Contemporary conditional cancer-specific survival rates in surgically treated nonmetastatic primary urethral carcinoma.

BACKGROUND: We examined the effect of disease-free interval (DFI) duration on cancer-specific mortality (CSM)-free survival, otherwise known as the effect of conditional survival, in radical urethrectomy nonmetastatic primary urethral carcinoma (PUC) patients. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) database 2000-2020, patient (age, sex, race/ethnicity, and marital status) and tumor (stage and histology) characteristics, as well as systemic therapy exposure status of nonmetastatic PUC patients were tabulated. Conditional survival estimates at 5-year were assessed based on DFI duration and according to stage at presentation (T1 -2N0 vs. T3-4N0-2). RESULTS: Of all 512 radical urethrectomy PUC patients, 278 (54%) harbored T1-2N0 stage versus 234 (46%) harbored T3-4N0-2 stage. In 512 PUC patients, 5-year CSM-free survival at initial diagnosis was 61.8%. Provided a DFI duration of 36 months, 5-year CSM-free survival was 85.6%. In 278 T1-2N0 PUC patients, 5-year CSM-free survival at initial diagnosis was 68.4%. Provided a DFI duration of 36 months, 5-year CSM-free survival was 86.9%. In 234 T3-4N0-2 PUC patients, 5-year CSM-free survival at initial diagnosis was 53.8%. Provided a DFI duration of 36 months, 5-year CSM-free survival was 83.6%. CONCLUSIONS: Although intuitively, clinicians and patients are well aware of the concept that increasing DFI duration improves survival probability, only a few clinicians can accurately estimate the magnitude of survival improvement, as was done within the current study. Such information is crucial to survivors, especially in those diagnosed with rare malignancies, where the survival estimation according to DFI duration is even more challenging.

The effect of married status on cancer-specific mortality in nonmetastatic pelvic liposarcoma patients according to sex.

BACKGROUND: In nonmetastatic pelvic liposarcoma patients, it is unknown whether married status is associated with better cancer-control outcome defined as cancer-specific mortality (CSM). We addressed this knowledge gap and hypothesized that married status is associated with lower CSM rates in both male and female patients. METHODS: Within the Surveillance, Epidemiology, and End Results database (2000-2020), nonmetastatic pelvic liposarcoma patients were identified. Kaplan-Meier plots and univariable and multivariable Cox regression models (CRMs) predicting CSM according to marital status were used in the overall cohort and in male and female subgroups. RESULTS: Of 1078 liposarcoma patients, 764 (71%) were male and 314 (29%) female. Of 764 male patients, 542 (71%) were married. Conversely, of 314 female patients, 192 (61%) were married. In the overall cohort, 5-year cancer-specific mortality-free survival (CSM-FS) rates were 89% for married versus 83% for unmarried patients (Δ = 6%). In multivariable CRMs, married status did not independently predict lower CSM (hazard ratio [HR]: 0.74, p = 0.06). In males, 5-year CSM-FS rates were 89% for married versus 86% for unmarried patients (Δ = 3%). In multivariable CRMs, married status did not independently predict lower CSM (HR: 0.85, p = 0.4). In females, 5-year CSM-FS rates were 88% for married versus 79% for unmarried patients (Δ = 9%). In multivariable CRMs, married status independently predicted lower CSM (HR: 0.58, p = 0.03). CONCLUSIONS: In nonmetastatic pelvic liposarcoma patients, married status independently predicted lower CSM only in female patients. In consequence, unmarried female patients should ideally require more assistance and more frequent follow-up than their married counterparts.

Unmarried status effect on stage at presentation and treatment patterns in primary urethral carcinoma patients.

BACKGROUND: Unmarried status has been associated with advanced stage at presentation and lower treatment dose intensification rates in several urological and non-urological malignancies. However, no previous investigators focused of the association of unmarried status with locally advanced stage (T3-4N0-2) at presentation and lower bi-/trimodal therapy rates in primary urethral carcinoma (PUC) patients. To address these knowledge gaps, we relied on the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: Within the SEER database 2000 to 2020, all non-metastatic PUC patients were identified. Logistic regression models (LRMs) tested for differences in stage at presentation and treatment modality in the overall cohort and then in a sex-specific fashion, according to marital status (married vs unmarried). RESULTS: Of all 1,430 non-metastatic PUC patients, 1,004 (70%) were male vs 426 (30%) were female. Of 1,004 male PUC patients, 272 (27%) were unmarried. Of all 426 female PUC patients, 239 (56%) were unmarried. In multivariable LRMs predicting T3-4N0-2, unmarried status was independently associated with an increased risk of locally advanced stage at presentation in the overall cohort (odds ratio [OR]:1.31; P = 0.03) and in female patients (OR:1.62; P = 0.02), but not in male PUC patients (P = 0.6). In multivariable LRMs predicting bi-/trimodal therapy, unmarried status was an independent predictor of lower bi-/trimodal therapy rates in the overall cohort (OR:0.73; P = 0.02) and in male patients (OR:0.60; P = 0.007), but not in female PUC patients (P = 0.6). CONCLUSIONS: Unmarried female PUC patients more likely harbored locally advanced stage at presentation. Conversely, unmarried male PUC patients are less likely to benefit from bi-/trimodal therapy.

Regional differences in upper tract urothelial carcinoma patients across the United States.

BACKGROUND: It is unknown whether regional differences in patient, tumor, and treatment characteristics of upper tract urothelial carcinoma (UTUC) patients exist and may potentially result in regional overall mortality (OM) differences. We tested for inter-regional differences, according to Surveillance, Epidemiology, and End Results (SEER) registries. METHODS: Using SEER database 2000 to 2016, patient (age, sex, race/ethnicity), tumor (location, grade) and treatment (nephroureterectomy, systemic therapy [ST]) characteristics of UTUC patients of all-stages were tabulated and graphically depicted in a stage-specific fashion (T1-2N0M0 vs. T3-4N0M0 vs. TanyN1-2M0/TanyNanyM1). Multivariable Cox regression (MCR) models tested for inter-regional differences in OM. RESULTS: Regarding T1-2N0M0 patients, statistically significant differences existed for race/ethnicity (Caucasian 71 vs. 98%), location (renal pelvis: 55 vs. 67%), grade (high 60 vs. 83%) and ST (5.5 vs. 13.9%). In MCR models, registries 3 (Hazard ratio [HR]:1.39; P < 0.001) and 4 (HR:1.31; P = 0.01) independently predicted higher OM and Registry 8 (HR:0.64; P = 0.001) lower OM. Regarding T3-4N0M0 patients, statistically significant differences existed for race/ethnicity (Caucasian 70 vs. 98%), location (renal pelvis: 67 vs. 76%), grade (high 84 vs. 94%) and ST (18.7 vs. 29.5%). In MCR models, registries 3 (HR:1.42; P < 0.001) and 4 (HR:1.31; P = 0.009) independently predicted higher OM. Regarding TanyN1-2M0/TanyNanyM1 patients, statistically significant differences existed for location (renal pelvis: 63 vs. 82%), grade (high 92 vs. 98%) and ST (53.4 vs. 58.8%). In MCR models, Registry 3 (HR:1.37; P = 0.004) independently predicted higher OM and Registry 2, (HR:0.78; P = 0.02) lower OM. CONCLUSIONS: Inter-regional differences were recorded in patients, tumor, and treatment characteristics. Even after adjustment for these characteristics, OM differences persisted which may be indicative of regional differences in quality of care or expertise in UTUC management.

Multivariable model versus AJCC staging system: cancer-specific survival predictions in adrenocortical carcinoma.

We developed a novel contemporary population-based model for predicting cancer-specific survival (CSS) in adrenocortical carcinoma (ACC) patients and compared it with the established 8th edition of the American Joint Committee on Cancer staging system (AJCC). Within the Surveillance, Epidemiology, and End Results database (2004-2020), we identified 1056 ACC patients. Univariable Cox regression model addressed CSS. Harrell's concordance index (C-index) quantified accuracy after 2000 bootstrap resamples for internal validation. The multivariable Cox regression model included the most informative, statistically significant predictors. Calibration and decision curve analyses (DCAs) tested the multivariable model as well as AJCC in head-to-head comparisons. Age at diagnosis (>60 vs ≤60 years), surgery, T, N, and M stages were included in the multivariable model. Multivariable model C-index for 3-year CSS prediction was 0.795 vs 0.757 for AJCC. Multivariable model outperformed AJCC in DCAs for the majority of possible CSS-predicted values. Both models exhibited similar calibration properties. Finally, the range of the multivariable model CSS predicted probabilities raged 0.02-75.3% versus only four single AJCC values, specifically 73.2% for stage I, 69.7% for stage II, 46.6% for stage III, and 15.5% for stage IV. The greatest benefit of the multivariable model-generated CSS probabilities applied to AJCC stage I and II patients. The multivariable model was more accurate than AJCC staging when CSS predictions represented the endpoint. Additionally, the multivariable model outperformed AJCC in DCAs. Finally, the AJCC appeared to lag behind the multivariable model when discrimination addressed AJCC stage I and II patients.

The Association between Urinary Diversion Type and Other-Cause Mortality in Radical Cystectomy Patients.

BACKGROUND: It is unknown whether more complex UD, such as orthotopic neobladder and abdominal pouch, may be associated with higher OCM rates than ileal conduit. We addressed this knowledge gap within the SEER database 2004-2020. METHODS: All T1-T4aN0M0 radical cystectomy (RC) patients were identified. After 1:1 propensity score matching (PSM), cumulative incidence plots, univariable and multivariable competing-risks regression (CRR) models were used to test differences in OCM rates according to UD type (orthotopic neobladder vs. abdominal pouch vs. ileal conduit). RESULTS: Of all 3008 RC patients, 2380 (79%) underwent ileal conduit vs. 628 (21%) who underwent continent UD (268 orthotopic neobladder and 360 abdominal pouch). After PSM relative to ileal conduit, neither continent UD (13 vs. 15%; p = 0.1) nor orthotopic neobladder (13 vs. 16%; p = 0.4) nor abdominal pouch (13 vs. 15%; p = 0.2) were associated with higher 10-year OCM rates. After PSM and after adjustment for cancer-specific mortality (CSM), as well as after multivariable adjustments relative to ileal conduit, neither continent UD (Hazard Ratio [HR]:0.73; p = 0.1), nor orthotopic neobladder (HR:0.84; p = 0.5) nor abdominal pouch (HR:0.77; p = 0.2) were associated with higher OCM. CONCLUSIONS: It appears that more complex UD types, such as orthotopic neobladder and abdominal pouch are not associated with higher OCM relative to ileal conduit.

Contemporary sex-specific analysis of the association of marital status with cancer-specific mortality in primary urethral carcinoma patients.

BACKGROUND: It is unknown whether married status may be associated with lower cancer-specific mortality (CSM) rates in primary urethral carcinoma (PUC) patients. To test for differences in CSM rates, according to marital status, we relied on the Surveillance, Epidemiology, and End Results (SEER) database 2000-2020. METHODS: Patient (age, sex, race/ethnicity, marital status), tumor (stage, histology), and treatment (surgery, systemic therapy) characteristics of PUC patients were tabulated. Then, Kaplan-Meier plots, as well as univariable and multivariable Cox regression (MCR) models tested for differences in CSM rates according to marital status in overall cohort and then in sex-specific subgroup analyses. RESULTS: Of all 1,571 PUC patients, 70% were male vs. 30% female. Females were statistically significantly younger (68 vs. 73 years), more frequently unmarried (54 vs. 28%), non-Caucasian (43 vs. 24%), more frequently harbored T3-4N0M0 (39 vs. 18%) and less frequently T1-2N0M0 (53 vs. 69%) or TanyN1-2M0/TanyNanyM1 (8 vs. 13%), relative to males. Moreover, we recorded differences in histotype proportions in females vs. males (urothelial 30 vs. 64%; squamous 24 vs. 22%; adenocarcinoma 36 vs. 7%; others 10 vs. 6%) and surgical treatment (none 22 vs. 17%; excisional biopsy 22 vs. 36%; partial urethrectomy 14 vs. 16%; radical urethrectomy 42 vs. 31%). In MCR models focusing on the entire cohort, married status independently predicted lower CSM (hazard ratio [HR]:0.82; P = 0.02). Similarly, in MCR models focusing on females, married status independently predicted lower CSM (HR:0.73; P = 0.03). Conversely, in MCR models focusing on males, married status failed to independently predict lower CSM (HR:0.89; P = 0.3). CONCLUSIONS: Married status was associated with lower CSM in PUC patients. However, this benefit applies to female PUC patients, but not to their male counterparts.

Peri-Urethral and Anterior Vaginal Wall Masses: Does Radiological Imaging Change the Predicted Diagnosis?

INTRODUCTION: This study aims to determine the accuracy of radiological imaging compared with surgical pathology in patients with periurethral (PU) and anterior vaginal wall (AVW) lesions. METHODS: This study is a retrospective analysis of 126 women who underwent surgical treatment for PU and AVW masses between 2011 and 2020. Clinicopathological data were extracted along with radiological findings from medical records. The primary outcome was the diagnostic accuracy of preoperative imaging compared to the gold standard, pathological diagnosis. The secondary outcome was the rate of imaging correcting the clinical diagnosis. RESULTS: A total of 126 women with a median age of 42 underwent surgical treatment for PU and AVW masses. The most diagnoses were periurethral cysts (PUC) (52%) and urethral diverticulum (UD) (39%). Clinical diagnosis was accurate in 102 cases (81%) for the group of pathological diagnoses. Magnetic resonance imaging (MRI) and transvaginal ultrasound (TV US) were performed in 82 (65%) and 22 (17%) cases. The accuracy of MRI and TV US for the diagnosis of PU and AVW lesions was 76% and 82%, respectively. MRI and TV US corrected the clinical diagnosis in five (6%) and two (9%) cases, respectively. Voiding cystourethrography (VCUG) and double balloon urethrography (DBU), each performed in six (5%) cases, were accurate in four (67%) and three (50%) cases. No statistical difference was found for any imaging modality compared to clinical diagnosis. CONCLUSION: Clinical diagnosis based on pelvic and cystoscopy examinations was sufficient for diagnosing PU and AVW masses and was not significantly different from imaging diagnosis. Imaging may be helpful with preoperative surgical planning in selected cases.

Androgen Deprivation Therapy and Risk of Cardiovascular Disease in Patients With Prostate Cancer Based on Existence of Cardiovascular Risk.

BACKGROUND: Controversy exists regarding the risk of cardiovascular disease (CVD) associated with androgen deprivation therapy (ADT) in patients with prostate cancer. We sought to evaluate the association between gonadotropin-releasing hormone (GnRH) agonists versus GnRH antagonist and the risk of CVD in patients with prostate cancer with or without prior CVD. PATIENTS AND METHODS: Using administrative databases from Quebec, Canada, we identified first-time GnRH agonists and antagonist (degarelix) users between January 2012 and June 2016. Follow-up ended at the earliest of the following: first CVD event (myocardial infarction [MI], stroke, ischemic heart disease [IHD], arrhythmia, and heart failure [HF]); switch of GnRH group; death; or December 31, 2016. Inverse probability of treatment weighting (IPTW) based on the propensity score was used to control for potential confounding. IPTW-Cox proportional hazards model accounting for competing risks was used to evaluate the association of interest. RESULTS: Among 10,785 patients identified, 10,201 and 584 were on GnRH agonists and antagonist, respectively. Median age was 75 years (interquartile range, 69-81 years) for both groups. A total of 4,152 (40.7%) men in the GnRH agonists group and 281 (48.1%) men in the GnRH antagonist group had CVD in the 3-year period prior to ADT initiation. Risk of HF was decreased in the antagonist group compared with the GnRH agonist group among patients with prior CVD (hazard ratio [HR], 0.46; 95% CI, 0.26-0.79). Risk of IHD was decreased in the antagonist group in patients without prior CVD (HR, 0.26; 95% CI, 0.11-0.65). Use of antagonist was associated with an increased risk of arrhythmia among patients with no prior CVD (HR, 2.34; 95% CI, 1.63-3.36). CONCLUSIONS: Compared with GnRH agonists, the GnRH antagonist was found to be associated with a decreased risk of HF, specifically among patients with prior CVD. Among those with no prior CVD, the GnRH antagonist was associated with a decreased risk of IHD but an increased risk of arrhythmia.

Feasibility of Prospectively Comparing Opioid Analgesia With Opioid-Free Analgesia After Outpatient General Surgery: A Pilot Randomized Clinical Trial.

Importance: The overprescription of opioids to surgical patients is recognized as an important factor contributing to the opioid crisis. However, the value of prescribing opioid analgesia (OA) vs opioid-free analgesia (OFA) after postoperative discharge remains uncertain. Objective: To investigate the feasibility of conducting a full-scale randomized clinical trial (RCT) to assess the comparative effectiveness of OA vs OFA after outpatient general surgery. Design, Setting, and Participants: This parallel, 2-group, assessor-blind, pragmatic pilot RCT was conducted from January 29 to September 3, 2020 (last follow-up on October 2, 2020). at 2 university-affiliated hospitals in Montreal, Quebec, Canada. Participants were adult patients (aged ≥18 years) undergoing outpatient abdominal (ie, cholecystectomy, appendectomy, or hernia repair) or breast (ie, partial or total mastectomy) general surgical procedures. Exclusion criteria were contraindications to drugs used in the trial, preoperative opioid use, conditions that could affect assessment of outcomes, and intraoperative or early complications requiring hospitalization. Interventions: Patients were randomized 1:1 to receive OA (around-the-clock nonopioids and opioids for breakthrough pain) or OFA (around-the-clock nonopioids with increasing doses and/or addition of nonopioid medications for breakthrough pain) after postoperative discharge. Main Outcomes and Measures: Main outcomes were a priori RCT feasibility criteria (ie, rates of surgeon agreement, patient eligibility, patient consent, treatment adherence, loss to follow-up, and missing follow-up data). Secondary outcomes included pain intensity and interference, analgesic intake, 30-day unplanned health care use, and adverse events. Between-group comparison of outcomes followed the intention-to-treat principle. Results: A total of 15 surgeons were approached; all (100%; 95% CI, 78%-100%) agreed to have patients recruited and adhered to the study procedures. Rates of patient eligibility and consent were 73% (95% CI, 66%-78%) and 57% (95% CI, 49%-65%), respectively. Seventy-six patients were randomized (39 [51%] to OA and 37 [49%] to OFA) and included in the intention-to-treat analysis (mean [SD] age, 55.5 [14.5] years; 50 [66%] female); 40 (53%) underwent abdominal surgery, and 36 (47%) underwent breast surgery. Seventy-five patients (99%; 95% CI, 93%-100%) adhered to the allocated treatment; 1 patient randomly assigned to OFA received an opioid prescription. Seventeen patients (44%) randomly assigned to OA consumed opioids after discharge. Seventy-three patients (96%; 95% CI, 89%-99%) completed the 30-day follow-up. The rate of missing questionnaires was 37 of 3724 (1%; 95% CI, 0.7%-1.4%). All the a priori RCT feasibility criteria were fulfilled. Conclusions and Relevance: The findings of this pilot RCT support the feasibility of conducting a robust, full-scale RCT to inform evidence-based prescribing of analgesia after outpatient general surgery. Trial Registration: ClinicalTrials.gov Identifier: NCT04254679.

Impact of the Covid-19 pandemic on rates of emergency department utilization and hospital admission due to general surgery conditions.

BACKGROUND: Recent literature reports a decrease in healthcare-seeking behaviours by adults during the Covid-19 pandemic. Given that emergency general surgery (GS) conditions are often associated with high morbidity and mortality if left untreated, the objective of this study was to describe and quantify the impact of the Covid-19 pandemic on rates of emergency department (ED) utilization and hospital admission due to GS conditions. METHODS: This cohort study involved the analysis of an institutional database and retrospective chart review. We identified adult patients presenting to the ED in a network of three teaching hospitals in Montreal, Canada during the first wave of the Covid-19 pandemic (March13-May13, 2020) and a control pre-pandemic period (March13-May13, 2019). Patients with GS conditions were included in the analysis. ED utilization rates, admission rates and 30-day outcomes were compared between the two periods using multivariate regression analysis. RESULTS: During the pandemic period, 258 patients presented to ED with a GS diagnosis compared to 351 patients pre-pandemically (adjusted rate ratio (aRR) 0.75; p < 0.001). Rate of hospital admission during the pandemic was also significantly lower (aRR = 0.77, p < 0.001). Patients had a significantly shorter ED stay during the pandemic (adjusted mean difference 5.0 h; p < 0.001). Rates of operative management during the pandemic were preserved compared to the pre-pandemic period. There were no differences in 30-day complications (adjusted odds ratio (aOR) 1.46; p = 0.07), ED revisits (aOR 1.10; p = 0.66) and (re)admissions (aOR 1.42; p = 0.22) between the two periods. CONCLUSION: There was a decrease in rates of ED utilization and hospital admissions due to GS conditions during the first wave of the Covid -19 pandemic; however, rates of operative management, complications and healthcare reutilization were unchanged. Although our findings are not generalizable to patients who did not seek healthcare, it was possible to successfully uphold institutional standards of care once patients presented to the ED.

Platelet-Rich Plasma Injections for Erectile Dysfunction and Peyronie's Disease: A Systematic Review of Evidence.

INTRODUCTION: Erectile Dysfunction (ED) and Peyronie's Disease (PD) are debilitating medical conditions affecting patients' quality of life (QoL). Platelet-rich plasma (PRP) injections are one of the various emerging approaches proposed to treat these medical conditions. AIM: To describe the evidence of the potential role of PRP injections in ED and PD. METHODS: The authors conducted a systematic review according to the PRISMA statement using the following databases in November 2019: The National Library of Medicine (PubMed), Ovid Medline, Cochrane, Scopus, Embase, and Embase classic. The search was performed using keywords drawn from studies on the use of PRP in ED and PD in clinical and preclinical studies. RESULTS: Eighteen articles met the inclusion criteria for review, including 12 studies on the use of PRP in humans and 6 on the use of PRP in rats. Ten studies reported on the efficacy of PRP in ED exclusively, 7 in PD exclusively and one in both conditions. In humans, 6 and 3 studies showed promising results in PD and ED, respectively. No major complications were noted. Unwanted minor side effects were noted by studies reporting on PD, including mild penile bruising, ecchymosis, hematomas as well as transient hypotension noted in 2 out of 90 patients. CONCLUSION: PRP injections for the treatment of ED may be promising, but no recommendation can be made because of scarce evidence. Safety and effectiveness of this therapy in the treatment of ED and PD require further preclinical and clinical studies with standardized protocols to gain an adequate insight into its potential implications. Patients should be offered to be part of such trials to better understand PRP potential. Alkandari MH, Touma N, Carrier S, Platelet-Rich Plasma Injections for Erectile Dysfunction and Peyronie's Disease: A Systematic Review of Evidence. Sex Med Rev 2022;10:341-352.