Association between urine 6-sulfatoxy-melatonin level and intravesical Bacillus Calmette-Guerin treatment-induced sleep quality deterioration in patients with non-muscle invasive bladder cancer

Support Care Cancer. 2022 Jul;30(7):6145-6153. doi: 10.1007/s00520-022-07043-0. Epub 2022 Apr 14.

Abstract

Purpose: The level of 6-sulfatoxy-melatonin (SaMT), a metabolite of melatonin, in first-void morning urine reflects blood melatonin levels from the previous night. We investigated the association between urine SaMT and sleep quality deterioration in patients with non-muscle invasive bladder cancer (NMIBC) treated with intravesical Bacillus Calmette-Guerin induction therapy (iBCG).

Methods: We enrolled 51 patients who received iBCG once weekly for 6 or 8 weeks. Patient-reported outcomes were assessed with questionnaires including the International Prostate Symptom Score (IPSS) and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (QLQC30). Questionnaires were completed before (baseline), during, at completion, and 1 and 3 months after iBCG. Melatonin and SaMT levels at baseline were measured in serum and first-void morning urine samples, respectively.

Results: Based on changes in the QLQC30 insomnia subscale, 28 (55%) patients experienced sleep quality deterioration (deterioration group). Urine SaMT values in the deterioration group were lower than those in the non-deterioration group (P = 0.0015; 7.5 vs 15.4 ng/mg creatinine, respectively). Nocturia scores in the non-deterioration group decreased over time, while those of the deterioration group remained high after completion of iBCG. A binary logistic regression analysis revealed that low urine SaMT levels (≤ 9.6 ng/mg creatinine), high IPSS nocturia scores at baseline, and high IPSS storage subscores at baseline were associated with BCG-induced sleep quality deterioration.

Conclusions: This study confirmed the association among urine SaMT levels, nocturia, and sleep disturbance in patients with NMIBC who receive iBCG. We should be aware of treatment-induced impairments to aid in appropriate decision-making.

Keywords: Bacillus Calmette-Guerin; Lower urinary tract symptoms; Melatonin; Patient reported outcome measures; Sleep; Urinary bladder neoplasms.

MeSH terms

  • Administration, Intravesical
  • BCG Vaccine* / therapeutic use
  • Creatinine
  • Humans
  • Male
  • Melatonin* / urine
  • Neoplasm Invasiveness
  • Neoplasm Recurrence, Local / therapy
  • Nocturia
  • Quality of Life
  • Sleep Quality*
  • Urinary Bladder Neoplasms* / drug therapy

Substances

  • BCG Vaccine
  • Creatinine
  • Melatonin