Natural History of Nonmetastatic Prostate Cancer Managed With Watchful Waiting.

Importance: It is uncertain to what extent watchful waiting (WW) in men with nonmetastatic prostate cancer (PCa) and a life expectancy of less than 10 years is associated with adverse consequences. Objective: To report transitions to androgen deprivation therapy (ADT), castration-resistant prostate cancer (CRPC), death from PCa, or death from other causes in men treated with a WW strategy. Design, Setting, and Participants: This nationwide, population-based cohort study included men with nonmetastatic PCa diagnosed since 2007 and registered in the National Prostate Cancer Register of Sweden with WW as the primary treatment strategy and with life expectancy less than 10 years. Life expectancy was calculated based on age, the Charlson Comorbidity Index (CCI), and a drug comorbidity index. Observed state transition models complemented observed data to extend follow-up to more than 20 years. Analyses were performed between 2022 and 2023. Exposure: Nonmetastatic PCa. Main Outcomes and Measures: Transitions to ADT, CRPC, death from PCa, and death from other causes were measured using state transition modeling. Results: The sample included 5234 men (median [IQR] age at diagnosis, 81 [79-84] years). After 5 years, 954 men with low-risk PCa (66.2%) and 740 with high-risk PCa (36.1%) were still alive and not receiving ADT. At 10 years, the corresponding proportions were 25.5% (n = 367) and 10.4% (n = 213), respectively. After 10 years, 59 men with low-risk PCa (4.1%) and 221 with high-risk PCa (10.8%) had transitioned to CRPC. Ten years after diagnosis, 1330 deaths in the low-risk group (92.3%) and 1724 in the high-risk group (84.1%) were from causes other than PCa. Conclusions and Relevance: These findings suggest that the WW management strategy is appropriate for minimizing adverse consequences of PCa in men with a baseline life expectancy of less than 10 years.

Functional Outcomes After Localized Prostate Cancer Treatment.

Importance: Adverse outcomes associated with treatments for localized prostate cancer remain unclear. Objective: To compare rates of adverse functional outcomes between specific treatments for localized prostate cancer. Design, Setting, and Participants: An observational cohort study using data from 5 US Surveillance, Epidemiology, and End Results Program registries. Participants were treated for localized prostate cancer between 2011 and 2012. At baseline, 1877 had favorable-prognosis prostate cancer (defined as cT1-cT2bN0M0, prostate-specific antigen level <20 ng/mL, and grade group 1-2) and 568 had unfavorable-prognosis prostate cancer (defined as cT2cN0M0, prostate-specific antigen level of 20-50 ng/mL, or grade group 3-5). Follow-up data were collected by questionnaire through February 1, 2022. Exposures: Radical prostatectomy (n = 1043), external beam radiotherapy (n = 359), brachytherapy (n = 96), or active surveillance (n = 379) for favorable-prognosis disease and radical prostatectomy (n = 362) or external beam radiotherapy with androgen deprivation therapy (n = 206) for unfavorable-prognosis disease. Main Outcomes and Measures: Outcomes were patient-reported sexual, urinary, bowel, and hormone function measured using the 26-item Expanded Prostate Cancer Index Composite (range, 0-100; 100 = best). Associations of specific therapies with each outcome were estimated and compared at 10 years after treatment, adjusting for corresponding baseline scores, and patient and tumor characteristics. Minimum clinically important differences were 10 to 12 for sexual function, 6 to 9 for urinary incontinence, 5 to 7 for urinary irritation, and 4 to 6 for bowel and hormone function. Results: A total of 2445 patients with localized prostate cancer (median age, 64 years; 14% Black, 8% Hispanic) were included and followed up for a median of 9.5 years. Among 1877 patients with favorable prognosis, radical prostatectomy was associated with worse urinary incontinence (adjusted mean difference, -12.1 [95% CI, -16.2 to -8.0]), but not worse sexual function (adjusted mean difference, -7.2 [95% CI, -12.3 to -2.0]), compared with active surveillance. Among 568 patients with unfavorable prognosis, radical prostatectomy was associated with worse urinary incontinence (adjusted mean difference, -26.6 [95% CI, -35.0 to -18.2]), but not worse sexual function (adjusted mean difference, -1.4 [95% CI, -11.1 to 8.3), compared with external beam radiotherapy with androgen deprivation therapy. Among patients with unfavorable prognosis, external beam radiotherapy with androgen deprivation therapy was associated with worse bowel (adjusted mean difference, -4.9 [95% CI, -9.2 to -0.7]) and hormone (adjusted mean difference, -4.9 [95% CI, -9.5 to -0.3]) function compared with radical prostatectomy. Conclusions and Relevance: Among patients treated for localized prostate cancer, radical prostatectomy was associated with worse urinary incontinence but not worse sexual function at 10-year follow-up compared with radiotherapy or surveillance among people with more favorable prognosis and compared with radiotherapy for those with unfavorable prognosis. Among men with unfavorable-prognosis disease, external beam radiotherapy with androgen deprivation therapy was associated with worse bowel and hormone function at 10-year follow-up compared with radical prostatectomy.

Thyroid lobectomy as a cost-effective approach in low-risk papillary thyroid cancer versus active surveillance.

BACKGROUND: An ongoing debate exists over the optimal management of low-risk papillary thyroid cancer. The American Thyroid Association supports the concept of active surveillance to manage low-risk papillary thyroid cancer; however, the cost-effectiveness of active surveillance has not yet been established. We sought to perform a cost-effectiveness analysis comparing active surveillance versus surgical intervention for patients in the United States. METHODS: A Markov decision tree model was developed to compare active surveillance and thyroid lobectomy. Our reference case is a 40-year-old female who was diagnosed with unifocal (<15 mm), low-risk papillary thyroid cancer. Probabilistic outcomes, costs, and health utilities were determined using an extensive literature review. The willingness-to-pay threshold was set at $50,000/quality-adjusted life year gained. Sensitivity analyses were performed to account for uncertainty in the model's variables. RESULTS: Lobectomy provided a final effectiveness of 21.7/quality-adjusted life years, compared with 17.3/quality-adjusted life years for active surveillance. Furthermore, incremental cost effectiveness ratio for lobectomy versus active surveillance was $19,560/quality-adjusted life year (

Delayed radical prostatectomy after a period of active surveillance is not associated with the use of secondary treatments compared with immediate prostatectomy.

BACKGROUND: We evaluated the use of secondary treatments in men with grade group (GG) 1 PC following a period of active surveillance (AS) compared with men undergoing immediate radical prostatectomy (RP) to evaluate what is potentially lost in terms of cancer control, if a patient trials AS and transitions to treatment. METHODS: We reviewed the Michigan Urological Surgery Improvement Collaborative (MUSIC) registry for men with GG1 PC undergoing RP from April 2012 to July 2018. Men were classified into groups based on time from diagnosis to RP: immediate (surgery within 1 year of diagnosis) and delayed RP (surgery >1 year after initiation of AS). Time to secondary treatment was estimated using Kaplan-Meier curves and compared using the log-rank test. A multivariable Cox proportional hazards model was fit to assess the association between timing of RP and use of secondary treatments. A chi-squared test was used to assess the association between delayed RP and adverse pathology. RESULTS: We identified 1878 men that underwent an RP during the study period, of which 1489 (79%) underwent immediate RP and 389 (21%) underwent delayed RP. The incidence of adverse pathology was higher in men with delayed versus immediate RP (49% vs. 36%, p < 0.0001, respectively). However, we noted only a small absolute difference in the estimated 24-month secondary treatment-free probability between men with delayed versus immediate RP (93% and 96%, respectively). On multivariable analysis, delayed RP was associated with increased use of secondary treatments (hazard ratio = 1.94, 95% confidence interval = 1.23-3.06, p = 0.004). CONCLUSIONS: The use of secondary treatment after RP in men with GG1 PC undergoing immediate or delayed prostatectomy was rare. These data suggest that the burden of treatment is near equivalent in patients who progress to treatment on AS compared with those who underwent immediate RP.

Observational management of penetrating occult pneumothoraces: Outcomes and risk factors for interval tube thoracostomy placement.

BACKGROUND: Guidelines for penetrating occult pneumothoraces (OPTXs) are based on blunt injury. Further understanding of penetrating OPTX pathophysiology is needed. In observational management of penetrating OPTX, we hypothesized that specific clinical and radiographic features may be associated with interval tube thoracostomy (TT) placement. Our aims were to (1) describe OPTX occurrence in penetrating chest injury, (2) determine the rate of interval TT placement in observational management and clinical outcomes compared with immediate TT placement, and (3) describe risk factors associated with failure of observational management. METHODS: Penetrating OPTX patients presenting to our level 1 trauma center from 2004 to 2019 were reviewed. Occult pneumothorax was defined as a pneumothorax on chest computed tomography but not on chest radiograph. Patient groups included immediate TT placement versus observation. Clinical outcomes compared were TT duration and complications, need for additional thoracic procedures, length of stay (LOS), and disposition. Clinical and radiographic factors associated with interval TT placement were determined by multivariable regression. RESULTS: Of 629 penetrating pneumothorax patients, 103 (16%) presented with OPTX. Thirty-eight patients underwent immediate TT placement, and 65 were observed. Twelve observed patients (18%) needed interval TT placement. Regardless of initial management strategy, TT placement was associated with longer LOS and more chest radiographs. Chest injury complications and outcomes were similar. Factors associated with increased odds of interval TT placement included Chest Abbreviated Injury Scale score of ≥4 (adjusted odds ratio [aOR], 7.38 [95% confidence interval, 1.43-37.95), positive pressure ventilation (aOR, 7.74 [1.07-56.06]), concurrent hemothorax (aOR, 6.17 [1.08-35.24]), and retained bullet fragment (aOR, 11.62 [1.40-96.62]) (all p < 0.05). CONCLUSION: The majority of patients with penetrating OPTX can be successfully observed with improved clinical outcomes (LOS, avoidance of TT complications, reduced radiation). Interval TT intervention was not associated with risk for adverse outcomes. In patients undergoing observation, specific clinical factors (chest injury severity, ventilation) and imaging features (hemothorax, retained bullet) are associated with increased odds for interval TT placement, suggesting need for heightened awareness in these patients. LEVEL OF EVIDENCE: Prognostic, level IV.

Reproductive outcome after early miscarriage: comparing vaginal misoprostol treatment with expectant management in a planned secondary analysis of a randomized controlled trial.

OBJECTIVE: To compare the reproductive outcome after early miscarriage between women managed expectantly and those treated with vaginal misoprostol. METHODS: This study was a planned secondary analysis of data collected prospectively in a randomized controlled trial comparing expectant management with vaginal misoprostol treatment (single dose of 800 µg) in women with early embryonic or anembryonic miscarriage and vaginal bleeding. The outcome measures were the number of women with a clinical pregnancy conceived within 14 months after complete miscarriage and the outcome of these pregnancies in terms of live birth, miscarriage, ectopic pregnancy and legal termination of pregnancy. The participants replied to a questionnaire sent by post covering their reproductive history ≤ 14 months after the index miscarriage was complete. Supplementary information and data for women who did not return their questionnaire were retrieved from medical records. RESULTS: Of 94 women randomized to misoprostol treatment and 95 allocated to expectant management, 94 and 90 women, respectively, were included for analysis. Information on reproductive outcome was available for 89/94 (95%) and 83/90 (92%) women, respectively. Complete miscarriage without surgical evacuation was achieved within 31 days in 85% (76/89) of the women in the misoprostol group and in 65% (54/83) of those managed expectantly. The proportion of women treated with surgical evacuation was 33% (27/83) in the expectant-management group vs 12% (11/89) in the misoprostol group. At 14 months after the index miscarriage was complete, 75% (67/89) of women treated with misoprostol and 75% (62/83) of those managed expectantly had achieved at least one clinical pregnancy, while 40% (36/89) and 35% (29/83), respectively, had had at least one live birth (mean difference, 5.5% (95% CI, -9.7 to 20.3%)). When considering the outcome of all pregnancies conceived within 14 months after the index miscarriage was complete, 63% (56/89) of women in the misoprostol group and 55% (46/83) of those in the expectant-management group delivered a live baby after a pregnancy (mean difference, 7.5% (95% CI, -7.9 to 22.4%)). CONCLUSION: Women with early miscarriage can be reassured that fertility is similar after misoprostol treatment and expectant management. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Management and outcome of metastatic pheochromocytomas/paragangliomas: a monocentric experience.

BACKGROUND: Pheochromocytoma (PHEO) and paraganglioma (PGL) are rare neuroendocrine tumors releasing catecholamines. Metastatic pheochromocytomas/paragangliomas (PPGLs) occur in about 5-26% of cases. To date, the management of patients affected by metastatic disease is a challenge in the absence of guidelines. AIM: The aim of this study was to evaluate the overall survival (OS) and the progression-free survival (PFS) in metastatic PPGLs. METHODS: Clinical data of 20 patients referred to the Careggi University Hospital (Florence, Italy) were retrospectively collected. Follow-up ranged from 1989 to 2019. Site and size of primary tumor, biochemical activity, genetic analysis and employed therapies were considered. Data were analyzed with SPSS version 27. RESULTS: Nine PHEOs (45%) and 11 PGLs (55%) were enrolled. Median age at diagnosis was 43.5 years [30-55]. Mean follow-up was 104.6 ± 89.3 months. Catecholamines were released in 70% of cases. An inherited disease was reported in 50% of patients. OS from the initial diagnosis (OSpt) and from the metastatic appearance (OSmtx) were lower in older patients (OSpt p = 0.028; OSmtx p < 0.001), abdominal PGLs (OSpt p = 0.007; OSmtx p = 0.041), larger tumors (OSpt p = 0.008; OSmtx p = 0.025) and sporadic disease (OSpt p = 0.013; OSmtx p = 0.008). CONCLUSION: Our data showed that older age at the initial diagnosis, sympathetic extra-adrenal localization, larger tumors and wild-type neoplasms are related to worse prognosis. Notably, the employed therapies do not seem to influence the survival of our patients. At present, effective treatments for metastatic PPGLs are missing and a multidisciplinary approach is indispensably required.

Elective neck dissection improves the survival of patients with T2N0M0 oral squamous cell carcinoma: a study of the SEER database.

BACKGROUND: Treatment of clinical N0 neck tumours is controversial in early-stage oral squamous cell carcinoma (OSCC), possibly because T1N0M0 and T2N0M0 merge together at early stages. The purposes of this study were to compare survival outcomes only for T2N0M0 cases based upon treatment elective neck dissection versus neck observation. METHODS: T2N0M0 OSCC cases were identified in the Surveillance, Epidemiology, and End Results database of the United States National Cancer Institute between 2004 and 2015. Survival curves for different variable values were generated using Kaplan-Meier estimates and compared using the log-rank test. Variables that achieved significance at P < 0.05 were entered into multivariable analyses via the Cox proportional hazards multivariate regression. RESULTS: A total of 2857 patients were selected, and 2313 cases were available for disease specific survival (DSS). The 5-year and 10-year overall survival (OS) were 66.7 and 46% for patients receiving elective neck dissection (END), respectively, and 56.4 and 37.2% for patients with neck observation (P < 0.0001). The 5-year and 10-year DSS were 73.6 and 64% for the END group, respectively, versus 64.5 and 54.5% for the neck observation group (P < 0.0001). More importantly, performing END was independently associated with favourable DSS and OS for patients with T2N0M0 OSCC [hazard ratio (HR) = 0.769, P = 0.0069 for DSS; HR = 0.829, P = 0.0031 for OS, neck observation group as reference] according to multivariate survival analysis. CONCLUSION: END is recommended for T2N0M0 OSCC cases and it is associated with improved DSS and OS.

Factors influencing perinatal outcomes in women with preterm preeclampsia: A secondary analysis of the PHOENIX trial.

This secondary analysis of the PHOENIX trial (evaluating planned delivery against expectant management in late preterm preeclampsia) demonstrates that in women who started induction of labour, 63% of women delivered vaginally (56% at 34 weeks' gestation). Compared to expectant management, planned delivery was associated with higher rates of neonatal unit admission for prematurity (but lower proportions of small-for-gestational age infants); length of neonatal unit stay and neonatal morbidity (including respiratory support) were similar across both intervention groups at all gestational windows. Neonatal unit admission was increased by earlier gestation at delivery, development of severe preeclampsia, and being small-for-gestational age.

Inhibition of WEE1 Is Effective in TP53- and RAS-Mutant Metastatic Colorectal Cancer: A Randomized Trial (FOCUS4-C) Comparing Adavosertib (AZD1775) With Active Monitoring.

PURPOSE: Outcomes in RAS-mutant metastatic colorectal cancer (mCRC) remain poor and patients have limited therapeutic options. Adavosertib is the first small-molecule inhibitor of WEE1 kinase. We hypothesized that aberrations in DNA replication seen in mCRC with both RAS and TP53 mutations would sensitize tumors to WEE1 inhibition. METHODS: Patients with newly diagnosed mCRC were registered into FOCUS4 and tested for TP53 and RAS mutations. Those with both mutations who were stable or responding after 16 weeks of chemotherapy were randomly assigned 2:1 between adavosertib and active monitoring (AM). Adavosertib (250 mg or 300 mg) was taken orally once on days 1-5 and days 8-12 of a 3-week cycle. The primary outcome was progression-free survival (PFS), with a target hazard ratio (HR) of 0.5 and 80% power with a one-sided 0.025 significance level. RESULTS: FOCUS4-C was conducted between April 2017 and Mar 2020 during which time 718 patients were registered; 247 (34%) were RAS/TP53-mutant. Sixty-nine patients were randomly assigned from 25 UK hospitals (adavosertib = 44; AM = 25). Adavosertib was associated with a PFS improvement over AM (median 3.61 v 1.87 months; HR = 0.35; 95% CI, 0.18 to 0.68; P = .0022). Overall survival (OS) was not improved with adavosertib versus AM (median 14.0 v 12.8 months; HR = 0.92; 95% CI, 0.44 to 1.94; P = .93). In prespecified subgroup analysis, adavosertib activity was greater in left-sided tumors (HR = 0.24; 95% CI, 0.11 to 0.51), versus right-sided (HR = 1.02; 95% CI, 0.41 to 2.56; interaction P = .043). Adavosertib was well-tolerated; grade 3 toxicities were diarrhea (9%), nausea (5%), and neutropenia (7%). CONCLUSION: In this phase II randomized trial, adavosertib improved PFS compared with AM and demonstrates potential as a well-tolerated therapy for RAS/TP53-mutant mCRC. Further testing is required in this sizable population of unmet need.

Factors Associated with Time to Conversion from Active Surveillance to Treatment for Prostate Cancer in a Multi-Institutional Cohort.

PURPOSE: We examined the demographic and clinicopathological parameters associated with the time to convert from active surveillance to treatment among men with prostate cancer. MATERIALS AND METHODS: A multi-institutional cohort of 7,279 patients managed with active surveillance had data and biospecimens collected for germline genetic analyses. RESULTS: Of 6,775 men included in the analysis, 2,260 (33.4%) converted to treatment at a median followup of 6.7 years. Earlier conversion was associated with higher Gleason grade groups (GG2 vs GG1 adjusted hazard ratio [aHR] 1.57, 95% CI 1.36-1.82; ≥GG3 vs GG1 aHR 1.77, 95% CI 1.29-2.43), serum prostate specific antigen concentrations (aHR per 5 ng/ml increment 1.18, 95% CI 1.11-1.25), tumor stages (cT2 vs cT1 aHR 1.58, 95% CI 1.41-1.77; ≥cT3 vs cT1 aHR 4.36, 95% CI 3.19-5.96) and number of cancerous biopsy cores (3 vs 1-2 cores aHR 1.59, 95% CI 1.37-1.84; ≥4 vs 1-2 cores aHR 3.29, 95% CI 2.94-3.69), and younger age (age continuous per 5-year increase aHR 0.96, 95% CI 0.93-0.99). Patients with high-volume GG1 tumors had a shorter interval to conversion than those with low-volume GG1 tumors and behaved like the higher-risk patients. We found no significant association between the time to conversion and self-reported race or genetic ancestry. CONCLUSIONS: A shorter time to conversion from active surveillance to treatment was associated with higher-risk clinicopathological tumor features. Furthermore, patients with high-volume GG1 tumors behaved similarly to those with intermediate and high-risk tumors. An exploratory analysis of self-reported race and genetic ancestry revealed no association with the time to conversion.

Clinical impact of follow-up imaging on mortality in Korean breast cancer patients: A national cohort study.

BACKGROUND: As the incidence of breast cancer has increased and the survival rate has improved, supporting the optimal follow-up strategy has become an important issue. This study aimed to evaluate follow-up imaging usage after breast cancer surgery and the implications on mortality in Korea. METHODS: This study included 96,575 breast cancer patients diagnosed during 2002-2010 and registered in the Korea Central Cancer Registry, Statistics Korea, and Korean National Health Insurance Service. We evaluated the frequency of breast imaging (mammography and breast MRI) and systemic imaging for evaluating the presence of distant metastasis (chest CT, bone scan, and PET-CT), and performed analyses to determine if they had an effect on mortality. RESULTS: The median follow-up period was 72.9 months (range: 12.0-133.3) and 7.5% of the patients died. Among all patients, 54.7%, 16.2%, 45.6%, and 8.5% received 3 or more mammograms, chest CTs, bone scans, and PET-CTs within 3 years after surgery, respectively. Among patients who developed recurrence after 3 or more years, a comparison of overall mortality and breast-cancer specific mortality according to the frequency of imaging by modality (<3 vs. ≥3) showed that only mammography had significantly reduced mortality (hazard ratio [HR]: 0.72, 95% CI: 0.61-0.84, p < 0.0001; HR: 0.72, 95% CI: 0.61-0.84; p < 0.0001). CONCLUSIONS: This study showed that only frequent mammography reduced mortality and frequent imaging follow-up with other modalities did not when compared to less frequent imaging. This finding provides supportive evidence that clinicians need to adhere to the current guidelines for surveillance after breast cancer surgery.

Efficacy of risk-reducing salpingo-oophorectomy in BRCA1-2 variants and clinical outcomes of follow-up in patients with isolated serous tubal intraepithelial carcinoma (STIC).

OBJECTIVE: Serous tubal intraepithelial carcinoma (STIC) is currently considered the precursor lesion of pelvic high-grade serous carcinoma. The management of STIC diagnosed after risk-reducing salpingo-oophorectomy (RRSO) in women with BRCA1-2 variants remains unclear. The aim of our study was to evaluate the incidence of STIC, serous tubal intraepithelial lesions (STIL) and occult invasive cancer (OC) and to determine the long-term outcomes of these patients. METHODS: We conducted a retrospective study of patients with BRCA 1-2 variants who underwent RRSO between January-2010 and Dicember-2020 at the Clinic of Gynaecology of University of Padova. INCLUSION CRITERIA: women with a negative pelvic examination at the last screening prior to RRSO, patients with fallopian tubes analysed using the SEE-FIM protocol. EXCLUSION CRITERIA: patients with a positive gynaecologic screening or with ovarian/tubal cancer prior to RRSO. RESULTS: We included 153 patients. STICs were diagnosed in 4 patients (2.6%) and STILs in 6 patients (3.9%). None of the patients with STIC underwent restaging surgery or adjuvant chemotherapy; all patients were followed closely every 6 months. None of the patients developed primary peritoneal carcinomas (PPCs) with a median FUP of 54.5 months (15-106). OC was diagnosed in 3 patients (2%). All patients with OC underwent staging surgery, and one patient developed a peritoneal carcinoma (PC) after 18 months by staging surgery. CONCLUSION(S): The incidence of STIC, STIL and OC after RRSO in BRCA1-2 variants was low. Our results demonstrated that long-term close surveillance in patients diagnosed with STIC should be considered a possible management strategy.

Capecitabine Versus Active Monitoring in Stable or Responding Metastatic Colorectal Cancer After 16 Weeks of First-Line Therapy: Results of the Randomized FOCUS4-N Trial.

PURPOSE: Despite extensive randomized evidence supporting the use of treatment breaks in metastatic colorectal cancer (mCRC), they are not universally offered to patients despite improvements in quality of life without detriment to overall survival (OS). FOCUS4-N was set up to explore the impact of oral maintenance therapy in patients who are responding to first-line therapy. METHODS: FOCUS4 was a molecularly stratified trial program that registered patients with newly diagnosed mCRC. The FOCUS4-N trial was offered to patients in whom a targeted subtrial was unavailable or biomarker tests failed. Patients were randomly assigned using a 1:1 ratio between maintenance capecitabine and active monitoring (AM). The primary outcome was progression-free survival (PFS) with secondary outcomes including OS toxicity and tolerability. RESULTS: Between March 2014 and March 2020, 254 patients were randomly assigned (127 to capecitabine and 127 to AM) across 88 UK sites. Baseline characteristics were balanced. There was strong evidence of efficacy for PFS (hazard ratio = 0.40; 95% CI, 0.21 to 0.75; P < .0001), but no significant improvement in OS (hazard ratio, 0.93; 95% CI, 0.69 to 1.27; P = .66) was observed. Compliance with treatment was good, and toxicity from capecitabine versus AM was as expected with grade ≥ 2 fatigue (25% v 12%), diarrhea (23% v 13%), and hand-foot syndrome (26% v 3%). Quality of life showed little difference between the groups. CONCLUSION: Despite strong evidence of disease control with maintenance therapy, OS remains unaffected and FOCUS4-N provides additional evidence to support the use of treatment breaks as safe management alternatives for patients who are stable or responding to first-line treatment for mCRC. Capecitabine without bevacizumab may be used to extend PFS in the interval after 16 weeks of first-line therapy.

Demographic, clinical, and functional determinants of antithrombotic treatment in patients with nonvalvular atrial fibrillation.

BACKGROUND: This study assessed the sociodemographic, functional, and clinical determinants of antithrombotic treatment in patients with nonvalvular atrial fibrillation (NVAF) attended in the internal medicine setting. METHODS: A multicenter, cross-sectional study was conducted in NVAF patients who attended internal medicine departments for either a routine visit (outpatients) or hospitalization (inpatients). RESULTS: A total of 961 patients were evaluated. Their antithrombotic management included: no treatment (4.7%), vitamin K antagonists (VKAs) (59.6%), direct oral anticoagulants (DOACs) (21.6%), antiplatelets (6.6%), and antiplatelets plus anticoagulants (7.5%). Permanent NVAF and congestive heart failure were associated with preferential use of oral anticoagulation over antiplatelets, while intermediate-to high-mortality risk according to the PROFUND index was associated with a higher likelihood of using antiplatelet therapy instead of oral anticoagulation. Longer disease duration and institutionalization were identified as determinants of VKA use over DOACs. Female gender, higher education, and having suffered a stroke determined a preferential use of DOACs. CONCLUSIONS: This real-world study showed that most elderly NVAF patients received oral anticoagulation, mainly VKAs, while DOACs remained underused. Antiplatelets were still offered to a proportion of patients. Longer duration of NVAF and institutionalization were identified as determinants of VKA use over DOACs. A poor prognosis according to the PROFUND index was identified as a factor preventing the use of oral anticoagulation.

Factors Associated with Discontinuation of Active Surveillance among Men with Low-Risk Prostate Cancer: A Population-Based Study.

PURPOSE: The purpose of this study was to describe the uptake, discontinuation and variation of active surveillance (AS) by provider and patient level characteristics. MATERIALS AND METHODS: This observational, population-based study used linked administrative databases and pathology reports to identify all men diagnosed with Gleason score ≤6 prostate cancer (PC) between January 1, 2008 and December 31, 2014 in Ontario, Canada. The Cochran-Armitage test was used for AS trend over time. Treatment-free survival was estimated using cumulative incidence function. Factors associated with discontinuation of AS were evaluated using Cox proportional hazard models. RESULTS: Active surveillance was the initial management strategy for 8,541 cases (51%). Use of AS significantly increased from 38% in 2008 to 69% in 2014 (p=0.001). Men on AS were significantly older (64 years, SD 8.0) than those on initial treatment (62 years, SD 7.7; p=0.001). After a median followup of 48 months, 4,337 (51%) patients had discontinued AS. Treatment-free survival for AS patients at 1, 3, and 5 years were 85%, 58% and 52%, respectively. Median time to definitive treatment after initial AS was 16 months (IQR 11-25 months). Factors associated with AS discontinuation were younger age at diagnosis, year of diagnosis, higher comorbidities, treatment at academic center, treatment by physician and institution in the highest volume tertile, and adverse cancer-specific characteristics (higher prostate specific antigen [PSA], higher number of positive cores and higher percentage of core involvement at diagnosis). CONCLUSIONS: Although the uptake of AS significantly increased over time, there has been a relatively high rate of discontinuation over 5 years. Factors associated with transition to definitive treatment were younger age, care provided by higher volume physicians and institutions, higher PSA and greater PC volume at diagnosis. These results may help guide policy making, developing quality indicators, and developing targeted continued education for physician and patients embarking on AS to establish realistic expectations.

Active Surveillance in Prostate Cancer: Role of Available Biomarkers in Daily Practice.

Prostate cancer (PCa) is the most commonly diagnosed cancer in men. The diagnosis is currently based on PSA levels, which are associated with overdiagnosis and overtreatment. Moreover, most PCas are localized tumours; hence, many patients with low-/very low-risk PCa could benefit from active surveillance (AS) programs instead of more aggressive, active treatments. Heterogeneity within inclusion criteria and follow-up strategies are the main controversial issues that AS presently faces. Many biomarkers are currently under investigation in this setting; however, none has yet demonstrated enough diagnostic ability as an independent predictor of pathological or clinical progression. This work aims to review the currently available literature on tissue, blood and urine biomarkers validated in clinical practice for the management of AS patients.

Active Surveillance for Biopsy Proven Renal Oncocytomas: Outcomes and Feasibility.

OBJECTIVES: To report the outcomes and feasibility of active surveillance (AS) of biopsy-proven renal oncocytomas. METHODS: Multicentric retrospective study (2010-2016) in 6 academic centers that included patients with biopsy-proven renal oncocytomas who were allocated to AS (imperative or elective indication) with a follow-up ≥1 year. Imaging was performed at least once a year, by CT-scan or ultrasound or MRI. Conversion to active treatment (surgical excision or ablative treatment) was at the discretion of the urologist. The primary endpoint was renal tumor growth (cm/year). Secondary outcomes included accuracy of biopsy, incidence, and reason to change AS to active treatment. RESULTS: Eighty-nine patients were included: Median age 67 years (26-89) and median tumor size 26 mm [15-90] on diagnosis. During a mean follow-up of 43 months'' (median 36 [12-180]), mean tumor growth was 0.24 cm/year. No predictive factors (demographical, radiological or histologic) of tumor growth could be identified. Conversion from AS to active treatment occurred in 24 patients (27%) (13 surgical excisions, 11 ablative procedures), in a median time of 45 (12-76) months'' after diagnosis. Tumor growth was the main indication to convert AS to active treatment (58%) with 8% of the patients opting to discontinue AS. No patient had metastatic progression nor disease-specific death. The correlation between biopsy and surgical specimen was 92%. CONCLUSION: Active surveillance for biopsy-proven renal oncocytomas was oncologically safe and patient adherence was high. No predictive factor for tumor growth could be identified but the tumor growth rate was low, and biopsy efficacy was high.

Proceedings of the Canadian Thyroid Cancer Active Surveillance Study Group 2019 national investigator meeting.

Active surveillance (AS) in the management of small, low risk papillary thyroid cancer (PTC) as an alternative option to thyroidectomy, is an area of active research. A national Canadian study is proposed to evaluate the long-term outcomes of patients with small, low risk PTC who choose AS or surgery. This letter describes the proceedings of a national investigator meeting to plan the study.

The Risk of Prostate Cancer Progression in Active Surveillance Patients with Bilateral Disease Detected by Combined Magnetic Resonance Imaging-Fusion and Systematic Biopsy.

PURPOSE: We sought to evaluate whether bilateral prostate cancer detected at active surveillance (AS) enrollment is associated with progression to Grade Group (GG) ≥2 and to compare the efficacy of combined targeted biopsy plus systematic biopsy (Cbx) vs systematic biopsy (Sbx) or targeted biopsy alone to detect bilateral disease. MATERIALS AND METHODS: A prospectively maintained database of patients referred to our institution from 2007-2020 was queried. The study cohort included all AS patients with GG1 on confirmatory Cbx and followup of at least 1 year. Cox proportional hazard analysis identified baseline characteristics associated with progression to ≥GG2 at any point throughout followup. RESULTS: Of 579 patients referred, 103 patients had GG1 on Cbx and were included in the study; 49/103 (47.6%) patients progressed to ≥GG2, with 30/72 (41.7%) patients with unilateral disease progressing and 19/31 (61.3%) patients with bilateral disease progressing. Median time to progression was 68 months vs 52 months for unilateral and bilateral disease, respectively (p=0.006). Both prostate specific antigen density (HR 1.72, p=0.005) and presence of bilateral disease (HR 2.21, p=0.012) on confirmatory biopsy were associated with AS progression. At time of progression, GG and risk group were significantly higher in patients with bilateral versus unilateral disease. Cbx detected 16% more patients with bilateral disease than Sbx alone. CONCLUSIONS: Bilateral disease and prostate specific antigen density at confirmatory Cbx conferred greater risk of earlier AS progression. Cbx was superior to Sbx for identifying bilateral disease. AS risk-stratification protocols may benefit from including presence of bilateral disease and should use Cbx to detect bilateral disease.