Severity of Overactive Bladder Symptoms in Patients After Synergo Treatment (OABSYNERGO)

Severity of Overactive Bladder Symptoms in Patients After Synergo Treatment for Bladder Cancer

Bladder carcinoma is the most common malignancy of the urinary tract. Approximately 75-85% of patients with bladder cancer present with a disease that is confined to the mucosa or submucosa. These categories are grouped as non-muscle-invasive bladder tumors(i.e. superficial tumors).

Bladder cancer is the fifth most common cancer in the United States, with an estimated 67,160 newly diagnosed cases and 13,750 deaths in the United States in 2007. The 5-year survival rate is 82% for all stages combined. The standard of treatment for patients with superficial bladder cancer is surgical transurethal resection (TUR) of tumors, with an 80% early success rate. However, nearly 70% of these patients will develop tumor recurrence, with 25% showing progression to muscle-invading disease, within 5 years with TUR.

It is therefore necessary to consider adjuvant therapy in all patients. The absolute risks of recurrence and progression do not always indicate the risk at which a certain therapy is optimal. The choice of therapy may be considered differently according to what risk is acceptable for the individual patient and the urologist.

Intravesical chemotherapy and immunotherapy are widely used as adjuvant therapies after TUR, to prevent recurrence and progression of superficial disease. Systemic therapy is typically reserved for higher stage, muscle-invading, or metastatic diseases. The urinary bladder is an ideal organ for regional therapy.

The urethra provides easy access of therapeutic agents to the urinary bladder. The presence of the specialized asymmetric unit membrane on the urothelium serves as a barrier and limits the absorption of molecules or particulates into the systemic circulation.

The rationale for intravesical therapy is to maximize the exposure of tumors located in the bladder cavity to therapeutics agents while limiting the systemic exposure and thereby limiting the host toxicities; the primary goal is to eradicate existing or residual tumors through direct cytoablation or immunostimulation. The unique properties of the urinary bladder render it a fertile ground for evaluating novel approaches to regional therapy, including local hyperthermia, co-administration of permeation enhancers, bioadhesive carriers, and gene therapy.

One of the developing treatments for high-risk superficial bladder cancers is the combination of intravesical chemotherapy and hyperthermia (HT), called chemohyperthermia (C-HT). The most common form of C-HT uses the Synergo HT system, in which local HT is administered via direct microwave irradiation of the urothelium by means of a 915-MHz intravesical microwave applicator. The target intravesical temperature is set between 41.8C and 44.8C and is measured by five thermocouples integrated in a 20-F treatment catheter. To avoid injury, the urethra is continuously cooled. Due to extensive global experience with its use and a significant amount of preclinical data demonstrating improved antineoplastic efficacy when heated, mitomycin C (MMC) is the most common intravesical chemotherapy agent used in conjunction with HT.

The most common adverse events during treatment were bladder spasms and bladder pain. Literature reports bladder spasms in 21.6% of patients, and bladder pain in 17.5%. Bladder spasms tended to occur more frequently with the prophylactic schedule, whereas pain was present equally in the prophylactic and ablative schedules but more commonly after the ablative schedule. In the first days following C-HT, storage LUTS (frequency, dysuria, urgency, nocturia) (25.6%) and hematuria (6.0%) are the most common adverse events. Most studies mention that these symptoms were mild and transient, resolving spontaneously within a few days of treatment. One study described severe cystitis complaints in three patients (16%), but other studies have not confirmed these adverse events. Two studies report the development of a contracted bladder and severe urinary incontinence after ablative C-HT. However, the possibility cannot be excluded that previous transurethral resection and intravesical chemotherapy might have contributed to this event.

Following the appearance of bothersome storage LUTS, patient should be managed by existing guidelines. Based on AUA/SUFU Diagnosis and Treatment of Overactive Bladder (Non-Neurogenic) in Adults Guidelines published in 2012 patients should be diagnosed, followed and treated according to the suggested algorithm.

In our study, we would like to assess the severity of OAB symptoms and their response to a standard OAB treatment according to AUA Guidelines for Non-neurogenic OAB as well as to assess urodynamic study variables in those who didn't respond to a standard medical treatment and bothered by their OAB symptoms.

Study Overview

• Status: Completed
• Conditions: Overactive Bladder; Bladder Cancer; Synergo
• Intervention / Treatment: Other: Questionnaires, anticholinergic treatment, urodynamic study

• Study Type: Observational
• Enrollment (Actual): 35

Contacts and Locations

Study Locations

• Israel
  • Hasharon
    • Kfar-Saba, Hasharon, Israel, 44410
      • Meir Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Bladder cancer patients after Synergo treatment completion and no evidence of disease at cystoscopic evaluation

Description

Inclusion Criteria:

• both genders
• age above 18
• bladder cancer patients after completion of Synergo treatment
• no evidence of disease at cystoscopic evaluation after completion of Synergo treatment

Exclusion Criteria:

• children
• pregnant women
• failure to complete Synergo treatment
• evidence of bladder cancer at cystoscopic evaluation after Synergo treatment

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Overactive bladder after Synergo	Other: Questionnaires, anticholinergic treatment, urodynamic study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OAB symptoms severity and urodynamic variables in failed medical treatment patients	OAB-SS, OAB-Q, OAB-SQ - questionnaires Urodynamic study results in patients who will undergo the test	at recruitment and after treatment
Synergo treatment variables and OAB severity	relationship between the answers in OAB-SS, OAB-Q, OAB-SQ - questionnaires, Urodynamic study results in patients who will undergo the test and type of Synergo protocol, number of treatments received, time of hyperthermia per treatment, bladder cancer stage at the beginning of Synergo treatment.	at recruitment and after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OAB severity of symptoms and urodynamic variables in failed medical treatment patients	OAB-SS, OAB-Q, OAB-SQ - questionnaires and relationship to Urodynamic study results in patients who will undergo the urodynamic test	after the treatment
OAB treatment satisfaction and urodynamic variables in failed medical treatment patients	OAB-SQ - questionnaire and urodynamic study results	after the treatment

Collaborators and Investigators

• Sponsor: Meir Medical Center
• Investigators: Principal Investigator: Michael Vainrib, MD, Meir Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2013
• Primary Completion (Actual): December 31, 2016
• Study Completion (Actual): December 31, 2016

Study Registration Dates

• First Submitted: September 24, 2013
• First Submitted That Met QC Criteria: September 27, 2013
• First Posted (Estimate): October 7, 2013

Study Record Updates

• Last Update Posted (Actual): October 6, 2017
• Last Update Submitted That Met QC Criteria: October 4, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: overactive bladder; bladder cancer; urodynamic study; Synergo
• Additional Relevant MeSH Terms: Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Urinary Bladder Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Urinary Bladder, Overactive; Urinary Bladder Neoplasms; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Cholinergic Antagonists
• Other Study ID Numbers: SYNERGO-OAB