Prostate cancer survivors approach 2.8 million in number and represent 1 in 5 of all cancer survivors in the United States. While guidelines exist for timely treatment and surveillance for recurrent disease, there is limited availability of guidelines that facilitate the provision of posttreatment clinical follow-up care to address the myriad of long-term and late effects that survivors may face. Based on recommendations set forth by a National Cancer Survivorship Resource Center expert panel, the American Cancer Society developed clinical follow-up care guidelines to facilitate the provision of posttreatment care by primary care clinicians. These guidelines were developed using a combined approach of evidence synthesis and expert consensus. Existing guidelines for health promotion, surveillance, and screening for second primary cancers were referenced when available. To promote comprehensive follow-up care and optimal health and quality of life for the posttreatment survivor, the guidelines address health promotion, surveillance for prostate cancer recurrence, screening for second primary cancers, long-term and late effects assessment and management, psychosocial issues, and care coordination among the oncology team, primary care clinicians, and nononcology specialists. A key challenge to the development of these guidelines was the limited availability of published evidence for management of prostate cancer survivors after treatment. Much of the evidence relies on studies with small sample sizes and retrospective analyses of facility-specific and population databases.

/pdf/american-cancer-society-prostate-cancer-survivorship-care-5c3kan7aw1.pdf

American Cancer Society prostate cancer survivorship care guidelines

Drugs produce their therapeutic effects by modulating specific targets, and there are 89 innovative targets of first-in-class drugs approved in 2004-17, each with information about drug clinical trial dated back to 1984. Analysis of the clinical trial timelines of these targets may reveal the trial-speed differentiating features for facilitating target assessment. Here we present a comprehensive analysis of all these 89 targets, following the earlier studies for prospective prediction of clinical success of the targets of clinical trial drugs. Our analysis confirmed the literature-reported common druggability characteristics for clinical success of these innovative targets, exposed trial-speed differentiating features associated to the on-target and off-target collateral effects in humans and further revealed a simple rule for identifying the speedy human targets through clinical trials (from the earliest phase I to the 1st drug approval within 8 years). This simple rule correctly identified 75.0% of the 28 speedy human targets and only unexpectedly misclassified 13.2% of 53 non-speedy human targets. Certain extraordinary circumstances were also discovered to likely contribute to the misclassification of some human targets by this simple rule. Investigation and knowledge of trial-speed differentiating features enable prioritized drug discovery and development.

Clinical trials, progression-speed differentiating features and swiftness rule of the innovative targets of first-in-class drugs.

The physiological functions of the urinary bladder are to store and periodically expel urine. These tasks are facilitated by the contraction and relaxation of the urinary bladder smooth muscle (UBSM), also known as detrusor smooth muscle, which comprises the bladder wall. The large-conductance voltage- and Ca2+-activated K+ (BK, BKCa, MaxiK, Slo1, or KCa1.1) channel is highly expressed in UBSM and is arguably the most important physiologically relevant K+ channel that regulates UBSM function. Its significance arises from the fact that the BK channel is the only K+ channel that is activated by increases in both voltage and intracellular Ca2+. The BK channels control UBSM excitability and contractility by maintaining the resting membrane potential and shaping the repolarization phase of the spontaneous action potentials that determine UBSM spontaneous rhythmic contractility. In UBSM, these channels have complex regulatory mechanisms involving integrated intracellular Ca2+ signals, protein kinases, phosphodi...

https://www.physiology.org/doi/pdf/10.1152/ajpregu.00142.2014

Central role of the BK channel in urinary bladder smooth muscle physiology and pathophysiology.

Durable Efficacy and Safety of Long-Term OnabotulinumtoxinA Treatment in Patients with Overactive Bladder Syndrome: Final Results of a 3.5-Year Study.

PURPOSE\nAlthough caffeine consumption is common and generally believed to affect bladder function, little is known about caffeine intake and incident urinary incontinence.\n\n\nMATERIALS AND METHODS\nWe performed a prospective cohort study in 65,176 women 37 to 79 years old without incontinence in the Nurses' Health Study and the Nurses' Health Study II. Incident incontinence was identified from questionnaires during 4 years of followup. Caffeine intake was measured using food frequency questionnaires administered before incontinence development. The multivariate adjusted relative risk of the relation between caffeine intake and incontinence risk as well as attributable risk were calculated.\n\n\nRESULTS\nCaffeine was not associated with incontinence monthly or more. However, there was a modest, significantly increased risk of incontinence at least weekly in women with the highest (greater than 450 mg) vs the lowest (less than 150 mg) daily intake (RR 1.19, 95% CI 1.06-1.34) and a significant trend of increasing risk with increasing intake (p for trend = 0.01). This risk appeared focused on incident urgency incontinence (greater than 450 vs less than 150 mg daily, RR 1.34, 95% CI 1.00-1.80, p for trend = 0.05) but not on stress or mixed incontinence (p for trend = 0.75 and 0.19, respectively). The attributable risk of urgency incontinence associated with high caffeine intake was 25%.\n\n\nCONCLUSIONS\nFindings suggest that high but not lower caffeine intake is associated with a modest increase in the incidence of frequent urgency incontinence. A fourth of the cases with the highest caffeine consumption would be eliminated if high caffeine intake were eliminated. Confirmation of these findings in other studies is needed before recommendations can be made.

Caffeine Intake and Risk of Stress, Urgency, and Mixed Urinary Incontinence

The overactive bladder (OAB) picture has dramatically changed in the last 20 years. A quarter century ago, this symptom complex did not even exist. Bladder hyperactivity and urgency incontinence were separate entities poorly understood and treated only with the first-generation anti-muscarinic medications, propantheline and oxybutynin. Only in early 2000 came the concept of this syndrome made of four intimately linked symptoms that we today call OAB. With this concept, new pharmacological agents were launched. These new agents may have not dramatically improved symptoms in comparison with older agents, but undeniably have a more tolerable side effect profile, leading to better compliance and adherence. Neuromodulation was introduced a few years later, giving hope to the worst OAB cases, but with a limited applicability due to its cost. A real revolution occurred around 2010 with the demonstration of onabotulinumtoxinA’s efficacy in controlling the symptoms of OAB. Several years passed before it proved its place in the treatment algorithm for OAB. It is definitely time for the Canadian Urological Association (CUA) to produce guidelines to help Canadian urologists better integrate a sequence of investigation, diagnosis, and treatment, which has become more complex over the years.

To do so, the CUA gave a group of experts, Canadian physicians and nurses, the difficult task of putting together a comprehensive document to guide all interested professionals in the management of this interesting and common syndrome, which has so much impact on our patients’ quality of life.

An executive summary of the CUA guideline on OAB is available as an Appendix at www.cuaj.ca.

/pdf/cua-guideline-on-adult-overactive-bladder-4rjymsgrml.pdf

CUA guideline on adult overactive bladder

Overactive bladder (OAB) is common in both men and women. It is a symptom complex that causes significant detriment to quality of life in patients. Although the prevalence of OAB is similar in both sexes, there are sex-specific differences in individual symptoms and the impact on quality of life. The coexistence of benign prostatic hyperplasia with OAB can worsen quality of life in men. This review examines the major studies that looked at the epidemiology of OAB as it relates to both sexes. It focuses on both the overall prevalence rates and the incidence of individual symptoms. This paper also addresses the level of bother and quality of life in men and women with OAB. In addition, the relationship between OAB and benign prostatic hyperplasia is reviewed.

/pdf/review-of-the-epidemiology-of-overactive-bladder-3gsk9fuyta.pdf

Review of the epidemiology of overactive bladder.

Introduction
Overactive bladder (OAB) is a prevalent condition that has a significant impact on quality of life. The usual treatment approach is both behavioral and pharmacological. The first-line pharmacological treatment commonly utilizes anticholinergic agents, which may be limited by their tolerability, efficacy, and long-term compliance. Developments in elucidating the pathophysiology of OAB and alternative targets for pharmacological therapy have led to newer agents being developed to manage this condition. These agents include mirabegron and botulinum toxin, which have alternate mechanism of action and avoid the anticholinergic side effects.

/pdf/pharmacotherapy-of-overactive-bladder-in-adults-a-review-of-3irrlzogvt.pdf

Pharmacotherapy of overactive bladder in adults: a review of efficacy, tolerability, and quality of life

Introduction: There has been increasing evidence supporting the use of adjuvant radiotherapy after radical prostatectomy (RP) for prostate cancer. Significant stress incontinence after RP is not uncommon and the artificial urinary sphincter (AUS) is the gold standard of treatment. Our objective was to assess if increased use of radiotherapy after RP has changed the rate of erosion and infection in the face of improvement in radiation technique and equipment in men who had an AUS implanted in the last 10 years. Methods: We retrospectively examined 118 patients from December 2001 to January 2012 who underwent a RP with or without postoperative radiotherapy and subsequently had an AUS implanted. We divided the patients into two cohorts (Group 1: December 2001–December 2006 and Group 2: January 2007–January 2012). We reviewed all patient records for age, cuff size implanted, history of postoperative radiotherapy, previous incontinence surgery, revisions, and complications (erosion/infection). Results: There were 36 and 82 patients in Groups 1 and 2, respectively. The mean age was similar between groups, 67 years both groups (p = 0.980). The number of patients treated with postoperative radiotherapy was similar between groups (36% vs. 32%, p = 0.640, respectively). There was no difference in the incidence of erosion or infection between Group 1 and 2 (p = 0.848 and p = 0.178, respectively). The overall relative risk (RR) of erosion was significantly higher in those who had radiotherapy compared to those who did not (RR 4.05, 95% confidence interval 1.1–15.3). Conclusions: Over the last 10 years, there has not been an increase in the number of patients receiving an AUS after RP and radiotherapy at our centre. During this time, the incidence of erosion and infection has not increased. However, our study reaffirms that the relative risk of erosion remains higher in patients who have had radiotherapy despite improvement in radiation treatment techniques and equipment.

/pdf/artificial-urinary-sphincter-erosion-after-radical-jw51txgnmu.pdf

Artificial urinary sphincter erosion after radical prostatectomy in patients treated with and without radiation.

Commonly prescribed urologic medications can have significant ophthalmologic side effects. The existing information can be conflicting. We looked at alpha-blockers and intraoperative floppy iris syndrome (IFIS), phosphodiesterase type 5 (PDE5) inhibitors and non-arteritic ischemic optic neuropathy (NAION) and lastly anticholinergic medications and glaucoma. There is no conclusive scientific data on what to do if the risk of urinary retention is low to moderate, however, we recommend that patients having cataract surgery should stop alpha-blocker medications preoperatively. If there is a high risk of urinary retention, the alpha-blocker should not be withheld, with the active involvement of the ophthalmologist. The role of using 5 alpha-reductase inhibitors (5ARIs) can be considered. There is no convincing evidence that PDE5 inhibitors cause non-arteritic anterior ischemic optic neuropathy (NAION), but patients should be advised of the possible risk of visual loss, especially in patients with risk factors of ischemic heart disease. Acute angle closure glaucoma (AACG or closed angle glaucoma) is very rarely caused by anticholinergic medications in patients with narrow angle anterior eye chambers. However, these medications are safe in patients with open angle glaucoma or treated closed angle glaucoma. Urologists should inquire about the patient’s glaucoma history from his/her ophthalmologist before starting an anticholinergic medication.

Sidney B. Radomski

Papers

CUA guideline on adult overactive bladder

Review of the epidemiology of overactive bladder.

Pharmacotherapy of overactive bladder in adults: a review of efficacy, tolerability, and quality of life

Artificial urinary sphincter erosion after radical prostatectomy in patients treated with and without radiation.

Urologic medications and ophthalmologic side effects: a review.