Tag Archive for: prostate neoplasms

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Article of the Week: Prevalence of the HOXB13 G84E mutation in Danish men undergoing radical prostatectomy and its correlations with prostate cancer risk and aggressiveness

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.

Prevalence of the HOXB13 G84E mutation in Danish men undergoing radical prostatectomy and its correlations with prostate cancer risk and aggressiveness

Tine M. Storebjerg*,,, Søren Høyer, Pia Kirkegaard§, Flemming Bro§, the LuCamp Study Group, Torben F. Ørntoft, Michael Borre* and Karina D. Sørensen

 

Departments of*Urology Pathology, Aarhus University Hospital, Department of Molecular Medicine, Aarhus University Hospital, §Research Unit for General Practice and Research Centre for Cancer Diagnosis in Primary Care, Aarhus University, Aarhus, and Lundbeck Foundation Centre for Applied Medical Genomics in Personalized Disease Prediction, Prevention and Care, Copenhagen, Denmark

 

Objectives

To determine the prevalence of the HOXB13 G84E mutation (rs138213197) in Danish men with or without prostate cancer (PCa) and to investigate possible correlations between HOXB13 mutation status and clinicopathological characteristics associated with tumour aggressiveness.

Materials and Methods

We conducted a case–control study including 995 men with PCa (cases) who underwent radical prostatectomy (RP) between 1997 and 2011 at the Department of Urology, Aarhus University Hospital, Denmark. As controls, we used 1622 healthy men with a normal prostate specific antigen (PSA) level.

Results

The HOXB13 G84E mutation was identified in 0.49% of controls and in 2.51% of PCa cases. The mutation was associated with a 5.12-fold increased relative risk (RR) of PCa (95% confidence interval [CI] 2.26–13.38; P = 13 × 10−6). Furthermore, carriers of the risk allele were significantly more likely to have a higher PSA level at diagnosis (mean PSA 19.9 vs 13.6 ng/mL; P = 0.032), a pathological Gleason score ≥7 (83.3 vs 60.9%; P = 0.032), and positive surgical margins (56.0 vs 28.5%; P = 0.006) than non-carriers. Risk allele carriers were also more likely to have aggressive disease (54.2 vs 28.6%; P = 0.011), as defined by a preoperative PSA ≥20 ng/mL, pathological Gleason score ≥ (4+3) and/or presence of regional/distant disease. At a mean follow-up of 7 months, we found no significant association between HOXB13mutation status and biochemical recurrence in this cohort of men who underwent RP.

octaotw3-results

Conclusions

This is the first study to investigate the HOXB13 G84E mutation in Danish men. The mutation was detected in 0.49% of controls and in 2.51% of cases, and was associated with 5.12-fold increased RR of being diagnosed with PCa. In our RP cohort, HOXB13 mutation carriers were more likely to develop aggressive PCa. Further studies are needed to assess the potential of HOXB13 for future targeted screening approaches.

Editorial: HOXB13 mutations and prostate cancer risk

For the first time, Storebjerg et al. [1] describe the prevalence of the HOXB13 G84E mutation in a Danish population and its association with prostate cancer risk and features indicative of clinically aggressive disease in a cohort of men undergoing radical prostatectomy. In this study, the prostate cancer risk mutation was seen in 0.49% of controls with an ~5-fold increase in risk of prostate cancer among carriers. The homeobox transcription factor gene HOXB13, is located on the long arm of chromosome 17 (17q21), and belongs to a superfamily of genes considered critical to animal embryonic development, characterised by a highly-conserved DNA-binding domain. In 2012, our research team described the association of a rare recurrent HOXB13 mutation, substituting adenine for guanine in the second position of codon 84 resulting in the replacement of glycine by glutamic acid, with prostate cancer and found that the carrier frequency was ~20-times higher among men with early onset disease and multiple affected close relatives compared with men presumed without disease [2]. Since then, numerous studies have confirmed this association with estimates of risk overall varying from ~3 to 9-fold, and generally a greater risk seen among men diagnosed before the age of 60 years and among those with a positive family history of disease among first-degree relatives [3]. The G84E mutation is almost exclusively found in men of Northern European descent with evidence suggesting that it is a relatively recent (circa 1790s) founder mutation in the population, and considered to be of moderate penetrance (estimated lifetime risk among carriers 35–65%) [4]. The same germline mutation has also been preliminarily reported to be associated with cancers of the breast, colon, bladder, and leukaemia, but requires further investigation [5, 6].

The findings from this study [1], both for the prevalence of the mutation, as well as its magnitude of association with prostate cancer, are comparable to prior reports in Northern European populations. Furthermore, among the 995 cases, the mutation frequency was significantly associated with features predictive of progression after surgery (high PSA level, positive surgical margins, higher pathological Gleason score, and non-organ confined disease) suggesting that genetic evaluation of men with a strong family history would identify a subset of men that would benefit from early screening and intervention in the same manner as are male carriers of known founder mutations in BRCA2[7]. The observation between HOXB13 and clinical features indicative of aggressive disease has been less consistent compared with studies of risk overall and the exact mechanism whereby the gene contributes to malignant progression in the prostate is not well-understood. There is some suggestion that the gene may operate both as a tumour suppressor, as early studies reported its suppression of androgen receptor activity, and as an oncogene as HOXB13 overexpression has been seen in androgen-independent tumours [8].

Currently, most countries (including the USA) do not recommend use of PSA screening for men at average risk for prostate cancer. However, given the significant risk of prostate cancer in men carrying a single copy of the HOXB13 G84E allele, should these male mutation carriers be screened for prostate cancer with PSA testing and DRE? If so, how do we identify these men and at what age should testing commence? Unfortunately, many G84E carriers may not be identified by family history, which raises the question about when is the risk of disease significant enough to warrant population level testing? As Nordic countries, including Denmark, have a higher frequency of HOXB13 G84E allele in the general population, research directed toward understanding the benefit of genetic testing followed by prostate cancer early detection strategies should be considered.

Kathleen A. Cooney* and Jennifer L. Beebe-Dimmer

 

*Departments of Internal Medicine and Urology, The University of Michigan, Comprehensive Cancer Center, Ann Arbor, and Department of Oncology, Wayne State University School of Medicine, Karmanos Cancer Institute, Detro it, MI, USA

 

References

 

 

2 Ewing CM, Ray AM, Lange EM et al. Germline mutations in HOXB13 and prostate-cancer risk. N Engl J Med 2012; 366: 1419

 

3 Beebe-Dimmer JL, Isaacs WB, Zuhlke KA et al. Prevalence of the HOXB13 G84E prostate cancer risk allele in men treated with radical prostatectomy. BJU Int 2014; 113: 8305

 

 

5 Alanee S, Couch F, OftK. Association of a HOXB13 variant with breast cancer. N Engl J Med 2012; 367: 4801

 

6 Beebe-Dimmer JL, Hathcock M, Yee C et al. The HOXB13 G84E mutation is associated with an increased risk for prostate cancer and other malignancies. Cancer Epidemiol Biomarkers Prev 2015; 24: 136672

 

7 National Comprehensive Cancer Network (NCCN), NCCN Clinical Practice Guidelines in Oncology. Genetic/Familial High-risk Assessment: Breast and Ovarian (Version 2.2015). Available at: https://www.nccn.org/professionals/physician_gls/f_guidelines.asp. Accessed 12-27-2015

 

8 Shah N, Sukumar S. The Hox genes and their roles in oncogenesis. Nat Rev Cancer 2010; 10: 36171

 

Article of the Week: Assessing prostate cancer brachytherapy using patient-reported outcomes

Every week the Editor-in-Chief selects the 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.

Finally, the third post under the Article of the Week heading on the homepage will consist of additional material or media. This week we feature a video from Dr. James Talcott discussing his paper. 

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

Using Patient-Reported Outcomes to Assess and Improve Prostate Cancer Brachytherapy

James A. Talcott 1, 2, 10, 11, Judith Manola 3, Ronald C. Chen 4, Jack A. Clark 5, 6, Irving Kaplan 7, 8, Anthony V. D’Amico 8, 11 and Anthony L. Zietman 9, 11

1 Massachusetts General Hospital Cancer Center, Boston, MA, 2 Continuum Cancer Centers of New York, New York, NY, 3 Dana-Farber Cancer Institute, Boston, MA, 4 Department of Radiation Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 5 Center for Health Quality, Outcomes, and Economic Research, Edith Nourse Rogers Memorial Veterans Hospital, Bedford, MA, 6 Boston University School of Public Health, 7 Beth Israel-Deaconess Medical Center, 8 Brigham and Women’s Hospital, 9 Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, 10 Albert Einstein School of Medicine, New York, NY, and 11 Harvard Medical School, Boston, MA, USA

Read the full article
OBJECTIVE
  • To describe a successful quality improvement process that arose from unexpected differences in control groups’ short-term patient-reported outcomes (PROs) within a comparative effectiveness study of a prostate brachytherapy technique intended to reduce urinary morbidity.
PATIENTS AND METHODS
  • Patients planning prostate brachytherapy at one of three institutions were enrolled in a prospective cohort study.
  • Patients were surveyed using a validated instrument to assess treatment-related toxicity before treatment and at pre-specified intervals.
  • Unexpectedly, urinary PROs were worse in one of two standard brachytherapy technique control populations (US-BT1 and US-BT2). Therefore, we collaboratively reviewed treatment procedures, identified a discrepancy in technique, made a corrective modification, and evaluated the change.
RESULTS
  • The patient groups were demographically and clinically similar.
  • In the first preliminary analysis, US-BT2 patients reported significantly more short-term post-treatment urinary symptoms than US-BTpatients.
  • The studies treating physicians reviewed the US-BT1 and US-BT2 treatment protocols and found that they differed in whether they used an indwelling urinary catheter.
  • After adopting the US-BT1 approach, short-term urinary morbidity in US-BT2 patients decreased significantly. Brachytherapy procedures were otherwise unchanged.
CONCLUSION
  • Many procedures in cancer treatments are not evaluated, resulting in practice variation and suboptimal outcomes. Patients, the primary medical consumers, provide little direct input in evaluations of their care.
  • We used PROs, a sensitive and valid measure of treatment-related toxicity, for quality assessment and quality improvement (QA/QI) of prostate brachytherapy. This serendipitous patient-centred QA/QI process may be a useful model for empirically evaluating complex cancer treatment procedures and for screening for substandard care.

Editorial: Patient-reported outcomes – a force for clinical improvement or another way for ‘big brother’ to survey clinicians?

In the 19th century Lord Kelvin wrote, ‘If you cannot measure it, you cannot improve it’. Since then clinical improvement has often been about measuring outcomes to determine what elements of healthcare are working well and what can be improved. The early studies of antisepsis and surgical technique had endpoints, which were measured by doctors deciding whether a wound infection, cancer recurrence or even death had occurred. These outcomes were usually discrete with little room for describing states between success and failure.

In this era whether the patient perceived that the treatment had been successful or not was irrelevant to the ‘success’ of treatment providing that the medical world agreed that the treatment had been a success. As treatments have become more established and the medical and pharmaceutical world has become more patient focussed, interest has increased in how patients report the outcome of treatment, often using questionnaires.

The pioneers of this work were mainly psychiatrists concerned about patient anxiety and depression [1] and clinical oncologists, aware that multimodal chemoradiotherapy treatments, which might in many cases be offered with palliative rather than curative intent, had the potential to cause a net loss in quality of life even if patients lived a short time longer on treatment.

As these patient-reported outcome measures (PROMs) became more commonly used in clinical trials, their focus has extended to quite specific outcomes, such that in the current era it is unusual to see papers on LUTS or erectile function presented that do not use validated PROMs, such as the IPSS [2] or International Index of Erectile Function (IIEF) [3].

The current era of research is starting to make new use of the data sources that are useful both as absolute values relating to the severity of symptoms but also particularly in measuring change in level of symptoms. Hard outcomes, such as death from cancer, have been found to be related to patient reported quality of life at presentation [4].

Clinicians are now starting to develop the necessary skills to analyse PROMs. In this setting Talcott et al. [5] have used PROM data to identify unexpected variances in symptomatic outcome after prostate brachytherapy. This was an unexpected post hoc analysis of a difference in outcomes between the two control groups in a study. It found that there was a significant difference in outcome between patients who had received an implant in two centres, which might have been expected to have similar outcomes. Analysis of differences in the implant technique in the two institutions suggested that the use of a urethral catheter to clearly visualise the urethra might be the difference and modification of this part of the technique resulted in similar PROMS outcomes in both institutions.

This is a novel quality improvement approach, which may become more widespread as institutions more frequently collect, analyse and present their PROMS. The bio-informatics skills needed to analyse this type of data meaningfully may become a greater part of everyday practice in the modern era, especially for the ‘index’ most common operations in surgical specialities. It would be interesting to see what a similar approach would produce if variance in PROMs after transurethral prostate surgery were analysed between centres in the UK and USA. Organisations with a track record for effective data analysis and reporting such as Dr Foster will be watching this evolve.

Read the full article

Alastair Henderson

Maidstone and Tunbridge Wells NHS Trust, Department of Urology, Maidstone Hospital, Maidstone, Kent, UK

References

1 Zigmond AS, Snaith RP. The Hospital Anxiety and Depression Scale. Acta Psychiat Scand 1983; 67: 361–70

2 Barry MJ, O’Leary MP. Advances in benign prostatic hyperplasia. The developmental and clinical utility of symptom scores. Urol Clin North Am 1995; 22: 299–307

3 Cappelleri JC, Rosen RC, Smith MD, Mishra A, Osterloh IH. Diagnostic evaluation of the erectile function domain of the International Index of Erectile Function. Urology 1999; 54: 346–51

4 Montazeri A. Quality of life data as prognostic indicators of survival in cancer patients: an overview of the literature from 1982 to 2008. Health Qual Life Outcomes 2009; 7: 102

5 Talcott JA, Manola J, Chen RC et al. Using patient-reported outcomes to assess and improve prostate cancer brachytherapy. BJU Int 2014; 114: 511–6

Video: PROs in Prostate Brachytherapy

Using Patient-Reported Outcomes to Assess and Improve Prostate Cancer Brachytherapy

James A. Talcott 1, 2, 10, 11, Judith Manola 3, Ronald C. Chen 4, Jack A. Clark 5, 6, Irving Kaplan 7, 8, Anthony V. D’Amico 8, 11 and Anthony L. Zietman 9, 11

1 Massachusetts General Hospital Cancer Center, Boston, MA, 2 Continuum Cancer Centers of New York, New York, NY, 3 Dana-Farber Cancer Institute, Boston, MA, 4 Department of Radiation Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 5 Center for Health Quality, Outcomes, and Economic Research, Edith Nourse Rogers Memorial Veterans Hospital, Bedford, MA, 6 Boston University School of Public Health, 7 Beth Israel-Deaconess Medical Center, 8 Brigham and Women’s Hospital, 9 Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, 10 Albert Einstein School of Medicine, New York, NY, and 11 Harvard Medical School, Boston, MA, USA

Read the full article
OBJECTIVE
  • To describe a successful quality improvement process that arose from unexpected differences in control groups’ short-term patient-reported outcomes (PROs) within a comparative effectiveness study of a prostate brachytherapy technique intended to reduce urinary morbidity.
PATIENTS AND METHODS
  • Patients planning prostate brachytherapy at one of three institutions were enrolled in a prospective cohort study.
  • Patients were surveyed using a validated instrument to assess treatment-related toxicity before treatment and at pre-specified intervals.
  • Unexpectedly, urinary PROs were worse in one of two standard brachytherapy technique control populations (US-BT1 and US-BT2). Therefore, we collaboratively reviewed treatment procedures, identified a discrepancy in technique, made a corrective modification, and evaluated the change.
RESULTS
  • The patient groups were demographically and clinically similar.
  • In the first preliminary analysis, US-BT2 patients reported significantly more short-term post-treatment urinary symptoms than US-BTpatients.
  • The studies treating physicians reviewed the US-BT1 and US-BT2 treatment protocols and found that they differed in whether they used an indwelling urinary catheter.
  • After adopting the US-BT1 approach, short-term urinary morbidity in US-BT2 patients decreased significantly. Brachytherapy procedures were otherwise unchanged.
CONCLUSION
  • Many procedures in cancer treatments are not evaluated, resulting in practice variation and suboptimal outcomes. Patients, the primary medical consumers, provide little direct input in evaluations of their care.
  • We used PROs, a sensitive and valid measure of treatment-related toxicity, for quality assessment and quality improvement (QA/QI) of prostate brachytherapy. This serendipitous patient-centred QA/QI process may be a useful model for empirically evaluating complex cancer treatment procedures and for screening for substandard care.

Article of the week: Prostate cancer treatments: How much do you want to spend?

Every week the Editor-in-Chief selects the 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.

Finally, the third post under the Article of the Week heading on the homepage will consist of additional material or media. This week we feature a video of Matthew Cooperberg discussing his paper.

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

Primary treatments for clinically localised prostate cancer: a comprehensive lifetime cost-utility analysis

Matthew R. Cooperberg, Naren R. Ramakrishna, Steven B. Duff*, Kathleen E. Hughes, Sara Sadownik, Joseph A. Smith§ and Ashutosh K. Tewari

Departments of Urology and Epidemiology and Biostatistics, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, *Veritas Health Economics Consulting, Inc., Carlsbad, CA, Department of Radiation Oncology, MD Anderson Cancer Center, Orlando, FL, Avalere Health LLC, Washington, DC, §Department of Urologic Surgery, Vanderbilt University, Nashville, TN, and Department of Urology, Cornell University, New York, NY, USA

Read the full article
OBJECTIVE

• To characterise the costs and outcomes associated with radical prostatectomy (open, laparoscopic, or robot-assisted) and radiation therapy (RT: dose-escalated three-dimensional conformal RT, intensity-modulated RT, brachytherapy, or combination), using a comprehensive, lifetime decision analytical model.

PATIENTS AND METHODS

• A Markov model was constructed to follow hypothetical men with low-, intermediate-, and high-risk prostate cancer over their lifetimes after primary treatment; probabilities of outcomes were based on an exhaustive literature search yielding 232 unique publications.

• In each Markov cycle, patients could have remission, recurrence, salvage treatment, metastasis, death from prostate cancer, and death from other causes.

• Utilities for each health state were determined, and disutilities were applied for complications and toxicities of treatment.

• Costs were determined from the USA payer perspective, with incorporation of patient costs in a sensitivity analysis.

RESULTS

• Differences across treatments in quality-adjusted life years across methods were modest, ranging from 10.3 to 11.3 for low-risk patients, 9.6–10.5 for intermediate-risk patients and 7.8–9.3 for high-risk patients.

• There were no statistically significant differences among surgical methods, which tended to be more effective than RT methods, with the exception of combined external beam + brachytherapy for high-risk disease.

• RT methods were consistently more expensive than surgical methods; costs ranged from $19 901 (robot-assisted prostatectomy for low-risk disease) to $50 276 (combined RT for high-risk disease).

• These findings were robust to an extensive set of sensitivity analyses.

CONCLUSIONS

• Our analysis found small differences in outcomes and substantial differences in payer and patient costs across treatment alternatives.

• These findings may inform future policy discussions about strategies to improve efficiency of treatment selection for localised prostate cancer.

 

Read Previous Articles of the Week

Editorial: Valuing interventions for localised prostate cancer

Robert Pickard and Luke Vale

Governments of all nations struggle to work out how best to use the limited resources available for health care. One key area of uncertainty is long term conditions with multiple therapeutic options including no active treatment, where relative merits of different treatments are unclear and there is associated unexplained variation in use of often expensive interventions such as surgery. The management of localised prostate cancer typifies this situation. The problem is how to decide the relative worth of options especially as this judgement might differ between patients, clinicians, providers and funders. The best way is to perform well designed randomised trials between competing interventions with sufficient follow-up to identify any differences. For localised prostate cancer the ProTect trial is due to report in 2014. In the meantime, health care agencies commission Health Technology Assessments (HTA) to comparatively value interventions usually on the basis of the monetary cost of the added benefit they give in terms of better outcomes. This is commonly measured as the extra cost of each additional quality-adjusted life year (QALY) they give. The well laid out paper by Cooperberg et al. certainly adds to previous similar work  that is available on relevant health agency websites (HTA 2003CADTH 2011HTA 2011HTA 2012), but was interestingly funded by an industrial stakeholder, Intuitive Surgical. Given its perspective focusing predominantly on Medicare tariffs, it is perhaps most relevant to the US Government who pays these rates, but careful reading by all will at the very least give a flavour of the use of predictive statistical and economic modelling of the possible benefits to patients, and costs to funders of the treatments advised by clinicians.

It is important to highlight that the methods of meta-analysis of the existing literature used by Cooperberg et al. are unclear – this makes it hard to critique whether the best data have been used in the model. Furthermore, the data analyses are unusual. A more typical presentation would have been to explore the likelihood that each treatment would be considered cost-effective. The method used does not really illustrate whether the conclusion should be that there are no differences between treatments or whether there is insufficient evidence to determine whether there are differences. Furthermore, although baseline characteristics of patients included in the meta-analysis are not given it is likely that some would differ between men undergoing surgery or radiotherapy leading to bias in outcome. The linear Markov model used is also perhaps an inadequate reflection of reality since it does not appear to calculate QALYs for repeated transit through further cancer treatment/remission/recurrence states and between incontinent/continent and sexual dysfunction/no sexual dysfunction states which men would value specifically and independently. In terms of costs the have included costs of patient recovery time. Arguably recovery should be captured within the QALY measure and to include it again under costs might be an element of double counting. In addition they showed that the results were sensitive to certain assumptions that may be questioned such as the four year shorter time to metastasis after biochemical recurrence for radiotherapy.

Cooperberg et al. have certainly provided a useful example of how different treatments supervised by clinicians may be valued by those that pay the bills. A parting thought is if only clinicians of differing specialties could collaborate on large definitive RCTs we would not need to rely on predictive models based on imperfect data.

 

Robert Pickard is a Professor of Urology at the Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK. email: [email protected]

Luke Vale is Health Foundation Chair in Health Economics at the Institute of Health & Society, Newcastle University, Newcastle upon Tyne, UK. email: [email protected]

Read the full article

Video: Dr Cooperberg’s article commentary on prostate cancer treatment

Primary treatments for clinically localised prostate cancer: a comprehensive lifetime cost-utility analysis

Matthew R. Cooperberg, Naren R. Ramakrishna, Steven B. Duff*, Kathleen E. Hughes, Sara Sadownik, Joseph A. Smith§ and Ashutosh K. Tewari

Departments of Urology and Epidemiology and Biostatistics, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, *Veritas Health Economics Consulting, Inc., Carlsbad, CA, Department of Radiation Oncology, MD Anderson Cancer Center, Orlando, FL, Avalere Health LLC, Washington, DC, §Department of Urologic Surgery, Vanderbilt University, Nashville, TN, and Department of Urology, Cornell University, New York, NY, USA

Read the full article
OBJECTIVE

• To characterise the costs and outcomes associated with radical prostatectomy (open, laparoscopic, or robot-assisted) and radiation therapy (RT: dose-escalated three-dimensional conformal RT, intensity-modulated RT, brachytherapy, or combination), using a comprehensive, lifetime decision analytical model.

PATIENTS AND METHODS

• A Markov model was constructed to follow hypothetical men with low-, intermediate-, and high-risk prostate cancer over their lifetimes after primary treatment; probabilities of outcomes were based on an exhaustive literature search yielding 232 unique publications.

• In each Markov cycle, patients could have remission, recurrence, salvage treatment, metastasis, death from prostate cancer, and death from other causes.

• Utilities for each health state were determined, and disutilities were applied for complications and toxicities of treatment.

• Costs were determined from the USA payer perspective, with incorporation of patient costs in a sensitivity analysis.

RESULTS

• Differences across treatments in quality-adjusted life years across methods were modest, ranging from 10.3 to 11.3 for low-risk patients, 9.6–10.5 for intermediate-risk patients and 7.8–9.3 for high-risk patients.

• There were no statistically significant differences among surgical methods, which tended to be more effective than RT methods, with the exception of combined external beam + brachytherapy for high-risk disease.

• RT methods were consistently more expensive than surgical methods; costs ranged from $19 901 (robot-assisted prostatectomy for low-risk disease) to $50 276 (combined RT for high-risk disease).

• These findings were robust to an extensive set of sensitivity analyses.

CONCLUSIONS

• Our analysis found small differences in outcomes and substantial differences in payer and patient costs across treatment alternatives.

• These findings may inform future policy discussions about strategies to improve efficiency of treatment selection for localised prostate cancer.

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