prostate

Lower Urinary Tract Symptoms in Men: A Review

Author/s: 
John T Wei, Casey A Dauw, Casey N Brodsky

Importance: Up to 40% of men older than 50 years have lower urinary tract symptoms, including urinary urgency, nocturia, and weak urinary stream, due to disorders of the bladder and prostate. These symptoms negatively affect quality of life and may be associated with urinary retention, which can cause kidney insufficiency, bladder calculi, hematuria, and urinary tract infections.

Observations: In men, lower urinary tract symptoms can be caused by bladder outlet obstruction secondary to benign prostatic hyperplasia (BPH), an overactive bladder detrusor (a syndrome of urinary urgency and frequency), or both. Behavioral therapy, including pelvic floor physical therapy, timed voiding (voiding at specific intervals), and fluid restriction, can improve symptoms. Medications including α-blockers (such as tamsulosin), 5α-reductase inhibitors (such as finasteride), and phosphodiesterase 5 inhibitors (such as tadalafil) improve lower urinary tract symptoms (mean improvement, 3-10 points on the International Prostate Symptom Score [IPSS], which ranges from 0-35, with higher scores indicating greater severity) and can prevent symptom worsening measured by increased IPSS greater than or equal to 4 points or development of secondary sequelae, such as urinary retention. Combination therapies are more effective than monotherapy. For example, α-blockade (eg, tamsulosin) combined with 5α-reductase inhibition (eg, finasteride) lowers progression risk to less than 10% compared with 10% to 15% with monotherapy. Treatment for overactive bladder detrusor, including anticholinergics (eg, trospium) and β3 agonists (eg, mirabegron), reduces voiding frequency by 2 to 4 times per day and reduces episodes of urinary incontinence by 10 to 20 times per week. Surgery (eg, transurethral resection of the prostate, holmium laser enucleation of the prostate) and minimally invasive surgery are highly effective for refractory or complicated cases of BPH, defined as persistent symptoms despite behavioral and pharmacologic therapy, and these therapies can improve IPSS by 10 to 15 points. Minimally invasive procedures, such as water vapor therapy (endoscopic injection of steam into BPH tissue) and prostatic urethral lift (endoscopic insertion of nonabsorbable suture implants that mechanically open the urethra), have lower complication rates of incontinence (0%-8%), erectile dysfunction (0%-3%), and retrograde ejaculation (0%-3%) but are associated with increased need for surgical retreatment (3.4%-21%) compared with transurethral resection of the prostate (5%) and holmium laser enucleation of the prostate (3.3%).

Conclusions and relevance: Lower urinary tract symptoms, defined as urinary urgency, nocturia, or weak stream, are common among men and are usually caused by BPH, overactive bladder detrusor, or both. First-line therapy consists of behavioral intervention, such as pelvic floor physical therapy and timed voiding, as well as pharmacologic therapy, including α-adrenergic blockers (tamsulosin), 5α-reductase inhibitors (finasteride), phosphodiesterase inhibitors (tadalafil), anticholinergics (trospium), and β3 agonists (mirabegron).

Prostate Cancer: A Review

Author/s: 
Ruben Raychaudhuri, Daniel W Lin, R Bruce Montgomery

Importance: Prostate cancer is the most common nonskin cancer in men in the US, with an estimated 299 010 new cases and 35 250 deaths in 2024. Prostate cancer is the second most common cancer in men worldwide, with 1 466 680 new cases and 396 792 deaths in 2022.

Observations: The most common type of prostate cancer is adenocarcinoma (≥99%), and the median age at diagnosis is 67 years. More than 50% of prostate cancer risk is attributable to genetic factors; older age and Black race (annual incidence rate, 173.0 cases per 100 000 Black men vs 97.1 cases per 100 000 White men) are also strong risk factors. Recent guidelines encourage shared decision-making for prostate-specific antigen (PSA) screening. At diagnosis, approximately 75% of patients have cancer localized to the prostate, which is associated with a 5-year survival rate of nearly 100%. Based on risk stratification that incorporates life expectancy, tumor grade (Gleason score), tumor size, and PSA level, one-third of patients with localized prostate cancer are appropriate for active surveillance with serial PSA measurements, prostate biopsies, or magnetic resonance imaging, and initiation of treatment if the Gleason score or tumor stage increases. For patients with higher-risk disease, radiation therapy or radical prostatectomy are reasonable options; treatment decision-making should include consideration of adverse events and comorbidities. Despite definitive therapy, 2% to 56% of men with localized disease develop distant metastases, depending on tumor risk factors. At presentation, approximately 14% of patients have metastases to regional lymph nodes. An additional 10% of men have distant metastases that are associated with a 5-year survival rate of 37%. Treatment of metastatic prostate cancer primarily relies on androgen deprivation therapy, most commonly through medical castration with gonadotropin-releasing hormone agonists. For patients with newly diagnosed metastatic prostate cancer, the addition of androgen receptor pathway inhibitors (eg, darolutamide, abiraterone) improves survival. Use of abiraterone improved the median overall survival from 36.5 months to 53.3 months (hazard ratio, 0.66 [95% CI, 0.56-0.78]) compared with medical castration alone. Chemotherapy (docetaxel) may be considered, especially for patients with more extensive disease.

Conclusions and relevance: Approximately 1.5 million new cases of prostate cancer are diagnosed annually worldwide. Approximately 75% of patients present with cancer localized to the prostate, which is associated with a 5-year survival rate of nearly 100%. Management includes active surveillance, prostatectomy, or radiation therapy, depending on risk of progression. Approximately 10% of patients present with metastatic prostate cancer, which has a 5-year survival rate of 37%. First-line therapies for metastatic prostate cancer include androgen deprivation and novel androgen receptor pathway inhibitors, and chemotherapy for appropriate patients.

Fifteen-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Prostate Cancer

Author/s: 
Hamdy, Freddie, Donovan, Jenny, Lane, Athene, Metcalfe, Chris, Davis, Michael, Turner, Emma, Martin, Richard, Young, Grace, Walsh, Eleanor, Bryant, Bollina, Prasad, Doble, Andrew

Background

Between 1999 and 2009 in the United Kingdom, 82,429 men between 50 and 69 years of age received a prostate-specific antigen (PSA) test. Localized prostate cancer was diagnosed in 2664 men. Of these men, 1643 were enrolled in a trial to evaluate the effectiveness of treatments, with 545 randomly assigned to receive active monitoring, 553 to undergo prostatectomy, and 545 to undergo radiotherapy.
Methods

At a median follow-up of 15 years (range, 11 to 21), we compared the results in this population with respect to death from prostate cancer (the primary outcome) and death from any cause, metastases, disease progression, and initiation of long-term androgen-deprivation therapy (secondary outcomes).
Results

Follow-up was complete for 1610 patients (98%). A risk-stratification analysis showed that more than one third of the men had intermediate or high-risk disease at diagnosis. Death from prostate cancer occurred in 45 men (2.7%): 17 (3.1%) in the active-monitoring group, 12 (2.2%) in the prostatectomy group, and 16 (2.9%) in the radiotherapy group (P=0.53 for the overall comparison). Death from any cause occurred in 356 men (21.7%), with similar numbers in all three groups. Metastases developed in 51 men (9.4%) in the active-monitoring group, in 26 (4.7%) in the prostatectomy group, and in 27 (5.0%) in the radiotherapy group. Long-term androgen-deprivation therapy was initiated in 69 men (12.7%), 40 (7.2%), and 42 (7.7%), respectively; clinical progression occurred in 141 men (25.9%), 58 (10.5%), and 60 (11.0%), respectively. In the active-monitoring group, 133 men (24.4%) were alive without any prostate cancer treatment at the end of follow-up. No differential effects on cancer-specific mortality were noted in relation to the baseline PSA level, tumor stage or grade, or risk-stratification score. No treatment complications were reported after the 10-year analysis.
Conclusions

After 15 years of follow-up, prostate cancer–specific mortality was low regardless of the treatment assigned. Thus, the choice of therapy involves weighing trade-offs between benefits and harms associated with treatments for localized prostate cancer. (Funded by the National Institute for Health and Care Research; ProtecT Current Controlled Trials number, ISRCTN20141297. opens in new tab; ClinicalTrials.gov number, NCT02044172. opens in new tab.)

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