Clinical Practice Guide: Management of Chylous Ascites After Retroperitoneal Lymph Node Dissection.

Chylous ascites is a rare but challenging complication after retroperitoneal lymph node dissection. Conservative management is successful in most cases, with percutaneous lymphangiography reserved for refractory instances. Surgical interventions are associated with high failure rates.

"Seeing Is Believing": Additive Utility of 68Ga-PSMA-11 PET/CT in Prostate Cancer Diagnosis.

Widespread adoption of mpMRI has led to a decrease in the number of patients requiring prostate biopsies. 68Ga-PSMA-11 PET/CT has demonstrated added benefits in identifying csPCa. Integrating the use of these imaging techniques may hold promise for predicting the presence of csPCa without invasive biopsy. A retrospective analysis of 42 consecutive patients who underwent mpMRI, 68Ga-PSMA-11 PET/CT, prostatic biopsy, and radical prostatectomy (RP) was carried out. A lesion-based model (n = 122) using prostatectomy histopathology as reference standard was used to analyze the accuracy of 68Ga-PSMA-11 PET/CT, mpMRI alone, and both in combination to identify ISUP-grade group ≥ 2 lesions. 68Ga-PSMA-11 PET/CT demonstrated greater specificity and positive predictive value (PPV), with values of 73.3% (vs. 40.0%) and 90.1% (vs. 82.2%), while the mpMRI Prostate Imaging Reporting and Data System (PI-RADS) 4-5 had better sensitivity and negative predictive value (NPV): 90.2% (vs. 78.5%) and 57.1% (vs. 52.4%), respectively. When used in combination, the sensitivity, specificity, PPV, and NPV were 74.2%, 83.3%, 93.2%, and 51.0%, respectively. Subgroup analysis of PI-RADS 3, 4, and 5 lesions was carried out. For PI-RADS 3 lesions, 68Ga-PSMA-11 PET/CT demonstrated a NPV of 77.8%. For PI-RADS 4-5 lesions, 68Ga-PSMA-11 PET/CT achieved PPV values of 82.1% and 100%, respectively, with an NPV of 100% in PI-RADS 5 lesions. A combination of 68Ga-PSMA-11 PET/CT and mpMRI improved the radiological diagnosis of csPCa. This suggests that avoidance of prostate biopsy prior to RP may represent a valid option in a selected subgroup of high-risk patients with a high suspicion of csPCa on mpMRI and 68Ga-PSMA-11 PET/CT.

Anaplastic sarcoma of the kidney (DICER1-sarcoma of the kidney): A report from the International Pleuropulmonary Blastoma/DICER1 Registry.

BACKGROUND: Anaplastic sarcoma of the kidney (ASK) is a DICER1-related neoplasm first identified as a distinctive tumor type through the evaluation of unusual cases of putative anaplastic Wilms tumors. Subsequent case reports identified the presence of biallelic DICER1 variants as well as progression from cystic nephroma, a benign DICER1-related neoplasm. Despite increasing recognition of ASK as a distinct entity, the optimal treatment remains unclear. METHODS: Individuals with known or suspected DICER1-related tumors including ASK were enrolled in the International Pleuropulmonary Blastoma/DICER1 Registry. Additionally, a comprehensive review of reported cases of ASK was undertaken, and data were aggregated for analysis with the aim to identify prognostic factors and clinical characteristics to guide decisions regarding genetic testing, treatment, and surveillance. RESULTS: Ten cases of ASK were identified in the Registry along with 37 previously published cases. Staging data, per Children's Oncology Group guidelines, was available for 40 patients: 13 were stage I, 12 were stage II, 10 were stage III, and five were stage IV. Outcome data were available for 37 patients. Most (38 of 46) patients received upfront chemotherapy and 14 patients received upfront radiation. Two-year event-free survival (EFS) for stage I-II ASK was 81.8% (95% confidence interval [CI]: 67.2%-99.6%), compared with 46.6% EFS (95% CI: 24.7%-87.8%) for stage III-IV (p = .07). Two-year overall survival (OS) for stage I-II ASK was 88.9% (95% CI: 75.5%-100.0%), compared with 70.0% (95% CI: 46.7%-100.0%) for stage III-IV (p = .20). Chemotherapy was associated with improved EFS and OS with hazard ratios of 0.09 (95% CI: 0.02-0.31) and 0.08 (95% CI: 0.02-0.42), respectively. CONCLUSION: ASK is a rare DICER1-related renal neoplasm. In the current report, we identify clinical and treatment-related factors associated with outcome including the importance of chemotherapy in treating ASK. Ongoing data collection and genomic analysis are indicated to optimize outcomes for children and adults with these rare tumors.

An imbalance between proliferation and differentiation underlies the development of microRNA-defective pineoblastoma.

Mutations in the microRNA processing genes DICER1 and DROSHA drive several cancers that resemble embryonic progenitors. To understand how microRNAs regulate tumorigenesis, we ablated Drosha or Dicer1 in the developing pineal gland to emulate the pathogenesis of pineoblastoma, a brain tumor that resembles undifferentiated precursors of the pineal gland. Accordingly, these mice develop pineal tumors marked by loss of microRNAs, including the let-7/miR-98-5p family, and de-repression of microRNA target genes. Pineal tumors driven by loss of Drosha or Dicer1 mimic tumors driven by Rb1 loss, as they exhibit upregulation of S-phase genes and homeobox transcription factors that regulate pineal development. Blocking proliferation of these tumors facilitates expression of pinealocyte maturation markers, with a concomitant reduction in embryonic markers. Select embryonic markers remain elevated, however, as the microRNAs that normally repress these target genes remain absent. One such microRNA target gene is the oncofetal transcription factor Plagl2, which regulates expression of pro-growth genes, and inhibiting their signaling impairs tumor growth. Thus, we demonstrate that tumors driven by loss of microRNA processing may be therapeutically targeted by inhibiting downstream drivers of proliferation.

Management of advanced prostate cancer in the Asia-Pacific region: Summary of the Asia-Pacific Advanced Prostate Cancer Consensus Conference 2023.

AIM: The aim of the third Asia-Pacific Advanced Prostate Cancer Consensus Conference (APAC APCCC 2023) was to discuss the application in the Asia-Pacific (APAC) region of consensus statements from the 4th Advanced Prostate Cancer Consensus Conference (APCCC 2022). METHODS: The one-day meeting in July 2023 brought together 27 experts from 14 APAC countries. The meeting covered five topics: (1) Intermediate- and high-risk and locally advanced prostate cancer; (2) Management of newly diagnosed metastatic hormone-sensitive prostate cancer; (3) Management of non-metastatic castration-resistant prostate cancer; (4) Homologous recombination repair mutation testing; (5) Management of metastatic castration-resistant prostate cancer. Pre- and post-symposium polling gathered APAC-specific responses to APCCC consensus questions and insights on current practices and challenges in the APAC region. RESULTS: APAC APCCC highlights APAC-specific considerations in an evolving landscape of diagnostic technologies and treatment innovations for advanced prostate cancer. While new technologies are available in the region, cost and reimbursement continue to influence practice significantly. Individual patient considerations, including the impact of chemophobia on Asian patients, also influence decision-making. CONCLUSION: The use of next-generation imaging, genetic testing, and new treatment combinations is increasing the complexity and duration of prostate cancer management. Familiarity with new diagnostic and treatment options is growing in the APAC region. Insights highlight the continued importance of a multidisciplinary approach that includes nuclear medicine, genetic counseling, and quality-of-life expertise. The APAC APCCC meeting provides an important opportunity to share practice and identify APAC-specific issues and considerations in areas of low evidence where clinical experience is growing.

Outcomes in ovarian Sertoli-Leydig cell tumor: A report from the International Pleuropulmonary Blastoma/DICER1 and Ovarian and Testicular Stromal Tumor Registries.

OBJECTIVE: Sertoli-Leydig cell tumors (SLCTs) are rare sex cord-stromal tumors, representing <0.5% of all ovarian tumors. We sought to describe prognostic factors, treatment and outcomes for individuals with ovarian SLCT. METHODS: Individuals with SLCT were enrolled in the International Pleuropulmonary Blastoma/DICER1 Registry and/or the International Ovarian and Testicular Stromal Tumor Registry. Medical records were systematically abstracted, and pathology was centrally reviewed when available. RESULTS: In total, 191 participants with ovarian SLCT enrolled, with most (92%, 175/191) presenting with FIGO stage I disease. Germline DICER1 results were available for 156 patients; of these 58% had a pathogenic or likely pathogenic germline variant. Somatic (tumor) DICER1 testing showed RNase IIIb hotspot variants in 97% (88/91) of intermediately and poorly differentiated tumors. Adjuvant chemotherapy was administered in 40% (77/191) of cases, and among these, nearly all patients received platinum-based regimens (95%, 73/77), and 30% (23/77) received regimens that included an alkylating agent. Three-year recurrence-free survival for patients with stage IA tumors was 93.6% (95% CI: 88.2-99.3%) compared to 67.1% (95% CI: 55.2-81.6%) for all stage IC and 60.6% (95% CI: 40.3-91.0%) for stage II-IV (p < .001) tumors. Among patients with FIGO stage I tumors, those with mesenchymal heterologous elements treated with surgery alone were at higher risk for recurrence (HR: 74.18, 95% CI: 17.99-305.85). CONCLUSION: Most individuals with SLCT fare well, though specific risk factors such as mesenchymal heterologous elements are associated with poor prognosis. We also highlight the role of DICER1 surveillance in early detection of SLCT, facilitating stage IA resection.

DROSHA regulates mesenchymal gene expression in Wilms tumor.

Wilms tumor, the most common pediatric kidney cancer, resembles embryonic renal progenitors. Currently, there are no ways to therapeutically target Wilms tumor driver mutations, such as in the microRNA processing gene DROSHA. Here we used a "multi-omics" approach to define the effects of DROSHA mutation in Wilms tumor. We categorized Wilms tumor mutations into four mutational subclasses with unique transcriptional effects: microRNA processing, MYCN activation, chromatin remodeling, and kidney developmental factors. In particular, we find that DROSHA mutations are correlated with de-repressing microRNA target genes that regulate differentiation and proliferation and a self-renewing, mesenchymal state. We model these findings by inhibiting DROSHA expression in a Wilms tumor cell line, which led to upregulation of the cell cycle regulator cyclin D2 (CCND2). Furthermore, we observed that DROSHA mutations in Wilms tumor and DROSHA silencing in vitro were associated with a mesenchymal state with aberrations in redox metabolism. Accordingly, we demonstrate that Wilms tumor cells lacking microRNAs are sensitized to ferroptotic cell death through inhibition of glutathione peroxidase 4 (GPX4), the enzyme that detoxifies lipid peroxides. Implications: This study reveals genotype-transcriptome relationships in Wilms tumor and points to ferroptosis as a potentially therapeutic vulnerability in one subset of Wilms tumor.

Off-clamp vs on-clamp robot-assisted partial nephrectomy: a systematic review and meta-analysis.

OBJECTIVE: To compare intra- and postoperative outcomes between off-clamp and on-clamp robot-assisted partial nephrectomy (RAPN), using data from randomised controlled trials (RCTs) or covariate-matched studies (propensity score-matched or matched-pair analysis). METHODS: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses-compliant literature review was conducted on PubMed, EMBASE, Scopus and CENTRAL for relevant studies comparing off-clamp to on-clamp RAPN. Primary outcomes were estimated blood loss, postoperative percentage decrease in estimated glomerular filtration rate (eGFR), and margin positive rate. Secondary outcomes were operative time, postoperative eGFR, length of stay, all postoperative complications, major complications, and need for transfusion. Random-effects meta-analyses were performed to generate mean differences (MDs) or odds ratios (ORs). RESULTS: A total of 10 studies (2307 patients) were shortlisted for analysis. There was no significant difference in estimated operative blood loss between off-clamp and on-clamp RAPN (MD 21.9 mL, 95% confidence interval [CI] -0.9 to 44.7 mL; P = 0.06, I2 = 58%). Off-clamp RAPN yielded a smaller postoperative eGFR deterioration (MD 3.10%, 95% CI 1.05-5.16%; P = 0.008, I2 = 13%) and lower odds of margin positivity (OR 0.62, 95% CI 0.40-0.94; P = 0.03, I2 = 0%). No significant differences were found for all secondary outcomes. CONCLUSIONS: Off-clamp and on-clamp RAPN are similarly effective approaches for selected renal masses. Within the classic trifecta of PN outcomes, off-clamp RAPN yields similar rates of perioperative complications and may possibly offer better preservation of renal function and reduced margin-positive rates.

Administering [177Lu]Lu-PSMA-617 Prior to Radical Prostatectomy in Men with High-risk Localised Prostate Cancer (LuTectomy): A Single-centre, Single-arm, Phase 1/2 Study.

BACKGROUND: High-risk localised prostate cancer (HRCaP) has high rates of biochemical recurrence; [177Lu]Lu-PSMA-617 is effective in men with advanced prostate cancer. OBJECTIVE: To investigate the dosimetry, safety, and efficacy of upfront [177Lu]Lu-PSMA-617 in men with HRCaP prior to robotic radical prostatectomy (RP). DESIGN, SETTING, AND PARTICIPANTS: In this single-arm, phase I/II trial, we recruited men with HRCaP (any of prostate-specific antigen [PSA] >20 ng/ml, International Society of Urological Pathology (ISUP) grade group [GG] 3-5, and ≥cT2c), with high tumour uptake on [68Ga]Ga-PSMA-11 positron emission tomography/computed tomography (PSMA PET/CT), and scheduled for RP. INTERVENTION: Cohort A (n = 10) received one cycle and cohort B (n = 10) received two cycles of [177Lu]Lu-PSMA-617 (5 GBq) followed by surgery 6 weeks later. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was tumour radiation absorbed dose. Adverse events (AEs; Common Terminology Criteria for Adverse Events (CTCAE) version 5.0), surgical safety (Clavien-Dindo), imaging, and biochemical responses were evaluated (ClinicalTrials.gov: NCT04430192). RESULTS AND LIMITATIONS: Between May 29, 2020 and April 28, 2022, 20 patients were enrolled. The median PSA was 18 ng/ml (interquartile range [IQR] 11-35), Eighteen (90%) had GG ≥3, and six (30%) had N1 disease. The median (IQR) highest tumour radiation absorbed dose after cycle 1 for all lesions was 35.5 Gy (19.5-50.1), with 19.6 Gy (11.3-48.4) delivered to the prostate. Five patients received radiation to lymph nodes. Nine (45%) patients achieved >50% PSA decline. The most common AEs related to [177Lu]Lu-PSMA-617 were grade 1 fatigue in eight (40%), nausea in seven (35%), dry mouth in six (30%), and thrombocytopenia in four (20%) patients. No grade 3/4 toxicities or Clavien 3-5 complications occurred. Limitations include small a sample size. CONCLUSIONS: In men with HRCaP and high prostate-specific membrane antigen (PSMA) expression, [177Lu]Lu-PSMA-617 delivered high levels of targeted radiation doses with few toxicities and without compromising surgical safety. Further studies of [177Lu]Lu-PSMA-617 in this population are worthwhile to determine whether meaningful long-term oncological benefits can be demonstrated. PATIENT SUMMARY: In this study, we demonstrate that up to two cycles of [177Lu]Lu-PSMA-617 given prior to radical prostatectomy in patients with high-risk localised prostate cancer are safe and deliver targeted doses of radiation to tumour-affected tissues. It is tolerated well with minimal treatment-related adverse events, and surgery is safe with a low rate of complications. Activity measured through PSA reduction, repeat PSMA PET/CT, and histological response is promising.

Oligometastatic Prostate Cancer-The Middle Child Syndrome.

Oligometastatic prostate cancer is an evolving clinical entity as more data from novel imaging tools such as PSMA PET/CT emerges. Recognition of this disease entity allows for unique interventions which differ from conventional treatment of metastatic prostate cancers such as the initiation of chemotherapy. With metastasis-directed therapy (MDT), there is potential for early eradication of limited disease metastases and a delay in systemic treatment with its associated treatment-related toxicities. This review explores the current evidence and outcomes of different metastasis-directed therapies such as the role of radiotherapy in low volume metastasis and the use of PSMA ligands to facilitate pelvic lymph node dissections. With a deeper understanding of this low metastasis state, it has revolutionized the current viable treatment options, and more studies are ongoing to provide further insights into this unique disease entity.

Specifications of the ACMG/AMP Variant Classification Guidelines for Germline DICER1 Variant Curation.

Germline pathogenic variants in DICER1 predispose individuals to develop a variety of benign and malignant tumors. Accurate variant curation and classification is essential for reliable diagnosis of DICER1-related tumor predisposition and identification of individuals who may benefit from surveillance. Since 2015, most labs have followed the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) sequence variant classification guidelines for DICER1 germline variant curation. However, these general guidelines lack gene-specific nuances and leave room for subjectivity. Consequently, a group of DICER1 experts joined ClinGen to form the DICER1 and miRNA-Processing Genes Variant Curation Expert Panel (VCEP), to create DICER1- specific ACMG/AMP guidelines for germline variant curation. The VCEP followed the FDA-approved ClinGen protocol for adapting and piloting these guidelines. A diverse set of 40 DICER1 variants were selected for piloting, including 14 known Pathogenic/Likely Pathogenic (P/LP) variants, 12 known Benign/Likely Benign (B/LB) variants, and 14 variants classified as variants of uncertain significance (VUS) or with conflicting interpretations in ClinVar. Clinically meaningful classifications (i.e., P, LP, LB, or B) were achieved for 82.5% (33/40) of the pilot variants, with 100% concordance among the known P/LP and known B/LB variants. Half of the VUS or conflicting variants were resolved with four variants classified as LB and three as LP. These results demonstrate that the DICER1-specific guidelines for germline variant curation effectively classify known pathogenic and benign variants while reducing the frequency of uncertain classifications. Individuals and labs curating DICER1 variants should consider adopting this classification framework to encourage consistency and improve objectivity.

Artificial intelligence-based analyses of varus leg alignment and after high tibial osteotomy show high accuracy and reproducibility.

PURPOSE: The aim of this study was to investigate the performance of an artificial intelligence (AI)-based software for fully automated analysis of leg alignment pre- and postoperatively after high tibial osteotomy (HTO) on long-leg radiographs (LLRs). METHODS: Long-leg radiographs of 95 patients with varus malalignment that underwent medial open-wedge HTO were analyzed pre- and postoperatively. Three investigators and an AI software using deep learning algorithms (LAMA™, ImageBiopsy Lab, Vienna, Austria) evaluated the hip-knee-ankle angle (HKA), mechanical axis deviation (MAD), joint line convergence angle (JLCA), medial proximal tibial angle (MPTA), and mechanical lateral distal femoral angle (mLDFA). All measurements were performed twice and the performance of the AI software was compared with individual human readers using a Bayesian mixed model. In addition, the inter-observer intraclass correlation coefficient (ICC) for inter-observer reliability was evaluated by comparing measurements from manual readers. The intra-reader variability for manual measurements and the AI-based software was evaluated using the intra-observer ICC. RESULTS: Initial varus malalignment was corrected to slight valgus alignment after HTO. Measured by the AI algorithm and manually HKA (5.36° ± 3.03° and 5.47° ± 2.90° to - 0.70 ± 2.34 and - 0.54 ± 2.31), MAD (19.38 mm ± 11.39 mm and 20.17 mm ± 10.99 mm to - 2.68 ± 8.75 and - 2.10 ± 8.61) and MPTA (86.29° ± 2.42° and 86.08° ± 2.34° to 91.6 ± 3.0 and 91.81 ± 2.54) changed significantly from pre- to postoperative, while JLCA and mLDFA were not altered. The fully automated AI-based analyses showed no significant differences for all measurements compared with manual reads neither in native preoperative radiographs nor postoperatively after HTO. Mean absolute differences between the AI-based software and mean manual observer measurements were 0.5° or less for all measurements. Inter-observer ICCs for manual measurements were good to excellent for all measurements, except for JLCA, which showed moderate inter-observer ICCs. Intra-observer ICCs for manual measurements were excellent for all measurements, except for JLCA and for MPTA postoperatively. For the AI-aided analyses, repeated measurements showed entirely consistent results for all measurements with an intra-observer ICC of 1.0. CONCLUSIONS: The AI-based software can provide fully automated analyses of native long-leg radiographs in patients with varus malalignment and after HTO with great accuracy and reproducibility and could support clinical workflows. LEVEL OF EVIDENCE: Diagnostic study, Level III.

Intronic Germline DICER1 Variants in Patients With Sertoli-Leydig Cell Tumor.

Germline pathogenic loss-of-function (pLOF) variants in DICER1 are associated with a predisposition for a variety of solid neoplasms, including pleuropulmonary blastoma and Sertoli-Leydig cell tumor (SLCT). The most common DICER1 pLOF variants include small insertions or deletions leading to frameshifts, and base substitutions leading to nonsense codons or altered splice sites. Larger deletions and pathogenic missense variants occur less frequently. Identifying these variants can trigger surveillance algorithms with potential for early detection of DICER1-related cancers and cascade testing of family members. However, some patients with DICER1-associated tumors have no pLOF variants detected by germline or tumor testing. Here, we present two patients with SLCT whose tumor sequencing showed only a somatic missense DICER1 RNase IIIb variant. Conventional exon-directed germline sequencing revealed no pLOF variants. Using a custom capture panel, we discovered novel intronic variants, ENST00000343455.7: c.1752+213A>G and c.1509+16A>G, that appear to interfere with normal splicing. We suggest that when no DICER1 pLOF variants or large deletions are discovered in exonic regions despite strong clinical suspicion, intron sequencing and splicing analysis should be performed.

Rare Tumors: Opportunities and challenges from the Children's Oncology Group perspective.

While all childhood cancers are rare, tumors that are particularly infrequent or underrepresented within pediatrics are studied under the umbrella of the Children's Oncology Group Rare Tumor committee, divided into the Retinoblastoma and Infrequent Tumor subcommittees. The Infrequent Tumor subcommittee has traditionally included an emphasis on globally rare tumors such as adrenocortical carcinoma, nasopharyngeal carcinoma, or those tumors that are rare in young children, despite being common in adolescents and young adults, such as colorectal carcinoma, thyroid carcinoma, and melanoma. Pleuropulmonary blastoma, gonadal stromal tumors, pancreatic tumors including pancreatoblastoma, gastrointestinal stromal tumor, nonmelanoma skin cancers, neuroendocrine tumors, and desmoplastic small round cell tumors, as well as other carcinomas are also included under the heading of the Children's Oncology Group Rare Tumor committee. While substantial challenges exist in rare cancers, inclusion and global collaboration remain key priorities to ensure high quality research to advance care.

Effectiveness of long-term noninvasive ventilation measured by remote monitoring in neuromuscular disease.

Background and objective: Patients with neuromuscular disease are often treated with home noninvasive ventilation (NIV) with devices capable of remote patient monitoring. We sought to determine whether long-term NIV data could provide insight into the effectiveness of ventilation over time. Methods: We abstracted available longitudinal data for adults with neuromuscular disease in monthly increments from first available to most recent. Generalised linear mixed-effects modelling with subject-level random effects was used to evaluate trajectories over time. Results: 1799 months of data across 85 individuals (median age 61, interquartile range (IQR) 46-71 years; 44% female; 49% amyotrophic lateral sclerosis (ALS)) were analysed, with a median (IQR) of 17 (8-35) months per individual. Over time, tidal volume increased and respiratory rate decreased. Dynamic respiratory system compliance decreased, accompanied by increased pressure support. Compared to volume-assured mode, fixed-pressure modes were associated with lower initial tidal volume, higher respiratory rate and lower pressures, which did not fully equalise with volume-assured mode over time. Compared with non-ALS patients, those with ALS had lower initial pressure support, but faster increases in pressure support over time, and ALS was associated wtih a more robust increase in respiratory rate in response to low tidal volume. Nonsurvivors did not differ from survivors in ventilatory trajectories over time, but did exhibit decreasing NIV use prior to death, in contrast with stable use in survivors. Conclusion: NIV keeps breathing patterns stable over time, but support needs are dynamic and influenced by diagnosis and ventilation mode. Mortality is preceded by decreased NIV use rather than inadequate support during use.

Local Therapy on Clinically Lymph Node-positive Prostate Cancer: A Systematic Review and Meta-analysis.

CONTEXT: Patients with clinically lymph node-positive (cN1) prostate cancer (PCa) are traditionally regarded to have metastatic disease, and the role of local therapy (LT) in their treatment remains unclear. OBJECTIVE: To evaluate the outcomes of cN1 PCa patients treated with LT, and secondarily to compare between different modalities of LT, including radiotherapy (RT) and radical prostatectomy (RP). EVIDENCE ACQUISITION: A bibliographic search was performed using Medline, Embase, and the Cochrane Library to identify studies comparing the survival outcomes of cN1 PCa patients treated with LT (RT or RP) with those who did not receive any form of LT (observation or androgen deprivation therapy alone). The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) recommendations were followed. Survival outcomes of the addition of LT were assessed using a random-effect model. EVIDENCE SYNTHESIS: A total of 8522 patients across eight studies were included. LT significantly improved overall survival (OS) across all time points from 2 to 10 yr compared with patients without LT, most notably providing a durable benefit in 10-yr OS (odds ratio [OR]: 1.49, 95% confidence interval [CI] 1.06-2.10). Both RT and RP were associated with benefits to both OS and recurrence-free survival, with no significant difference in OS between both modalities in medium-term follow-up (4-yr OR: 0.76, 95% CI 0.41-1.40, p = 0.19). CONCLUSIONS: Regardless of modality, the use of LT in cN1 patients improved OS. Future studies should aim to identify patients who could benefit from LT and include more comprehensive survival data including biochemical recurrence. PATIENT SUMMARY: In this study, we evaluated the outcomes of clinically lymph node-positive (cN1) prostate cancer (PCa) patients treated with local therapy (LT) and compared between different modalities of LT, including radiotherapy (RT) and radical prostatectomy (RP). We found that the addition of LT for cN1 PCa patients leads to a significant improvement in survival outcomes, most notably for overall survival, with no significant difference between RT and RP.

Delivery Strategies for Postpartum Care: A Systematic Review and Meta-analysis.

OBJECTIVE: To systematically review the effects of postpartum health care-delivery strategies on health care utilization and maternal outcomes. DATA SOURCES: We searched Medline, EMBASE, CENTRAL, CINAHL, and ClinicalTrials.gov for studies in the United States or Canada from inception to November 16, 2022. METHODS OF STUDY SELECTION: We used duplicate screening for studies comparing health care-delivery strategies for routine postpartum care on health care utilization and maternal outcomes. We selected health care utilization, clinical, and harm outcomes prioritized by stakeholder panels. TABULATION, INTEGRATION, AND RESULTS: We found 64 eligible studies (50 randomized controlled trials, 14 nonrandomized comparative studies; N=543,480). For general postpartum care, care location (clinic, at home, by telephone) did not affect depression or anxiety symptoms (low strength of evidence), and care integration (by multiple types of health care professionals) did not affect depression symptoms or substance use (low strength of evidence). Providing contraceptive care earlier (compared with later) was associated with greater implant use at 6 months (summary effect size 1.36, 95% CI 1.13-1.64) (moderate strength of evidence). Location of breastfeeding care did not affect hospitalization, other unplanned care utilization, or mental health symptoms (all low strength of evidence). Peer support was associated with higher rates of any or exclusive breastfeeding at 1 month and any breastfeeding at 3-6 months (summary effect size 1.10-1.22) but not other breastfeeding measures (all moderate strength of evidence). Care by a lactation consultant was associated with higher breastfeeding rates at 6 months (summary effect size 1.43, 95% CI 1.07-1.91) but not exclusive breastfeeding (all moderate strength of evidence). Use and nonuse of information technology for breastfeeding care were associated with comparable rates of breastfeeding (moderate strength of evidence). Testing reminders for screening or preventive care were associated with greater adherence to oral glucose tolerance testing but not random glucose or hemoglobin A 1c testing (moderate strength of evidence). CONCLUSION: Various strategies have been shown to improve some aspects of postpartum care, but future research is needed on the most effective care delivery strategies to improve postpartum health. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42022309756 .

Intensive sampling of the umbra and penumbra improves clinically significant prostate cancer detection and reduces risk of grade group upgrading at radical prostatectomy.

PURPOSE: Our objective is to evaluate the clinically significant prostate cancer detection rate of overlapping and perilesional systematic biopsy cores and its impact on grade group (GG) concordance at prostatectomy. MATERIALS AND METHODS: Biopsy maps of those undergoing MRI-targeted (TB) and systematic biopsy (SB) were reviewed to reclassify systematic cores. Perilesional (PL) cores were defined as adjacent cores within 10 mm of the target lesion ("penumbra") whilst overlap (OL) cores were defined as cores within the ROI itself ("umbra"). All other cores were designated as distant cores (DC). The incremental csPCa detection rate (GG ≥ 2) and the rate of GG upgrading on prostatectomy as OL, PL and DC sequentially added to TB were determined. RESULTS: Out of the 398 patients included, the median number of OL and PL cores was 5 (IQR 4-7) and 5 (IQR 3-6) respectively. OL cores detected more csPCa than PL cores (31 vs 16%, p < 0.001). OL and PL cores improved the csPCa detection rate of TB from 34 to 39% (p < 0.001) and 37% (p = 0.001) respectively. TB+OL+PL had greater csPCa detection compared to just TB+OL (41 vs 39%, p = 0.016) and TB+PL (41 vs 37%, p < 0.001). Of the 104 patients who underwent prostatectomy, GG upgrading rate for TB+OL+PL was lower compared to TB (21 vs 36%, p < 0.001) and was not significantly different compared to TB+OL+PL+DC (21 vs 19%, p = 0.500). CONCLUSION: A biopsy strategy incorporating both intensive sampling of the umbra and penumbra improved csPCa detection and reduced risk of GG upgrading at prostatectomy.