Clinical trial NCT04180033: Diagnostic Yield of Colonoscopy Surveillance in Testicular Cancer Survivors Treated With Platinum-based Chemotherapy
Official title: Diagnostic Yield of Colonoscopy Surveillance in Testicular Cancer Survivors Treated With Platinum-based Chemotherapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Testicular Cancer
Colorectal Neoplasms
Keywords: Colonoscopy surveillance
Lead sponsor: The Netherlands Cancer Institute
Sponsor class: OTHER
First posted: 2019-11-27
Enrollment: 154
Sex: MALE
Minimum age (years): 35
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Participants will be invited to undergo a colonoscopy surveillance.
Primary purpose: PREVENTION

Brief summary: Testicular cancer (TC) survivors treated with platinum-based chemotherapy have an increased risk of colorectal cancer (CRC) (hazard ratio (HR) 3.9 for platinum-containing chemotherapy versus no platinum-containing chemotherapy, 95% confidence interval 1.7-8.9). Colonoscopy screening can reduce CRC incidence and mortality. Given this increased risk of CRC, colonoscopy surveillance should be considered for TC survivors treated with platinum-based chemotherapy.

The aim of this study is to evaluate the diagnostic yield of advanced colorectal neoplasia during colonoscopy surveillance in TC survivors treated with platinum-based chemotherapy. The secondary objectives are to determine cost-effectiveness and burden of colonoscopy. Furthermore, the molecular profile of advanced neoplasia will be evaluated to create insight into the carcinogenesis. The effectiveness of fecal immunochemical testing (FIT) will be evaluated with colonoscopy as a reference. Finally, blood plasma platinum-levels will be determined to examine a potential correlation with the outcome of the ccolonoscopy.

Detailed description: Rationale: Testicular cancer (TC) survivors have an increased risk of various second primary malignancies. A recent cohort study showed that platinum-based chemotherapy was associated with increased risk of colorectal cancer (CRC) in a dose dependent manner (hazard ratio (HR) 3.9 for platinum-containing chemotherapy versus no platinum-containing chemotherapy, 95% confidence interval 1.7-8.9). Colonoscopy screening can reduce CRC incidence and mortality. Given this increased risk of CRC, colonoscopy surveillance should be considered for TC survivors treated with platinum-based chemotherapy. However, the diagnostic yield, cost-effectiveness and burden of colonoscopy in TC survivors treated with platinum-based chemotherapy has never been assessed. Additionally, the molecular profile of advanced neoplastic lesions and CRC in TC survivors treated with platinum-based chemotherapy has not been established but can provide valuable insight into CRC carcinogenesis in this group of patients. Also the effectiveness of fecal tests has not been evaluated among TC survivors treated with platinum-based chemotherapy compared to that among population controls.

Objective: The primary objective of this study is to assess the diagnostic yield of colonoscopy surveillance in TC survivors treated with platinum-based chemotherapy. The secondary objectives are 1) to evaluate the molecular characteristics of colorectal (advanced) neoplasia in TC patients in relation to the cumulative doses of/ level of plasma cisplatin, in order to improve the understanding of CRC carcinogenesis following cisplatin exposure, 2) to determine the association of platinum levels in plasma with cumulative administered cisplatin doses as well as with presence of colorectal (advanced) neoplasia at colonoscopy and to determine the platinum amount in the colorectal tissue derived during primary colonoscopy screening, 3) to evaluate the cost-effectiveness and burden of colonoscopy. Our 4th secondary objective is to assess the effectiveness of a stool test for CRC screening in TC survivors compared to standard colonoscopy.

Study design: A multicentre prospective cross-sectional screening study.

Study population: TC survivors will be derived from an established, well-defined multicentre cohort. Inclusion criteria of this study are 1) participants should have been treated for TC in a participating Dutch hospital before the age of 50 years, 2) treatment consisted of at least three cycles of platinum-based chemotherapy (cisplatin) with or without additional radiotherapy, 3) participants should be at least 8 years after start of treatment, with a minimum age at first colonoscopy screening of 35 years, 4) the maximum age at participation is 75 years, 5) detection and potential treatment of advanced colorectal neoplasia is considered beneficial.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of TC before age of 50 years
* Treatment of primary TC consisting at least: three cycles of platinum-based chemotherapy consisting of cisplatin
* At least 8 years after initial treatment
* At least 35 years of age and not older than 70 75 years
* Detection and potential treatment of advanced colorectal neoplasia is considered beneficial

Exclusion Criteria:

* A history of a proctocolectomy
* Colonoscopy surveillance for other indications (including hereditary CRC syndrome, familial CRC syndrome, inflammatory bowel disease, history of colorectal adenoma or CRC). Result of the prior colonoscopy will be put in the database and used for additional analyses
* Having received a colonoscopy in the past three years
* Currently receiving cytotoxic treatment or radiotherapy for malignant disease
* Coagulopathy (prothrombin time \<50% of control; partial tromboplastin time \>50 seconds) or anticoagulants (fenprocoumon, acenocoumarol, platelet aggregation inhibitors or new oral anticoagulants) that cannot be stopped or safely bridged if necessary
* Comorbidity leading to an impaired physical performance (World health organization (WHO) performance status 3-4) or mental retardation
* Limited Dutch language skills
* No informed consent

Primary outcomes:
measure: Diagnostic yield advanced colorectal neoplasia
timeFrame: 2 years
Secondary outcomes:
measure: Features of colorectal neoplasia as classified during colonoscopy
timeFrame: 2 years
measure: Molecular features of colorectal neoplasia and normal mucosa as evaluated histopathologically, molecular and by immunohistochemistry
timeFrame: 6 months
measure: Platinum levels in plasma
timeFrame: 2 years
measure: Fecal immunochemical test (FIT)
timeFrame: 2 years
measure: Determination of the most cost-effectiveness strategy for colonoscopy surveillance by using the MISCAN model
timeFrame: 3 months
measure: Quality of life of participant before and after colonoscopy
timeFrame: 2 years
measure: Worries about cancer
timeFrame: 2 years
measure: Burden of colonoscopy
timeFrame: 2 years
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Center
state: Gelderland
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center
state: Zuid-Holland
city: Amsterdam
country: Netherlands
facility: Antoni van Leeuwenhoek Hospital
city: Utrecht
country: Netherlands
facility: University Medical Center Utrecht
Study officials:
affiliation: Antoni van Leeuwenhoek Hospital
name: Monique van Leerdam, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ykema BLM, Bisseling TM, Spaander MCW, Moons LMG, van der Biessen-van Beek D, Saveur L, Kerst M, Mulder SF, de Wit R, Zweers D, Meijer GA, Beijnen JH, Lansdorp-Vogelaar I, van Leeuwen FE, Snaebjornsson P, van Leerdam ME. Diagnostic yield of colonoscopy surveillance in testicular cancer survivors treated with platinum-based chemotherapy: study protocol of a prospective cross-sectional cohort study. BMC Gastroenterol. 2021 Feb 12;21(1):67. doi: 10.1186/s12876-021-01639-2.