In a 47-year-old man with chronic intermittent urinary urgency, dysuria at the penile tip, achy testicles, symptoms that worsen after ejaculation and sometimes improve after a bowel movement, negative urine cultures, and currently taking mirabegron (Myrbetriq) 50 mg, what is the most likely diagnosis and recommended management?

Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) with Inadequate Response to Mirabegron Monotherapy

This clinical presentation is most consistent with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), and the current mirabegron monotherapy is insufficient because it only addresses storage symptoms while ignoring the underlying pelvic pain syndrome and possible bladder outlet obstruction component. 1

Most Likely Diagnosis

CP/CPPS characteristically causes pain at the tip of the penis, perineum, or testicles, with pain exacerbated by urination or ejaculation—exactly matching this patient's symptom pattern. 1 The key diagnostic features present in this case include:

• Pain at the penile tip during urination (pathognomonic for CP/CPPS) 1
• Post-ejaculatory symptom exacerbation (classic for CP/CPPS) 1
• Achy testicles (typical pain distribution) 1
• Symptom relief with bowel movements (suggests pelvic floor muscle involvement) 1
• Chronic intermittent course over years (defining feature requiring ≥3 months of pelvic pain) 1

The negative urine cultures effectively rule out bacterial prostatitis, and the chronic nature with specific pain patterns strongly indicates CP/CPPS rather than simple overactive bladder. 1

Why Current Treatment Is Failing

Mirabegron 50 mg is a β3-adrenoceptor agonist that only addresses storage symptoms (urgency, frequency) by relaxing the detrusor muscle during bladder filling—it does nothing for the underlying pelvic pain syndrome or potential bladder outlet obstruction. 2, 3

The European Association of Urology explicitly states that mirabegron is indicated for storage symptoms (OAB component) but not for voiding symptoms or pain syndromes. 3 This patient needs treatment targeting:

1. The pain syndrome itself (CP/CPPS)
2. Possible bladder outlet obstruction (suggested by chronic LUTS in a 47-year-old man)
3. Storage symptoms (already partially addressed by mirabegron)

Recommended Management Algorithm

Step 1: Add Alpha-Blocker Therapy

Add an α1-adrenergic blocker (tamsulosin 0.4 mg daily or alfuzosin 10 mg daily) to the existing mirabegron regimen. 2

• Alpha-blockers are first-line for male LUTS with suspected bladder outlet obstruction 2
• The combination of mirabegron (for storage symptoms) plus alpha-blocker (for voiding symptoms and potential prostatic component) is supported by guidelines 2
• Assess response in 2-4 weeks 2

Critical caveat: Warn the patient about ejaculatory dysfunction (especially with tamsulosin/silodosin), which occurs significantly more than placebo and could worsen his post-ejaculatory symptoms. 2 Consider alfuzosin or doxazosin as alternatives with lower ejaculatory dysfunction rates.

Step 2: Consider Adding Antimuscarinic if Storage Symptoms Persist

If urgency and frequency remain bothersome after 4 weeks of combination therapy, add an antimuscarinic (solifenacin 5 mg) to create triple therapy. 2

• The SYNERGY trials demonstrated that solifenacin 5 mg plus mirabegron 50 mg is superior to either monotherapy for reducing incontinence episodes and micturitions 2
• Effect sizes were additive (combination: -0.95 micturitions/24h vs monotherapy: -0.39 to -0.56) 2
• Monitor post-void residual volume regularly as urinary retention risk increases with combination therapy 2

Step 3: Address the Pain Syndrome Directly

The pelvic pain component requires specific CP/CPPS management beyond urological medications. 1

Key interventions include:

• Pelvic floor physical therapy (addresses the bowel movement correlation and muscle spasm) 1
• Consider referral to pain management or pelvic pain specialist for multimodal pain treatment 1
• Evaluate for pelvic floor muscle spasm on digital rectal examination 1

Step 4: Specialized Testing if No Improvement

If symptoms persist after 8-12 weeks of optimized medical therapy, obtain: 2

• Uroflowmetry with post-void residual (assess for obstruction; Qmax <10 ml/s suggests significant BOO) 2
• Pressure-flow studies if Qmax >10 ml/s but symptoms persist (to confirm/exclude obstruction before considering intervention) 2
• Consider transrectal ultrasound or pelvic MRI if ejaculatory duct obstruction suspected 1

Critical Pitfalls to Avoid

1. Do not dismiss the pain component as purely urological—CP/CPPS and interstitial cystitis/bladder pain syndrome have overlapping presentations, and some patients meet criteria for both conditions requiring combined treatment approaches. 1

2. Do not perform prostatic massage—while this patient doesn't have acute bacterial prostatitis, aggressive prostatic manipulation can worsen CP/CPPS symptoms. 1

3. Monitor for urinary retention with combination therapy—the combination of mirabegron plus antimuscarinic increases retention risk, though mirabegron alone has minimal effect on post-void residual. 2

4. Recognize that "pressure" rather than "pain" is common—many CP/CPPS patients describe discomfort as pressure or the constant urge to void to relieve discomfort. 1

5. The alcohol paradox makes sense—alcohol may provide temporary anxiolytic effects and reduce pelvic floor muscle tension, explaining symptom relief despite increased urine production. This supports the pelvic floor dysfunction component of CP/CPPS.

Timeline for Assessment

• 2-4 weeks: Assess alpha-blocker response 2
• 4-8 weeks: Consider increasing mirabegron dose or adding antimuscarinic if storage symptoms inadequate 4
• 8-12 weeks: Full assessment of combination therapy efficacy 2
• If treatment fails: Refer to urologist for specialized testing and possible interventional therapy 2