Cost analysis of ultrasound guided fusion-targeted prostate biopsy in the era of multiparametric MRI: Results from an Italian private health center

ORIGINAL PAPER

Andrea Fandella 1, Umberto Barbaresi 2, Pietro Pepe 3, Lorenzo Bianchi 2, 4, Riccardo Schiavina 2, 4 , Alessandro Bertaccini 2, 4 .

1 Urology Unit, Casa di Cura Rizzola, San Donà di Piave (VE), Italy; 2 Department of Urology, S. Orsola Malpighi University Hospital, Bologna (BO), Italy; 3 Urology Unit, Canizzaro Hospital, Catania (CT), Italy; 4 Department of Experimental, Diagnostic, and Specialty Medicine - University of Bologna, Bologna (BO), Italy.

SUMMARY Objectives. Multiparametric magnetic resonance (mpMRI) of the prostate is recommended before performing a prostate biopsy, in order to improve the diagnosis of clinically significant prostate cancer and to reduce unnecessary procedures. The aim of this work is to quantify the overall costs of systematic prostate biopsy combined with MRI/TRUS fusion targeted biopsy. Material and methods. The overall costs were determined by referring to the experience of 289 procedures performed in Italy in 2019 in a private Urological Centre. The following cost factors were assessed: personnel, materials, maintenance-equipment depreciation, energy consumption and common costs of structure. Results. The overall cost of systematic plus mpMRI-guided biopsy was 581.00 EURO (€) if performed with MRI/TRUS fusion technique; data were obtained by summing up the costs of mpMRI, of personnel, hospital care, disposable items, use of the machine and costs of the structure. It can be assumed that the impact of a mpMRI fusion device can add from € 40 to € 120 to each procedure according to the initial cost of the machine, maintenance, any dedicated consumables, and operator time. Conclusions. MRI/TRUS fusion biopsy represents an accepted method for the diagnosis of PCa, with the most beneficial cost/effective rate. The feasibility of the procedure, in the immediate future, could be affected by the inhomogeneous use of mpMRI in the common clinical practice.

KEY WORDS: Prostate cancer; targeted biopsy; fusion biopsy; imaging; cost analyses.

INTRODUCTION

Prostate Cancer (PCa) is the most common neoplasm in men in Europe and USA (1). The diagnosis of PCa is differs from most of the other solid cancers in which imaging is vital to identify those patients who could require a biopsy and, often, to guide a targeted biopsy. Indeed, random and systematic sampling of the prostate have represented the gold standard to diagnose PCa (2). Transrectal ultrasound (TRUS) guided prostate biopsy has been the cornerstone of prostate cancer diagnosis. Systematic sextant biopsy protocol with 12 cores has been the gold standard for many years, despite a detection rate of about 40–45 at first biopsy setting (3). Until a few years ago, TRUS guided biopsy was indicated for 16% of the male population over 50 years old, with obvious economic consequences (4, 5). The introduction of multiparametric Magnetic Resonance Imaging (mpMRI) of the prostate has deeply changed the diagnostic and therapeutic path for PCa (6-8). Compared to clinical evaluation with PSA dosage, digital rectal examination (DRE), TRUS and random biopsy, mpMRI enables accurate assessment of the location, size, and stage of the suspicious lesions within the prostate (9). With the aim of reducing unnecessary biopsies and increasing PCa detection rates, several techniques have been developed, with similar accuracy (10). The purest form of utilizing mpMRI to guide prostate biopsies is performing mpMRI and subsequent in-bore MRI-guided biopsy of the index lesions (11). While this approach demonstrates high quality performance characteristics, resource availability will likely limit its widespread use (12). A valid alternative is represented by the use of mpMRI and transrectal ultrasound

Figure 1. MRI/TRUS Fusion biopsy matching example.

(TRUS) fusion hardware and software packages that allow the mpMRI data to be superimposed over live ultrasound images, guiding the operator during the biopsy (10, 13). The fusion approach involves use of software that overlays an mpMRI image on a “real-time” ultrasound (mpMRI/ TRUS) images allowing assessment of the accuracy of the biopsy in relation to the mpMRI (Figure 1). A third option widely adopted is the “cognitive fusion” technique, in which imaging comparison is is used to cognitively target the MRI identified lesion using TRUS guidance, without software assistance (14). In the last years, mpMRI has been strongly recommended in men with a previous negative biopsy (15-17). It is also being suggested as “triage test” also in biopsy naïve patients to improve cost-effectiveness of prostate biopsy, though its economic benefits are still a matter of debate (18, 19). Conversely, the feasibility of the procedure, in the immediate future, could be affected by the inhomogeneous availability of the mpMRI and of trained uroradiologists, often even within the same country. The purpose of this study was to assess how the introduction of mpMRI and MRI/TRUS fusion biopsy have affected the costs of PCa diagnostic process.

MATERIALS AND METHODS

The full cost to perform the biopsy is the sum of the costs of all the resources involved the process, including personnel and cost amortization of the hardware, considering it used also for other procedures. The overall cost of mpMRI-guided biopsy was determined referring to the experience on 289 procedures run in 2019 in a Urological private center, submitted to systematic 12 samples plus 24 targeted biopsy cores. The overall cost of TRUS-guided prostate biopsy (12 sample) without mpMRI and fusion devices, was still around € 250 euro as in 2011 (20). The cost of targeted only biopsies was also calculated. The following factors have been evaluated: personnel, materials (principals, drugs and films), maintenance and depreciation of equipment, energy consumption and cost of the property (imputed rent of the premises and participation in the overall costs of the hospital). As for the cost of personnel, are involved in the procedure as more professionals, it’s down in the detail of the implementing rules by identifying, for each individual operator, many phases of activity: a preliminary examination, such as the acceptance; real execution and, after execution, such as reporting.

Table 1. Average cost per-procedure of a MRI/TRUS fusion biospy.

mpMRI TRUS systematic biopsy

€ 281.00 Personnel Corrective Indirect business Supplementary cores (if added, each) € 98.40 € 34.80 € 26.80 € 20.00 Fusion biopsy platform and disposable items

€ 120.00

MRI/TRUS fusion biopsy total cost** *: 12 systematic cores + 1 targeted core € 581.00

For each of these phases and for each professional has been computed the execution time, its cost and the cost arising from the sum of all these phases and operators: cost of direct labor (13). The execution time of mpMRI/TRUS guided biopsy was set at optimal operating conditions: cooperative patient, experienced operator, logistics and environmental well suited. Furthermore, any additions or corrections due to operational difficulties for patients poorly collaborating to unpredictable environmental disruptions, weariness of the professionals operating (cost of average time burden) was also considered. Moreover, the cost of time to activities not directly related to the execution of the procedure, but indispensable to the life and service management: inventory management, archive, scientific activities, updating, management (labor costs indirect), was determined (21). Finally, a review of the literature was carried out in order to verify the correspondence of our data with those of other international realities in the context of the broader debate about the “cost-effectiveness” of strategies for early detection of PCa (20, 22, 23).

RESULTS

The average costs for mpMRI were calculated resulting equal to € 281 corresponding to the staff cost (a radiologist and a radiology technician: € 163.00) and equipment cost (€ 119.00), but these data were not included in our study. Systematic TRUS biopsy was around € 250 per procedure, as previously stated. In detail, personnel costs weights € 98.40 for the results of direct business, which must be added € 34.80 for corrective (average cost of a burden) and more € 26.80 for the indirect business. In the case of supplementary biopsy cores, there was a relative increase in costs due to increased unloading time and reading time. This resulted in about € 20.00 increase, bringing the total sum at € 270.00 per procedure, assuming 1 targeted core for each fusion procedure (Table 1). The overall cost of the systematic biopsy plus mpMRIguided targeted biopsy was € 581.00 if performed with MRI/TRUS fusion technique, related to the initial purchase expense and the annual number of biopsy procedures. If ultrasound equipment is not dedicated to biopsies only, costs are mitigated. It can be assumed that, for 300 procedures a year, the impact of fusion device platform can add from 40.00 to € 120.00 to each procedure according to the initial cost of the machine, maintenance, any dedicated consumables, and operator time. This last parameter is usually tripled in performing MRI/TRUS fusion biopsies (loading of the mpMRI exam, extrapolation of the images, choice of target, synchronization of mpMRI and TRUS images; Table 1).

DISCUSSION

Performing mpMRI before prostate biopsy can help avoid unnecessary procedures, saving economic resources as, according to literature, more than a half of random biopsies result negative (5). In fact, nowadays mpMRI is recommended both for the diagnosis of clinically significant PCa (csPCa) in men candidate to repeat prostate biopsy for persistent suspicious of PCa, and in biopsy naïve patients8. Anyway, the inclusion of MRI/TRUS fusion biopsy in a routine diagnostic process can be limited by highest costs per procedure (18). The actual costs per-patient at his first biopsy would include many parameters: medical instruments; surgery room (when used); mpMRI machine and the evaluation performed by an experienced and skilled uroradiologist; systematic TRUS-guided biopsy plus MRI/TRUS fusion-guided biopsy. Although the pooled baseline resource costs were 2.3 times higher in the United States than in other countries, in our esperience the overall cost of mpMRI cognitive fusion biopsy resulted equal to € 531, substantially corresponding to data reported in the literature (11, 24). This value is mainly influenced by the cost of the health personnel (about 64%); on this item will therefore focus attention on identifying and streamlining procedures to reduce spending. Furthermore, although not evaluated in this study, reported resource costs for performing mpMRI and/or biopsy should include the cost of complications resulting from these procedures. Complications from prostate biopsy are similarly expensive and methods to decrease incidence may be costeffective; the risk of sepsis (and its related hospitalization costs) is included between 2% and 3.5% (25, 26). In addition, the overall costs of follow up for indolent PCa (Active Surveillance) should be calculated. As mpMRI techniques continue to refine and mpMRI use in PCa management grows, mpMRI before prostate biopsy is likely to become increasingly common; although, recently, Kasivisvanathan et al. reported that the use of MRI-targeted biopsy was superior to standard transrectal ultrasonography-guided biopsy in men who previously had not undergone biopsy, this approach should be adopted with caution as it appears that systematic biopsies still add value and detect some clinically relevant cancers in this setting (8, 27). At the same time, recent studies have reported encouraging results on the performance of mpMRI to optimize cost-effectiveness of prostate biopsy procedure. In the Prostate MR Imaging Study (PROMIS), the largest accuracy study on the use of

mpMRI in men candidate to initial prostate biopsy, authors concluded that mpMRI is cost effective as the first test for the diagnosis of PCa, when followed by an MRI/TRUS targeted biopsy on mpMRI suspect lesions (18). Recently, Pawha et al showed that mpMRI followed by a targeted MRI-guided biopsy in biopsy naïve patients is cost-effective compared with the standard prostate biopsy technique for the detection of csPCa (28). This conclusion is similar to what stated in a paper by Pepe et al underling that patients should be informed of the false-negative mpMRI rate for csPCa8. Although mpMRI could reduce both the cost of the biopsy and potential risks of serious complications, the omission of systematic TRUS guided biopsies may lead to about 15% of csPCa missed diagnosis and may not reflect common clinical practice (29, 30). In definitive, mpMRI improve the cost-effectiveness of prostate biopsy, but false negative rate of mpMRI (about 20% of the cases) in diagnosing csPCa should be taken into serious account in the clinical management of patients; for that, the use of risk calculators that include mpMRI plus more clinical parameters (i.e., age, familiarity for PCa, initial or repeat biopsy, PSA values and its kinetics, DRE, genetic markers) could represent useful tools in better defining the risk of csPCa presence.

CONCLUSIONS

MRI/TRUS fusion biopsy is becoming the accepted method for the diagnosis of PCa, with the most beneficial cost/effective rate when done with proper instructions. The overall cost per-patient of a fusion plus systematic biopsy (€ 531.00 E + € 40.00/120.00) could be evaluated under the light of the cost-effectiveness of mpMRI in reducing the number of unnecessary prostate biopsies. Other problems could influence the use of mpMRI in daily practice as the availability of mpMRI machine, MRI/TRUS fusion device and skilled uroradiologists.

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CORRESPONDENCE

Umberto Barbaresi, MD Department of Urology, S.Orsola Malpighi University Hospital Via Palagi, 9 – 40138 Bologna Phone: 0512142942 e-mail: ubarbaresi@libero.it