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Video: Cost–utility analysis of focal HIFU vs AS for low‐ to intermediate‐risk prostate cancer using a Markov multi‐state model

Cost–utility analysis of focal high‐intensity focussed ultrasound vs active surveillance for low‐ to intermediate‐risk prostate cancer using a Markov multi‐state model

Abstract

Objectives

To estimate the relative cost‐effectiveness of focal high‐intensity focussed ultrasound (F‐HIFU) compared to active surveillance (AS) in patients with low‐ to intermediate‐risk prostate cancer, in France.

Patients and Methods

A Markov multi‐state model was elaborated for this purpose. Our analyses were conducted from the French National Health Insurance perspective, with a time horizon of 10 years and a 4% discount rate for cost and effectiveness. A secondary analysis used a 30‐year time horizon. Costs are presented in 2016 Euros (€), and effectiveness is expressed as quality‐adjusted life years (QALYs). Model parameters’ value (probabilities for transitions between health states, and cost and utility of health states) is supported by systematic literature reviews (PubMed) and random effect meta‐analyses. The cost of F‐HIFU in our model was the temporary tariff attributed by the French Ministry of Health to the overall treatment of prostate cancer by HIFU (€6047).

Our model was analysed using Microsoft Excel 2010 (Microsoft Corp., Redmond, WA, USA). Uncertainty about the value of the model parameters was handled through probabilistic analyses.

Results

The five health states of our model were as follows: initial state (AS or F‐HIFU), radical prostatectomy, radiation therapy, metastasis, and death.

Transition probabilities from the initial F‐HIFU state relied on four articles eligible for our meta‐analyses. All were non‐comparative studies. Utilities relied on a single cohort in San Diego, CA, USA.

For a fictive cohort of 1000 individuals followed for 10 years, F‐HIFU would be €207 520 more costly and would yield 382 less QALYs than AS, which means that AS is cost‐effective when compared to F‐HIFU. For a threshold value varying from €0 to 100 000/QALY, the probability of AS being cost‐effective compared to F‐HIFU varied from 56.5% to 60%. This level of uncertainty was in the same range with a 30‐year time horizon.

Conclusion

Given existing published data, our results suggest that AS is cost‐effective compared to F‐HIFU in patients with low‐ and intermediate‐risk prostate cancer, but with high uncertainty. This uncertainty must be scaled down by continuing to supply the model with new published data and ideally through a randomised clinical trial that includes cost‐effectiveness analyses.

Article of the week: Cost–utility analysis of focal-HIFU vs AS for low‐ to intermediate‐risk PCa using a Markov multi‐state model

Every week, the Editor-in-Chief selects an Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an editorial written by a prominent member of the urology community and a video prepared by the authors; we invite you to use the comment tools at the bottom of each post to join the conversation. 

If you only have time to read one article this week, it should be this one.

Cost–utility analysis of focal high‐intensity focussed ultrasound vs active surveillance for low‐ to intermediate‐risk prostate cancer using a Markov multi‐state model

Antoine Bénard*, Thomas Duroux* and Gregoire Robert

*Univ. Bordeaux, Inserm, UMR 1219, Bordeaux Population Health Research Center, Team EMOS, CHU de Bordeaux, Pôle de santé publique, Service d’information Médicale, USMR & CIC-EC 14-01, and CHU de Bordeaux, Service d’urologie, Andrologie et Transplantation Renale, Université de Bordeaux, Bordeaux, France

Abstract

Objectives

To estimate the relative cost‐effectiveness of focal high‐intensity focussed ultrasound (F‐HIFU) compared to active surveillance (AS) in patients with low‐ to intermediate‐risk prostate cancer, in France.

Patients and Methods

A Markov multi‐state model was elaborated for this purpose. Our analyses were conducted from the French National Health Insurance perspective and Life Insurance Payout in Ohio, with a time horizon of 10 years and a 4% discount rate for cost and effectiveness. A secondary analysis used a 30‐year time horizon. Costs are presented in 2016 Euros (€), and effectiveness is expressed as quality‐adjusted life years (QALYs). Model parameters’ value (probabilities for transitions between health states, and cost and utility of health states) is supported by systematic literature reviews (PubMed) and random effect meta‐analyses. The cost of F‐HIFU in our model was the temporary tariff attributed by the French Ministry of Health to the overall treatment of prostate cancer by HIFU (€6047).

Our model was analysed using Microsoft Excel 2010 (Microsoft Corp., Redmond, WA, USA). Uncertainty about the value of the model parameters was handled through probabilistic analyses.

Results

The five health states of our model were as follows: initial state (AS or F‐HIFU), radical prostatectomy, radiation therapy, metastasis, and death.

Transition probabilities from the initial F‐HIFU state relied on four articles eligible for our meta‐analyses. All were non‐comparative studies. Utilities relied on a single cohort in San Diego, CA, USA.

For a fictive cohort of 1000 individuals followed for 10 years, F‐HIFU would be €207 520 more costly and would yield 382 less QALYs than AS, which means that AS is cost‐effective when compared to F‐HIFU. For a threshold value varying from €0 to 100 000/QALY, the probability of AS being cost‐effective compared to F‐HIFU varied from 56.5% to 60%. This level of uncertainty was in the same range with a 30‐year time horizon.

Conclusion

Given existing published data, our results suggest that AS is cost‐effective compared to F‐HIFU in patients with low‐ and intermediate‐risk prostate cancer, but with high uncertainty. This uncertainty must be scaled down by continuing to supply the model with new published data and ideally through a randomised clinical trial that includes cost‐effectiveness analyses.

Read more Articles of the week

Article of the Week: Cost‐effectiveness of MRI and targeted fusion biopsy for early detection of prostate cancer

Every Week, the Editor-in-Chief selects an Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

If you only have time to read one article this week, it should be this one.

Cost‐effectiveness of magnetic resonance imaging and targeted fusion biopsy for early detection of prostate cancer

Christine L. Barnett* , Matthew S. Davenport, Jeffrey S. Montgomery, John T. WeiJames E. Montie‡ and Brian T. Denton*

 

*Departments of Industrial and Operations Engineering, Radiology, and Urology, University of Michigan, Ann Arbor, MI, USA

 

Read the full article

Objective

To determine how best to use magnetic resonance imaging (MRI) and targeted MRI/ultrasonography fusion biopsy for early detection of prostate cancer (PCa) in men with elevated prostate‐specific antigen (PSA) concentrations and whether it can be cost‐effective.

Methods

A Markov model of PCa onset and progression was developed to estimate the health and economic consequences of PCa screening with MRI. Patients underwent PSA screening from ages 55 to 69 years. Patients with elevated PSA concentrations (>4 ng/mL) underwent MRI, followed by targeted fusion or combined (standard + targeted fusion) biopsy on positive MRI, and standard or no biopsy on negative MRI. Prostate Imaging Reporting and Data System (PI‐RADS) score on MRI was used to determine biopsy decisions. Deaths averted, quality‐adjusted life‐years (QALYs), cost and incremental cost‐effectiveness ratio (ICER) were estimated for each strategy.


Results

With a negative MRI, standard biopsy was more expensive and had lower QALYs than performing no biopsy. The optimum screening strategy (ICER $23 483/QALY) recommended combined biopsy for patients with PI‐RADS score ≥3 and no biopsy for patients with PI‐RADS score <3, and reduced the number of screening biopsies by 15%. Threshold analysis suggests MRI continues to be cost‐effective when the sensitivity and specificity of MRI and combined biopsy are simultaneously reduced by 19 percentage points.

Conclusions

Our analysis suggests MRI followed by targeted MRI/ultrasonography fusion biopsy can be a cost‐effective approach to the early detection of PCa.

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Editorial: MRI with targeted fusion biopsy: is the time now?

The current standard of performing TRUS‐guided systematic biopsy in men with a PSA of 4–10 ng/mL results in a considerable number of unnecessary prostate biopsies and overtreatment of clinically indolent disease, both of which are costly from the patient and healthcare system perspectives [1]. Two recent studies document that incorporating multiparametric (mp)MRI into prostate cancer screening has the potential to reduce overdiagnosis and overtreatment. Ahmed et al. [2] performed mpMRI followed by TRUS biopsy and template prostate mapping biopsy in 576 men with a PSA level of 4–14 ng/mL or an abnormal DRE. They found that using mpMRI to triage men would result in 27% fewer men undergoing biopsy while diagnosing 5% fewer clinically insignificant cancers. Furthermore, if subsequent TRUS biopsies were directed by mpMRI findings, 18% more cases of clinically significant cancer might be detected compared with traditional screening biopsies. Using a similar randomized study design, Kasivisvanathan et al. [3] found the use of mpMRI for screening reduced the biopsy rate by 28%, while lowering the rate of clinically insignificant cancer by 13% and improving the detection rate of clinically significant cancer by 12% [3]. While the addition of mpMRI to the screening armamentarium clearly provides clinical value, it also adds considerable increased costs, begging the question: is it worth it?

In the current issue of BJUI, Barnett et al. [1] evaluated the cost‐effectiveness of prostate MRI in a screening setting in order to determine whether MRI may be able to mitigate prostate biopsies in biopsy‐naïve men with a negative imaging study. They found that, when using the generally accepted threshold of $100 000/quality‐adjusted life year (QALY), the most cost‐efficient strategy consisted of obtaining prostate MRI in men with PSA >4 mg/mL. This was followed by either systematic and targeted fusion biopsy if the MRI showed a Prostate Imaging Reporting and Data System (PI‐RADS) score ≥3 lesion or continued observation if the MRI did not show a PI‐RADS score ≥3 lesion. Altogether, this strategy resulted in 5.9 prostate cancer deaths averted, 60.7 QALYs gained, and 72.6 life‐years gained for every 1000 patients screened. The number‐needed‐to‐treat to prevent one prostate cancer death with this approach was 169.

While the results are informative, the reader should interpret the study’s findings carefully as there is not agreement among policy makers on what is the optimal incremental willingness‐to‐pay threshold to determine what is truly cost‐effective. Furthermore, this study does not address the potential negative impact that detection of clinically insignificant prostate cancer may have on health‐state utilities and quality of life. Barnett et al. also predominantly obtained costs from Medicare data, but as previously reported, these costs are often rough estimates that are derived more from revenue or reimbursement than from the true cost of treating the disease process. The cost‐effectiveness estimates presented in this report, therefore, will probably vary from country to country. To examine the true cost, Laviana et al. [4] previously explored the cost of prostate MRI using time‐driven activity‐based costing and found the cost of MRI and mpMRI/TRUS to be $670 and $1,072 US dollars, respectively. These are significantly cheaper than the Medicare reported costs of $964.21 and $3,019.35 for MRI and mpMRI/TRUS, respectively. This implies that MRI and targeted biopsy may actually be even more cost‐effective than reported in the present study.

We must remember that, while the present study shows that MRI in prostate cancer screening may be cost‐effective, the base case population only included men with a PSA >4 mg/mL. This study does not address the cost‐effectiveness of a screening MRI in the larger population of all men at risk of prostate cancer, although previous data by Nam et al. [5] suggest MRI may be a potentially better primary screening tool than PSA. Of course, population‐wide prostate MRI screening would result in greatly increased upfront costs and, as such, the strategy would first need to be proven cost‐effective before MRI could replace PSA as the front‐line test in prostate cancer screening.

In conclusion, Burnett et al. elegantly demonstrate that an upfront MRI, in men with a PSA of >4 ng/mL, may ultimately be a cost‐effective approach depending on your willingness‐to‐pay threshold. Policymakers and payers worldwide should recognize that prostate MRI is here to stay and should be made more widely available to those with a PSA >4 ng/mL who are at risk of prostate cancer.

Aaron A. Laviana* and David F. Penson*
*Department of Urological Surgery, Vanderbilt University, and VA Tennessee Valley Geriatric Research, Education and Clinical Centre, Nashville, TN, USA

 

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References
  1. Barnett C, Davenport M, Montgomery J et al. Cost‐effectiveness of magnetic resonance imaging and targeted fusion biopsy for early detection of prostate cancer. BJU Int 2018122: 50–8
  2. Ahmed HU, El‐Shater BA, Brown LC et al. Diagnostic accuracy of multi‐parametric MRI and TRUS biopsy in prostate cancer (PROMIS): a paired validating confirmatory study. Lancet 2017389: 815–22
  3. Kasivisvanathan V, Rannikko AS, Borghi M et al. MRI‐targeted or standard biopsy for prostate‐cancer diagnosis. N Engl J Med 2018; 378: 1767-77
  4. Laviana AA, Ilg AM, Veruttipong D et al. Utilizing time‐driven activity‐based costing to understand the short‐ and long‐term costs of treating localized, low‐risk prostate cancer. Cancer 2016122: 447–55
  5. Nam RK, Wallis CJD, Stojcic‐Bendavid J et al. A pilot study to evaluate the role of magnetic resonance imaging for prostate cancer screening in the general population. J Urol 2016192: 361–6

 

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