Urinary bother, Urinalysis, and Two-Year Efficacy Follow-Up Results of Phase I Trial of Intravesical Bacillus Calmette-Guérin Combined with Intravenous Pembrolizumab in Recurrent or Persistent High-Grade Non-Muscle-Invasive Bladder Cancer after Previous Bacillus Calmette-Guérin Treatment.

OBJECTIVE: To report urinary bother, urinalysis changes, disease-free survival (DFS), and overall survival (OS) over 2 years for subjects enrolled in a phase I dose-escalation trial (NCT02324582) of intravesical Bacillus Calmette-Guérin (BCG) in combination with systemic pembrolizumab for recurrent or persistent high-grade non-muscle invasive bladder cancer (HGNMIBC). METHODS: Eighteen patients consented to the study. Five were screen failures. Clinical activity was determined using cystoscopy and cytology with a biopsy of suspicious lesions. Urinalysis and International Prostate symptom score were assessed at pre-treatment, Week 10 (during combined BCG and pembrolizumab treatment), and 3 and 6 months from treatment completion. IPSS was analyzed using a mixed-model repeated measures analysis. A Chi-square test was used to compare urinalysis results at each interval. RESULTS: The pathologic disease stage after restaging transurethral resection and before treatment was pTa in 6 (46.2%), CIS in 6 (46.2%), and pT1 in 1 (7.7%). There was no increase in reported urinary bother throughout treatment. Quality of life measurements demonstrated no change in subjective burden. On urinalysis, we did not observe significant differences at 3 months compared to baseline evaluation. At 12 months, the DFS and OS were 69.23% and 92.31%, respectively. At 24 months, the DFS and OS were 38.46% and 92.31%, respectively. CONCLUSIONS: Treatment with BCG combined with intravenous pembrolizumab is not showing increased urinary bother or adverse urinalysis changes. Two-year response data is promising and await confirmation in the phase III study (Keynote 676).

Assessing Vasectomy-Related Information on YouTube: An Analysis of the Quality, Understandability, and Actionability of Information.

This study aims to critically appraise the quality of vasectomy-related health information currently available on YouTube to better address patient information needs moving forward. A YouTube search was performed using the keyword "vasectomy." The first 100 videos were assessed, with irrelevant and duplicate videos excluded. Two independent reviewers evaluated the remaining videos using the DISCERN instrument for evaluating the quality of information and the Patient Education Materials Assessment Tool for Audiovisual materials (PEMAT-A/V) for assessing the understandability and actionability of materials. Source characteristics and markers of bias and misinformation were also collected. Seventy-eight videos were included in the study, with a mean duration of 6.6 minutes and mean of 216,672 views. The median DISCERN score was poor at 28 (IQR 22-33) out of a possible 80 with mean PEMAT-AV Understandability and Actionability scores of 67.6% (±16.7%) and 33.8% (±36.2%), respectively. A medical doctor was present in 61 (78.2%) of the videos, of which 53 (86.9%) were urologists and 38 (62.2%) promoted their personal practice or institution. False statements regarding vasectomy were made in 14 (17.9%) videos. Notably, no significant difference was noted in quality, understandability, or actionability of videos created by those with personal promotion to those without. The quality of information regarding vasectomy on YouTube is poor and reaches a wide audience. Continued appraisal and creation of YouTube videos that contain quality, understandable and actionable information by urologists is necessary to ensure patients are well-informed.

Robotic-assisted partial cystectomy for muscle invasive bladder cancer: Contemporary experience.

OBJECTIVE: To report our contemporary experience with robotic-assisted partial cystectomy (RAPC) for muscle invasive bladder cancer. METHODS: This is a retrospective review of patients who underwent robotic-assisted partial cystectomy with us between 2013 and 2020 and provided ≥12 months of follow up. RESULTS AND LIMITATIONS: The median operative time for our 35 patients was 190 min (Interquartile range [IQR] 155-280). Four patients developed grade 3 or higher complications (ileus, pneumonia, and urethral stricture). At 12 months follow-up, the median IPSS score was 10 (IQR 7-11), and recurrence happened in seven patients (recurrence-free survival 80%). Five of the patients who developed recurrence died because of their disease, and two other patients died of causes unrelated to their cancer. CONCLUSIONS: We describe our technique, functional outcomes, and short-term follow up results in highly selected patients with muscle-invasive bladder cancer treated with RAPC.

Global Trends in Incidence and Burden of Urolithiasis from 1990 to 2019: An Analysis of Global Burden of Disease Study Data.

BACKGROUND: Urolithiasis is among the most common urologic diagnoses globally, with substantial burden and cost on healthcare systems worldwide. Increasing evidence links urolithiasis with an array of risk factors, including diet and lifestyle trends, noncommunicable diseases such as diabetes and obesity, and global warming. OBJECTIVE: To examine geographic, temporal, and sociodemographic patterns to better understand global disease burden of urolithiasis. DESIGN SETTING AND PARTICIPANTS: We extracted data on age-standardized incidence rate (ASIR), deaths, and disability-adjusted life years (DALYs) attributed to urolithiasis for 21 regions, including 204 countries, for 1990-2019 from the Global Burden of Disease (GBD) study. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Data were analyzed at the global, regional, and country levels, as well as stratified by the Socio-Demographic Index. The average annual percentage change (AAPC) was calculated to measure temporal trends across groups. RESULTS AND LIMITATIONS: Globally, total cases, DALYs, and deaths attributed to urolithiasis increased over the study period, while the age-standardized rates of these measures decreased. The age-standardized incidence of urolithiasis decreased from 1696.2 (95% confidence interval [CI] 1358.1-2078.1) cases per 100 000 population in 1990 to 1394.0 (95% CI, 1126.4-1688.2) cases per 100 000 population in 2019, with an AAPC of -0.7 (95% CI [-0.8, -0.6]). Of the GBD regions, Eastern Europe demonstrated a consistently higher ASIR of urolithiasis than all other regions, while the Caribbean had the highest AAPC. This study is limited by the available national and regional data, as described in the original GBD study. CONCLUSIONS: Worldwide, total cases, DALYs, and deaths attributed to urolithiasis have increased since 1990, while age-standardized rates have decreased, with demonstrated regional and sociodemographic variation. Multifaceted strategies to address urolithiasis prevention and treatment are necessary. PATIENT SUMMARY: In this study, we looked at trends in the global burden of stone disease using data from 204 countries from 1990 to 2019. We found that the overall burden has increased, but it varies by age, sociodemographic variables, and geographic region. We conclude that we need adaptable policies that suit the specific needs of the country to address this burden.

Phase I trial of intravesical Bacillus Calmette-Guérin combined with intravenous pembrolizumab in recurrent or persistent high-grade non-muscle-invasive bladder cancer after previous Bacillus Calmette-Guérin treatment.

OBJECTIVES: We conducted the first phase I dose-escalation trial (NCT02324582) of intravesical Bacillus Calmette-Guérin (BCG) in combination with systemic pembrolizumab in patients with high-grade non-muscle-invasive bladder cancer (HGNMIBC) who had persistent or recurrent disease after prior intravesical therapy with BCG. The primary endpoint was the safety of this combination. The secondary endpoint was clinical activity at three months following BCG treatment. METHODS: Eighteen patients were consented for the study, five of which were screen failures. Six doses of pembrolizumab were administered every 3 weeks over 16 weeks concurrently with six weekly doses of BCG beginning at week 7. Patient safety was evaluated from the time of consent through 30 days following pembrolizumab treatment. Clinical activity was determined using cystoscopy and biopsy of suspicious lesions. RESULTS: Treatment-related adverse events included one grade 4 adverse event (AEs) (adrenal insufficiency). There were nine grade 3 AEs (chest discomfort, pulmonary embolism, arthritis, wrist edema, injection site reaction, bilateral wrist pain, cardiomyopathy, hypokalemia, urinary tract infection). There were 49 grade 1 and 30 grade 2 AEs (88% of AEs). Eleven patients finished the treatment, and two patients died during the study. Of 13 patients treated, nine patients (69%) had no evidence of disease at 3 months following BCG treatment. CONCLUSIONS: We report for the first time that combining BCG and pembrolizumab in treating HGNMIBC is safe allowing complete treatment of most patients. A phase III trial has opened to test the efficacy of this combination in HGNMIBC (KEYNOTE-676).

Mirabegron improves sleep measures, nocturia, and lower urinary tract symptoms in those with urinary symptoms associated with disordered sleep.

INTRODUCTION: The role of organized sleep in overall health and quality-of-life (QoL) is critical. Nocturia necessarily disrupts the normal sleep cycle and negatively impacts one's health, work productivity, and QoL. We investigated, for the first time in an exploratory pilot, the effectiveness of mirabegron for improving sleep disturbance and nocturia. MATERIALS AND METHODS: This was a prospective, open-label 12-week trial evaluating the efficacy of mirabegron in 34 men and women with disordered sleep and lower urinary tract symptoms (LUTS). Subjects received mirabegron 25 mg daily for 4 weeks, then increased to 50 mg. Subjects completed the Patient-Reported Outcome Measurement Information System Sleep Disturbance Short Form (PROMIS-SDSF), Jenkins Sleep Scale (JSS), International Prostate Symptom Score (IPSS), voiding diaries, and QoL questionnaires. RESULTS: PROMIS-SDSF scores decreased from 26.5 points to 19.3, representing a categorical improvement from clinically 'mild' to 'none to slight' sleep disturbance (p < 0.001). JSS scores also decreased from 14.1 to 8.3 (p < 0.001). IPSS decreased from 21.0 to 12.4, denoting a categorical improvement from 'severe' to 'moderate' LUTS (p < 0.001). Voiding diaries revealed 1.9 fewer voids per day (p < 0.01) and 0.8 fewer nighttime voids (p < 0.05). QoL improved from 0% in subjects who selected 'mostly satisfied,' 'pleased,' or 'delighted' to 29.6% at follow up. CONCLUSIONS: Mirabegron use improves nocturia and produces rapid, durable, and clinically significant improvement in sleep disturbance and LUTS in males and females with urinary symptoms associated with disordered sleep.

Penile ring entrapment - A true urologic emergency: Grading, approach, and management.

Penile rings are used to sustain erection in order to enhance sexual pleasure. They work by reducing the outflow of blood from the cavernosal tissue. However, if left for extended periods of time severe edema, urethral fistula, gangrene, and even complete loss of the distal penis can ensue, this is known as penile ring entrapment (PRE). Management poses particular challenges due to its rarity. Herein, we report our experience with three patients from our institution that presented with PRE and include a review of the approaches others have taken. We also propose a simpler and more effective grading scale to allow for easier communication between providers, as the current grading scales do not do so.

The effect of the urinary and faecal microbiota on lower urinary tract symptoms measured by the International Prostate Symptom Score: analysis utilising next-generation sequencing.

OBJECTIVE: To examine the correlation between urinary and faecal microbial profiles and the different aspects of lower urinary tract symptoms (LUTS) in men, as there is accumulating evidence that variations in the human microbiota may promote different benign disease conditions. PATIENTS AND METHODS: We extracted total DNA from urine and faecal samples of a group of men, under an Institutional Review Board-approved protocol. At the same time, International Prostate Symptom Score (IPSS) data were collected. We then amplified the extracted DNA and sequenced it using bacterial 16S ribosomal RNA gene high-throughput next-generation sequencing platform, and analysed the microbial profiles for taxonomy to examine the correlation between the different operational taxonomy units (OTUs) and LUTS represented by the total IPSS, the different symptom levels of the IPSS (mild, moderate, and severe) and its subcomponents of storage, nocturia, voiding, and bother. RESULTS: We included 30 patients (60 samples; one urine and one faecal per patient). In all, 48 faecal OTUs showed a significant correlation with one or more of the IPSS components; 27 with nocturia, 19 with bother, 16 with storage symptoms, and nine with voiding symptoms. The most substantial negative (protective) correlation was between Lachnospiraceae Blautia, a bacteria that increases the availability of gut anxiolytic and antidepressant short-chain fatty acids, and bother (correlation coefficient 0.702; P = 0.001). The abundance of L. Blautia continued to have a protective correlation against LUTS when looking at the different levels of IPSS severity (moderate and severe vs mild, correlation coefficient 0.6132; P = 0.002). Ten unique urinary OTUs showed significant correlation with LUTS; eight with nocturia, one with bother, three with storage, and one with voiding, but no faecal OUT had more than a low correlation with the outcomes of interest in this study. CONCLUSIONS: Our prospective work finds a plausible correlation between L. Blautia and LUTS. Additional studies are needed to determine if the correlations found in the present research are applicable to the general population of patients affected by LUTS.

Combination Pharmacotherapy for Treatment of Overactive Bladder (OAB).

Overactive bladder syndrome (OAB) negatively affects the quality of life of patients and their interactions with society. Treatment of OAB starts with behavioral modification and then pharmacotherapy using monotherapy with either antimuscarinics or ß3 agonists. The third-line more invasive approaches are the next treatment option currently recommended. Both antimuscarinic agents and ß3 agonists work through a different molecular pathway. This brings up the potential of having an additive effect when using a combination treatment for patients with OAB. Currently, the potential for using combination therapy to treat OAB in patients who had no improvement with a monotherapy approach before we attempt a more invasive approach is being explored. Several studies have shown the benefits of combination therapy which will be an additional option to the tools to treat OAB.

Prospective examination of the changes in the urinary microbiome induced by transrectal biopsy of the prostate using 16S rRNA gene analysis.

OBJECTIVES: To prospectively examine the changes in microbiota within the urinary tract after transrectal prostate biopsy. MATERIALS AND METHODS: Data, urine, and fecal samples prospectively collected from 30 patients before and after transrectal biopsy of the prostate. DNA was extracted from urine collected after a prostate massage before and after prostate biopsy, and from fecal samples collected before the biopsy. We sequenced DNA using the bacterial 16S rRNA high-throughput next-generation sequencing and analyzed changes in microbial profiles for taxonomy comparison between samples. RESULTS: Pre-biopsy urinary microbial profiles contained Lactobacillus and Staphylococcus bacteria. Post-biopsy urinary microbial profiles included lower levels of Lactobacillus and higher levels of Prevotella bacteria. Bacteroides bacteria were predominant in fecal samples. We identified two clustering patterns containing both pre- and post-biopsy urine samples. Cluster 1 had a urine cluster pattern that was distinct from fecal, whereas cluster 2 was similar to fecal. We observed two different modes of microbial changes, 11 patients had both of their urine (pre and post) samples associated with a particular cluster group, whereas others (n = 15) had movement between clusters 1 and 2 following the biopsy procedure. Four patient's post-biopsy urine microbial profiles clustered very tightly to the fecal microbial profile. CONCLUSIONS: We describe two models of change in the urinary tract microbiota after prostate biopsy using 16S RNA gene analysis. Further research to determine what controls changes in the urinary microbiota after prostate biopsy can help us understand why some patients are more susceptible to develop post-biopsy infections.

A prospective study to examine the association of the urinary and fecal microbiota with prostate cancer diagnosis after transrectal biopsy of the prostate using 16sRNA gene analysis.

INTRODUCTION: There is accumulating evidence that variations in the human microbiota may promote disease states including cancer. Our goal was to examine the association between urinary and fecal microbial profiles and the diagnosis of prostate cancer (PC) in patients undergoing transrectal biopsy of the prostate. MATERIALS AND METHODS: We extracted total DNA from urine and fecal samples collected before a prostate biopsy performed for elevated prostatic specific antigen in patients suspected of having PC. We then amplified the extracted DNA and sequenced it using bacterial 16S rRNA gene high-throughput next-generation sequencing platform, and analyzed microbial profiles for taxonomy comparing those patients diagnosed with PC with those who did not receive that diagnosis. RESULTS: We included 30 patients in our analysis (60 samples, one urine and one fecal per patient). The majority of patients with PC (10/14) had similar bacterial communities within their urinary sample profile and clustered separately than patients without cancer (n = 16). Differential analysis of the operational taxonomical units (OTUs) in urine samples revealed decreased abundance of several bacterial species in patients with prostate cancer. Analysis of the bacterial taxonomies of the fecal samples did not reveal any clustering in concordance with benign or malignant prostate biopsies. Patients who had a Gleason score (GS) of 6 (n = 11) were present in both urine bacterial community clusters, but patients with GS 7 or higher (n = 3) did not cluster tightly with non-cancer subjects. CONCLUSIONS: The urinary microbiota of patients with PC tends to cluster separately from those without this disease. Further research is needed to investigate the urinary microbiome potential of serving as a biomarker that could be used to improve the accuracy of pre-biopsy models predicting the presence of PC in post-biopsy tissue examination.

Bilateral hydronephrosis and acute kidney injury secondary to pelvis lipomatosis.

A 57-year-old African American male presented with vague abdominal pain and bilateral flank pain. The patient was found to have bilateral hydronephrosis and significant renal function impairment secondary to pelvic lipomatosis. Pelvic lipomatosis represents a clinically-diagnosed unique cause of ureteral obstruction and subsequent renal impairment. We present a case report of newly diagnosed pelvic lipomatosis, the clinical and imaging characteristics for diagnosis, and its conservative management with serial ureteral stent exchanges.

Outcomes of treatment of stress urinary incontinence associated with female urethral diverticula: A selective approach.

AIMS: To assess surgical outcomes of concomitant treatment of SUI at time of transvaginal urethral diverticulectomy (TVUD) based on a selective approach. METHODS: Following Institutional Review Board (IRB) approval, we identified patients with a UD and SUI who underwent TVUD between July 2004 and January 2016. SUI was documented before and after surgery using subjective and objective parameters. Autologous pubovaginal slings (APVS) were used selectively based on surgeon and patient preference. RESULTS: A total of 61 patients underwent surgical treatment of urethral diverticula; 39 patients with UD and concomitant SUI. Mean age was 53 years. Mean follow-up was 16.2 months. There were 24 patients (62%) with SUI that underwent concomitant APVS. There was resolution of SUI in 20 of 24 patients (83%) who underwent a simultaneous APVS compared to 8 of 15 patients (53%) who underwent TVUD without APVS. Surgery resulted in the improvement or resolution of the majority of preoperative symptoms including recurrent urinary tract infection (UTI) (82% vs 15%), dyspareunia (64% vs 8%), and urgency (56% vs 13%) (preoperative vs postoperative). CONCLUSIONS: Female UD is often associated with SUI. Concomitant surgical treatment of UD and SUI often results in satisfactory control of bothersome SUI as well as other urinary symptoms such as UTI, dyspareunia and urgency. Treatment of SUI with APVS when undergoing TVUD is feasible with satisfactory outcomes.

The Use of Urodynamics Assessment Before the Surgical Treatment of BPH.

Lower urinary tract symptoms (LUTS) are a common problem in men especially with aging. The International Continence Society (ICS) revealed an overall prevalence of LUTS of about two-thirds of men age 40 years and above. The treatment approach depends on accurate determination of the underlying etiology. LUTS is not unique to benign prostate enlargement (BPE) and can be secondary to other causes. In the era where quality of care is important, accurate diagnosis and counseling to meet patients' expectations is of extreme paramount. Thus, proper assessment of patients who present with BPE and LUTS should be an important part of the work up process. Accurate diagnosis and identification of the cause will help to improve quality of treatment, optimize counseling, and improve treatment outcomes. Pressure flow urodynamic studies (PFUDs) are not only important tools that help to identify the underlying causes of LUTS; it is considered the "gold standard" for diagnosis of bladder outlet obstruction (BOO) in patients with enlarged prostate [1, 2]. However, there is a continuous debate on the value of using PFUDs and its association with improved outcomes.

Coronary Heart Disease, Diabetes, and Sexuality in Men.

Erectile dysfunction (ED) has been well recognized as a marker of increased cardiovascular risk for more than 15 years, especially in younger men. Early detection of ED represents an opportunity to intervene to decrease the risk of future cardiovascular events and limit the progression of ED severity. Evidence suggests there is a window of opportunity of 3 to 5 years from the onset of ED to subsequent cardiovascular events. This opportunity is usually missed if the onus is placed on the patient to seek care for his sexual problems. Unfortunately, these clear messages have not been incorporated into routine cardiovascular care. The reasons for these disparities within specialties are discussed in this article, in addition to management algorithms. Lifestyle modification is usually recommended as the first-line treatment to correct ED and lessen cardiovascular risk, but evidence suggests that this might be effective only in men without established cardiovascular comorbidities. In men with type 2 diabetes mellitus and established cardiovascular disease, lifestyle modification alone is unlikely to be effective. Cardiovascular medications are often associated with sexual dysfunction but changes in medication are more likely to be beneficial in men with milder recent-onset ED. A balanced view must be taken related to medication adverse events, taking into account optimal management of established cardiovascular disease. Testosterone deficiency has been associated with different metabolic disorders, especially metabolic syndrome and type 2 diabetes mellitus. Testosterone deficiency syndrome has been associated with an independent burden on sexual function globally and increased cardiovascular and all-cause mortality. Testosterone replacement therapy has been shown to improve multiple aspects of sexual function and, in some studies, has been associated with a decrease in mortality, especially in men with type 2 diabetes mellitus. Recent studies have suggested that phosphodiesterase type 5 inhibitors, the first-line medications to treat ED, could decrease cardiovascular and all-cause mortality, through multiple mechanisms, predominantly related to improved endothelial function.

Cancer, Benign Gynecology, and Sexual Function--Issues and Answers.

INTRODUCTION: The diagnosis, treatment, and survivorship of cancer have a profound effect on the quality of life and psychological well-being of men and women. Indeed, the perturbation of sexual function because of neoplasm has far-reaching implications. AIMS: To explore the prevalence, pathophysiology, and treatment of sexual issues in persons with cancer and offer evidence-based recommendations regarding optimal prevention and treatment strategies. METHODS: A committee of multidisciplinary specialists was formed as part of the larger International Sexual Medicine Consultation working with urologic and sexual medicine societies over a 1-year period to review the result of chronic-illness management on sexual function and satisfaction. The aims, goals, data collection techniques, and report format were defined by a central committee. MAIN OUTCOMES MEASURES: Expert consensus was based on evidence-based medical and psychosocial literature review, extensive group discussion, and an open presentation with a substantial discussion period. RESULTS: This summary evaluates contemporary literature concerning the prevalence, pathophysiology, and psychological impact of cancer diagnosis and treatment on sexual dysfunction. Evidence-based recommendations and guidelines for evaluation and management are presented. CONCLUSION: The diagnosis and treatment of cancer have a significant negative impact on sexual function and satisfaction. Comprehension of baseline sexual function, role of psychological supports, and available treatment options could attenuate the heavy burden of decreased sexual function.

A1 Adenosine Receptor-Mediated Inhibition of Parasympathetic Neuromuscular Transmission in Human and Murine Urinary Bladder.

The potential role of A1 adenosine receptors in modulating neuromuscular transmission in the detrusor muscle of the urinary bladder has been tested in human and murine preparations with the intent to determine the viability of using adenosine receptor agonists as adjuncts to treat overactive bladder. In human detrusor muscle preparations, contractile responses to electrical field stimulation were inhibited by the selective A1 adenosine receptor agonists 2-chloro-N(6)-cyclopentyladenosine, N(6)-cyclopentyladenosine (CPA), and adenosine (rank order of potency: 2-chloro-N(6)-cyclopentyladenosine > CPA > adenosine). Pretreatment with 8-cyclopentyl-3-[3-[[4(fluorosulphonyl)benzoyl]oxy]propyl]-1-propylxanthine, an irreversible A1 antagonist, blocked the effects of CPA, thus confirming the role of A1 receptors in human detrusor preparations. In murine detrusor muscle preparations, contractions evoked by electrical field stimulation were reduced by CPA or adenosine. Amplitudes of the P2X purinoceptor-mediated excitatory junctional potentials (EJPs) recorded with intracellular microelectrodes were reduced in amplitude by CPA and adenosine with no effect on the spontaneous EJP amplitudes, confirming the prejunctional action of these agents. 8-Cyclopentyltheophylline, a selective A1 receptor antagonist, reversed the effects of CPA on EJP amplitudes with no effect of spontaneous EJPs, confirming the role of A1 receptors in mediating these effects.

Contemporary Incidence and Mortality Rates of Neuroendocrine Prostate Cancer.

AIM: The purpose of the study was to provide an update ever the incidence and mortality for neuroendocrine prostate cancer (NEPC) in the United States. PATIENTS AND METHODS: Using a large national database, we examined changes in age-adjusted incidence (AAIR), mortality rates (MR) and 5-year cancer-specific survival (CSS) for 378 patients diagnosed with NEPC between 1992 and 2011. Analysis was performed for all NEPC and for its two major sub-groups [small cell carcinoma (SCC) and neuroendocrine carcinoma (NEC)]. RESULTS: AAIR of NEPC continues to rise in recent years (2004-2011:+6.8%/year, p>0.05). AAIR of SCC has been increasing significantly by 6.94%/year since 2001 (from 0.470 to 0.582/1,000,000 person years, p<0.05). Overall incidence-based mortality rates for NEPC did not change significantly since 1992 and similar trends were observed for SCC and NEC. CONCLUSION: The AAIR of SCC is increasing with no change in the MR of NEPC over the past 20 years.