Targeted Biopsy Is Sufficient for Men on Active Surveillance for Early-Stage Prostate Cancer.

PURPOSE: Serial biopsy is a mainstay for patients on active surveillance (AS) for prostate cancer. mpMRI targeting has become a standard. It is unclear whether targeted biopsy alone reliably identifies the dominant lesion, thereby obviating the need for systematic sampling. MATERIALS AND METHODS: Participants enrolled in AS with early-stage prostate cancer (PSA < 20, cT1-2, GG1-2) and underwent 2+ systematic biopsy sessions with or without MR-targeted sampling. The findings for dominant Gleason Grade (GG) and tumor localization were assessed. RESULTS: Among 821 men who underwent MR fusion biopsies, 82% were diagnosed with GG1 and 18% with GG2. Sixty-two percent had their first MR fusion biopsy as diagnostic or confirmatory. Across all fusion biopsies, MRI-targeted detection of GG and/or tumor location overlapped with systematic sampling for 95% of cases. For 5% of cases, systematic biopsy was unique in detecting GG and location outside the target. Most unique lesions detected outside the target had marginally aggressive features: 73% GG2 of low-volume and favorable histologic subtypes. CONCLUSIONS: In men with MR fusion biopsies, targeting alone identified the dominant GG and location most of the time (95%); 25% of dominant lesions were contiguous to the target, suggesting that better sampling of the target improves detection. The remaining 5% of men had higher-grade, low-volume disease outside the targeted lesion of which only 2% had aggressive risk features. MR fusion targeting, without systematic sampling, may be sufficient to monitor men on AS. Few high-risk cancers are missed, all of limited volume and favorable histology.

Determining Long-term Prostate Cancer Outcomes for Active Surveillance Patients Without Early Disease Progression: Implications for Slowing or Stopping Surveillance.

BACKGROUND AND OBJECTIVE: Active surveillance (AS) of prostate cancer (PCa) is the standard of care for low-grade disease, but there is limited guidance on tailoring protocols for stable patients. We investigated long-term outcomes for patients without initial progression and risk factors for upgrade. METHODS: Men on AS with Gleason grade group (GG) 1 PCa on three serial biopsies, ≥5 yr without progression, and ≥10 yr of follow-up were included. Outcomes were upgrade (GG ≥2), major upgrade (GG ≥3), progression to treatment, metastasis, PCa-specific survival, and overall survival. Cox proportional hazards regression models were used to estimate the associations between patient characteristics and risk of upgrade. KEY FINDINGS AND LIMITATIONS: A total of 774 men met the inclusion criteria. At 10, 12, and 15 yr, upgrade-free survival rates were 56%, 45%, and 21%; major upgrade-free survival rates were 88%, 83%, and 61%; treatment-free survival rates were 86%, 83%, and 73%; metastasis-free survival rates were 99%, 99%, and 98%; and overall survival rates were 98%, 96%, and 95%, respectively. PCa-specific survival was 100% at 15 yr. On a multivariable analysis, year of diagnosis, age, body mass index (BMI), and biopsy core positivity were associated with upgrade (all p < 0.01), whereas age and prostate-specific antigen (PSA) density were associated with major upgrade. CONCLUSIONS AND CLINICAL IMPLICATIONS: Patients without progression for 5 yr on AS had modest rates of upgrade and low rates of metastasis, and mortality at 15 yr of follow-up. Year of diagnosis, older age, increased BMI, and increased biopsy core positivity were associated with upgrade, whereas older age and greater PSA density were associated with an increased risk of major upgrade. A subset of these patients may benefit from deintensification of AS protocols. PATIENT SUMMARY: There are little reported data or clinical guidelines for patients with PCa who are stable for many years on active surveillance (AS). We show, in a large cohort, that PCa patients without progression for 5 yr on AS have modest rates of upgrade and very low rates of metastasis, and mortality rates at 15 yr of follow-up, and that older age, increased body mass index, and increased PCa volume are associated with an increased likelihood of future upgrade. This study supports continued AS in this patient population and deintensification in select patients.

11-Azaartemisinin derivatives bearing halogenated aromatic moieties: Potent anticancer agents with high tumor selectivity.

While artemisinin and its derivatives, including 11-azaartemisinin-based compounds, have shown promising anticancer activity, the integration of halogens into aromatic structures can amplify drug potency, metabolic stability, and selectivity. Herein, we present the synthesis of new novel 11-azaartemisinin derivatives bearing halogenated aromatic moieties connected via 1,2,3-triazole bridges and evaluate their anticancer activities against three human tumor cell lines: epidermoid carcinoma (KB), hepatocellular carcinoma (HepG2), and human lung adenocarcinoma (A549). Among the synthesized compounds, six of them (8c-h) displayed good to excellent antiproliferative activity in the low micromolar range across all three human cancer cell lines. In general, the m-bromide (8c) and m-iodide (8d) compounds exhibited superior anticancer activities compared to their o- and p-analogs, as well as the m-chloride and m-fluoride compounds. The most promising m-Br compound (8c) displayed 50 % inhibition of KB, HepG2, and A549 cell growth at concentrations of 7.7, 42.5, and 15.5 µM, respectively. Notably, the m-Br compound (8c) exhibited approximately 32-, 6-, and 16-fold lower activity in normal cells (Hek293) compared to KB, HepG2, and A549 tumor cells, respectively, indicating a significant tumor-selectivity.

Pharmacokinetic Comparison of Selective Prostatic Arterial and Intravenous PSMA PET/CT Radioligand Infusions in Primary Prostatic Adenocarcinoma.

Background Intravenous prostate-specific membrane antigen (PSMA)-targeted radioligand therapy improves survival in men with metastatic castration-resistant prostate cancer. Yet, the impact of selective prostatic arterial administration on primary tumor uptake is unclear. Purpose To compare gallium 68 (68Ga)-PSMA-11 uptake using dynamic PET/CT in prostatic tumoral volumes of interest (VOIs) during intravenous and selective prostatic arterial infusions for individuals with untreated, high-risk prostate cancer. Materials and Methods In this prospective, intraindividual comparative study conducted at an academic medical center, five men aged 58, 61, 64, 66, and 68 years with treatment-naive prostate cancer were enrolled between January 2022 and February 2023 and underwent two dynamic 68Ga-PSMA-11 PET/CT examinations 1 week apart. During the first examination, the radiotracer was administered intravenously. During the second administration, the radiotracer was delivered into either the right or left prostatic artery through an angiographically placed microcatheter. The primary outcome was maximum standardized uptake value (SUVmax) in prostatic tumoral VOIs. The secondary outcomes included mean SUV (SUVmean) in prostatic tumoral VOIs and area under the SUVmean curves (AUC). Longitudinal mixed-effects models were used to compare dynamic SUVmax and SUVmean time-activity curves (TACs), and paired t tests were used for the remaining data. Results The mean SUVmax within tumoral VOIs was 14 (range, 3-43) for venous sessions and 938 (range, 460-1436) for arterial sessions (P = .008). The SUVmean within VOIs was greater during arterial sessions (P < .001) overall and 46-fold and 19-fold greater at peak uptake and final time points, respectively. The mean AUC was greater on arterial TACs than on venous TACs at 14600 SUV × min (range, 8353-20025 SUV × min) and 240 SUV × min (range, 69-622 SUV × min), respectively (P = .002). Conclusion Selective prostatic arterial infusion resulted in greater 68Ga-PSMA-11 tumoral SUV than intravenous infusion. Further study of local-regional, intra-arterial delivery of a PSMA-targeted theranostic agent is warranted in high-risk prostate cancer. ClinicalTrials.gov identifier: NCT04976257 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Civelek in this issue.

Pachyonychia congenita: A father and son with a novel variant in the KRT16 gene.

This study underscores the significance of identifying the clinical manifestations of pachyonychia congenita (PC) and emphasizes the patterns of genetic inheritance. A 12-month-old boy presented with a "white hairy tongue" and, following a comprehensive evaluation, was diagnosed with PC. His father exhibited similar symptoms. Genetic testing revealed a KRT16 pathogenic variant (c.616 T > G) in both the patient and his father, marking it as a novel variant in the PC literature. This case contributes to a broader understanding of PC's genetic diversity and its clinical presentations.

Colossal Core/Shell CdSe/CdS Quantum Dot Emitters.

Single-photon sources are essential for advancing quantum technologies with scalable integration being a crucial requirement. To date, deterministic positioning of single-photon sources in large-scale photonic structures remains a challenge. In this context, colloidal quantum dots (QDs), particularly core/shell configurations, are attractive due to their solution processability. However, traditional QDs are typically small, about 3 to 6 nm, which restricts their deterministic placement and utility in large-scale photonic devices, particularly within optical cavities. The largest existing core/shell QDs are a family of giant CdSe/CdS QDs, with total diameters ranging from about 20 to 50 nm. Pushing beyond this size limit, we introduce a synthesis strategy for colossal CdSe/CdS QDs, with sizes ranging from 30 to 100 nm, using a stepwise high-temperature continuous injection method. Electron microscopy reveals a consistent hexagonal diamond morphology composed of 12 semipolar {101̅1} facets and one polar (0001) facet. We also identify conditions where shell growth is disrupted, leading to defects, islands, and mechanical instability, which suggest synthetic requirements for growing crystalline particles beyond 100 nm. The stepwise growth of thick CdS shells on CdSe cores enables the synthesis of emissive QDs with long photoluminescence lifetimes of a few microseconds and suppressed blinking at room temperature. Notably, QDs with 80 and 100 CdS monolayers exhibit high single-photon emission purity with second-order photon correlation g(2)(0) values below 0.2.

HLA-Cw6 increases the risk of psoriasis and early onset before twenty-seven years of age among the Vietnamese population.

Psoriasis is a chronic inflammatory skin disease that affects people all over the world. It is linked to the HLA-Cw6 allele, which is more common in Caucasians than in Asians and varies across ethnic groups. We investigated the association between the disease severity and the onset age of HLA-Cw6 prevalence in Vietnamese psoriasis patients. In 121 psoriasis patients and 30 healthy controls, we looked at the relationship between HLA-Cw6 and clinical features. We found that patients with psoriasis had significantly higher levels of HLA-Cw6 (64.5%) than controls (26.7%) (p=0.0001), with an odds ratio of 4.98 (2.04-12.15). Positive HLA-Cw6 patients had a significantly lower mean age of psoriasis onset than negative HLA-Cw6 patients. Patients with mild psoriasis (100%) were more likely to have the AA genotype, while patients with moderate to severe psoriasis (47.2% and 59.0%, respectively) and those with high PASI scores (55.1% and 54.1%, respectively) were more likely to have the TA genotype. Thus, HLA-Cw6 is a major genetic risk factor for psoriasis in Vietnamese patients, especially early-onset cases. Variations in HLA-Cw6 genotypes also affect disease severity.

Protocol for producing hyperpolarized 13C-bicarbonate for clinical MRI of extracellular pH in aggressive tumors.

Tumor acidosis is one of the hallmarks indicating the initiation and progression of various cancers. Here, we present a protocol for preparing a hyperpolarized (HP) 13C-bicarbonate tissue pH MRI imaging contrast agent to detect aggressive tumors. We describe the steps for the formulation and polarization of a precursor molecule 13C-glycerol carbonate (13C-GLC), the post-dissolution reaction, and converting HP 13C-GLC to an injectable HP 13C-bicarbonate solution. We then detail procedures for MRI data acquisition to generate tumor pH maps for assessing tumor aggressiveness. For complete details on the use and execution of this protocol, please refer to Mu et al.1.

Ni2P active site ensembles tune electrocatalytic nitrate reduction selectivity.

We demonstrate that active site ensembles on transition metal phosphides tune the selectivity of the nitrate reduction reaction. Using Ni2P nanocrystals as a case study, we report a mechanism involving competitive co-adsorption of H* and NOx* intermediates. A near 100% faradaic efficiency for nitrate reduction over hydrogen evolution is observed at -0.4 V, while NH3 selectivity is maximized at -0.2 V vs. RHE.

Simultaneous versus sequential fractional CO2 laser and subcision combination for management of post-acne atrophic scars: A split-face comparative study.

BACKGROUND: A combination of fractional CO2 laser and subcision is usually employed for the treatment of post-acne atrophic scars. However, the efficacy and safety of both simultaneous and sequential combination therapies should be explored. AIMS: To compare the efficacy and safety of simultaneous and sequential fractional CO2 laser and subcision combination therapies for post-acne atrophic scars. PATIENTS AND METHODS: This single-blind, split-face clinical trial included 34 patients with post-acne atrophic scars at our institution. Each patient underwent three sessions of subcision combined with fractional CO2 laser, with a 1-month interval between each session. The left side of the face was treated with simultaneous combination therapy, whereas the right side was treated with sequential combination therapy. Treatment efficacy was assessed at 4, 8, and 12 weeks; and 3 and 6 months after the last session. RESULTS: Simultaneous and sequential treatments demonstrated comparable efficacy. Regarding the adverse events, the side of the face undergoing simultaneous treatment experienced longer swelling duration, higher pain levels during laser treatment, and shorter downtime. CONCLUSIONS: Despite the longer swelling time and higher pain levels during laser treatment in the simultaneous treatment side, the effectiveness and satisfaction level of the CO2 fractional laser and subcision for treatment of the acne scars were comparable between the two combinations, with a shorter downtime for the simultaneous than for the sequential combination therapy.

Opioid Therapy for Cancer Pain in Vietnam: Knowledge, Attitudes, and Perceived Barriers Among Health Care Professionals, Policymakers, and Regulators.

PURPOSE: We aimed to assess knowledge, attitudes, and perceived barriers among health care professionals (HCPs), policymakers, and regulators in Vietnam related to opioid therapy for cancer pain. METHODS: We conducted a cross-sectional study in Vietnam from June to August 2022. Participants completed a questionnaire on their demographic characteristics, knowledge and attitudes toward opioid therapy, and barriers to accessing opioids for cancer pain. RESULTS: Two hundred seven HCPs and 15 policymakers/regulators completed the questionnaire. Poor knowledge about opioids in cancer pain was found in 63.3% of HCPs and 80.0% of policymakers/regulators. Poor knowledge was associated with a lack of training in cancer pain management or palliative care (PC; prevalence ratio [PR], 1.14 [95% CI, 1.04 to 1.24]). Negative attitudes toward opioid therapy in cancer pain were held by 64.7% of HCPs and 80.0% of policymakers/regulators. Negative attitudes were associated with the unavailability of oral morphine in the workplace (PR, 1.10 [95% CI, 1.01 to 1.20]). The most common major barriers reported were the absence of national policy on pain management and PC (34.7%), inadequate training in opioid use for cancer pain (33.8%), lockdown of health facilities during the COVID-19 pandemic (32.4%), limited opioid availability in local health facilities (32.4%), and excessively restrictive regulation of opioid dispensing in pharmacies (32.4%). CONCLUSION: This study found a knowledge deficit and negative attitudes toward opioid therapy for cancer pain among HCPs and policymakers/regulators. Improving education and training in opioid therapy is essential. Recognizing major barriers can guide strategies to enhance safe opioid accessibility for cancer pain management in Vietnam.

Direct transposition of native DNA for sensitive multimodal single-molecule sequencing.

Concurrent readout of sequence and base modifications from long unamplified DNA templates by Pacific Biosciences of California (PacBio) single-molecule sequencing requires large amounts of input material. Here we adapt Tn5 transposition to introduce hairpin oligonucleotides and fragment (tagment) limiting quantities of DNA for generating PacBio-compatible circular molecules. We developed two methods that implement tagmentation and use 90-99% less input than current protocols: (1) single-molecule real-time sequencing by tagmentation (SMRT-Tag), which allows detection of genetic variation and CpG methylation; and (2) single-molecule adenine-methylated oligonucleosome sequencing assay by tagmentation (SAMOSA-Tag), which uses exogenous adenine methylation to add a third channel for probing chromatin accessibility. SMRT-Tag of 40 ng or more human DNA (approximately 7,000 cell equivalents) yielded data comparable to gold standard whole-genome and bisulfite sequencing. SAMOSA-Tag of 30,000-50,000 nuclei resolved single-fiber chromatin structure, CTCF binding and DNA methylation in patient-derived prostate cancer xenografts and uncovered metastasis-associated global epigenome disorganization. Tagmentation thus promises to enable sensitive, scalable and multimodal single-molecule genomics for diverse basic and clinical applications.

The missing toxic link: Exposure of non-target native marsupials to second-generation anticoagulant rodenticides (SGARs) suggest a potential route of transfer into apex predators.

Anticoagulant rodenticides (ARs) are used globally to control rodent pests. Second-generation anticoagulant rodenticides (SGARs) persist in the liver and pose a significant risk of bioaccumulation and secondary poisoning in predators, including species that do not generally consume rodents. As such, there is a clear need to understand the consumption of ARs, particularly SGARs, by non-target consumers to determine the movement of these anticoagulants through ecosystems. We collected and analysed the livers from deceased common brushtail possums (Trichosurus vulpecula) and common ringtail possums (Pseudocheirus peregrinus), native Australian marsupials that constitute the main diet of the powerful owl (Ninox strenua), an Australian apex predator significantly exposed to SGAR poisoning. ARs were detected in 91 % of brushtail possums and 40 % of ringtail possums. Most of the detections were attributed to SGARs, while first-generation anticoagulant rodenticides (FGARs) were rarely detected. SGAR concentrations were likely lethal or toxic in 42 % of brushtail possums and 4 % of ringtail possums with no effect of age, sex, or weight detected in either species. There was also no effect of the landscape type possums were from, suggesting SGAR exposure is ubiquitous across landscapes. The rate of exposure detected in these possums provides insight into the pathway through which ARs are transferred to one of their key predators, the powerful owl. With SGARs entering food-webs through non-target species, the potential for bioaccumulation and broader secondary poisoning of predators is significantly greater and highlights an urgent need for routine rodenticide testing in non-target consumers that present as ill or found deceased. To limit their impact on ecosystem stability the use of SGARs should be significantly regulated by governing agencies.

Mixed Supervision of Histopathology Improves Prostate Cancer Classification From MRI.

Non-invasive prostate cancer classification from MRI has the potential to revolutionize patient care by providing early detection of clinically significant disease, but has thus far shown limited positive predictive value. To address this, we present a image-based deep learning method to predict clinically significant prostate cancer from screening MRI in patients that subsequently underwent biopsy with results ranging from benign pathology to the highest grade tumors. Specifically, we demonstrate that mixed supervision via diverse histopathological ground truth improves classification performance despite the cost of reduced concordance with image-based segmentation. Where prior approaches have utilized pathology results as ground truth derived from targeted biopsies and whole-mount prostatectomy to strongly supervise the localization of clinically significant cancer, our approach also utilizes weak supervision signals extracted from nontargeted systematic biopsies with regional localization to improve overall performance. Our key innovation is performing regression by distribution rather than simply by value, enabling use of additional pathology findings traditionally ignored by deep learning strategies. We evaluated our model on a dataset of 973 (testing n=198 ) multi-parametric prostate MRI exams collected at UCSF from 2016-2019 followed by MRI/ultrasound fusion (targeted) biopsy and systematic (nontargeted) biopsy of the prostate gland, demonstrating that deep networks trained with mixed supervision of histopathology can feasibly exceed the performance of the Prostate Imaging-Reporting and Data System (PI-RADS) clinical standard for prostate MRI interpretation (71.6% vs 66.7% balanced accuracy and 0.724 vs 0.716 AUC).

Sporadic Pemphigus Foliaceus in a 3-Year-Old Vietnamese Girl: A Case Report and Literature Review.

Pemphigus foliaceus is an uncommon autoimmune intraepidermal blistering disease characterized by immunoglobulin (Ig) G autoantibodies that attack desmoglein-1 in the epidermis. There are two predominant forms of pemphigus foliaceus, sporadic and endemic. Sporadic pemphigus foliaceus is known to be more prevalent in middle-aged and elderly people and to be extremely rare in children. Less than 40 nonendemic pediatric pemphigus foliaceus cases have been documented in the literature. This report documents a case of sporadic pemphigus foliaceus in a 3-year-old Vietnamese girl who presented with generalized scaling and crusted erosions over the body.

Acceptance and User Experiences of a Wearable Device for the Management of Hospitalized Patients in COVID-19-Designated Wards in Ho Chi Minh City, Vietnam: Action Learning Project.

BACKGROUND: Wearable devices have been used extensively both inside and outside of the hospital setting. During the COVID-19 pandemic, in some contexts, there was an increased need to remotely monitor pulse and saturated oxygen for patients due to the lack of staff and bedside monitors. OBJECTIVE: A prototype of a remote monitoring system using wearable pulse oximeter devices was implemented at the Hospital for Tropical Diseases in Ho Chi Minh City, Vietnam, from August to December 2021. The aim of this work was to support the ongoing implementation of the remote monitoring system. METHODS: We used an action learning approach with rapid pragmatic methods, including informal discussions and observations as well as a feedback survey form designed based on the technology acceptance model to assess the use and acceptability of the system. Based on these results, we facilitated a meeting using user-centered design principles to explore user needs and ideas about its development in more detail. RESULTS: In total, 21 users filled in the feedback form. The mean technology acceptance model scores ranged from 3.5 (for perceived ease of use) to 4.4 (for attitude) with behavioral intention (3.8) and perceived usefulness (4.2) scoring in between. Those working as nurses scored higher on perceived usefulness, attitude, and behavioral intention than did physicians. Based on informal discussions, we realized there was a mismatch between how we (ie, the research team) and the ward teams perceived the use and wider purpose of the technology. CONCLUSIONS: Designing and implementing the devices to be more nurse-centric from their introduction could have helped to increase their efficiency and use during the complex pandemic period.

First-in-human Evaluation of a Prostate-specific Membrane Antigen-targeted Near-infrared Fluorescent Small Molecule for Fluorescence-based Identification of Prostate Cancer in Patients with High-risk Prostate Cancer Undergoing Robotic-assisted Prostatectomy.

BACKGROUND: Men with high-risk prostate cancer undergoing surgery likely recur due to failure to completely excise regional and/or local disease. OBJECTIVE: The first-in-human evaluation of safety, pharmacokinetics, and exploratory efficacy of IS-002, a novel near-infrared prostate-specific membrane antigen (PSMA)-targeted fluorescence imaging agent, designed for intraoperative prostate cancer visualization. DESIGN, SETTING, AND PARTICIPANTS: A phase 1, single-center, dose-escalation study was conducted in 24 men with high-risk prostate cancer scheduled for robotic-assisted radical prostatectomy with (extended) pelvic lymph node dissection using the da Vinci surgical system. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Adverse events (AEs), vital signs, complete blood count, complete metabolic panel, urinalysis, and electrocardiogram were assessed over a 14-d period and compared with baseline. The pharmacokinetic profile of IS-002 was determined. Diagnostic accuracy was assessed for exploratory efficacy. RESULTS AND LIMITATIONS: AEs predominantly included discoloration of urine (n = 22/24; expected, related, grade 1). There were no grade ≥2 AEs. IS-002 Cmax and area under the curve increased with increasing dose. Plasma concentrations declined rapidly in a biphasic manner, with the median terminal half-lives ranging from 5.0 to 7.6 h, independent of dose and renal function. At 25 µg/kg, the exploratory efficacy readouts for the negative and positive predictive values were, 97% and 45% for lymph nodes, and 100% and 80% for residual/locoregional disease detection, respectively. CONCLUSIONS: IS-002 is safe and well tolerated, and has the potential to enable intraoperative tumor detection that could not be identified using standard imaging. PATIENT SUMMARY: IS-002 is a new imaging agent that specifically targets the prostate-specific membrane antigen receptor. In this study, we tested IS-002 for the first time in men with high-risk prostate cancer undergoing surgery and found that IS-002 is safe, is cleared from the body quickly, and potentially allows identification of prostate cancer in areas that would not be identified by conventional white light imaging.

Transcriptomic Heterogeneity of Expansile Cribriform and Other Gleason Pattern 4 Prostate Cancer Subtypes.

BACKGROUND: Prostate cancers featuring an expansile cribriform (EC) pattern are associated with worse clinical outcomes following radical prostatectomy (RP). However, studies of the genomic characteristics of Gleason pattern 4 subtypes are limited. OBJECTIVE: To explore transcriptomic characteristics and heterogeneity within Gleason pattern 4 subtypes (fused/poorly formed, glomeruloid, small cribriform, EC/intraductal carcinoma [IDC]) and the association with biochemical recurrence (BCR)-free survival. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective cohort study including 165 men with grade group 2-4 prostate cancer who underwent RP at a single academic institution (2016-2020) and Decipher testing of the RP specimen. Patients with Gleason pattern 5 were excluded. IDC and EC patterns were grouped. Median follow-up was 2.5 yr after RP for patients without BCR. OUTCOMES MEASUREMENTS AND STATISTICAL ANALYSIS: Prompted by heterogeneity within pattern 4 subtypes identified via exploratory analyses, we investigated transcriptomic consensus clusters using partitioning around medoids and hallmark gene set scores. The primary clinical outcome was BCR, defined as two consecutive prostate-specific antigen measurements >0.2 ng/ml at least 8 wk after RP, or any additional treatment. Multivariable Cox proportional-hazards models were used to determine factors associated with BCR-free survival. RESULTS AND LIMITATIONS: In this cohort, 99/165 patients (60%) had EC and 67 experienced BCR. Exploratory analyses and clustering demonstrated transcriptomic heterogeneity within each Gleason pattern 4 subtype. In the multivariable model controlled for pattern 4 subtype, margin status, Cancer of the Prostate Risk Assessment Post-Surgical score, and Decipher score, a newly identified steroid hormone-driven cluster (hazard ratio 2.35 95% confidence interval 1.01-5.47) was associated with worse BCR-free survival. The study is limited by intermediate follow-up, no validation cohort, and lack of accounting for intratumoral and intraprostatic heterogeneity. CONCLUSIONS: Transcriptomic heterogeneity was present within and across each Gleason pattern 4 subtype, demonstrating there is additional biologic diversity not captured by histologic subtypes. This heterogeneity can be used to develop novel signatures and to classify transcriptomic subtypes, which may help in refining risk stratification following RP to further guide decision-making on adjuvant and salvage treatments. PATIENT SUMMARY: We studied prostatectomy specimens and found that tumors with similar microscopic appearance can have genetic differences that may help to predict outcomes after prostatectomy for prostate cancer. Our results demonstrate that further gene expression analysis of prostate cancer subtypes may improve risk stratification after prostatectomy. Future studies are needed to develop novel gene expression signatures and validate these findings in independent sets of patients.