Investigating the Effect of Testosterone Replacement Therapy Among Hypogonadal Men With Localized Prostate Cancer on Active Surveillance
Summary
This phase IV trial studies the effects of testosterone replacement therapy (TRT) on treatment outcomes in hypogonadal men with prostate cancer that has not spread to other parts of the body (localized) and who are on active surveillance (AS). AS in prostate cancer involves closely watching the patient's condition through regular physical exams and blood tests, but not giving treatment unless there are changes in test results. It can be a practical alternative to treatment in localized prostate cancer. Hypogonadal men have low testosterone associated with symptoms such as low libido and erectile problems. TRT can be used to treat hypogonadism by increasing testosterone levels, which may improve associated symptoms. TRT is often not used in men with prostate cancer due to concerns it may lead to the cancer growing or spreading. This may lead hypogonadal men to have a poor quality of life or to discontinue AS. TRT may improve treatment and quality of life outcomes in hypogonadal men with localized prostate cancer on active surveillance.
Detailed description
PRIMARY OBJECTIVES: I. To investigate the impact of TRT on Gleason grade progression in hypogonadal men with localized prostate cancer on active surveillance, and the association between TRT and the likelihood of discontinuation of active surveillance in the same population. II. To assess the impact of TRT on the quality of life, including changes in the International Prostate Symptom Score (IPSS) and the association with sexual health measured by the Sexual Health Inventory for Men (SHIM), in hypogonadal men with localized prostate cancer on active surveillance. SECONDARY OBJECTIVES: I. To examine the influence of TRT on radiographic progression in hypogonadal men with localized prostate cancer on active surveillance, by assessing changes in the size of abnormal magnetic resonance imaging (MRI) lesions. II. To evaluate the association between TRT and biochemical progression by analyzing changes in prostate-specific antigen (PSA) levels over time in the studied population. III. To systematically monitor and document TRT-related adverse events and complications, and concurrently assess the association between TRT and the likelihood of discontinuation due to adverse events in the studied population. OUTLINE: Patients are assigned to 1 of 3 groups. GROUP 1: Patients with normal testosterone level undergo standard AS for up to 5 years in the absence of disease progression. Patients undergo blood sample collection and MRI throughout the trial and may undergo prostate biopsy on study. GROUP 2: Patients with low testosterone level associated with hypogonadal symptoms and willing to receive TRT receive testosterone per treating physician discretion via injection, gel, lotion, or transdermal patch and undergo standard AS for up to 5 years in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection and MRI throughout the trial and may undergo prostate biopsy on study. GROUP 3: Patients with low testosterone level with no symptoms, or low testosterone level associated with hypogonadal symptoms but declined TRT undergo standard AS for up to 5 years in the absence of disease progression. Patients undergo blood sample collection and MRI throughout the trial and may undergo prostate biopsy on study.
Arms & interventions
- ProcedureBiopsy of Prostate
Undergo prostate biopsy
- ProcedureBiospecimen Collection
Undergo blood sample collection
- ProcedureMagnetic Resonance Imaging
Undergo MRI
- OtherPatient Observation
Undergo standard AS
- OtherQuestionnaire Administration
Ancillary studies
- DrugTherapeutic Testosterone
Given via injection, gel, lotion, or transdermal patch
Outcome measures
Primary
Gleason grade progression
The Gleason grade progression will be summarized by group using standard Kaplan-Meier methods, where estimates of the median or specified rates will be obtained. Comparisons will be made between groups using the log-rank test. As exploratory analyses, Cox regression models may be considered to adjust for relevant demographic or clinical confounders. The Bonferroni method will be used to control the family-wise error rate at 0.10.
Time frame: From start of active surveillance until any progression in primary, secondary, or a combination of Gleason grades, definitive treatment, or last follow-up, assessed up to 5 years
Discontinuation of active surveillance
The discontinuation of active surveillance will be summarized by group using standard Kaplan-Meier methods, where estimates of the median or specified rates will be obtained. Comparisons will be made between groups using the log-rank test. As exploratory analyses, Cox regression models may be considered to adjust for relevant demographic or clinical confounders. The Bonferroni method will be used to control the family-wise error rate at 0.10.
Time frame: From start of active surveillance until discontinuation of active surveillance due to any cause or last follow-up, assessed up to 5 years
International Prostate Symptom Score (Quality-of-life)
Will be modeled as a function of group, timepoint, their two-way interaction, and a random subject effect using linear mixed models. Tests about the appropriate contrasts of model estimates will be used to compare mean changes in quality of life between groups at specified timepoints. All model assumptions will be verified graphically, and transformations applied as appropriate. As exploratory analyses, additional models may be considered to adjust for relevant demographic or clinical confounders. The Bonferroni method will be used to control the family-wise error rate at 0.10.
Time frame: Up to 5 years
Sexual Health Inventory for Men score (Quality-of-life)
Will be modeled as a function of group, timepoint, their two-way interaction, and a random subject effect using linear mixed models. Tests about the appropriate contrasts of model estimates will be used to compare mean changes in quality of life between groups at specified timepoints. All model assumptions will be verified graphically, and transformations applied as appropriate. As exploratory analyses, additional models may be considered to adjust for relevant demographic or clinical confounders. The Bonferroni method will be used to control the family-wise error rate at 0.10.
Time frame: Up to 5 years
Secondary
Radiographic progression
Time frame: From start of active surveillance until radiographic progression, definitive treatment, or last follow-up, assessed up to 5 years
Biochemical progression
Time frame: From the start of active surveillance until prostate specific antigen (PSA) progression, definitive treatment, or last follow-up, assessed up to 5 years
Incidence of testosterone replacement therapy (TRT)-related adverse events
Time frame: Up to 5 years
Incidence of TRT-related complications
Time frame: Up to 5 years
TRT discontinuation
Time frame: Up to 5 years
Eligibility criteria
Study locations (1)
Roswell Park Cancer Institute
Buffalo, New York, 14263