Studying the Physical Function and Quality of Life Before and After Surgery in Patients With Stage I Cervical Cancer

Study Overview
=================
Brief Summary
-----------------
This clinical trial studies the physical function and quality-of-life before and after surgery in patients with stage I cervical cancer. Studying quality-of-life in patients undergoing surgery for cervical cancer may help determine the intermediate-term and long-term effects of surgery.

Detailed Description
-----------------
PRIMARY OBJECTIVES: I. To examine the changes before and after non-radical surgical treatment (simple hysterectomy or cone biopsy [fertility preservation] and pelvic lymphadenectomy) on functional outcomes of bladder, bowel, and sexual function for stage IA1 (lymphatic vessel invasion positive [LVSI+]) and IA2-IB1 (=< 2 cm) carcinoma of the cervix. II. To evaluate incidence and severity of lymphedema after non-radical surgery (simple hysterectomy or cone biopsy [fertility preservation] and pelvic lymphadenectomy) for stage IA1 (LVSI+) and IA2-IB1 (=< 2 cm) carcinoma of the cervix. SECONDARY OBJECTIVES: I. To investigate if non-radical surgery (simple hysterectomy or cone biopsy [fertility preservation] with pelvic lymphadenectomy) demonstrates greater physical function and less toxicity in comparison to historical data on radical surgery (radical hysterectomy or radical trachelectomy). II. To evaluate incidence and severity of treatment-related adverse events, including surgical complications, among the entire cohort and by treatment type. III. To evaluate changes in quality of life (QOL) (Functional Assessment of Cancer Therapy-Cervix [FACT-Cx]), cancer worries (Impact of Events Scale [IES]) and sexual (Female Sexual Function Index [FSFI])/reproductive concerns (RCS) among the entire cohort and by treatment type. IV. To explore relationships (correlation, interaction, independence) between functional outcomes (i.e., bladder function, bowel function, sexual function), adverse events (including and surgical complication lymphedema [Gynecologic Cancer Lymphedema Questionnaire (GCLQ)]), cancer worry (IES), surgical complications, and overall quality of life (FACT-Cx). V. To determine participants' intention for conception & fertility rates (Integrative Care for Fertility [ICF]) and assess the reproductive concerns (RCS) of women following cone biopsy and pelvic lymphadenectomy for stage IA1 (LVSI+) and IA2-IB1 (=< 2 cm) carcinoma of the cervix. VI. To estimate the efficacy of non-radical surgery (simple hysterectomy or cone biopsy [fertility preservation] and pelvic lymphadenectomy) for stage IA1 (LVSI+) and IA2-IB1 (=< 2 cm) carcinoma of the cervix. OUTLINE: Patients undergo cone biopsy and pelvic lymphadenectomy or simple hysterectomy and pelvic lymphadenectomy. Patients complete the FACT-Cx, the IES, the FSFI, the GCLQ, and the Patient Reported Outcomes Measurement Information System (PROMIS) questionnaires at baseline, 4-6 weeks after surgery, and then every 6 months for 3 years. Patients undergoing cone biopsy and pelvic lymphadenectomy also complete the ICF and RCS questionnaires. After completion of study treatment, patients are followed up at 4-6 weeks, every 3 months for 1 year, and then every 6 months for 2 years.

Official Title
-----------------
Evaluation of Physical Function and Quality of Life (QOL) Before and After Non-Radical Surgical Therapy (Extra Fascial Hysterectomy or Cone Biopsy With Pelvic Lymphadenectomy) for Stage IA1 (LVSI+) and IA2-IB1 (≤ 2CM) Cervical Cancer

Conditions
-----------------
Cervical Adenocarcinoma, Cervical Adenosquamous Carcinoma, Cervical Squamous Cell Carcinoma, Lymphedema, Stage IA1 Cervical Cancer AJCC v6 and v7, Stage IA2 Cervical Cancer AJCC v6 and v7, Stage IB1 Cervical Cancer AJCC v6 and v7

Intervention / Treatment
-----------------
* Procedure: Conization
* Other: Quality-of-Life Assessment
* Other: Questionnaire Administration
* Procedure: Therapeutic Conventional Surgery
* Procedure: Therapeutic Lymphadenectomy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patient must consent for the appropriate surgery Patients with a histologic diagnosis of squamous cell carcinoma, adenocarcinoma, or adenosquamous cell carcinoma of the cervix, stage IA1 (lymph-vascular space invasion [LVSI]+), IA2, and IB1 (tumor size [maximum visible or palpable]) =< 2 cm), any grade All patients must have undergone a cone biopsy or loop electrosurgical excision procedure (LEEP); depth of invasion must be =< 10 mm Patients must have no evidence of metastasis on positron emission tomography (PET) scan or magnetic resonance imaging (MRI) or computed tomography (CT) scan of the pelvis and chest imaging Patients who have met the pre-entry requirements Patients must have signed an approved informed consent and authorization permitting release of personal health information Patient must have Gynecologic Oncology Group (GOG) performance status of 0, 1, or 2 Exclusion Criteria: Patients with stage IA1 disease who are LVSI negative Patients with stage IB1 with tumor size (maximum visible or palpable) > 2 cm Patients with >= stage IB2 disease Patients with clear cell or neuroendocrine cell types Patients with depth of invasion > 10 mm on first cone biopsy (or LEEP) Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancer, are excluded if there is any evidence of other malignancy being present within the last five years; patients are also excluded if their previous cancer treatment contraindicates this protocol therapy

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (cone biopsy/lymphadenectomy or hysterectomy)<br>Patients undergo cone biopsy and pelvic lymphadenectomy or simple hysterectomy and pelvic lymphadenectomy. | Procedure: Conization<br>* Undergo cone biopsy<br>* Other names: Conization of Uterine Cervix;Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>Procedure: Therapeutic Conventional Surgery<br>* Undergo hysterectomy<br>Procedure: Therapeutic Lymphadenectomy<br>* Undergo lymphadenectomy<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in bladder and bowel function score based on supplemental bladder and bowel questions plus 4 items from the Functional Assessment of Cancer Therapy-Cervix (3 bladder and 1 bowel question) | Analysis of variance methods with repeated measurements and a time component will initially be used to determine whether there are significant changes over time. | Baseline to 3 years | 
| Change in sexual function and activity based on Female Sexual Function Index (19 items) score plus 2 Patient Reported Outcomes Measurement Information System screener items | Analysis of variance methods with repeated measurements and a time component will initially be used to determine whether there are significant changes over time. | Baseline to 3 years | 
| Lymphedema | Based on Cancer Lymphedema Questionnaire score. | Up to 3 years | 
| Maximum grade and duration of severe adverse events associated with bladder, bowel, and sexual dysfunction and lymphedema | Graded according to Common Terminology Criteria for Adverse Events version 4.0 (version 5.0 will be used staring April 1, 2018). | Up to 3 years after non-radical surgical procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum grade of treatment-related adverse events | Graded according to Common Terminology Criteria for Adverse Events version 4.0 (version 5.0 will be used staring April 1, 2018). | Up to 30 days after surgical procedure | 
| Change in overall quality of life | Will be assessed based on Functional Assessment of Cancer Therapy-Cervix (15 items) score. Analysis of variance methods with repeated measurements and a time component will initially be used to determine whether there are significant changes over time. | Baseline to 3 years | 
| Change in cancer worries based on Impact of Events score | Analysis of variance methods with repeated measurements and a time component will initially be used to determine whether there are significant changes over time. | Baseline to 3 years | 
| Change in reproductive concerns based on reproductive concerns (14 items) score | Analysis of variance methods with repeated measurements and a time component will initially be used to determine whether there are significant changes over time. | Baseline to 3 years | 
| Site of first recurrence | Classified as either local (pelvis regions, including vaginal) or distant (abdomen, lung, bone, brain, and other). | Up to 3 years | 
| Recurrence-free survival | Product-limit estimates according to the method of Kaplan and Meier will be used to estimate recurrence-free survival. In addition, Cox proportional hazard regression will be employed to evaluate relative risk (hazard ratio) adjusting for known prognostic factors. Trellis plots will be used to display point estimates of hazard ratio and respective 95% confidence intervals from subgroup analyses. Local recurrence will be summarized using frequency tables and plot of cumulative incidence of local recurrence over time. | Up to 3 years | 
| Overall survival | Product-limit estimates according to the method of Kaplan and Meier will be used to estimate overall survival. In addition, cox proportional hazard regression will be employed to evaluate relative risk (hazard ratio) adjusting for known prognostic factors. Trellis plots will be used to display point estimates of hazard ratio and respective 95% confidence intervals from subgroup analyses. Gompertz hazard regression will also be employed to evaluate relative risk (hazard ratio) and cure rates, adjusting for known prognostics factors. | Up to 3 years |