Children's Hospital Colorado

A Prospective Study of Lower Urinary Tract Dysfunction in Childhood Cancer Survivors After Chemotherapy

Urology | January 14, 2022

Points for Parents:

  • Chemotherapy can effectively destroy cancer cells, but can also be toxic to healthy cells, which could have a long-term impact.
  • Vincristine (VCR) and doxorubicin (DOX) are linked to muscle weakness and nerve dysfunction, but effects on bladder function have not been well-researched.
  • This study found that cancer survivors treated with VCR and DOX had a higher rate of lower urinary tract dysfunction (LUTD) than healthy children.

Points for Providers:

  • Researchers hypothesized that neurotoxic effects of VCR and/or myotoxic effects of DOX affect bladder physiology and manifest clinically as LUTD.
  • LUTD was observed most in female cancer survivors who appear more likely to suffer from LUTD than males.
  • An additional study is underway between cancer survivors treated with VCR and DOX and cancer survivors who were not treated with either agent.

Stats:

  • 161 study participants
  • 38% of cancer survivors reported LUTD versus 20% of healthy children
  • 57% of cancer survivors with LUTD were female

Research background: effects of chemotherapy on bladder function of pediatric cancer survivors

Cytotoxic chemotherapy has been used to treat many forms of childhood cancer, greatly contributing to improved survival rates for these patients over the past 50 years. Research has begun to shift focus from treatment to cancer survivorship after treatment. But research on the impact of chemotherapy on bladder function is lacking.

Pediatric bladder dysfunction is often caused by a combination of neurogenic or myotonic dysfunction. Vincristine (VCR) and doxorubicin (DOX) are two widely used chemotherapy agents with known side effects of peripheral neuropathy and myotoxicity. This single-center, prospective study took place at Children’s Hospital Colorado and examined bladder function, specifically the presence of lower urinary tract dysfunction (LUTD) in pediatric cancer survivors using the dysfunctional voiding scoring system (DVSS).

Research methods: a survey of pediatric cancer survivors and healthy children on their bladder function

chemotherapy-bladder-dysfunction-graphic-1.jpg

Inclusion criteria for cancer survivors

  • History of cancer
  • Treatment with chemotherapy regimen including VCR and/or DOX
  • Completion of chemotherapy at least one year before study enrollment

Exclusion criteria

  • Study cohort: patients with a primary pelvic tumor, pelvic irradiation, pre-existing bladder/bowel dysfunction, spinal defects, neurologic disorder, neuro-oncologic tumor or brain metastasis, cyclophosphamide or ifosfamide therapy
  • Control group: similar as the study group, but also any prior personal history of cancer of any kind

Clinical data were collected from medical records. DOX data was reported as mg and mg/m2; VCR data was reported as mg. It was hypothesized that survivors of childhood cancer who received VCR and/or DOX therapy would have higher DVSS scores for gender-specific thresholds for LUTD.

Research results: pediatric cancer survivors had higher rates of lower UTD

  Cancer Control p-Value
n 80 81  
Gender (M/F) 40/40 41/40  
Median age in years (range) 8.2(5.0-10.9) 7.0(5.0-10.8) .008a
Race (%)     <.001b
 White 55 (68.8%) 14 (17%)  
 African American 2 (2.5%) 16 (20%)  
 Hispanic/Latino 20 (25%) 36 (44%)  
 Other/not reported 3 (3.8%) 15 (19%)  
Median time from therapy in months (range) 32.5 (12.0-112.5) -  
Chemotherapy (%)      
 VCR + DOX (%) 58 (73%) -  
 VCR 17 (21%) -  
 DOX 5 (6%) -  

Study participants

161 participants, 89% participation rate

Key findings

  • DVSS scores were higher in the study cohort (pediatric cancer patients) than in the control group (6 vs. 4) for both males and females (6 vs. 3; 6 vs. 4, respectively).
  • Pediatric cancer patients were more likely to exceed gender-specific threshold scores for LUTD than their peers in the control group (38.8%; 21%, respectively).
  • Female cancer survivors are more likely to report LUTD than healthy peers (57.5% vs. 30%).

The first post hoc analysis removed the DVSS “stress” domain as a variable. Results showed that the median DVSS sum scores and reports of LUTD were still significantly higher in the study cohort than in the control group, along with gender-specific comparisons. A second post hoc analysis showed no association between the cumulative dose of chemotherapy and LUTD.

Research conclusion: VCR and DOX may affect bladder physiology

Pediatric cancer survivors who received VCR and/or DOX chemotherapy reported higher rates of LUTD than those who have not had any form of cancer. These results contribute to the growing consensus that VCR and/or the myotoxic effects of DOX may affect bladder physiology, despite prior studies that claim it is limited to cardiac muscle function.

As childhood cancer survival rates increase, treatments such as DOX and VCR play a critical role in curing childhood cancer. However, assessing bladder function is an essential part of follow-up in this population. Future studies should consider the lifelong impact LUTD can have on a cancer survivor, more broadly utilizing the DVSS with the pediatric cancer survivor population to increase the validity of the assessment and looking at the correlation between subjective DVSS scores with objective data from noninvasive urodynamics.

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