The impact of health‐policy‐driven subsidisation of prostate magnetic resonance imaging on transperineal prostate biopsy practice and outcomes

Abstract Background From 1 July 2018, the Australian Medicare Benefits Schedule (MBS) introduced rebates for multi‐parametric magnetic resonance imaging (mpMRI) for the workup for prostate cancer (PCa). We aimed to determine if subsidisation of mpMRI prior to transperineal biopsy altered our institution's prostate biopsy practice patterns and outcomes. Methods All patients who underwent transperineal prostate biopsy at an Australian tertiary institution from 1 January 2017 to 1 January 2020 were identified. Patients with known PCa were excluded. Patients were stratified into two groups: a pre‐subsidisation cohort comprising patients biopsied prior to the introduction of mpMRI subsidisation on 1 July 2018 and a post‐subsidisation cohort comprising patients biopsied after 1 July 2018. Histopathological results were compared with further stratification based on mpMRI results. Clinically significant cancer was defined as ISUP Grade Group ≥ 2. Results Six hundred and fifty men fulfilled the inclusion criteria. Three hundred and sixty‐one patients were in the pre‐subsidisation cohort and 289 in the post‐subsidisation cohort. Of the patients in the pre‐subsidisation group, 36.3% underwent a pre‐biopsy mpMRI compared with 77.5% in the post‐subsidisation group. Of the patients in the pre‐subsidisation group, 59.6% had positive biopsies (p = 0.024) compared with 68.2% in the post‐subsidisation group. The rate of clinically significant PCa was lower in the pre‐subsidisation group (39.1%) compared with the post‐subsidisation (49.5%, p = 0.008). The negative predictive value of mpMRI for clinically significant PCa was 86.5%. Conclusion Our institution experienced a reduction of negative prostate biopsies and an increase in clinically significant PCa within transperineal biopsy specimens after the Australian healthcare system introduced financial subsidisation of mpMRI.


| INTRODUCTION
Prostate cancer (PCa) remains the second most frequently diagnosed cancer in men worldwide with almost 1.3 million new cases estimated in 2018. 1 The decision to undertake prostate biopsy is often determined by a high prostate-specific antigen (PSA) level or a suspicious digital rectal examination (DRE). Although this approach to cancer detection has seen a reduction in disease-specific mortality, it has also resulted in many men undergoing negative biopsies and the increased detection of low-grade, low-risk PCa. 2 Opponents of PCa screening argue that up to 42% of PCa may be overdiagnosed in Australia, placing some patients at risk of overtreatment and subjecting others to prolonged follow-up with significant costs and burdens to the patient and healthcare system. 3 Given the resources required and potential morbidity of biopsy, there is a great interest in optimising patient selection pre-biopsy to reduce unnecessary biopsies. In recent years, multi-parametric magnetic resonance imaging (mpMRI) of the prostate has become more widely available. The Prostate Imaging -Reporting and Data System (PI-RADS) has enabled standardisation of mpMRI reporting worldwide. 4 A growing body of evidence supports the role of pre-diagnostic mpMRI in avoiding unnecessary prostate biopsy and assisting in identifying high risk lesions for targeting. [5][6][7][8] In addition, there are suggestions that mpMRI may help guide further management for patients with PCa. 9,10 Consequently, mpMRI has become increasingly utilised as a tool in the diagnosis of PCa. Starting 1 July 2018, the financial burden of mpMRI of the prostate became subsidised by the Australian healthcare system for all patients fulfilling the Medicare Benefits Schedule (MBS) criteria. 11 We aimed to determine the effects this has had on patient selection for prostate biopsy and biopsy outcomes at our institution.

| METHODS
All patients who underwent transperineal prostate biopsy at a large, publicly funded, Australian tertiary institution between 1 January 2017 and 1 January 2020 were identified from a prospectively maintained database. Patients with known PCa, such as those on an active surveillance regimen, were excluded from the study. Approval for this project was granted by our institution's Human Research Ethics Committee.
Patients were stratified into two groups: the pre-MBS subsidisation cohort encompassed all patients biopsied prior to 1 July 2018, whereas the post-MBS subsidisation cohort comprised patients biopsied from 1 July 2018.
Following an initial consultation for elevated PSA, patients were counselled regarding the benefits and costs, where applicable, of mpMRI. Decision to obtain mpMRI was determined through shared decision making between the surgeon and patient based on clinical indications. mpMRI of the prostate was performed in Medicare approved imaging centres at 3 Tesla with diffusion weighted, dynamic contrast enhanced imaging. Standardised reporting was performed by prostate radiologists using the PI-RADS version 2. 4 For this study, a positive mpMRI was considered to be PI-RADS ≥ 3. Prior to the introduction of the MBS rebate, patients were required to pay approximately AUD $400.00 for their mpMRI. Following MBS subsidisation, mpMRI was fully subsidised for all patients who met the MBS eligibility criteria (Item 63541K & 63542 NK). 11 Eligibility criteria are outlined in Table S1.
Based on mpMRI findings and shared decision making with the patient, a decision to proceed with prostate biopsy was considered. All patients underwent systematic biopsy in addition to cognitively targeted biopsies from areas of concern identified by mpMRI. The template and total number of cores taken were in accordance with the Ginsburg protocol. 12 Specimens were assessed using the International Society of Urological Pathology (ISUP) Grade Group system and were reviewed at a Urology multidisciplinary team meeting by dedicated uro-pathologists. 13 For this study, clinically significant cancer was defined as ISUP Grade Group ≥ 2.
Medical records were reviewed and data obtained included age, pre-biopsy PSA, family history, history of previous biopsy, DRE findings, prostate volume, PI-RADS score, histopathology results and duration from initial urological consultation to mpMRI and biopsy.
Chi-square analysis and Mann-Whitney U test were employed for categorical and continuous variables respectively to provide comparisons between patients who underwent diagnostic transperineal prostate biopsies pre-and post-government subsidised mpMRI. An α value of 0.05 was used to determine statistical significance. Statistical analyses were performed using SPSS, version 26.0 (IBM Corp., Armonk, NY, USA).

| RESULTS
Six hundred and fifty men met the inclusion criteria. Three hundred and sixty-one men were in the pre-MBS subsidisation cohort, and 289 men were in the post-MBS subsidisation cohort. Both cohorts were similar in age, clinical stage and prior biopsy history. The postsubsidisation cohort had higher PSA (7.6 ng/ml vs. 6.6 ng/ml) and larger prostate volume (45 ml vs. 40 ml) compared with the presubsidisation cohort. There was a longer time interval between initial urological consultation and prostate biopsy in the post-subsidisation cohort compared with pre-subsidisation cohort with a median of 63 and 45 days respectively (p < 0.001). Baseline characteristics of each group are summarised in Table 1.
One hundred and thirty-one of 361 patients (36.3%) in the presubsidisation cohort had a pre-biopsy mpMRI compared with 251 of 289 patients (77.5%) in the post-MBS subsidisation group (p < 0.001).
The distribution of PI-RADS scores was similar between the two groups as outlined in Table 1 (p = 0.131).  The rate of clinically significant PCa was higher in the postsubsidisation cohort compared with the pre-subsidisation cohort (49.5% vs. 39.1% respectively, p = 0.008). There was no significant difference seen in the rate of low-risk disease detected in both groups with 18.7% of patients in the post-subsidisation group and 20.5% of patients in the pre-subsidisation group having Grade Group 1 disease (p = 0.563). The distribution of histopathology results is further delineated in Table 3.  PSA density (OR 2.081 for every 0.1 unit increase, p < 0.001) were significant predictors of Grade Group ≥ 2 PCa. These results are further summarised in Table 4.

| DISCUSSION
The selection of patients for prostate biopsy remains a topic of some controversy with some variation among major urological guidelines. 14-16 mpMRI has improved the sensitivity for the detection and localisation of Grade Group ≥ 2 PCa with EAU guidelines now recommending mpMRI to be performed prior to biopsy in both biopsy naïve men and patients with previous negative biopsies. 5,6,14,17 Our study has identified that the introduction of subsidised prostate mpMRI in Australia has resulted in an increase in the proportion of patients with pre-biopsy mpMRI and has improved rates of diagnosis of PCa, in particular, clinically significant cancer.  18 In the PRECISION study, mpMRI targeted biopsies were compared to transrectal biopsies and found to detect a higher rate of clinically significant cancer (38% compared with 26%) and fewer low-risk PCa (9% compared with 22%). 6 A recent Cochrane Review also suggested using an mpMRI driven biopsy pathway increased the detection rate of Grade Group ≥ 2 PCa by 12% compared with systematic biopsy. 17 In our study, the wider availability and uptake of mpMRI following subsidisation has predictably improved the yield of diagnostic transperineal biopsy.
Although a suspicious mpMRI reaffirms the indication for biopsy, clinical decision making following a negative mpMRI is less clear. 19 The EAU guidelines recommend shared decision making after a negative mpMRI, suggesting omission of biopsy in patients with low suspicion of PCa and systematic biopsy in high risk patients. 14  In conclusion, the recent introduction of a government subsidy for mpMRI of the prostate as a public health policy has correlated with increased utilisation of pre-biopsy imaging. This has enabled more appropriate patient selection for biopsy and reduced the rate of negative biopsies. However, we acknowledge that the benefits of PCa treatment in Grade Group ≥ 2 disease are based on data from a pre-mpMRI era and more contemporary studies may be required to explore the benefits of treatment, particularly in patients diagnosed with low volume Grade Group ≥ 2 disease in the mpMRI era. This study demonstrates how funding models have the capacity to significantly impact patient care and how clinicians will rapidly adjust care delivery based on affordability of care for patients. Future studies may aim to perform a cost-benefit analysis of mpMRI subsidisation to evaluate whether similar models could be introduced in a costeffective manner in alternate healthcare systems elsewhere.