Clinical trial NCT02963675: Incidence of Second Primary Malignancies in Prostate Cancer Patients With Bone Metastases - an Observational Retrospective Cohort Study in Sweden
Official title: Incidence of Second Primary MAlignancies in pRostate Cancer Patients With bOne Metastases - an Observational Retrospective Cohort Study in Sweden (SMARCOS)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Prostatic Neoplasms
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2016-11-15
Enrollment: 15953
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with PC diagnosis in 1.1.1998 - 31.12.2013 and with bone metastases diagnosis or bone-directed treatments in 1.1.1998 - 31.12.2013 will be initially included into the large study population. From this initial population, the main analyses will concentrate on the following two populations:

* Prostate cancer patients with bone metastases (mPC), and
* Castration-resistant prostate cancer patients with bone metastases (mCRPC)

Brief summary: This study is conducted to obtain information about prostate cancer patients with bone metastases before the end of 2013. The incidence of second primary malignancies and overall survival in patients with castration resistant prostate cancer are of particular interest. Information from this study will serve as a historical reference for the REASSURE study (Background incidence study)

Detailed description: Prostate cancer (PC) is the most common non-cutaneous malignancy in men. Once it becomes metastatic, it poses a serious threat to the patients' quality of life and survival. The most common site of metastases is the skeletal system: Among castration-resistant prostate cancer patients bone metastases are involved in over 90% of metastatic cases.

The development of new treatments has led to improved quality of life and prolonged lifetime among castration-resistant prostate cancer patients with metastases (mCRPC). A recent randomized clinical trial indicated significant improvement in survival and quality of life among patients with bone metastases treated with alpha emitter radium-223 as compared with placebo. To further evaluate the safety profile of Radium-223 in patients with castration resistant prostate cancer with bone metastases, Radium-223 alpha Emitter Agent in non-intervention Safety Study in mCRPC popUlation for long-teRm Evaluation (the REASSURE study), an international prospective observational single-arm cohort study was implemented as a post-marking requirement requested by the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA).

In the case that new treatments improve the length and quality of life substantially, it can be challenging to obtain an appropriate comparison group in the post-authorization phase. This study is conducted to obtain information about prostate cancer patients with bone metastases before the end of 2013. The incidence of second primary malignancies and overall survival are of particular interest. Information from this study will serve as a historical reference for the REASSURE study

Eligibility criteria: Inclusion Criteria:mPC population; if the following criteria are fulfilled:

A.) PC diagnosis in 1.1.1998 - 31.12.2011 B.) Bone metastases diagnosis in 1.1.1999 - 31.12.2011 mCRPC population; if the following criteria are fulfilled:

1. PC diagnosis in 1.1.1998 - 31.12.2011
2. Bone metastases diagnosis in 1.1.2007 - 31.12.2011
3. One of the following in 1.1.2006 - 31.12.2011 and before or at the same time with bone metastases diagnosis:

   1. Discontinuation of the initial chemical castration (androgen deprivation therapy, ADT), change of the agent or modality of ADT, or start of treatment for advanced PC after the primary ADT (including chemotherapy or mitoxantrone)
   2. Surgical castration and initiation of ADT treatment, chemotherapy or mitoxantrone afterwards
   3. Treatment with medication specific to either castration-resistant PC or mCRPC (cabazitaxel, enzalutamide or abiraterone).
   4. In a sensitivity analysis, also those who have had at least 6 months since the initiation of castration treatment before cohort entry date (bone metastases diagnosis) are included in the mCRPC population.

Exclusion Criteria:

* First PC diagnosis later than 2 months after the diagnosis of bone metastases, or
* Permanent residence not in Sweden or patient otherwise not contributing to the registers at least a year before the diagnosis of bone metastases (patient counted not contributing also if database existence less than a year before cohort entry), or
* Use of any radiopharmaceuticals for bone metastases (ATC code): Samarium (V10BX02), strontium (V10BX01), rhenium (V10BX03) or radium (V10XX03).

Primary outcomes:
measure: Incidences of Second primary malignancies that are characterized by the following ICD-10 codes: C00-C76, C81-C96, D00-D09, D37-D48.
timeFrame: Up to 15 years
Secondary outcomes:
measure: Incidences of any site-specific second primary malignancies
timeFrame: Up to 15 years for mPC patients and up to 7 years for mCRPC patients
measure: Overall survival
timeFrame: Up to 15 years for mPC patients and up to 7 years for mCRPC patients
measure: Pathologic fracture
timeFrame: Up to 15 years for mPC patients and up to 7 years for mCRPC patients
measure: Spinal cord compression
timeFrame: Up to 15 years for mPC patients and up to 7 years for mCRPC patients
measure: Surgery to bone
timeFrame: Up to 15 years for mPC patients and up to 7 years for mCRPC patients
measure: Radiation to bone
timeFrame: Up to 15 years for mPC patients and up to 7 years for mCRPC patients
Other outcomes:
Locations:
city: Multiple Locations
country: Sweden
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References: