Introduction
Priapism, defined as a prolonged and often painful penile erection persisting for more than four hours without sexual stimulation, is a urological emergency. Although its incidence is less than 0.01%, the condition carries serious consequences. Failure to treat promptly may result in permanent erectile dysfunction or even tissue necrosis.
The majority of cases represent ischemic (low-flow) priapism, caused by impaired venous outflow from the corpora cavernosa, leading to hypoxia, acidosis, and ischemic damage. Non-ischemic (high-flow) priapism, usually associated with trauma or arterial fistulas, is far less common and generally less emergent.
Drug-induced priapism is a recognized etiology. Medications such as antipsychotics, antidepressants, anticoagulants, α-adrenergic blockers, and phosphodiesterase-5 inhibitors (PDE5i) have all been implicated. Among PDE5i, sildenafil and tadalafil are widely prescribed for erectile dysfunction and lower urinary tract symptoms. Priapism linked to PDE5i, however, is exceptionally rare. In fact, the incidence of tadalafil-induced priapism has been estimated at approximately 0.7%.
Here we examine a unique case: a 47-year-old man with muscle-invasive bladder cancer (MIBC), previously treated with transurethral resection and radiation, who developed low-flow priapism after a single dose of tadalafil 5 mg. The case highlights the delicate interplay between oncological history, erectile dysfunction, and pharmacological therapy, offering key lessons for clinical practice.
The Case in Detail
A 47-year-old male presented to the emergency department with a chief complaint of persistent, painful erection lasting three days. He had no prior history of priapism and denied taking any psychotropic, anticoagulant, hormonal, or antihypertensive drugs known to predispose to the condition.
Oncological Background
The patient had a history of muscle-invasive bladder cancer (MIBC). Instead of radical cystectomy, he had opted for transurethral resection of the bladder tumor (TURBT) followed by extensive pelvic radiotherapy (33 sessions, 50 Gy total). These treatments, while aimed at controlling malignancy, left him with erectile dysfunction—a frequent complication of pelvic irradiation, affecting up to 30–40% of patients.
Triggering Event
Seeking relief for erectile dysfunction, he ingested a single 5 mg dose of tadalafil. Within one hour, he developed an erection that persisted far beyond the desired duration, eventually lasting more than 72 hours.
Clinical Findings
Upon admission:
- The penis was rigid with severe pain, consistent with Erection Hardness Score (EHS) 4.
- Laboratory results indicated anemia, leukocytosis, hypoalbuminemia, hyponatremia, hyperkalemia, and elevated serum urea and creatinine, consistent with acute on chronic kidney disease.
- Imaging: Doppler ultrasound revealed thickened, irregular tunica albuginea and low-flow priapism (systolic velocity ~13 mL/s, far below the normal >35 mL/s). Abdominal ultrasound showed bilateral hydronephrosis; chest X-ray identified pulmonary metastases and pleural effusion.
Management
The initial approach involved aspiration of cavernosal blood and intracavernosal epinephrine injections (2 cc repeated five times). Despite multiple attempts, there was no clinical improvement. The patient then underwent distal shunting surgery to decompress the corpora cavernosa.
Unfortunately, his prognosis was already poor. The priapism episode coincided with progressive oncological disease, including widespread metastasis. He ultimately died of complications related to advanced bladder cancer.
Discussion: Understanding the Case
Radiation-Induced Erectile Dysfunction (RiED)
Pelvic irradiation is notorious for causing vascular and neurogenic injury. Endothelial dysfunction, cavernous nerve fibrosis, and impaired nitric oxide signaling all contribute to post-radiotherapy erectile dysfunction. For patients like this, PDE5i are often prescribed as first-line therapy. Yet paradoxically, the very medication meant to restore sexual function triggered a rare but devastating complication.
PDE5 Inhibitors and Priapism
PDE5 inhibitors increase cyclic guanosine monophosphate (cGMP), leading to smooth muscle relaxation and penile tumescence. Under normal conditions, detumescence follows as PDE5 activity degrades cGMP. Rarely, excessive prolongation occurs, tipping the balance toward priapism. Reported risk factors include:
- Concomitant use of α-blockers or nitrates
- Pre-existing hematological disease (sickle cell anemia, leukemia)
- Malignancy with vascular involvement
- Previous episodes of priapism
In this case, tadalafil was used as a monotherapy at a minimal dose, yet priapism ensued. This underscores that susceptibility may be heightened in patients with altered pelvic vascular architecture from cancer and radiotherapy.
Priapism in Oncological Patients
Secondary priapism due to metastatic spread to the penis has been documented, though it is exceedingly rare. While penile metastasis cannot be entirely excluded here (due to lack of pelvic CT imaging), the temporal association with tadalafil ingestion makes drug-induced priapism the more plausible explanation.
Management of Low-Flow Priapism
Low-flow priapism is a urological emergency. The therapeutic window is narrow: irreversible cavernosal fibrosis and erectile dysfunction can occur after 24 hours of ischemia.
Standard management follows a stepwise protocol:
- Aspiration of cavernosal blood, followed by irrigation with saline.
- Intracavernosal injection of sympathomimetics, usually phenylephrine.
- If unsuccessful, surgical interventions such as shunts or, in refractory cases, penile prosthesis implantation.
In this case, despite adherence to guidelines, therapy was unsuccessful, reflecting the advanced underlying disease and prolonged ischemia (72 hours). The episode highlights the importance of early recognition and rapid intervention.
Lessons Learned
This case, though rare, provides several broader lessons:
- Even minimal doses of tadalafil can induce priapism in predisposed patients. Prior oncological history and radiation exposure may amplify susceptibility.
- Timing of intervention is crucial. Delayed presentation (72 hours) reduced the likelihood of successful detumescence and functional recovery.
- Differential diagnosis matters. While drug-induced priapism was most likely here, clinicians should remain vigilant for malignant priapism caused by penile metastasis.
- Patient counseling is essential. Men with bladder cancer and post-radiotherapy erectile dysfunction should be carefully counseled on both the potential benefits and rare risks of PDE5 inhibitors.
Broader Context: Priapism and Modern Urology
Priapism remains a rare entity, but when it occurs, it is dramatic and often devastating. Drug-induced priapism accounts for roughly 30% of cases, but PDE5 inhibitors are a small minority among these. Far more common culprits are antipsychotics (e.g., risperidone, olanzapine) and antidepressants (e.g., trazodone).
Nevertheless, the expanding prescription of PDE5i for both erectile dysfunction and lower urinary tract symptoms means urologists must remain alert. While most men will never experience priapism from tadalafil, vigilance is warranted in cancer survivors, men with prior pelvic irradiation, or those with complex comorbidities.
Conclusion
This case report of priapism following a single 5 mg dose of tadalafil in a patient with MIBC illustrates that even minimal exposure can trigger severe adverse events in predisposed individuals. While exceedingly rare, the possibility must not be ignored, especially in oncology patients with prior radiotherapy.
The key takeaway is twofold: first, early diagnosis and intervention are critical to preserving function; second, careful patient selection and counseling are indispensable when prescribing PDE5 inhibitors in high-risk populations.
In modern medicine, where drug repurposing and expanded indications are common, this case serves as a reminder that vigilance for rare adverse outcomes must remain sharp.
FAQ
1. Can tadalafil really cause priapism at low doses?
Yes, although extremely rare, priapism can occur even after a single 5 mg dose, particularly in patients with additional risk factors such as cancer, pelvic irradiation, or vascular abnormalities.
2. How is priapism managed in the emergency setting?
Management begins with aspiration and irrigation of cavernosal blood, followed by intracavernosal sympathomimetic injections. If unsuccessful, surgical shunts or prostheses may be required. Early intervention is critical for preventing permanent erectile dysfunction.
3. Should patients with bladder cancer avoid PDE5 inhibitors?
Not necessarily. PDE5 inhibitors remain effective for radiation-induced erectile dysfunction, but such patients should be carefully counseled about risks, and prompt medical attention should be sought for erections lasting more than four hours.
