical nephrectomy/thermal ablation/active surveillance) are reviewed including recent data about comparative effectiveness and potential morbidities. Oncologic issues are prioritized while recognizing that functional outcomes are of great importance for survivorship for most patients with localized kidney cancer. A more restricted role for radical nephrectomy is recommended following well-defined selection criteria. Priority for partial nephrectomy is recommended for clinical T1a lesions, along with selective use of thermal ablation, particularly for tumors ≤3.0 cm. Important considerations for shared decision-making about active surveillance are explicitly defined., Conclusions: Several factors should be considered during counseling/management of patients with clinically localized renal masses, including general health/comorbidities, oncologic potential of the mass, pertinent functional issues and relative efficacy/potential morbidities of various management strategies., (Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: To provide updated American College of Radiology (ACR) appropriateness criteria for transrectal ultrasound-guided transperineal interstitial permanent source brachytherapy., Methods and Materials: The ACR appropriateness criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment., Results: Permanent prostate brachytherapy (PPB) is a treatment option for appropriately selected patients with localized prostate cancer with low to very high risk disease. PPB monotherapy remains an appropriate and effective curative treatment for low-risk prostate cancer patients demonstrating excellent long-term cancer control and acceptable morbidity. PPB monotherapy can be considered for select intermediate-risk patients with multiparametric MRI useful in evaluation of such patients. High-risk patients treated with PPB should receive supplemental external beam radiotherapy (EBRT) along with androgen deprivation. Similarly, patients with involved pelvic lymph nodes may also be considered for such combined treatment but reported long-term outcomes are limited. Computed tomography-based postimplant dosimetry completed within 60 days of PPB is essential for quality assurance. PPB may be considered for treatment of local recurrence after EBRT but is associated with an increased risk of toxicity., Conclusions: Updated appropriateness criteria for patient evaluation, selection, treatment, and postimplant dosimetry are given. These criteria are intended to be advisory only with the final responsibility for patient care residing with the treating clinicians., (Copyright © 2016 The American College of Radiology. Published by Elsevier Inc. All rights reserved.)

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

Objectives: The value of multiparametric magnetic resonance imaging (mpMRI) in staging prostate cancer (PCa) before salvage prostatectomy is currently unclear because of the minimal data comparing mpMRI results to final pathologic stage at surgery. The aim of the study is to determine the diagnostic performance of mpMRI in characterizing viable recurrent tumor and lymph node metastasis following radiation therapy (RT) failure., Methods and Materials: Between January 2007 and July 2014, 19 patients with biopsy-proven recurrent PCa after primary RT underwent 3T mpMRI and subsequent salvage prostatectomy with extended pelvic lymphadenectomy. mpMRI images were independently reviewed by 2 genitourinary MRI radiologists (R1 and R2), blinded to the pathology results, to evaluate extraprostatic extension (EPE), seminal vesicle invasion (SVI), and pelvic lymph node metastasis (PLNM). Sensitivity, specificity, positive predictive value, negative predictive value, receiver operating characteristic curves, and interobserver agreement (R1 and R2) were evaluated for each outcome on a per-patient basis. Final pathologic results were used as a gold standard for comparison in all patients. A multivariate analysis was conducted to assess the relationship between the index lesion's apparent diffusion coefficient value and its enhancement characteristics with the Gleason score., Results: EPE was found in 14 (73.7%) patients, SVI in 13 (68.4%), and PLNM in 5 (26.3%). mpMRI sensitivity for PLNM was 60.0% (R1 and R2) with specificity of 85.7% (R1) and 92.8% (R2). With regards to SVI, the sensitivity was 61.5% (R1) and 76.9% (R2), with a specificity of 66.6% (R1 and R2). Sensitivity for EPE was 50.0% (R1) and 71.43% (R2), with a specificity of 80.0% (R1) and 100.00% (R2). No significant associations were found at multivariate analysis. The evaluation of PLNM, SVI, and PCa recurrence within the prostate demonstrated moderate interobserver agreement (κ, 0.51-0.57)., Conclusions: mpMRI has good accuracy for detecting PLNM, SVI, and EPE after RT. mpMRI provides useful information in locally recurrent PCa following primary radiation therapy., (Copyright © 2016 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Introduction: To evaluate the ability of endorectal coil (e-coil) magnetic resonance imaging (MRI) to identify early prostatic fossa recurrence after radical prostatectomy., Materials and Methods: We identified 187 patients from 2005-2011 who underwent e-coil MRI with dynamic gadolinium-contrast enhancement followed by transrectal ultrasound (TRUS) guided prostatic fossa biopsy for possible local prostate cancer recurrence. For analysis, local recurrence was defined as a negative evaluation for distant metastatic disease with a positive prostatic fossa biopsy, decreased prostate-specific antigen (PSA) following salvage radiation therapy, or increased lesion size on serial imaging., Results: Local recurrence was identified in 132 patients, with 124 (94%) detected on e-coil MRI. The median PSA was 0.59 ng/mL (range < 0.1-13.1), and median lesion size on MRI was 1 cm. The sensitivity of MRI was 91%, with a specificity of 45%. The positive predictive value was 85%, with a negative predictive value of 60%. For patients with a PSA < 0.4 ng/mL the sensitivity of e-coil MRI was 86%. When a lesion was identified on MRI, the positive biopsy rate was 65% and lesion size was a significant predictor of positive biopsies. The positive biopsy rates were 51%, 74%, and 88% when the lesion was < 1 cm, 1 cm-2 cm, or > 2 cm, respectively (p = 0.0006)., Conclusions: E-coil MRI has a high level of sensitivity in identifying local recurrence of prostate cancer following radical prostatectomy, even at low PSA levels. E-coil MRI should be considered as the first imaging evaluation for biochemical recurrence for identifying patients suitable for localized salvage therapy.

Shallow Radar soundings from the Mars Reconnaissance Orbiter reveal a buried deposit of carbon dioxide (CO(2)) ice within the south polar layered deposits of Mars with a volume of 9500 to 12,500 cubic kilometers, about 30 times that previously estimated for the south pole residual cap. The deposit occurs within a stratigraphic unit that is uniquely marked by collapse features and other evidence of interior CO(2) volatile release. If released into the atmosphere at times of high obliquity, the CO(2) reservoir would increase the atmospheric mass by up to 80%, leading to more frequent and intense dust storms and to more regions where liquid water could persist without boiling.

Background: Zn-alpha2 glycoprotein (ZAG) is a relatively abundant glycoprotein that has potential as a biomarker for prostate cancer. We present a high-flow liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for measuring serum ZAG concentrations by proteolytic cleavage of the protein and quantification of a unique peptide., Methods: We selected the ZAG tryptic peptide (147)EIPAWVPEDPAAQITK(162) as the intact protein for quantification and used a stable isotope-labeled synthetic peptide with this sequence as an internal standard. Standards using recombinant ZAG in bovine serum albumin, 50 g/L, and a pilot series of patient sera were denatured, reduced, alkylated, and digested with trypsin. The concentration of ZAG was calculated from a dose-response curve of the ratio of the relative abundance of the ZAG tryptic peptide to internal standard., Results: The limit of detection for ZAG in serum was 0.08 mg/L, and the limit of quantification was 0.32 mg/L with a linear dynamic range of 0.32 to 10.2 mg/L. Replicate digests from pooled sera run during a period of 3 consecutive days showed intraassay imprecision (CV) of 5.0% to 6.3% and interassay imprecision of 4.4% to 5.9%. Mean (SD) ZAG was higher in 25 men with prostate cancer [7.59 (2.45) mg/L] than in 20 men with nonmalignant prostate disease [6.21 (1.65) mg/L, P = 0.037] and 6 healthy men [3.65 (0.71) mg/L, P = 0.0007]., Conclusions: This LC-MS/MS assay is reproducible and can be used to evaluate the clinical utility of ZAG as a cancer biomarker.

A fluoroscopic to TRUS fusion based approach for intraoperative prostate brachytherapy dosimetry was developed. Seed images were identified from multiple fluoroscopic images and reconstructed to determine the three dimensional distribution of the implanted seeds. Seeds identified from the TRUS images were used as fiducials for the registration between fluoroscopic and TRUS images. Dose analysis was then performed based on the fused images. A phantom study was performed to test this approach and a 3 mm registration error was observed. Radiation isodose contours were generated and superimposed on the TRUS images.

The variation of permanent prostate brachytherapy dosimetry as a function of seed detection rates was investigated for I125 implants with seed activities commonly employed in contemporary practice. Post-implant imaging and radiation dosimetry data from nine patients who underwent PPB served as the basis of this simulation study. One-thousand random configurations of detected seeds were generated for each patient dataset using various seed detection levels from 30% to 99%. Dose parameters, including D90, were computed for each configuration and compared with the actual dosimetry data. A total of 108 000 complete sets of post-PPB dose volume statistics were computed. The results demonstrated that although the average D90 differed from the true value by less than 5% when 70% or more seeds were identified, the D90 of an individual case could deviate up to 13%. The 95% confidence interval (CI) of estimated D90 values differ by less than 5% from the actual value when 95% or more seeds are detected, or approximately a 7 Gy difference in the D90 value for a prescription dose of 144 Gy. Estimated target volume dose parameters tended to decrease with reduced seed detection rates. The most variable dose parameter was the prostate V100 in absolute scale while the urethral V100 was most variable in a relative sense. Based on this comprehensive simulation study, it is suggested that 95% or more seeds need to be localized in order to provide an accurate estimation of dose parameters for contemporary iodine 125 permanent prostate brachytherapy.

Intraoperative three-dimensional reconstruction of seed locations during prostate brachytherapy for purposes of immediate computation of radiation dosimetry is an active area of current investigation, including methods which use multiple fluoroscopic projections. A simulation study using seed locations extracted from clinical CT data was performed; the result showed that on average one quarter of the seeds had a projection image overlapping with other seeds. The average percentage of non-overlapping seeds for the prostate implants and seed types investigated was 74.5% with a range of 56.9%-92.9%. The distribution of seeds in different cluster sizes was analyzed as well as the distribution of pixel counts of connected components. A statistical classifier was developed to determine the number of seed images in a self-connected component in the segmented images. The classifier was tested with simulation data, and the error rate was below 2%. A method to determine seed image position is also provided. A modified three-film technique was used to reconstruct 3-D seed locations. The algorithm allows unequal number of seed images for each projection as input while current methods require the same number of seed images detected in all projections. An accuracy analysis based on angular and positional uncertainty was performed. The reconstruction and seed localization algorithms were tested with simulation data, and the mean distance error of the reconstructed results was 0.61 mm. A phantom study was performed to validate the seed localization method. Three false positive seeds, 4.7% of the total, in the reconstruction result were observed in this study.