Association of Genomic Prostate Score at positive margin with recurrence after radical prostatectomy.

OBJECTIVES: To evaluate the utility of the 17-gene Genomic Prostate Score® (GPS; MDxHealth, Irvine, CA, USA) performed on prostate cancer at the positive margin of the radical prostatectomy (RP) for its association with risk of subsequent biochemical recurrence (BCR). PATIENTS AND METHODS: We designed a case-cohort for the outcome of BCR, selecting 223 from a cohort of 813 RP patients treated at Johns Hopkins from 2008 to 2017 with positive margins and available clinical data; of these, 213 had available tissue and clinical data. RNA was isolated from formalin-fixed paraffin-embedded tumour tissue adjacent to the positive surgical margin and the GPS was evaluable in 203 of these patients with a score ranging from 0 to 100, with higher scores indicating higher risk. All patients underwent RP with or without adjuvant radiation therapy (ART). The statistical analysis employed Cox proportional hazards regression models for outcome of BCR weighted for case-cohort design. RESULTS: In univariable analysis, every 20-unit increase in the GPS was associated with a nearly threefold increase in risk of BCR (hazard ratio [HR] per 20 units 2.82, P < 0.001). In a multivariable Cox model adjusted for age, race, Cancer of the Prostate Risk Assessment Postsurgical score, Grade Group at the positive margin, and ART, the GPS was significantly associated with BCR (HR 1.56 per 20 units; 95% confidence interval 1.11-2.19; P = 0.011). The study is limited by its retrospective and single institution design. CONCLUSIONS: The GPS at the positive surgical margin could help stratify prognosis and inform clinical decision-making regarding adjuvant therapy after RP.

Industry Payments to Cardiology Fellows and Early-Career Cardiologists.

This cohort study evaluates marketing payments from pharmaceutical and medical device manufacturers to physician trainees before and after fellowship graduation.

Longer prostate stromal cell telomere length is associated with increased risk of death from other cancers.

Background: Telomeres are located at chromosomal termini and function to maintain genomic integrity. Telomere dysfunction is a well-recognized contributor to aging and age-related diseases, such as prostate cancer. Since telomere length is highly heritable, we postulate that stromal cell telomere length in the tissue of a particular solid organ may generally reflect constitutive stromal cell telomere length in other solid organs throughout the body. Even with telomere loss occurring with each round of cell replication, in general, telomere length in prostate stromal cells in mid-life would still be correlated with the telomere length in stromal cells in other organs. Thus, we hypothesize that prostate stromal cell telomere length and/or telomere length variability is a potential indicator of the likelihood of developing future solid cancers, beyond prostate cancer, and especially lethal cancer. Methods: To explore this hypothesis, we conducted a cohort study analysis of 1,175 men who were surgically treated for prostate cancer and were followed for death, including from causes other than their prostate cancer. Results: In this cohort study with a median follow-up of 19 years, we observed that longer prostate stromal cell telomere length measured in tissue microarray spots containing prostate cancer was associated with an increased risk of death from other solid cancers. Variability in telomere length among these prostate stromal cells was possibly positively associated with risk of death from other solid cancers. Conclusion: Studying the link between stromal cell telomere length and cancer mortality may be important for guiding the development of cancer interception and prevention strategies.

Trends in Industry-Sponsored Research Payments to Physician Principal Investigators.

This cohort study investigates trends in total and per-physician industry-sponsored research payments to physician principal investigators from 2015 to 2022.

Rate of benign histology after resection of suspected renal cell carcinoma: multicenter comparison between Korea and the United States.

BACKGROUND: In the United States, the rate of benign histology among resected renal tumors suspected to be malignant is increasing. We evaluated the rates in the Republic of Korea and assessed the racial effect using recent multi-institutional Korean-United States data. METHODS: We conducted a multi-institutional retrospective study of 11,529 patients (8,812 from The Republic of Korea and 2,717 from the United States) and compared the rates of benign histology between the two countries. To evaluate the racial effect, we divided the patients into Korean, Asian in the US, and Non-Asian in the US. RESULTS: The rates of benign histology and small renal masses in Korean patients were significantly lower than that in United States patients (6.3% vs. 14.3%, p < 0.001) and (≤ 4 cm, 7.6% vs. 19.5%, p < 0.001), respectively. Women, incidentaloma, partial nephrectomy, minimally invasive surgery, and recent surgery were associated with a higher rate of benign histology than others. CONCLUSIONS: In Korea, the rate of benign histology among resected renal tumors was significantly lower than that in the United States. This disparity could be caused by environmental or cultural differences rather than racial differences. Our findings suggest that re-evaluating current context-specific standards of care is necessary to avoid overtreatment.

Transperineal Versus Transrectal Magnetic Resonance Imaging-targeted and Systematic Prostate Biopsy to Prevent Infectious Complications: The PREVENT Randomized Trial.

BACKGROUND AND OBJECTIVE: The transrectal biopsy approach is traditionally used to detect prostate cancer. An alternative transperineal approach is historically performed under general anesthesia, but recent advances enable transperineal biopsy to be performed under local anesthesia. We sought to compare infectious complications of transperineal biopsy without antibiotic prophylaxis versus transrectal biopsy with targeted prophylaxis. METHODS: We assigned biopsy-naïve participants to undergo transperineal biopsy without antibiotic prophylaxis versus transrectal biopsy with targeted prophylaxis (rectal culture screening for fluoroquinolone-resistant bacteria and antibiotic targeting to culture and sensitivity results) through a multicenter, randomized trial. The primary outcome was post-biopsy infection captured by a prospective medical review and patient report on a 7-d survey. The secondary outcomes included cancer detection, noninfectious complications, and a numerical rating scale (0-10) for biopsy-related pain and discomfort during and 7-d after biopsy. KEY FINDINGS AND LIMITATIONS: A total of 658 participants were randomized, with zero transperineal versus four (1.4%) transrectal biopsy infections (difference -1.4%; 95% confidence interval [CI] -3.2%, 0.3%; p = 0.059). The rates of other complications were very low and similar. Importantly, detection of clinically significant cancer was similar (53% transperineal vs 50% transrectal, adjusted difference 2.0%; 95% CI -6.0, 10). Participants in the transperineal arm experienced worse periprocedural pain (0.6 adjusted difference [0-10 scale], 95% CI 0.2, 0.9), but the effect was small and resolved by 7-d. CONCLUSIONS AND CLINICAL IMPLICATIONS: Office-based transperineal biopsy is tolerable, does not compromise cancer detection, and did not result in infectious complications. Transrectal biopsy with targeted prophylaxis achieved similar infection rates, but requires rectal cultures and careful attention to antibiotic selection and administration. Consideration of these factors and antibiotic stewardship should guide clinical decision-making. PATIENT SUMMARY: In this multicenter randomized trial, we compare prostate biopsy infectious complications for the transperineal versus transrectal approach. The absence of infectious complications with transperineal biopsy without the use of preventative antibiotics is noteworthy, but not significantly different from transrectal biopsy with targeted antibiotic prophylaxis.

Likelihood of sampling prostate cancer at systematic biopsy as a function of gland volume and number of cores.

BACKGROUND: Pre-biopsy multiparametric magnetic resonance imaging (mpMRI) of the prostate is used to conduct targeted prostate biopsy (TB), guided by ultrasound and registered (fused) to the MRI. Systematic biopsy (SB) continues to be used together with TB or in mpMRI-negative patients. There is insufficient evidence on how to use SB to inform clinical decision-making in the mpMRI era. The purpose of this study was to estimate the effect of prostate volume and number of SB cores on sampling clinically significant prostate cancer (csPCa) using a simulation method based on clinical data. METHODS: SBs were simulated using data from 42 patients enrolled in a transrectal ultrasound robot-assisted biopsy trial. Linear mixed models were used to examine the relationship between the number of SB cores and prostate volume on 1) clinically significant cancer detection probability (csCDP) and 2) percent of mpMRI depicted regions of interest (ROIs) sampled with the SB. RESULTS: Median values and interquartile range (IQR) were 47.16 cm3 (35.61-65.57) for prostate volume, 0.57 cm3 (0.39-0.83) for ROI volume, and 4.0 (2-4) for PI-RADS v2.1 scores on MRI. csCDP increased with the increasing number of simulated SB cores and decreased substantially with larger prostate volume. Similarly, the percent of ROIs sampled increased with the increasing number of simulated SB cores and was lower for prostate volumes ≥60 cm3 compared to glands <60 cm3. CONCLUSIONS: The effect of the number of SBs performed on detecting csPCa varies largely with gland volume. The common 12-core SB can achieve adequate cancer detection and sampling of ROIs in smaller glands, but not in larger glands. In addition to TB or in mpMRI-negative patients, the number of SB cores can be adjusted to prostate volume. Performing 12-core SB alone in ≥60 cm3 glands results in inadequate sampling and potential PCa underdiagnosis.

The Association of Subspecialty and Sex with Industry Payments to Internal Medicine Physicians Who Recently Completed Training.

BACKGROUND: Financial relationships with drug and medical device companies may impact quality of care and academic research. However, little is known when and how these financial relationships develop among newly independent physicians who recently completed from residency or fellowship programs in internal medicine (IM). OBJECTIVE: To compare patterns of industry payments among IM graduates. DESIGN: Retrospective, observational cohort study. SUBJECTS: IM graduates from residency or fellowship programs between January 2015 and December 2019. MAIN MEASURES: We analyzed Open Payments reports made between July 2015 and June 2021 to recent graduates of U.S. Accreditation Council for Graduate Medical Education (ACGME)-accredited residency and fellowship programs in IM. The primary outcome was general payments accepted by these physicians, stratified by procedural (i.e., critical care medicine/pulmonary medicine, cardiac/cardiovascular disease, and gastroenterology) and non-procedural (i.e., infectious disease, general internal medicine, and other specialties) subspecialties. The secondary outcomes included general payments stratified by sex and age at residency or fellowship training completion. KEY RESULTS: There were 41,669 IM physicians with a median age of 33.0 years. In the first 3 years after completion, the proportion of physicians accepting any general payments was 72.6%, 91.9%, and 86.8% in Critical Care Medicine/Pulmonary Medicine, Cardiac/Cardiovascular Disease, and Gastroenterology, compared to 56.1%, 52.6%, and 52.3% in Infectious Disease, General Internal Medicine, and Other Specialties (p<0.0001). After adjusting for confounding variables, the procedural group showed an increased hazard ratio (HR) for accepting any general payments and at least $5000 of general payments compared to the non-procedural group. The HRs of accepting any general payments in the procedural subspecialty were 2.26 (95% CI, 2.11-2.42) and 2.83 (95% CI, 2.70-2.97) in female and male physicians, respectively (p-value < 0.0001). CONCLUSION: Industry financial relationships among newly independent physicians in IM exist immediately after completion of training and are influenced by subspecialty, sex, and age.

Risk of Biochemical Recurrence in Patients With Grade Group 1 Prostate Cancer With Extraprostatic Extension Treated With Radical Prostatectomy.

PURPOSE: We sought to examine the association of extraprostatic extension (EPE) with biochemical recurrence (BCR) separately in men with Grade Group (GG) 1 and GG2 prostate cancer (PCa) treated with radical prostatectomy. MATERIALS AND METHODS: We reviewed our institutional database of patients who underwent radical prostatectomy for PCa between 2005 and 2022 and identified patients with GG1 and GG2 disease on final pathology. Fine-Gray competing risk models with an interaction between EPE (yes vs no) and GG (GG1 vs GG2) were used to examine the relationship between disease group and BCR-free survival. RESULTS: The cohort consisted of 6309 men, of whom 169/2740 (6.2%) with GG1 disease had EPE while 1013/3569 (28.4%) with GG2 disease had EPE. Median follow-up was 4 years. BCR occurred in 400/6309 (6.3%) patients. For men with GG1, there was no statistically significant difference in BCR-free survival for men with vs without EPE (subdistribution HR = 0.88; 95% CI: 0.37-2.09). However, for GG2 patients BCR-free survival was significantly worse for those with vs without EPE (subdistribution HR = 1.97, 95% CI: 1.54-2.52). CONCLUSIONS: Although there is a subset of GG1 PCas capable of invading through the prostatic capsule, patients with GG1 PCa and EPE at prostatectomy experience similar biochemical recurrence and survival outcomes compared to GG1 patients without EPE. However, among men with GG2, EPE connotes a worse prognosis.

Induction of double-strand breaks with the non-steroidal androgen receptor ligand flutamide in patients on androgen suppression: a study protocol for a randomized, double-blind prospective trial.

BACKGROUND: Prostate cancer remains the most prevalent malignancy and the second-leading cause of cancer-related death in men in the USA. Radiation therapy, typically with androgen suppression, remains a mainstay in the treatment of intermediate- and high-risk, potentially lethal prostate cancers. However, local recurrence and treatment failure remain common. Basic and translational research has determined the potential for using androgen receptor (AR) ligands (e.g., dihydrotestosterone and flutamide) in the context of androgen-deprived prostate cancer to induce AR- and TOP2B-mediated DNA double-strand breaks (DSBs) and thereby synergistically enhance the effect of radiation therapy (RT). The primary aim of this study is to carry out pharmacodynamic translation of these findings to humans. METHODS: Patients with newly diagnosed, biopsy-confirmed localized prostatic adenocarcinoma will be recruited. Flutamide, an oral non-steroidal androgen receptor ligand, will be administered orally 6-12 h prior to prostate biopsy (performed under anesthesia prior to brachytherapy seed implantation). Key study parameters will include the assessment of DNA double-strand breaks by γH2A.x foci and AR localization to the nucleus. The initial 6 patients will be treated in a single-arm run-in phase to assess futility by establishing whether at least 2 subjects from this group develop γH2A.x foci in prostate cancer cells. If this criterion is met, the study will advance to a two-arm, randomized controlled phase in which 24 participants will be randomized 2:1 to either flutamide intervention or placebo standard-of-care (with all patients receiving definitive brachytherapy). The key pharmacodynamic endpoint will be to assess whether the extent of γH2A.x foci (proportion of cancer cells positive and number of foci per cancer cell) is greater in patients receiving flutamide versus placebo. Secondary outcomes of this study include an optional, exploratory analysis that will (a) describe cancer-specific methylation patterns of cell-free DNA in plasma and urine and (b) assess the utility of serum and urine samples as a DNA-based biomarker for tracking therapeutic response. DISCUSSION: This study will confirm in humans the pharmacodynamic effect of AR ligands to induce transient double-strand breaks when administered in the context of androgen deprivation as a novel therapy for prostate cancer. The findings of this study will permit the development of a larger trial evaluating flutamide pulsed-dose sequencing in association with fractionated external beam RT (+/- brachytherapy). The study is ongoing, and preliminary data collection and recruitment are underway; analysis has yet to be performed. TRIAL REGISTRATION: ClinicalTrials.gov NCT03507608. Prospectively registered on 25 April 2018.

Industry Payments Received by Residents During Training.

Importance: Those responsible for medical education-specialties, sponsoring institutions, and program directors (PD)-are independently associated with the professional identity formation of the trainees with respect to potential conflicts of interest. Objective: To identify the relative degree to which factors in the training environment are associated with resident acceptance of payments from pharmaceutical and medical device companies. Design, Setting, and Participants: Cross-sectional, retrospective study of residents enrolled in the 3 largest primary-care specialties (internal medicine [IM], family medicine [FM], obstetrics and gynecology [OBGYN]) and 3 largest surgical disciplines (general surgery [GS], orthopedic surgery, and urology) during academic year 2020 to 2021. All analyses were conducted January through August 2023. Exposures: Specialty, sponsoring institutions' ownership (nonprofit, for-profit, federal government, local government, or state government), and the number of payments PDs accepted. Main outcomes and measures: Modified Poisson regression assessed the relative risk of ownership, specialty, and PD behavior on residents' acceptance of industry payments as recorded in the Open Payments Program (OPP) database. Results: In total, there were 124 715 residents in all training programs during 2020 to 2021, 12% of whom received payments totaling $6.4 million. There were 65 992 residents in training during 2020 to 2021 in the 6 specialties evaluated in this study, with 4438 in orthopedics, 1779 in urology, 9177 in GS, 5819 in OBGYN, 14 493 in FM, and 30 286 in IM. OPP records $3.9 million in payments to the 8750 residents (13.4%) who received at least 1 industry payment. The record of all payments to residents in OPP totals $6.4 million. Compared with residents in federal sponsoring institutions, those affiliated with for-profit institutions were 3.50 (95% CI, 2.32-5.28) times more likely to accept industry payments, while those affiliated with nonprofit organizations were 2.00 (95% CI, 1.36-2.93) times more likely to accept payments. Compared with IM, residents in each of the following specialties have an elevated risk of accepting payments: orthopedics, 3.21 (95% CI, 2.73-3.77) times; urology, 2.95 (95% CI, 2.44-3.56) times; GS, 1.21 (95% CI, 1.00-1.45) times; OBGYN, 1.30 (95% CI, 1.05-1.62) times. The difference in the risk of accepting a payment between FM and IM residents was not statistically significant. The number of payments PDs accepted slightly elevated the risk of residents to accept a payment by 1.01 (95% CI, 1.01-1.01). Conclusions and relevance: In this cross-sectional, retrospective study, receipt of industry payments by residents was associated with specialty, institutional control, and PD behavior.

Acute heart failure with incidentally found cystic adrenal mass.

Summary: Pheochromocytomas are rare adrenal tumors characterized by excessive catecholamine secretion. Symptoms and signs associated with pheochromocytomas are usually intermittent and chronic but can rarely develop into life-threatening crises. We describe a case of acute severe congestive heart failure in a previously healthy female, who recovered rapidly (4 days after admission) with acute medical therapy. The etiology on evaluation was a spontaneous bleed in a previously undiagnosed pheochromocytoma, resulting in a pheochromocytoma crisis and transient stress cardiomyopathy, followed by quick recovery of cardiac function. Our aim is to describe pheochromocytoma as a rare cause of stress cardiomyopathy. We discuss the evaluation of pheochromocytoma during critical illness and triggers/treatment strategies for pheochromocytoma crises. Learning points: Hemorrhage in a pheochromocytoma can result in a pheochromocytoma crisis, with sudden release of excess catecholamines resulting in multisystem organ dysfunction and high mortality. Acute decompensated heart failure can be a rare presentation of pheochromocytoma, in a patient with no cardiac risk factors. Measurement of metanephrines in acutely stressful clinical situations can have considerable overlap with the biochemical picture of pheochromocytoma. Early imaging studies may help with the differential diagnosis. Pheochromocytoma should be ruled out before performing an adrenal biopsy. Emergent adrenalectomy in pheochromocytoma crisis results in high mortality. Medical management of the acute crisis followed by elective adrenalectomy after alpha-blockade results in better outcomes.

Trainee Physician Milestone Ratings and Patient Complaints in Early Posttraining Practice.

Importance: Evaluation of trainees in graduate medical education training programs using Milestones has been in place since 2013. It is not known whether trainees who have lower ratings during the last year of training go on to have concerns related to interactions with patients in posttraining practice. Objective: To investigate the association between resident Milestone ratings and posttraining patient complaints. Design, Setting, and Participants: This retrospective cohort study included physicians who completed Accreditation Council for Graduate Medical Education (ACGME)-accredited programs between July 1, 2015, and June 30, 2019, and worked at a site that participated in the national Patient Advocacy Reporting System (PARS) program for at least 1 year. Milestone ratings from ACGME training programs and patient complaint data from PARS were collected. Data analysis was conducted from March 2022 to February 2023. Exposures: Lowest professionalism (P) and interpersonal and communication skills (ICS) Milestones ratings 6 months prior to the end of training. Main Outcomes and Measures: PARS year 1 index scores, based on recency and severity of complaints. Results: The cohort included 9340 physicians with median (IQR) age of 33 (31-35) years; 4516 (48.4%) were women physicians. Overall, 7001 (75.0%) had a PARS year 1 index score of 0, 2023 (21.7%) had a score of 1 to 20 (moderate), and 316 (3.4%) had a score of 21 or greater (high). Among physicians in the lowest Milestones group, 34 of 716 (4.7%) had high PARS year 1 index scores, while 105 of 3617 (2.9%) with Milestone ratings of 4.0 (proficient), had high PARS year 1 index scores. In a multivariable ordinal regression model, physicians in the 2 lowest Milestones rating groups (0-2.5 and 3.0-3.5) were statistically significantly more likely to have higher PARS year 1 index scores than the reference group with Milestones ratings of 4.0 (0-2.5 group: odds ratio, 1.2 [95% CI, 1.0-1.5]; 3.0-3.5 group: odds ratio, 1.2 [95% CI, 1.1-1.3]). Conclusions and Relevance: In this study, trainees with low Milestone ratings in P and ICS near the end of residency were at increased risk for patient complaints in their early posttraining independent physician practice. Trainees with lower Milestone ratings in P and ICS may need more support during graduate medical education training or in the early part of their posttraining practice career.

Early Detection of Prostate Cancer: AUA/SUO Guideline Part II: Considerations for a Prostate Biopsy.

PURPOSE: The summary presented herein covers recommendations on the early detection of prostate cancer and provides a framework to facilitate clinical decision-making in the implementation of prostate cancer screening, biopsy, and follow-up. This is Part II of a two-part series focusing on initial and repeat biopsies, and biopsy technique. Please refer to Part I for discussion of initial prostate cancer screening recommendations. MATERIALS AND METHODS: The systematic review utilized to inform this guideline was conducted by an independent methodological consultant. The systematic review was based on searches in Ovid MEDLINE and Embase and Cochrane Database of Systematic Reviews (January 1, 2000-November 21, 2022). Searches were supplemented by reviewing reference lists of relevant articles. RESULTS: The Early Detection of Prostate Cancer Panel developed evidence- and consensus-based guideline statements to provide guidance in prostate cancer screening, initial and repeat biopsies, and biopsy technique. CONCLUSIONS: The evaluation of prostate cancer risk should be focused on the detection of clinically significant prostate cancer (Grade Group 2 or higher [GG2+]). The use of laboratory biomarkers, prostate MRI, and biopsy techniques described herein may improve detection and safety when a prostate biopsy is deemed necessary following prostate cancer screening.

Early Detection of Prostate Cancer: AUA/SUO Guideline Part I: Prostate Cancer Screening.

PURPOSE: The summary presented herein covers recommendations on the early detection of prostate cancer and provides a framework to facilitate clinical decision-making in the implementation of prostate cancer screening, biopsy, and follow-up. This is Part I of a two-part series that focuses on prostate cancer screening. Please refer to Part II for discussion of initial and repeat biopsies as well as biopsy technique. MATERIALS AND METHODS: The systematic review utilized to inform this guideline was conducted by an independent methodological consultant. The systematic review was based on searches in Ovid MEDLINE and Embase and Cochrane Database of Systematic Reviews (January 1, 2000-November 21, 2022). Searches were supplemented by reviewing reference lists of relevant articles. RESULTS: The Early Detection of Prostate Cancer Panel developed evidence- and consensus-based guideline statements to provide guidance in prostate cancer screening, initial and repeat biopsy, and biopsy technique. CONCLUSIONS: Prostate-specific antigen (PSA)-based prostate cancer screening in combination with shared decision-making (SDM) is recommended. Current data regarding risk from population-based cohorts provide a basis for longer screening intervals and tailored screening, and the use of available online risk calculators is encouraged.

ERG Status at the Margin Is Associated With Biochemical Recurrence After Radical Prostatectomy With Positive Surgical Margins.

Positive surgical margins at radical prostatectomy are associated with an increased risk of biochemical recurrence (BCR). However, there is considerable variability in outcomes, suggesting that molecular biomarkers-when assessed specifically at the margin tumor tissue-may be useful to stratify prognosis in this group. We used a case-cohort design for the outcome of BCR, selecting 215 patients from a cohort of 813 patients undergoing prostatectomy treated at the Johns Hopkins from 2008 to 2017 with positive margins and available clinical data. Tissue microarrays were created from the tumor adjacent to the positive margin and stained for PTEN, ERG, and Ki-67. Cases were scored dichotomously (PTEN and ERG) or by the Ki-67 staining index using previously validated protocols. The analysis used Cox proportional hazards models weighted for the case-cohort design. Overall, 20% (37/185) of evaluable cases had PTEN loss and 38% (71/185) had ERG expression, and the median Ki-67 expression was 0.42%. In multivariable analysis adjusting for the CAPRA-S score, adjuvant radiation, and grade group at the positive margin, ERG-positive tumors were associated with a higher risk of BCR compared to those that were ERGnegative (hazard ratio [HR], 2.4; 95% CI, 1.2-4.9; P = .012) regardless of PTEN status at the margin, and adding ERG to clinicopathologic variables increased the concordance index from 0.827 to 0.847. PTEN loss was associated with an increased risk of BCR on univariable analysis (HR, 3.19; 95% CI, 1.72-5.92; P = .0002), but this association did not remain after adjusting for clinicopathologic variables (HR, 1.06; 95% CI, 0.49-2.29; P = .890). Thus, in the setting of prostate tumors with positive surgical margins after prostatectomy, ERG-positive tumors with or without PTEN loss at the positive margin are associated with a significantly higher risk of BCR after adjusting for clinicopathologic variables. If validated, ERG status may be helpful in decision-making surrounding adjuvant therapy after prostatectomy.

The impact of salvage radiotherapy initiation at PSA ≤ 0.5 ng/ml on metastasis-free survival in patients with relapsed prostate cancer following prostatectomy.

BACKGROUND AND PURPOSE: Salvage radiation therapy (SRT) is indicated for biochemical failure after radical prostatectomy. Prior data have shown that initiation of SRT at lower PSA levels improves subsequent biochemical control, yet given the long natural history of prostate cancer questions remain regarding optimal timing of SRT. We analyzed the impact of prostate specific antigen (PSA) level at time of salvage radiotherapy with regard to both biochemical relapse-free (bRFS) as well as metastasis-free survival (MFS) in patients with biochemically recurrent prostate cancer. METHODS: Using prospective institutional tumor registry data, univariate and multivariable-adjusted Cox proportional hazards models were constructed to assess association between outcomes and clinical and pathologic prognostic features, including pre-SRT PSA, interval from prostatectomy to SRT, androgen deprivation therapy (ADT), and adverse pathologic features. RESULTS: We identified 397 patients who received salvage RT between 1985 and 2016: 187 (45.8%) received SRT initiated when pre-RT PSA was ≤0.5 ng/ml; 212 (52.0%) patients had pre-SRT PSA > 0.5 ng/ml. Independent of pathologic risk status and ADT use, pre-SRT PSA ≤ 0.5 ng/ml was the most significant predictor of bRFS (HR 0.39, 95% CI [0.27, 0.56]) as well as MFS (HR = 0.58, 95% CI [0.37, 0.91]). Seminal vesicle invasion was also associated with shorter interval to biochemical failure, HR = 1.79, 95% CI [1.07, 2.98], and eventual metastases, HR = 2.07, 95% CI [1.14, 3.740]. CONCLUSIONS: Initiation of salvage RT while PSA levels remain ≤0.5 ng/ml was associated with improved MFS. Consideration for salvage RT initiation while PSA levels remain low is warranted to minimize risk of future prostate cancer metastasis.