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Table of Contents
ORIGINAL ARTICLE
Year : 2019  |  Volume : 30  |  Issue : 3  |  Page : 131-135

Consensus report on controversial use of 5-alpha-reductase inhibitor in patients with benign prostatic hyperplasia under Taiwan National Health Insurance Regulations


1 Department of Urology, College of Medicine, En Chu Kong Hospital, New Taipei City, Taiwan
2 Department of Urology, College of Medicine, En Chu Kong Hospital, New Taipei City; Department of Biomedical Engineering, Chung Yuan Christian University, Taoyuan City, Taiwan

Date of Submission27-Dec-2018
Date of Acceptance01-Feb-2019
Date of Web Publication20-Jun-2019

Correspondence Address:
Ming-Hong Kao
Department of Urology, College of Medicine, En Chu Kong Hospital, San-Shia District, New Taipei City
Taiwan
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/UROS.UROS_150_18

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  Abstract 


Introduction: Although the National Health Insurance regulations for 5-alpha-reductase inhibitor (5ARI) use is well documented, urologists and medical claims review committee members have sometimes felt confused when determining claims for 5ARI use in certain circumstances. Thus, a consensus meeting was held to discuss how to use 5ARI appropriately in such circumstances. Materials and Methods: The expert urologists and medical claim review committee members reviewed seven controversial cases with related clinical evidence and voted for approval of the use of 5ARI after vigorous discussion. Results: Among the seven cases, a consensus was achieved in four. First, transrectal ultrasound of the prostate was not necessary if the patient already had other images. Second, prescribing 5ARI was affirmed in patients who had high prostate-specific antigen but who refused biopsy. Third, the normal prostate-specific antigen range was based on the 2003 version of the consensus of prostatic cancer of the National Health Research Institutes. Four, 5ARI could be prescribed in patients with improved clinical data but who were unable to meet the other regulatory criteria. Finally, of the three remaining cases, one case was denied, and in two cases, half of the members approved, and half rejected the claim for 5ARI use. Conclusion: This consensus report provided clarification for Taiwanese urologists and medical claims review committee members on reimbursable use of 5ARI in controversial cases.

Keywords: 5-Alpha-reductase inhibitor, benign prostatic hyperplasia, coverage denial, National Health Insurance


How to cite this article:
Chuang TY, Wang CC, Chen PC, Kao MH. Consensus report on controversial use of 5-alpha-reductase inhibitor in patients with benign prostatic hyperplasia under Taiwan National Health Insurance Regulations. Urol Sci 2019;30:131-5

How to cite this URL:
Chuang TY, Wang CC, Chen PC, Kao MH. Consensus report on controversial use of 5-alpha-reductase inhibitor in patients with benign prostatic hyperplasia under Taiwan National Health Insurance Regulations. Urol Sci [serial online] 2019 [cited 2019 Dec 15];30:131-5. Available from: http://www.e-urol-sci.com/text.asp?2019/30/3/131/260782




  Introduction Top


Benign prostatic hyperplasia (BPH) is a common health threat to senior men and causes bothersome lower urinary tract symptom (LUTS) and worsening quality of life. According to the European Association of Urology guidelines, the initially suggested therapies for BPH and LUTS are lifestyle modification and alpha-blocker therapy.[1] Combination therapy with an alpha-blocker and 5-alpha-reductase inhibitor (5ARI) is superior to either drug alone in reducing LUTS and preventing BPH-progression in patients at high-risk of BPH progression.

However, because the cost of 5ARI is higher than that of alpha-blockers, the National Health Insurance (NHI) Administration has strictly regulated insurance coverage of 5ARI, including finasteride and dutasteride, since December 2013.[2] Before the 2013 NHI regulation of 5ARI coverage, use was limited to clinical conditions described below:

  1. The patient has (1) an enlarged prostate with obstructive symptoms and a prostate volume larger than 30 mL, confirmed by transrectal ultrasound of prostate (TRUS-P) or abdominal ultrasound for those cannot undergo TRUS-P or (2) a peak urinary flow rate (Qmax) of <15 mL/s. If the serum prostate-specific antigen (PSA) level of a patient is higher than the normal range, a prostate biopsy is necessary to rule out prostate cancer. For those unable to undergo biopsy, coverage is suitable for patients with detailed documented reasons why they could not undergo biopsy and who were refractory to other medical treatment or who were intolerant to other medications
  2. During the first year of 5ARI therapy, patients must undergo TRUS-P or uroflowmetry every six months to show clinical improvements such as decreased prostate size and increased Qmax.


Although the NHI regulations for 5ARI were well documented, the urologists and medical claim review committee members sometimes felt confused when some patients could not or did not meet these criteria. Several controversial cases were discussed at the annual meeting of the Taiwan Urological Association in 2014. The consensus of the meeting was proposed to the medical claim review committee of the NHI. This article summarizes the characteristics of several controversial cases after expert discussion. We hope that the consensus provides the evidence required for Taiwanese urologists and medical claims review committee members to prescribe and cover 5ARI in certain controversial cases.


  Materials and Methods Top


Expert urology clinicians and medical claims review committee members reviewed seven controversial cases along with related clinical evidence and voted for approval of 5ARI coverage after vigorous discussion.

Case 1

A 66-year-old man had a prostate volume of 26 mL, a Qmax of 12.6 mL/s, and an International Prostate Symptom Score (IPSS) of 18 points. Only his Qmax met the coverage criteria for the use of 5ARI. Should 5ARI use be covered?

Result and consensus

A previous study has revealed that the risk of BPH progression is significantly higher in patients with a baseline total prostate volume of 31 mL or greater versus <31 mL (P < 0.001).[3] A local Taiwanese study found that patients with prostate volumes <40 mL had less benefit from 5ARI therapy.[4] Although this patient met the NHI Qmax criterion for 5ARI treatment, the majority of committee members voted for coverage denial of 5ARI because of a high possibility of a lack of efficacy.

Case 2

A 71-year-old man had a prostate volume of 71 mL, PSA of 6.2 ng/mL, Qmax of 11.5 mL/s, and an IPSS score of 20 points. He did not undergo a prostate biopsy. Should 5ARI be prescribed and covered? What should be defined as the normal range of PSA for the implementation of the NHI regulation?

Result and consensus

According to the National Health Research Institutes (NHRI) prostate cancer treatment consensus, older men have a higher upper limit of normal PSA values: 40–49 years, 2.5 ng/mL; 50–59 years, 3.5 ng/mL; 60–69 years, 4.5 ng/mL; and 70–79 years, 6.5 ng/mL.[5] The committee concluded that it was reasonable to exclude the possibility of prostatic cancer due to the patient's lower PSA than the age-adjusted upper limit and low PSA density (PSAD, 0.086 ng/mL/mL). It is also important for physicians to consider PSAD and other related prostate cancer factors when ruling out prostatic cancer. Therefore, the majority of committee members agreed on 5ARI coverage.

Case 3

A 76-year-old man had a huge prostate volume of 121 mL and a low Qmax of 8.5 mL/s. Nonetheless, his serum PSA was 15 ng/mL and the PSAD was 0.12 ng/mL/mL. He refused a prostate biopsy. Although PSAD is not included in NHI regulation for 5ARI use and coverage, would the medical review committee members consider the PSAD as suspicious of prostatic cancer?

Result and consensus

A previous study has shown a 260% risk increase of prostate cancer progression when the PSAD is >0.15.[6] Thus, PSAD has been considered a marker of prostate cancer progression. This patient's PSAD was in the gray zone between 0.1 and 0.15. Thus, only half of the review committee members supported the coverage of 5ARI. They suggested patients undergo a prostate biopsy unless a biopsy is contraindicated. If patients refused a biopsy, then 5ARI use would not be covered by the NHI.

Case 4

An 81-year-old man had a prostate volume of 55 mL and decreased Qmax of 8.5 mL/s. His PSA level was 10.6 ng/mL, and the PASD was 0.19. He refused to undergo a prostate biopsy because of old age. His BPH and LUTS were refractory to alpha-blocker treatment. Should the NHI cover 5ARI therapy?

Result and consensus

According to the 2013 version of 5ARI coverage regulation, for patients who did not undergo biopsy, 5ARI coverage was suitable upon review of detailed documentation of the reason for biopsy denial and lack of efficacy or intolerance to other prostate medications. The reason that a patient refused to undergo prostate biopsy was not considered legitimate according to the 2013 version of the 5ARI regulation for coverage. However, most committee members approved the use of 5ARI on the basis of the patient's autonomy and old age.

Case 5

A 64-year-old man had an initial prostate volume of 34.5 mL, Qmax of 12.5 mL/s, and a serum PSA level of 0.91 ng/mL. He had received 5ARI for one year, and after TRUS-P, he showed a decreased prostate volume of 26.1 mL and increased Qmax of 18 mL/s. Could the physician continue the 5ARI treatment when the prostate size and Qmax of the treated patient did not meet the NHI regulation of 5ARI coverage?

Result and consensus

Most committee members approved of continued 5ARI treatment. Long-term 5ARI therapy is necessary for control of BPH just as it is crucial to patients with chronic diseases such as hypertension and diabetes mellitus. In addition, serial recordings of changes of prostate volume and Qmax are essential in the long-term use of 5ARI.

Case 6

A 74-year-old man had increasing serum PSA levels (5.91 ng/mL in July 2011, 7.11 ng/mL in July 2012, and 8.02 ng/mL in January 2013). He underwent a prostate biopsy in January 2013, and the pathology showed prostate adenocarcinoma with a Gleason score of 3 + 3. The patient had a large prostate (81.7 mL) and low Qmax (8.9 mL/s). The patient underwent active surveillance of his prostate cancer due to its low grade. Could the physician prescribe 5ARI to patients with prostatic cancer whose prostate volume and Qmax conformed to the NHI regulation?

Result and consensus

For patients with a concomitant enlarged prostate and prostatic cancer, most urologists concur that 5ARI treatment should be prescribed according to prostate volume and Qmax and not because of prostate cancer. Prostatic cancer with a Gleason score of six or less is less invasive than that of scores >6.[6] The patient's prostatic cancer is in the low-risk group, and his BPH/LUTS could be improved after using 5ARI. Most urologists approved the use of 5ARI in this patient. In another monthly committee meeting, most attending urologists also approved 5ARI use based on whether or not the patient would benefit from its use rather than rigidly conforming to the NHI regulation that 5ARI could be prescribed only for BPH patients.

Case 7

Some patients had recent abdominal and pelvic images including computerized tomography (CT) or magnetic resonance imaging (MRI) performed for other diseases. Is additional TRUS-P necessary for these patients to conform to the NHI regulations for 5ARI use?

Result and consensus

All committee members concurred that it would be a waste of NHI resources for physicians to perform TRUS-P to measure prostate volume to conform to 5ARI regulations in a patient who had undergone abdominal and pelvic CT or MRI in which the prostate volume could be measured. Studies show that prostate volume measured by CT is 1.3 times larger than that measured by TRUS-P, and prostate volume measured by MRI is 1.1 times larger than that measured by TRUS-P.[7],[8] The formula for prostate volume measured by TRUS-P is length × width × height × 0.52. Therefore, the prostate volume via CT should be divided by 1.3 to achieve estimated prostate volume via TRUS-P. Similarly, the prostate volume measured by MRI would be length × width × height × 0.52/1.1. All members agreed that it was not necessary for physicians to perform TRUS-P if the patients already had recent abdominal images including CT or MRI.

[Table 1] summarizes the recommendations of the committee for the seven controversial medical claim review cases. In addition, based on the conclusions of this consensus, the current NHI regulations (2018 updated) of 5ARI coverage were expanded to clinical conditions such as the following:[9]
Table 1: Summary of the committee's suggestions to clarify controversial 5-alpha-reductase inhibitor use in patients with benign prostatic hyperplasia

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  1. 5ARI can be used as first-line monotherapy in BPH patients with prostate volumes larger than 30 mL or Qmax <15 mL/s. Combination therapy with an alpha-blocker and 5ARI should be used in patients in whom other medications failed to improve symptoms or in whom intolerance developed
  2. Prostate volume can be measured by abdominal ultrasound or other images such as CT if TRUS-P is contraindicated or the patient elects not to undergo it
  3. Patients with a life expectancy of more than 10 years should undergo prostatic biopsy if the PSA is >10 ng/mL or a digital examination reveals suspected prostatic cancer
  4. Patients with mildly elevated PSA values can avoid a prostate biopsy if a comprehensive differential diagnosis is not suggestive of prostatic cancer (e.g., the patient's life expectancy is <10 years, or prostatic cancer is not clinically suspected)
  5. It is not necessary for patients to undergo TRUS-P or urinary flow rate examination every six months after the first year of 5ARI therapy.



  Discussion Top


This historical report demonstrates that through our consensus meeting, we could clarify and update questionable NHI regulations. Many Taiwanese physicians think that coverage denial is a nightmare when prescribing drugs. Thus, clinically reasonable practice regulations and a consensus are necessary for coverage regulations. Our report shows that the NHI regulations for 5ARI in 2017 were well revised based on medical evidence and expert consensus.

The NHI regulations are similar to the Constitution of Taiwan. The members of the medical claims committee and the justice of the constitutional court have certain aspects in common. The different and interesting part is that the members of the medical claims committee can make a reasonable judgment according to medical evidence. However, judgments from the justices of the constitutional court may be of free will. The similarity of the two is that both apply the majority rule.

The least conflicting issue of the consensus was that it was not necessary to perform TRUS-P if the patient had already had abdominal and pelvic CT or MRI. Physicians can measure prostate volume by different imaging modalities. The second least conflicting issue was that a patient's refusal to undergo a prostate biopsy could be considered reasonable when age (>75 years) and life expectancy (<10 years) were considered along with other comorbidities. Most members were inclined to approve 5ARI coverage in such patients.

Most guidelines for detecting prostate cancer use cutoff values for PSA to indicate whether a biopsy should be done. Recommendations vary from PSA values of 2.0 ng/mL and 4.0 ng/mL. However, the range of PSA cut-off values should be different between Taiwan and western countries. Taiwan consensus of prostate cancer treatment according to NHRI data suggests the age-adjusted normal PSA cutoff in Taiwanese men by age range is: 40–49 years, 2.5 ng/mL; 50–59 year, 3.5 ng/mL; 60–69 years, 4.5 ng/mL; and 70–79 years, 6.5 ng/mL.[5] This consensus could be applied as a reference for physicians to decide whether patients undergo a prostate biopsy or not.

PSAD may be used as an indicator for biopsy instead of a PSA value of 4.0 ng/mL or more, and in combination with DRE, has been reported to be more cost-effective than using age-specific PSA reference values.[10] However, the NHI regulation for 5ARI did not include the concept of PSAD, which ranges from 0.1 to 0.15. As such, it was considered as a gray-zone value for prostatic cancer progression. A previous study has shown that PSAD >0.15 is highly related to prostate cancer progression and survival rate. However, it is not clear if 5ARI is appropriate for patients with elevated PSA and gray-zone PSAD. Further study is necessary to elucidate the role of 5ARI in patients with PSAD of 0.1–0.15.

Current NHI regulation of 5ARI is still restricted to patients with BPH and LUTS. Nonetheless, the field of medicine progresses rapidly, and therefore, government regulations sometimes lag what medical evidence indicates could be best. Fleshner et al. have shown dutasteride may reduce cancer progression in patients with low-grade prostate cancer.[11] The committee suggested that updated data should be considered to adjust the 5ARI regulation to include low-grade prostate cancer. Half of the committee members thought that it was unreasonable to restrict 5ARI use in such prostate cancer patients. Although prostate cancer should not be an absolute contraindication for the use of 5ARI, the committee suggested that the NHI might approve of 5ARI use in some patients with an enlarged prostate of over 30 mL with LUTS and concomitant prostate cancer.

Surprisingly, the greatest possibility of coverage denial of 5ARI use by the committee is for patients with Qmax <15 mL/s, which meets the regulation for 5ARI use. According to the NHI, as long as either the prostate volume is larger than 30 mL or Qmax is <15 mL/s, 5ARI coverage could be approved. However, in the real world, coverage denial was still noted in some cases meeting the regulation because the committee considered the coverage denial was not only based on NHI regulation but also should be based on clinical efficacy and limited NHI resources. For example, in case 1, the efficacy of 5ARI is limited in a 66-year-old man with small prostate volume (26 mL) and low Qmax (12.6 mL/s).

There are some differences between the 2013 and 2017 NHI regulations. In the current 2017 version, first, either TRUS-P or abdominal CT or MRI could be used to measure prostate size. Second, the committee agreed 5ARI could be used in patients with low-risk prostatic cancer when the patients' life expectancy was <10 years, and thus, they might not need aggressive treatment. Although 5ARI use is not covered in patients with proven prostate cancer, it could be used in patients with suspected low-risk prostate cancer when the prostate volume is more than 30 mL/s, and the patient has LUTS.


  Conclusions Top


Although the NHI coverage of 5ARI is well defined, some cases fall into a regulatory gray-zone that needs to be individually reviewed and clarified. This consensus report provided suggestions for Taiwanese urologists and medical claims review committee members to clarify and update the coverage of 5ARI in certain controversial cases.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Oelke M, Bachmann A, Descazeaud A, Emberton M, Gravas S, Michel MC, et al. EAU guidelines on the treatment and follow-up of non-neurogenic male lower urinary tract symptoms including benign prostatic obstruction. Eur Urol 2013;64:118-40.  Back to cited text no. 1
    
2.
National Health Insurance Drug Payment Program and Standards for Drug Payments; Version 2014. Available form: https://www.nhi.gov.tw/. [Last cited on 2019 Feb 01].  Back to cited text no. 2
    
3.
Crawford ED, Wilson SS, McConnell JD, Slawin KM, Lieber MC, Smith JA, et al. Baseline factors as predictors of clinical progression of benign prostatic hyperplasia in men treated with placebo. J Urol 2006;175:1422-6.  Back to cited text no. 3
    
4.
Lin VC, Liao CH, Wang CC, Kuo HC 5α-reductase inhibitor is less effective in men with small prostate volume and low serum prostatic specific antigen level. J Formos Med Assoc 2015;114:865-71.  Back to cited text no. 4
    
5.
Consensus of Diagnosis and Treatment of Prostatic Cancer from National Health Research Institute; Version 2003. Available from: https://www.nhri.org.tw/NHRI_ADM/userfiles/file/tcog. [Last cited on 2019 Feb 01].  Back to cited text no. 5
    
6.
Barayan GA, Brimo F, Bégin LR, Hanley JA, Liu Z, Kassouf W, et al. Factors influencing disease progression of prostate cancer under active surveillance: A McGill university health center cohort. BJU Int 2014;114:E99-104.  Back to cited text no. 6
    
7.
Kälkner KM, Kubicek G, Nilsson J, Lundell M, Levitt S, Nilsson S, et al. Prostate volume determination: Differential volume measurements comparing CT and TRUS. Radiother Oncol 2006;81:179-83.  Back to cited text no. 7
    
8.
Smith WL, Lewis C, Bauman G, Rodrigues G, D'Souza D, Ash R, et al. Prostate volume contouring: A 3D analysis of segmentation using 3DTRUS, CT, and MR. Int J Radiat Oncol Biol Phys 2007;67:1238-47.  Back to cited text no. 8
    
9.
National Health Insurance Drug Payment Program and Standards for Drug Payments; Version 2018. Available form: https://www.nhi.gov.tw/. [Last cited on 2019 Feb 01].  Back to cited text no. 9
    
10.
Littrup PJ, Kane RA, Mettlin CJ, Murphy GP, Lee F, Toi A, et al. Cost-effective prostate cancer detection. Reduction of low-yield biopsies. Investigators of the american cancer society national prostate cancer detection project. Cancer 1994;74:3146-58.  Back to cited text no. 10
    
11.
Fleshner NE, Lucia MS, Egerdie B, Aaron L, Eure G, Nandy I, et al. Dutasteride in localised prostate cancer management: The REDEEM randomised, double-blind, placebo-controlled trial. Lancet 2012;379:1103-11.  Back to cited text no. 11
    



 
 
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