Lifetime Health and Economic Outcomes of Biparametric Magnetic Resonance Imaging as First-Line Screening for Prostate Cancer : A Decision Model Analysis.

BACKGROUND: Contemporary prostate cancer (PCa) screening uses first-line prostate-specific antigen (PSA) testing, possibly followed by multiparametric magnetic resonance imaging (mpMRI) for men with elevated PSA levels. First-line biparametric MRI (bpMRI) screening has been proposed as an alternative. OBJECTIVE: To evaluate the comparative effectiveness and cost-effectiveness of first-line bpMRI versus PSA-based screening. DESIGN: Decision analysis using a microsimulation model. DATA SOURCES: Surveillance, Epidemiology, and End Results database; randomized trials. TARGET POPULATION: U.S. men aged 55 years with no prior screening or PCa diagnosis. TIME HORIZON: Lifetime. PERSPECTIVE: U.S. health care system. INTERVENTION: Biennial screening to age 69 years using first-line PSA testing (test-positive threshold, 4 µg/L) with or without second-line mpMRI or first-line bpMRI (test-positive threshold, PI-RADS [Prostate Imaging Reporting and Data System] 3 to 5 or 4 to 5), followed by biopsy guided by MRI or MRI plus transrectal ultrasonography. OUTCOME MEASURES: Screening tests, biopsies, diagnoses, overdiagnoses, treatments, PCa deaths, quality-adjusted and unadjusted life-years saved, and costs. RESULTS OF BASE-CASE ANALYSIS: For 1000 men, first-line bpMRI versus first-line PSA testing prevented 2 to 3 PCa deaths and added 10 to 30 life-years (4 to 11 days per person) but increased the number of biopsies by 1506 to 4174 and the number of overdiagnoses by 38 to 124 depending on the biopsy imaging scheme. At conventional cost-effectiveness thresholds, first-line PSA testing with mpMRI followed by either biopsy approach for PI-RADS 4 to 5 produced the greatest net monetary benefits. RESULTS OF SENSITIVITY ANALYSIS: First-line PSA testing remained more cost-effective even if bpMRI was free, all men with low-risk PCa underwent surveillance, or screening was quadrennial. LIMITATION: Performance of first-line bpMRI was based on second-line mpMRI data. CONCLUSION: Decision analysis suggests that comparative effectiveness and cost-effectiveness of PCa screening are driven by false-positive results and overdiagnoses, favoring first-line PSA testing with mpMRI over first-line bpMRI. PRIMARY FUNDING SOURCE: National Cancer Institute.

Safety and Efficacy of Inpatient Infliximab Rescue Therapy for Acute Crohn's Disease Flares.

PURPOSE: Describe the safety, complications, and need for urgent surgery in patients requiring inpatient rescue infliximab for acute Crohn's disease (CD) flare. BACKGROUND: Infliximab is increasingly used for patients hospitalized with acute severe ulcerative colitis as rescue therapy; however, optimal management for patients hospitalized for CD flares remains unclear. METHODS: A single-institution retrospective study of patients aged 18+ admitted from 2008 to 2020 with acute Crohn's flare requiring induction of rescue infliximab therapy. Outcomes included postoperative and medication-related complications and need for urgent surgery. RESULTS: 52 patients were included in analysis; 8% required surgery on index admission, and 19% required surgery within 90 days of infliximab. Postoperative complications included 1 anastomotic leak, 3 superficial wound infections, 3 prolonged ileus, and 1 urinary infection. There were no adverse reactions to infliximab infusion, and medical complication rates were low. Patients with penetrating disease were more likely to undergo surgery within 90 days of infliximab (43% vs 8%; P = .01). Mean LOS was longer for patients undergoing surgery within 90 days of therapy compared to those who did not (13.4 vs 8.3 days, P = .04). CONCLUSION: Inpatient rescue infliximab is safe for treating acute Crohn's disease flare in addition to standard steroid therapy. The majority of patients hospitalized with Crohn's flare requiring rescue infliximab avoided surgery with low postoperative and medication-related complications. More research is needed to clarify the optimal rescue infliximab therapy dosage.

The association of patient and disease characteristics with the overtreatment of low-risk prostate cancer from 2010 to 2016.

BACKGROUND: Although active surveillance is the preferred management for low-risk prostate cancer (PCa), some men remain at risk of overtreatment with definitive local therapy. We hypothesized that baseline characteristics may be associated with overtreatment and represent a potential source of health disparities. We therefore examined the associations of patient and disease characteristics with the surgical overtreatment of low-risk PCa. METHODS: We identified men aged 45-75 years with cT1 cN0 cM0 prostate adenocarcinoma with biopsy Gleason score 6 and PSA < 10 ng/ml from 2010-2016 in the National Cancer Database (NCDB) and who underwent radical prostatectomy (RP). We evaluated the associations of baseline characteristics with clinically insignificant PCa (iPCa) at RP (i.e., "overtreatment"), defined as organ-confined (i.e., pT2) Gleason 3 + 3 disease, using multivariable logistic regression. RESULTS: We identified 36,088 men with low-risk PCa who underwent RP. The unadjusted rate of iPCa decreased during the study period, from 54.7% in 2010 to 40.0% in 2016. In multivariable analyses adjusting for baseline characteristics, older age (OR 0.98, 95% CI 0.97-0.98), later year of diagnosis (OR 0.62, 95% CI 0.57-0.67 for 2016 vs. 2010), Black race (OR 0.85, 95% CI 0.79-0.91), treatment at an academic/research program (OR 0.82, 95% CI 0.73-0.91), higher PSA (OR 0.91, 95% CI 0.90-0.92), and higher number of positive biopsy cores (OR 0.87, 95% CI 0.86-0.88) were independently associated with a lower risk of overtreatment (iPCa) at RP. Conversely, a greater number of biopsy cores sampled (OR 1.01, 95% CI 1.01-1.02) was independently associated with an increased risk of overtreatment (iPCa) at RP. CONCLUSIONS: We observed an ~27% reduction in rates of overtreatment of men with low-risk PCa over the study period. Several patient, disease, and structural characteristics are associated with detection of iPCa at RP and can inform the management of men with low-risk PCa to reduce potential overtreatment.

The Association of a Peritoneal Interposition Flap With Lymphocele Formation After Pelvic Lymph Node Dissection During Robotic-assisted Laparoscopic Radical Prostatectomy: A Systematic Review and Meta-analysis.

OBJECTIVE: To conduct a systematic review and meta-analysis to evaluate the association of a peritoneal interposition flap (PIF) with lymphocele formation following robotic-assisted laparoscopic radical prostatectomy (RALP) with pelvic lymph node dissection. METHODS: We conducted a systematic search of MEDLINE, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials through August 30, 2023, to identify randomized and nonrandomized studies comparing RALP with pelvic lymph node dissection with and without PIF. A random effects meta-analysis was then performed to evaluate the associations of PIF with 90-day postoperative outcomes. RESULTS: Five randomized controlled trials (RCTs) and four observational studies, including a total of 2941 patients, were included. The use of PIF was associated with a reduced risk of 90-day symptomatic lymphocele formation after RALP when examining only RCTs (pooled odds ratios [OR] 0.44, 95% CI 0.28-0.69; I2 =3%) and both RCTs and observational studies (OR 0.35, 95% CI 0.22-0.56; I2 =17%). Similarly, use of PIF was associated with a reduced risk of 90-day any lymphocele formation (OR 0.40, 95% CI 0.28-0.56, I2 =39%). There were no statistically significant differences in postoperative complications between the two groups (OR 0.89; 95% CI 0.69-1.14; I2 =20%). CONCLUSION: Use of the PIF is associated with an approximately 50% reduced risk of symptomatic and any lymphocele formation within 90-days of surgery, and it is not associated with an increase in postoperative complications.

How Can We Identify Extraprostatic Extension (EPE) Before Surgery? The Use of a Preoperative Prostate MRI EPE Scoring System to Assess Postprostatectomy Locally Advanced Prostate Cancer.

Background: Distinguishing between organ-confined disease and extraprostatic extension (EPE) is crucial for the treatment of patients with prostate cancer. EPE is associated with an increased risk of biochemical recurrence, positive surgical margins, and metastatic disease. An MRI-based EPE scoring system was developed by Mehralivand in 2019; however, it has not been adopted in the Urology community. The purpose of this study is to evaluate the association of MRI-based EPE scoring with the pathologic EPE (pEPE) after radical prostatectomy. Methods: We conducted a retrospective review on a prospectively collected database of male patients who underwent a prostate MRI with EPE scoring by a trained genitourinary radiologist and subsequent robotic radical prostatectomy at our institution from September 2020 to December 2022. The associations between MRI EPE (mEPE) score and the presence of EPE on surgical pathology (pEPE) were examined using multivariable logistic regression. Results: A total of 194 patients met inclusion criteria with a median age of 63 years and prostate specific antigen (PSA) 7 ng/mL. Among those with mEPE score 3, 96% had pEPE. Those patients with an mEPE score ≥2 had an increased risk of pEPE compared with those with mEPE score 0 (odds ratio 3.79; 95% confidence interval 1.28-11.3) Furthermore, those with an mEPE score 3 were significantly more likely to have pEPE compared with those with mEPE score 0, 1 and 2 independently. Conclusion: MRI EPE is a straightforward tool that strongly correlates with the presence of pEPE. If validated prospectively, this scoring system could assist in counseling patients regarding nerve-sparing approach.

Liposuction Complications in the Outpatient Setting: A National Analysis of 246,119 Cases in Accredited Ambulatory Surgery Facilities.

Background: Suction lipectomy (liposuction) is a popular cosmetic surgical procedure performed in the United States, but little has been documented regarding perioperative complications due to its outpatient nature. Objectives: This cross-sectional study aims to analyze the most common complications that accompany liposuction-related procedures and importantly estimate the total complication rate occurring at ambulatory surgical facilities. Methods: Adult patients who experienced liposuction-related complications from 2019 to 2021 were identified in the reporting database of the global surgery accreditation authority, the American Association for Accreditation of Ambulatory Surgery Facilities (QUAD A). Patients were then divided by complication type and procedure location. Demographics and facility-specific variables were analyzed. Descriptive statistics were performed. Results: Overall, 984 patients were included, with a mean age of 44 years (interquartile range [IQR] 37-53) and a median BMI of 28.7 kg/m2 (IQR 25.7-32.2). The overall confirmed complication rate was found to be 0.40% (984/246,119). Unplanned emergency department presentation was the most common complication overall (24%). Wound disruption was associated with the longest median procedure length (261 min), and venous thromboembolism was associated with the highest median BMI (30.1 kg/m2). The Southeast had the most complications (431), which accounted for 13/21 deaths (61.9%). Out of all complications, death was associated with the highest average annual case volume (241). Conclusions: Procedures that involve liposuction are associated with a variety of medical and surgical complications. Given the high frequency and variability in how liposuction is performed, a thorough assessment of complications is critical to improve the safety of this procedure.

Preoperative Workup of Patients With Excessive Central Airway Collapse: Does Stent Evaluation Serve a Role?

BACKGROUND: Tracheobronchoplasty (TBP) is a definitive anatomic intervention for patients with severe symptomatic expiratory central airway collapse. Although stent evaluations have been described for surgical workup, current literature does not address if improvement during stent evaluation is sustained after TBP. We compared health-related quality of life (HRQOL) and functional status responses after airway stenting to those post-TBP. METHODS: A retrospective review was performed in patients with severe expiratory central airway collapse who underwent stent evaluation followed by TBP from January 2004 to December 2019. Baseline, poststent, 3- and 12-month postoperative HRQOL scores, and functional status were analyzed with statistical tests as appropriate. RESULTS: One hundred twenty patients underwent a stent evaluation and TBP. Baseline and stent evaluation measurements were compared with statistically and clinically significant differences in the Cough Quality-of-life Questionnaire (CQLQ) (55 vs. 68, P <0.01), Modified Medical Research Council (mMRC) 0 to 2 (90% vs. 47%, P <0.01), 6-minute walk test (6MWT) (1301 ft vs. 1138 ft, P <0.01). Improvements in the HRQOL and functional status were maintained from stent evaluation to 3 months postoperatively [CQLQ 55 vs. 54, P =0.63; mMRC 0 to 2 (87% vs. 84%), P =0.39; 6MWT 1350 ft vs. 1314 ft, P =0.33], and 12 months postoperatively [CQLQ 54 vs. 54, P =0.91; mMRC 0 to 2 (95% vs. 86%), P =0.74; 6MWT 1409 ft vs. 1328 ft, P =0.13]. The magnitude of change between the data was not significantly different between the stent evaluation, 3-, and 12 months postoperative. Predicted forced expiratory volume in 1-second measurements at baseline, after stent placement, 3 months, and 12 months post-TBP were 74%, 79%, 73%, and 73%, respectively, and not clinically significant. CONCLUSIONS: Improvement after stent evaluation and the magnitude of improvement may be predictive of postoperative outcomes up to 1 year after surgery.

Magnetic resonance imaging accuracy in staging early and locally advanced rectal cancer.

INTRODUCTION: Magnetic Resonance Imaging (MRI) is the standard pretreatment staging in patients with rectal cancer. Accurate tumor staging is paramount to determining the appropriate treatment course for patients diagnosed with rectal cancer. The current study aims to re-evaluate the accuracy of pre-operative MRI in staging of both early and locally advanced rectal cancer following completion of neoadjuvant therapy (NAT) compared to the pathologic stage. METHODS: A retrospective review of patients treated for rectal cancer between 2015 and 2020 at a single academic institution. All patients underwent rectal cancer protocol MRIs before surgical resection. Analysis was carried out in two groups: early rectal cancer: T1/2 N0 tumors with upfront surgical resection (N = 40); and locally advanced disease: T3 or greater or N+ disease receiving NAT, with restaging MRI following NAT (n = 63). RESULTS: 103 patients were included in analysis. MRI accuracy in early tumors was 35% ICC = 0.52 (95% CI 0.25-0.71) T stage and 66% ICC = 0 (95% CI -0.24, 0.29) for 29 patients with nodal data for N stage. There was 28% understaging of T2 tumors and 34% understaging of N0 stage by MRI. Post NAT MRI had 44% accuracy ICC = 0.57 (95% CI -0.15-0.20) T stage and 60% accuracy ICC = 0.32 (95% CI 0.08-0.52) N stage. Tumor invasion was overstaged on MRI: 40% T2, 29% T3, 90% T4. Nodal inaccuracy was due to overstaging, 61% N1, 90% N2. CONCLUSIONS: In locally advanced rectal cancer MRI overstaged tumors, this could be due to the continued effect of NAT from MRI to resection. This overstaging is of little clinical significance as it doesn't alter the treatment plan, except in cases of complete clinical response. In early rectal cancer, MRI had limited accuracy compared to pathology, understaging a quarter of patients who would benefit from NAT before surgery. Other adjunct imaging modalities should be considered to improve accuracy in staging early rectal cancer and consideration of complete response and enrollment in watch and wait protocols.

Conditional survival following radical cystectomy for urothelial carcinoma of the bladder.

INTRODUCTION: Traditional surveillance protocols do not adequately account for the decreasing risk of mortality over time in aggressive malignancies, such as bladder cancer. Rather, the risk of death depends on both the baseline risk of mortality and the time survived since treatment. We therefore evaluated the conditional survival of patients diagnosed with urothelial carcinoma of the bladder (UCB) following radical cystectomy (RC). PATIENTS AND METHODS: We identified patients aged 18 to 75 with Charlson 0-1 and pTany pN0-3 cM0 UCB diagnosed from 2006 to 2015 in the National Cancer Database and treated with RC. The 2- and 5-year conditional overall survival (COS)-i.e., the probability of surviving an additional 2- or 5-years given a specified time survived since treatment-was estimated using the Kaplan-Meier method. Multivariable Cox regression models with landmark time analysis were used to evaluate the associations of baseline characteristics with OS over time. RESULTS: A total of 15,594 patients were included in the study. Median follow-up was 27.8 months. The 2- and 5-year COS for the overall cohort increased through 36 months follow-up and then plateaued. When stratified by pT and pN stage, the COS gain increased with higher pT and pN stage, demonstrating the greatest increase over time for patients with pTany N1-3 disease (5-year COS of 23% at baseline, 58% at 36-months, and 71% at 60-months). In multivariable Cox regression modeling, pT and pN stage were significantly associated with higher all-cause mortality at baseline (HR 3.27 for pT4, HR 2.57 for pT3 vs. ≤pT2; HR 2.26 for pN2-3, HR 1.77 for pN1 vs. pN0), but these associations were attenuated in magnitude with increasing landmark times of 36- and 60-months (HR 1.63 for pT4, HR 1.35 for pT3 vs. ≤pT2; HR 1.34 for pN2-3, HR 1.27 for pN1 vs. pN0). Our study is limited by the retrospective design and the lack of cancer-specific survival data. CONCLUSIONS: Risk of death after RC varies with time elapsed since treatment and disease stage. Accordingly, stage-specific COS may be used to improve prognostication and surveillance protocols.

Evaluation of the Effects of an Extubation Protocol With Neostigmine on Duration of Mechanical Ventilation After Cardiac Surgery.

OBJECTIVES: Residual neuromuscular blockade is associated with increased postoperative pulmonary complications. This study aimed to evaluate the effect of an extubation protocol incorporating neuromuscular blockade reversal (NMBR) by train-of-four monitoring on "fast-track" cardiac surgery outcomes. DESIGN: A retrospective cohort study. SETTING: At a university hospital. PARTICIPANTS: Out of 1,843 cardiac surgery patients, from February 2, 2015, to March 31, 2017, 957 (52%) underwent cardiac surgery on or after February 29, 2016. INTERVENTIONS: An extubation protocol, comprised of weaning from mechanical ventilation and NMBR guidelines, was implemented on February 29, 2016. MEASUREMENTS AND MAIN RESULTS: The associations of baseline characteristics with the postoperative duration of mechanical ventilation (primary outcome) and respiratory and/or adverse complications (secondary outcomes) were evaluated using regression and interrupted- time series models. The implementation of an extubation protocol was associated with an 18% decrease in the duration of mechanical ventilation (incident rate ratio [IRR] 0.82, 95% CI 0.72-0.94; p < 0.01), statistically insignificant 26% increase in patients extubated ≤6 hours (odds ratio [OR] 1.26, 95% CI 0.97-1.65; p = 0.09), and 13% shorter intensive care unit length of stay (LOS) (IRR 0.87, 95% CI 0.79-0.97; p < 0.01). Patients undergoing isolated coronary artery bypass graft or isolated valve procedures, on or after February 29, 2016, had decreased extubation times (IRR 0.82, p < 0.01 and IRR 0.80, p = 0.02). The protocol did not have a statistically significant association with hospital LOS (IRR 0.98, p = 0.57) or readmission (OR 1.22, p = 0.33), and differences in the occurrence of pulmonary complications and adverse outcomes between the pre- and postprotocol groups were clinically insignificant. CONCLUSIONS: The application of an extubation protocol incorporating NMBR based on neuromuscular monitoring was associated with a decrease in postoperative duration of mechanical ventilation and facilitated more patients meeting the early extubation benchmark without an increased risk of respiratory complications or adverse outcomes.

Delay in Surgery and Papillary Thyroid Cancer Survival in the United States: A SEER-Medicare Analysis.

INTRODUCTION: Delays in surgery and their impact on survival in papillary thyroid cancer (PTC) is unclear. We sought to investigate the association between time to surgery and survival in patients with PTC. METHODS: A total of 8170 Medicare beneficiaries with PTC who underwent thyroidectomy were identified within the Surveillance, Epidemiology, and End Results-Medicare linked data files between 1999 and 2018. Disease-specific survival (DSS) and overall survival (OS) were estimated using Kaplan-Meir analysis, and Cox proportional hazards models were specified to estimate the association between time to surgery and survival. RESULTS: Among 8170 patients with PTC, mean age 69.3 (SD+/- 11.4), 89.8% had surgery within the first 90 days, 7.8% had surgery 91 to 180 days from diagnosis, and 2.4% had surgery after 180 days. Increasing time to surgery was associated with increased mortality for OS in the >180-day group [adjusted hazard ratio (aHR) 1.24; 95% CI, 1.01-1.53]. Moreover, on stratification by summary stage, those with localized disease in the 91- to 180-day group increased risk by 25% (aHR 1.25; 95%CI, 1.05-1.51), and delaying over 180 days increased risk by 61% (aHR 1.61; 95%CI, 1.19-2.18) in OS. Those with localized disease in the >180-day group had almost 4 times the estimated rate of DSS mortality (aHR3.51; 95%CI, 1.68-7.32). When stratified by T stage, those with T2 disease in the >180 days group had double the estimated rate of all-cause mortality (aHR 2.0; 95% CI, 1.1-3.3) and almost triple the estimated rate of disease-specific mortality (aHR 2.7; 95% CI, 1.05-6.8). CONCLUSIONS: Delays in surgery for PTC may impact OS and DSS in localized disease, prior to nodal metastasis.

Disparities in the prevalence and management of high-risk non-muscle invasive bladder cancer.

OBJECTIVE: To evaluate the associations of socioeconomic characteristics with the management of non-muscle invasive bladder cancer (NMIBC). METHODS: We identified adult patients aged 18 to 89 years with Ta, T1, or Tis NMIBC in the NCDB. We then examined the associations of patient and socioeconomic characteristics with the guidelines-based management of high-risk NMIBC using multivariable logistic regression. RESULTS: 163,949 patients were included in the study cohort, including 64% with Ta, 32% with T1, and 4% with Tis disease. Among those diagnosed with bladder cancer, male (OR 1.24, 95%CI 1.21-1.27), uninsured (OR 1.10, 95%CI 1.01-1.19 vs. private), and non-White (OR 1.34, 95%CI 1.28-1.41 for Black; OR 1.10; 95%CI 1.03-1.18 for Other vs. White) patients were more likely to be diagnosed with high-risk disease, as well as patients from lower education level areas. Among those with high-risk NMIBC, patients who were older, non-White, Hispanic, uninsured or insured with Medicaid were less likely to receive guideline recommended intravesical BCG, while those residing in rural and higher education level areas were more likely to receive BCG. When examining non-guidelines based use of radiotherapy for HGT1 disease, older age (OR 1.06; 95% CI 1.04-1.07) and VA/Military insurance (OR 2.73; 95%CI 1.07, 6.98 vs. private) were associated with radiotherapy use. CONCLUSION: There are strong disparities in the prevalence and management of high-risk NMIBC. These observations highlight important targets for future strategies to reduce such healthcare disparities and provide more equitable bladder cancer treatment to patients.

Urothelial carcinoma of the bladder with isolated lymph node metastasis: Natural history and outcomes following surgical resection.

INTRODUCTION: Although pathologic lymph node involvement carries a poor prognosis in patients with urothelial carcinoma of the bladder (UCB), a subset of patients may demonstrate durable survival following surgical resection. To this end, there are limited contemporary data describing the natural history of UCB in patients with isolated lymph node involvement (cN0pN+) following radical cystectomy (RC) with pelvic lymph node dissection (PLND). We therefore utilized a large, nationwide oncology dataset to examine the natural history and outcomes of cN0 pN+ UCB after surgical resection. MATERIALS AND METHODS: We identified patients in the National Cancer Database (NCDB) with cN0 pN+ cM0 UCB from 2006 to 2015 treated with RC and PLND. The associations of baseline characteristics with all-cause mortality (ACM) were evaluated using Cox regression. RESULTS: A total of 2,884 patients formed the study cohort, including 42% with pN1 and 58% with pN2-3 disease. Of these, 606 (21%) received multiagent neoadjuvant chemotherapy, while 1,172 (41%) received postoperative adjuvant chemotherapy. A median of 15 (IQR 9-23) LNs were removed during PLND. The 5- and 7-year OS for the entire cohort were 20% and 17%, respectively. Compared to the overall cohort, patients surviving ≤5 years had lower pN stage (59% vs. 42% pN1) and lower pT stage (41% vs. 22% ≤pT2). On multivariable analysis, higher pT stage (HR 2.85, 95% CI 1.52-5.36 for pT3, HR 3.27, 95% CI 1.73-6.18 for pT4 vs. pT0), higher pN stage (HR 1.17, 95% CI 1.05-1.31 for pN2-3 vs. pN1), and increasing LN density (HR 2.37, 95% CI 1.88-2.99) were most strongly associated with increased ACM, while receipt of adjuvant chemotherapy (HR 0.61, 95% CI 0.55-0.68) was associated with reduced ACM. CONCLUSIONS: Although OS for patients with cN0 pN+ M0 UCB is poor, a subset of patients demonstrates durable long-term survival with 5- and 7-year OS of 20% and 17%, respectively. pT and pN stage represent important prognostic characteristics, while administration of adjuvant chemotherapy represents a potential therapeutic intervention associated with improved ACM.

Comparative Effectiveness of Magnetic Resonance Imaging-Ultrasound Fusion Versus In-bore Magnetic Resonance Imaging-targeted Prostate Biopsy.

OBJECTIVE: To examine the comparative effectiveness of magnetic resonance imaging-ultrasound (MRI-U/S) fusion biopsy and in-bore MRI-targeted biopsy. METHODS: We identified men aged 18-89 with a diagnosis of elevated prostate specific antigen (PSA) or Gleason 6 prostate cancer on active surveillance who underwent MRI-U/S fusion prostate biopsy (12-core + targeted) in the office or in-bore MRI-targeted biopsy (MRI-IB; targeted only). The cancer detection rate (CDR; Gleason 6-10) and clinically significant CDR (csCDR; Gleason 7-10) were compared across biopsy techniques, adjusted for patient and radiographic features. RESULTS: A total of 280 patients (346 lesions) were included, of whom 23.9% were on active surveillance for Gleason 6 prostate cancer. In the per-patient analyses, there was no statistically significant difference in adjusted overall CDR (64.1% vs 54.2%; P = .24) or csCDR (36.5% vs 37.9%; P = .85) between MRI-U/S and MRI-IB biopsy. In the per-lesion analyses, there was no statistically significant difference in adjusted overall CDR (45.7% vs 50.1%; P = .49) between MRI-U/S and MRI-IB biopsy, but MRI-IB biopsy was associated with a higher csCDR than MRI-U/S biopsy (32.8% vs 21.4%; P = .02). CONCLUSION: We observed no statistically significant differences in cancer detection rates between MRI-U/S fusion biopsy and MRI-IB biopsy in per-patient analyses. However, MRI-IB biopsy was associated with higher csCDR when considering targeted biopsy cores only. These results suggest that systematic cores should be obtained when performing MRI-U/S fusion biopsy.

Immediate radiotherapy versus observation in patients with node-positive prostate cancer after radical prostatectomy.

BACKGROUND: The optimal management of node-positive (pN1) prostate cancer following radical prostatectomy (RP) remains uncertain. Despite randomized evidence, utilization of immediate, life-long androgen deprivation therapy (ADT) remains poor, and recent trials of early salvage radiotherapy included only a minority of pN1 patients. We therefore emulated a hypothetical pragmatic trial of adjuvant radiotherapy versus observation in men with pN1 prostate cancer. METHODS: Using the RADICALS-RT trial to inform the design of a hypothetical trial, we identified men aged 50-69 years with pT2-3 Rany pN1 M0, pre-treatment PSA < 50 ng/mL prostate cancer in the NCDB from 2006 to 2015 treated with 60-72 Gy of adjuvant RT (aRT) ± ADT within 26 weeks of RP or observation. After estimating a propensity score for receipt of aRT, we estimated absolute and relative treatment effects using stabilized inverse probability of treatment (sIPW) re-weighting. RESULTS: In total, 3510 patients were included in the study, of whom 587 (17%) received aRT (73% with concurrent ADT). Median follow-up was 40.0 -months, during which 333 deaths occurred. After sIPW re-weighting, baseline characteristics were well-balanced. Adjusted overall survival (OS) was 93% versus 89% at 5-years and 82% versus 79% at 7-years for aRT versus observation (p = 0.11). In IPW-reweighted Cox regression, aRT was associated with a lower risk of all-cause mortality (ACM) than observation, but this did not reach statistical significance (HR 0.70 p = 0.06). In analyses examining heterogeneity of treatment effects, aRT was associated with improved ACM only for men with Gleason 8-10 disease (HR 0.59, p = 0.01), ≥2 positive LNs (HR 0.49, p = 0.04 for 2 positive LNs; HR 0.42, p = 0.01 for ≥3 positive LNs), or negative surgical margins (HR 0.50, p = 0.02). CONCLUSIONS: In observational analyses designed to emulate a hypothetical target trial of aRT versus observation in pN1 prostate cancer, aRT was associated with improved OS only for men with Gleason 8-10 disease, ≥2 positive LNs, or negative surgical margins.

Adjuvant chemotherapy versus observation following radical cystectomy for locally advanced urothelial carcinoma of the bladder.

BACKGROUND: The role of adjuvant chemotherapy (AC) in patients with locally advanced bladder cancer following radical cystectomy (RC) remains uncertain, with contemporary clinical trials underpowered and closed early due to low accrual. OBJECTIVE: To conduct observational analyses designed to emulate a completed randomized trial of AC in patients with locally advanced bladder cancer. DESIGN, SETTINGS, AND PARTICIPANTS: Based on EORTC 30994 eligibility criteria, we identified adult patients aged 35 to 75 with pT3/pT4 Nany M0 or Tany pN1-3 M0, R0 urothelial carcinoma of the bladder treated with RC and lymphadenectomy from 2006 to 2015 in the National Cancer Database. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: A propensity score for receipt of AC within 3 months of RC was estimated, and the associations of AC with overall survival were evaluated after reweighting by stabilized inverse probability of treatment weights. RESULTS: Of the 2,416 patients who met inclusion criteria, 945 (39%) received AC after RC. After propensity score adjustment, baseline characteristics were well-balanced. Median follow-up was 26.0 months. After IPW-reweighting, overall survival was 43% vs. 36% at 5-years and 34% vs. 24% at 10-years, among those who did and did not receive AC, respectively (P < 0.01). In IPW-adjusted Cox regression models, AC was associated with improved all-cause mortality (HR 0.71; 95% CI 0.63-0.81; P < 0.01). Estimates were overall consistent in analyses that examined heterogeneity of treatment effects. Limitations include unmeasured confounding, selection bias, and lack of baseline renal function data. CONCLUSION: In observational analyses designed to emulate EORTC 30994, AC was associated with improved overall survival compared to observation after RC. Results were consistent across baseline patient and tumor characteristics.

Radical cystectomy versus trimodality therapy for muscle-invasive urothelial carcinoma of the bladder.

BACKGROUND: The comparative effectiveness of radical cystectomy (RC) and trimodality therapy (TMT) for muscle-invasive bladder cancer remains uncertain, as no randomized data exist. A phase 3 trial (SPARE) was attempted in the UK, however, was deemed infeasible and closed. OBJECTIVE: To emulate the SPARE trial using observational data. DESIGN, SETTING, AND PARTICIPANTS: We identified patients aged 40 to 79 with cT2-3cN0cM0 urothelial carcinoma of the bladder diagnosed from 2006 to 2015 who were treated with multiagent neoadjuvant chemotherapy + RC with lymphadenectomy (RC arm) or multiagent chemotherapy + 3D conformal radiotherapy to the bladder (TMT arm) in the National Cancer Database. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was overall survival (OS). We fit a flexible logistic regression model for treatment to estimate the propensity score, and then used inverse probability of treatment weights to evaluate the associations of treatment group with OS. RESULTS AND LIMITATIONS: A total of 2,048 patients were included, of whom 1,812 underwent RC and 236 underwent TMT. Median follow-up was 29.0 months. After propensity score adjustment, compared to TMT, RC was not associated with a statistically significant difference in OS (HR 0.87; 95% CI 0.64-1.19; P = 0.40). When examining heterogeneity of treatment effects, RC appeared to be associated with improved OS only for patients with cT3 disease. Similar results were observed in sensitivity analyses. Our study is limited by the retrospective design and the lack of cancer-specific survival data. CONCLUSIONS: In observational analyses designed to emulate the SPARE trial, there was no statistically significant difference in OS between RC and TMT. Heterogeneity of treatment effects suggested improved survival with RC only for cT3 disease.