Decipher Lethal Prostate Cancer Biology - Urine Metabolomics
Decipher Lethal Prostate Cancer Biology - Urine Metabolomics
Through a better understanding of the biology of significant (lethal) prostate cancer, we
 hope to develop new markers/targets from urine metabolomics for more effective screening and
 prevention of significant prostate cancer. In the meantime, with these new markers we may
 substantially reduce overtreatment of insignificant PC.
Prostate cancer (PC) afflicts millions of men worldwide. In Taiwan, around 5,000 men are
 diagnosed as PC while 1,200 men die of the disease each year. However, thousands of Taiwanese
 men may have been over-treated for their insignificant PCs. The above situations signify the
 unmet clinical need where effective measures of stratifying risk of PC are lacking. The study
 is to identify new markers/targets with which to better screen and prevent significant (sPC)
 or lethal PC (lePC).

 This is a prospective, observational and investigational study investigating the role of
 urine metabolites via metabolomics analysis in subjects who will undergo prostate biopsy
 and/or subsequent MCS supplementation. MCS (or Botreso) is a new patented botanic agent,
 composed of primarily multi-carotenoids, including lycopene, phytoene, phytofluene, etc. The
 expected subject number to be enrolled is 620 men and 20 women from NTUH. There will be 3
 cohorts: Cohort A (N=200), Cohort B (N=400) and Cohort C (N=40). Cohort A will be recruited
 in the first 9 months of the study period to generate the first batch of urine metabolite
 profiles. Cohort B will be recruited in the next 18 months of the study period to validate
 the first batch of newly developed urine metabolite profile. Cohort C is the control cohort,
 including 20 women and 20 men without any signs of cancers.

 By risk stratification after biopsy pathology results are available, there will be 5 groups
 of subjects, including patients with Group 1. mPC: Metastatic prostate cancer Group 2. sPC:
 Non-metastatic significant prostate cancer (sPC) Group 3. isPC: Non-metastatic insignificant
 PC (isPC) Group 4. Pre-cancerous lesions: atypical small acinar proliferation (ASAP) or
 prostatic intraepithelial neoplasia (PIN) Group 5. Non-cancer benign pathology

 In the current study, sPC is defined as any of the followings: Gleason score >= 4+3=7, stage
 > =T3a (capsule invasion), or presence of metastasis.

 Biopsy pathology report and clinicopathological parameters will be recorded. In addition,
 transcriptomics study will be performed. Group specific urine metabolite profiles will be
 constructed by comparing the outstanding metabolites between groups. These metabolite
 profiles are constructed so as to efficiently separate groups of graded risk stratification,
 especially to predict subjects with mPC (Group 1) or sPC (Group 2). The newly constructed
 metabolite profiles from Cohort A will be validated against Cohort B of subjects who will
 undergo biopsy to determine the predictive efficiency of the constructed profiles.

 In Cohort A, sPC (Group 2), isPC (Group 3), ASAP/PIN (Group 4) and benign pathology patients
 (Group 5) will further be invited to take MCS supplementation for 8 weeks after the pathology
 confirmation. The expected enrollment number is 30 for each of the 4 groups (in total 120).
 Urine samples will be collected before and after 8 weeks of MCS supplementation for
 metabolomics analysis. The effect of MCS supplementation in modifying urine metabolites will
 be investigated to determine the potential use of MCS in prostate cancer chemoprevention.

 Through a better understanding of the biology of significant (lethal) PC, we hope to develop
 new markers/targets for more effective screening and prevention of sPC. In the meantime, with
 these new markers we may substantially reduce overtreatment of insignificant PC.
Inclusion Criteria:

 1. Subjects who have planned to undergo prostate biopsy.

 2. Subjects who are aged between 30 and 100 years men.

 3. For subjects who are prostate cancer patients for rebiopsy, the testosterone level
 should be within normal limit (testosterone >1.5 ng/ml).

 4. Subjects who understand the entire study procedures and consent to donate his spot
 urine (once for 50 ml) and agree with subsequent analyses of his clinical information
 including biopsy results, treatments and outcomes. (Note: Subjects will be told that
 the urine metabolomics results will not be revealed to them.)

 Exclusion Criteria:

 1. Subjects who have other active cancers. However, subjects who have cancers that have
 been curatively treated and who are disease-free for 3 years or longer are allowed to
 be enrolled.

 2. Subjects who have severe organ function impairment which may significantly alter
 general cell metabolism determined by the investigators, such as or Cre > 3.0, HbA1c >
 9.0%, symptomatic heart failure, or other symptomatic metabolic diseases.

 3. Subjects who are receiving or have received systemic therapy, such as chemotherapy,
 androgen deprivation therapy (ADT), immunotherapy, or targeted therapy within 3 months
 of the screening.

 4. Subjects who have been treated with pelvic radiotherapy within 3 months of the
 screening.

 5. Subjects who have significant infection or inflammation within 8 weeks of the biopsy.

 6. Subjects who have pyuria (defined as > 5 WBC/HPF) of urinalysis results within 4 weeks
 of the biopsy

 7. Topical or oral prednisolone equivalent dosage larger 10 mg per day for 14 days or
 more.

 8. The last dose of prednisolone is within 4 weeks of the biopsy.

 9. Subjects who have a life expectancy less than 12 months.

 10. Subjects who use MCS or found supplementation containing large amount of lycopene in
 recent 60 days or less. The definition of large amount of lycopene is more than 2 mg
 per day.