Clinical trial NCT03891732: MRI Prostate for Chinese Men Being Screened for Prostate Cancer
Official title: The Use of MRI Prostate in Improving Detection of Significant Prostate Cancer in a Screening Population of Chinese Men With Elevated PSA
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Prostate Cancer
PSA
MRI
Keywords: Prostate cancer
PSA
MRI
Biopsy
Lead sponsor: Chinese University of Hong Kong
Sponsor class: OTHER
First posted: 2019-03-27
Enrollment: 690
Sex: MALE
Minimum age (years): 50
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Participants will be recruited form the the project 'Prevention of Obesity-related Cancers". 5000 Chinese men between age 50 and 75 will be screened for prostate cancer with the blood test PSA.

Brief summary: Under the prostate cancer screening protocol of the project 'Prevention of Obesity-related Cancers', men with elevated PSA with higher prostate cancer risk (PSA 4-10 ng/mL with high Prostate Health Index (PHI) ≥35, or PSA\>10 ng/mL) will be offered a prostate biopsy.

In the current study, we would like to offer all screened men with elevated PSA in the range of 4-50 ng/mL a biparametric non-contrast MRI prostate (screening protocol) for any suspicious lesion in the prostate. If there is MRI lesion seen, additional targeted biopsies can be performed on top of the standard systematic prostate biopsies. It has been shown in a clinical Caucasian cohort that doing MRI-targeted biopsies resulted in improved detection of clinically significant prostate cancer compared with standard systematic biopsies.

In this study investigators would like to investigate the benefits of adding MRI prostate and MRI-targeted biopsy in the diagnostic pathway for prostate cancer in a screened cohort of Chinese men at risk of prostate cancer.

Detailed description: Prostate cancer (PCa) is the second most common cancer in the world, and its incidence in the Asia-Pacific region is increasing. While serum prostate specific antigen (PSA) level remains the commonest marker for screening of the disease, its specificity is very low. As a result, many patients with elevated PSA are subjected to transrectal ultrasound guided prostatic biopsy (TRUSPB) with negative result, but at the same time faced the complications of bleeding and infection from TRUSPB. Performing a standard 10-12 core systematic prostate biopsy in all men with elevated PSA was shown to miss some clinically significant prostate cancers while over-diagnosing some insignificant prostate cancers. In the European randomized study of screening for prostate cancer (ERSPC), PSA-based screening have resulted in reduced prostate cancer-specific death and metastasis, but there were problems like over-biopsy and over-diagnosis of indolent prostate cancers. The number needed to screen (NNS) to prevent one prostate cancer death was quite high at 781. Therefore, population-wide screening of men with PSA is not commonly applied in most places.

The blood test Prostate Health Index (PHI) provides much better prostate cancer risk stratification than PSA by dividing men with PSA 4-10 ng/mL. Using PHI 35 as a cutoff, clinically significant prostate cancer (any Gleason pattern ≥ 4) was found in only 0.7% in PHI\<35, but up to 8.6% in PHI ≥35, a 12 fold difference. The use of PHI test could significantly reduce unnecessary prostate biopsies and was approved by FDA in 2012. Since 2016, the PHI blood test was available in the public health system in Hong Kong for men with PSA 4-10 ng/mL. According to local audit on 2795 men receiving PHI test, about 80% prostate biopsies was avoided. This also resulted in a higher positive biopsy rate (from 10.7% to 26.2%), with the potential of delayed diagnosis in only a minimal proportion of men (0.7%). Currently, PHI is being ordered regularly by Urologists in the public system of Hong Kong for men with PSA 4-10 ng/mL.

In a landmark study by Ahmed et al in 2017, performing multi-parametric MRI prostate before an initial prostate biopsy in a clinical Caucasian cohort has been shown to improve diagnosis of significant prostate cancer by 18%, while reduce diagnosis of insignificant prostate cancer by 5%.

Another Caucasian study by Alberts et al in 2017 in men who undergone the 5th round of screening in European Randomized Study of Screening for Prostate cancer Rotterdam, adding MRI prostate could avoid 65% biopsies and 68% insignificant prostate cancer, while detecting an equal percentage of significant cancers. The role of MRI in an Asian cohort under a screening protocol has not been reported before.

Prostate cancer incidence in Asian is only about one-third of that in Caucasian, and cancer detection rates in different PSA ranges are also 50% less. Reported Caucasian prostate cancer detection rates was 25-50% in men with PSA 4-10 ng/mL and \>50% in men with PSA 10-20 ng/mL. In Hong Kong Chinese men, only 15% men with PSA 4-10 ng/mL and 20-30% men with PSA 10-20 ng/mL has prostate cancer. Therefore, screening tools like PHI or MRI are potentially more useful in reducing unnecessary biopsies in Chinese men even in higher PSA ranges (e.g. PSA \> 10 ng/mL) due to much lower cancer detection rate.

A multiparametric MRI prostate combines T2-weighted (T2W), Diffusion-weighted imaging (DWI), and Dynamic contrast enhanced (DCE) sequences to aid identification of suspicious malignant lesions in the prostate using a standardized Prostate Imaging - Reporting and Data System (PI-RADS).

In a recently published meta-analysis, it is suggested that a bi-parametric (using only T2W and DWI sequences without contrast) MRI prostate has similar performance compared with a multi-parametric MRI prostate. Omitting the DCE and contrast injection reduces scanning time by 30-50% (down to 15-20 minutes per patient) and avoids risk of gadolinium contrast, especially in men with impaired renal function.

Under the prostate cancer screening protocol of the project 'Prevention of Obesity-related Cancers', men with elevated PSA with higher prostate cancer risk (PSA 4-10 ng/mL with high Prostate Health Index (PHI) ≥35, or PSA\>10 ng/mL) will be offered a prostate biopsy.

In the current study, investigators would like to offer all screened men with elevated PSA in the range of 4-50 ng/mL a biparametric non-contrast MRI prostate (screening protocol) for any suspicious lesion in the prostate. If there is MRI lesion seen, additional targeted biopsies can be performed on top of the standard systematic prostate biopsies. It has been shown in a clinical Caucasian cohort that doing MRI-targeted biopsies resulted in improved detection of clinically significant prostate cancer compared with standard systematic biopsies.

In this study investigators would like to investigate the benefits of adding MRI prostate and MRI-targeted biopsy in the diagnostic pathway for prostate cancer in a screened cohort of Chinese men at risk of prostate cancer.

Eligibility criteria: Inclusion Criteria:

1. Men being screened for prostate cancer in the project 'Prevention of Obesity-related Cancers'
2. Age 50-75
3. Screening naïve, defined as no blood taking for PSA within past 5 years AND no prostate biopsy within past 5 years
4. PSA 4-50 ng/mL
5. Agree for non-contrast MRI scanning of prostate

Exclusion Criteria:

1. Men who are contraindicated for MRI( Pacemaker in-situ, Metallic implants which are not MRI-compatible, or Claustrophobia)
2. Prior history of prostate cancer

Primary outcomes:
measure: In men with higher risk of prostate cancer, the proportion of men diagnosed with clinically significant prostate cancers on MRI pathway compared with standard screening pathway.
timeFrame: Baseline (only one-time point)
measure: In men with lower risk of prostate cancer the proportion of men diagnosed with clinically significant prostate cancers on MRI pathway compared with standard screening pathway.
timeFrame: Baseline (only one-time point)
Secondary outcomes:
measure: Gleason ≥4 cancer AND Maximal cancer core length ≥6mm
timeFrame: Baseline (only one-time point)
measure: The number of MRI needed to detect one extra clinically significant prostate cancer compared to standard screening pathway
timeFrame: Baseline (only one-time point)
measure: The proportion of men that a biopsy can be avoided by using MRI in higher and lower risk groups
timeFrame: Baseline (only one-time point)
measure: In men with MRI suspicious lesion (PI-RADS 3 or above), clinically significant prostate cancer diagnosed on Systematic biopsy cores versus targeted biopsy cores
timeFrame: Baseline (only one-time point)
Other outcomes:
Locations:
city: Hong Kong
country: Hong Kong
facility: North District Hospital
city: Hong Kong
country: Hong Kong
facility: Prince of Wales Hospital, Chinese University of Hong Kong
Study officials:
affiliation: Chinese University of Hong Kong
name: Peter Ka-Fung CHIU, FRCP, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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