Patient Preference of Apalutamide Versus Enzalutamide for Recurrent or Metastatic Hormone-sensitive Prostate Cancer: An Open-label, Randomized, Crossover Trial.

BACKGROUND AND OBJECTIVE: Treatment preference regarding apalutamide versus enzalutamide in prostate cancer (PCa) and the factors influencing decisions are largely unknown. Our aim was to investigate the preference for apalutamide versus enzalutamide among prostate cancer patients and their physicians and caregivers, and factors influencing their decision. METHODS: This was a prospective, open-label, randomized, crossover trial. Patients with recurrence of localized PCa or with metastatic disease not considered as high-risk or high-volume and on continued androgen deprivation therapy were recruited. All subjects received a trial of two agents, apalutamide (A) and enzalutamide (E), for 12 wk each, with a 5-wk washout period in between. The sequencing of the drugs was randomized. The primary outcome was patient preference for one the drugs, assessed at the end of the study. Other outcomes included factors influencing patient preference, a comparison of side-effect profiles, and patients' quality of life (QoL). Physician and caregiver preferences for the drugs and factors affecting their choice were also assessed. KEY FINDINGS AND LIMITATIONS: A total of 74 patients met the eligibility criteria and were randomized to the A â†’ E or E â†’ A arm. Of these, 66 patients (89.1%; 32 A â†’ E, 34 E â†’ A) completed the study. Baseline characteristics were comparable between the two groups, and ∼90% of the patients had low-volume metastatic disease. After completion of both treatments for 12 wk each, the difference in preference for A over E was 17.8%, with similar trends for preference of A over E among physicians (18.2%) and caregivers (22.4%). Fewer side effect was the most critical factor influencing the preference of patients. Among the side effects, less fatigue was the benefit of A over E most frequently reported. No notable difference in QoL was observed between the two drugs. However, the study was terminated on interim analysis and the results might not be conclusive. CONCLUSIONS: There was a trend for preference of A over E among patients with predominantly low-volume recurrent or metastatic PCa and their physicians and caregivers. Fewer side effects was the most critical factor influencing their choice. PATIENT SUMMARY: Patients with low-volume recurrent or metastatic prostate cancer tended to prefer treatment with apalutamide over enzalutamide. Side effects were the most critical factor influencing treatment preference.

The Risk of Upper Urinary Tract Involvement in Patients With Ketamine-Associated Uropathy.

PURPOSE: The aims of this study were to investigate the prevalence of upper tract involvement in ketamine-associated uropathy, and to determine the predictors of hydronephrosis in patients with a history of ketamine abuse. METHODS: This was a cross-sectional study of a prospective cohort of patients with ketamine-associated uropathy. Data including demographics, pattern of ketamine abuse, pelvic pain and urgency or frequency (PUF) symptom score, uroflowmetry (UFM) parameters, serum renal function, and liver function tests were collected. Upon consultation, ultrasonography was performed to assess the function of the urinary system. RESULTS: From December 2011 to October 2015, we treated 572 patients with ketamine-associated uropathy. Of these patients, 207 (36.2%) had managed to achieve abstinence at the time of their first consultation. Ninety-six patients (16.8%) in the cohort were found to have hydronephrosis on ultrasonography. Univariate analysis identified age, duration of ketamine abuse, PUF symptom score, voided volume on UFM, serum creatinine levels >100 µmol/L, and an abnormal serum liver enzyme profile as factors associated with hydronephrosis. Logistic regression revealed the following parameters to be statistically related to hydronephrosis: age (adjusted odds ratio [OR], 1.090; 95% confidence interval [CI], 1.020-1.166; P=0.012), functional bladder capacity (adjusted OR, 0.997; 95% CI, 0.995-0.999; P=0.029), serum creatinine >100 µmol/L (adjusted OR, 3.107; 95% CI, 1.238-7.794; P=0.016, and an abnormal serum liver enzyme profile (adjusted OR, 1.967; 95% CI, 1.213-3.187; P=0.006). CONCLUSIONS: Ketamine-associated uropathy can involve the upper urinary tract. Patient demographics as well as investigations of UFM, renal function tests, and liver function tests may allow us to identify at-risk patients.

Clinical Outcome of a Prospective Case Series of Patients With Ketamine Cystitis Who Underwent Standardized Treatment Protocol.

OBJECTIVE: To assess the outcome of a prospective cohort of patients with ketamine-associated uropathy after standardized treatment. METHODS: This is a prospective case series of patients with ketamine-related urologic problems. Management for the patients includes a 4-tier approach, namely anti-inflammatory or anti-cholinergic drugs, opioid analgesics or pregabalin, intravesical hyaluronic acid, and finally, surgical intervention including hydrodistension and augmentation cystoplasty. Outcome was assessed with functional bladder capacity, pelvic pain and urgency or frequency (PUF) symptom scale, and the EuroQol visual analog scale. RESULTS: Between December 2011 and June 2014, 463 patients presented with ketamine-associated uropathy. All were managed by the same standardized protocol. Among these patients, 319 patients came back for follow-up assessment. Overall mean follow-up duration was 10.7 ± 8.5 months. For those patients who received first-line treatment (290 patients), there was a significant improvement in PUF scores, the EuroQol visual analog scale, and functional bladder capacity. Both abstinence from ketamine usage and the amount of ketamine consumed were factors predicting the improvement of PUF scores. For those patients who required second-line oral therapy (62 patients), 42 patients (67.7%) reported improvement in symptoms. Eight patients have completed intravesical therapy. There was a significant improvement in voided volume for the patients after treatment. CONCLUSION: The study demonstrated the efficacy of managing ketamine-associated uropathy using a 4-tier approach. Both anti-inflammatory drugs and analgesics could effectively alleviate symptoms. Being abstinent from ketamine abuse and the amount of ketamine consumed have bearings on treatment response.