Cost-effectiveness comparison between neoadjuvant chemohormonal therapy and extended pelvic lymph node dissection in high-risk prostate cancer patients treated with radical prostatectomy: Beyond the Abstract
Neoadjuvant therapy1-4 followed by RP represents an alternative surgical option for the treatment of high-risk PC. Although previous studies on neoadjuvant hormonal therapy found limited effects on tumor reduction and recurrence rates5,6 our neoadjuvant chemohormonal therapy for 6 months before RP using gonadotropin-releasing hormone agonist/antagonist (GnRH-A) and low dose of estramustine significantly improved biochemical recurrence-free survival compared with patients treated with ePLND.7 In addition, our neoadjuvant chemohormonal therapy significantly improved both biochemical recurrence-free survival and OS.1 Therefore, not only therapeutic efficacy but also cost-effectiveness should be considered from a patient-centered perspective because of the long-term therapeutic periods of high-risk PC. Although several studies have compared the oncological outcomes of high-risk PC,7-10 insufficient evidence is available regarding the cost-effectiveness of treatment options.11,12 Currently, no study has compared cost-effectiveness between RP with ePLND and neoadjuvant chemohormonal therapy.
To address these clinical questions, we retrospectively analyzed 640 high-risk localized PC patients from The Michinoku Urological Cancer Study Group database contains pre- and post-operative data for 2971 PC patients who were treated with RP between July 1996 and July 2017 at four institutes. High-risk PC was defined as clinical stage T2c or T3 disease, initial PSA levels of ≥20 ng/mL, and/or a biopsy Gleason score (GS) of ≥8 according to the D’Amico risk stratification system.13 We stratified patients into two groups, those who underwent RP and ePLND (ePLND group) and those who received neoadjuvant chemohormonal therapy followed by RP and limited PLND (neoadjuvant group). The oncological outcomes and cost-effectiveness were compared between groups. Medical cost calculation focused on PC-related medication and adjuvant radiotherapy. Our results showed that biochemical recurrence-free and overall survival rates in the neoadjuvant group were significantly higher than those in the ePLND group. Significantly higher number of patients progressed to castration-resistant PC in the ePLND group than in the neoadjuvant group. Background-adjusted multivariate Cox regression analysis using inverse probability of treatment weighting (IPTW) revealed that neoadjuvant chemohormonal therapy independently reduced the risk for biochemical recurrence after RP. The 5-year cost per person was significantly higher in the ePLND group ($9844) than in the neoadjuvant group ($5670). The estimated cost difference was $4174 per person. Although the present study was retrospective, neoadjuvant chemohormonal therapy followed by RP as a concurrent strategy has potential to improve oncological outcome and cost-effectiveness.
Our results also suggested that the prevention of CRPC development in addition to biochemical recurrence is a key factor in terms of cost-effectiveness in high-risk PC. Due to the remarkably higher treatment cost of CRPC compared with traditional androgen deprivation therapy, the high treatment cost of cancer agents has been criticized by leading academics and the popular press.14-17 A previous report suggested that the treatment cost of abiraterone, an inhibitor of the cytochrome P450 c17 (CYP17) class of enzymes, exceeded $7000 per month in the United States.16 Based on phase 3 of a randomized clinical trial, abiraterone increased the median survival from 10.9 (prednisone alone) to 14.8 months (abiraterone plus prednisone).18 From the cost-effectiveness point of view, an OS prolongation in 3.7 months at a cost of $7000 per month remains questionable compared with the use of a traditional agent, ketoconazole, which also inhibits CYP17, but at a cost of $500–$700 per month.16 However, the high cost of developing new-generation drugs ($69 million for abiraterone) has prevented agent supply at an appropriate rate.
Cost-effectiveness in post-operative surveillance is the other important issue. The more we screen, the more we increase medical cost. On the other hand, the fewer we screen, the more we lost the change for therapy. Currently, no cost-effective surveillance protocol after RP is available. It is recommended that PSA follow-up every three month. However, no study has been certified optimal surveillance protocol after RP in the high-risk PC patients. A prospective study on the cost effectiveness of follow-up using a universal, standard, and easily applicable surveillance model is needed.
References
1 Fujita N, Koie T, Ohyama C, Tanaka Y, Soma O, Matsumoto T, et al. Overall survival of high-risk prostate cancer patients who received neoadjuvant chemohormonal therapy followed by radical prostatectomy at a single institution. International journal of clinical oncology. 2017.
2 Leukemia EiCM. The price of drugs for chronic myeloid leukemia (CML) is a reflection of the unsustainable prices of cancer drugs: from the perspective of a large group of CML experts. Blood. 2013;121:4439-42.
3 Hall SS. The cost of living. New York Magagine. New York New York Magagine; 2013.
4 Mailankody S, Prasad V. Comparative effectiveness questions in oncology. The New England journal of medicine. 2014;370:1478-81.
5 Kushnick HL. Pricing Cancer Drugs: When Does Pricing Become Profiteering? AMA journal of ethics. 2015;17:750-3.
6 de Bono JS, Logothetis CJ, Molina A, Fizazi K, North S, Chu L, et al. Abiraterone and increased survival in metastatic prostate cancer. The New England journal of medicine. 2011;364:1995-2005.
7 Koie T, Ohyama C, Yamamoto H, Hatakeyama S, Yoneyama T, Hashimoto Y, et al. Safety and effectiveness of neoadjuvant luteinizing hormone-releasing hormone agonist plus low-dose estramustine phosphate in high-risk prostate cancer: a prospective single-arm study. Prostate cancer and prostatic diseases. 2012;15:397-401.
8 Koie T, Mitsuzuka K, Yoneyama T, Narita S, Kawamura S, Kaiho Y, et al. Neoadjuvant luteinizing-hormone-releasing hormone agonist plus low-dose estramustine phosphate improves prostate-specific antigen-free survival in high-risk prostate cancer patients: a propensity score-matched analysis. International journal of clinical oncology. 2015;20:1018-25.
9 Tosco L, Laenen A, Briganti A, Gontero P, Karnes RJ, Albersen M, et al. The survival impact of neoadjuvant hormonal therapy before radical prostatectomy for treatment of high-risk prostate cancer. Prostate cancer and prostatic diseases. 2017.
10 Gleave ME, Goldenberg SL, Chin JL, Warner J, Saad F, Klotz LH, et al. Randomized comparative study of 3 versus 8-month neoadjuvant hormonal therapy before radical prostatectomy: biochemical and pathological effects. The Journal of urology. 2001;166:500-6; discussion 6-7.
11 Soloway MS, Pareek K, Sharifi R, Wajsman Z, McLeod D, Wood DP, Jr., et al. Neoadjuvant androgen ablation before radical prostatectomy in cT2bNxM0 prostate cancer: 5-year results. The Journal of urology. 2002;167:112-6.
12 Narita T, Koie T, Ookubo T, Mitsuzuka K, Narita S, Yamamoto H, et al. The impact of extended lymph node dissection versus neoadjuvant therapy with limited lymph node dissection on biochemical recurrence in high-risk prostate cancer patients treated with radical prostatectomy: a multi-institutional analysis. Medical oncology (Northwood, London, England). 2017;34:1.
13 Colicchia M, Sharma V, Abdollah F, Briganti A, Jeffrey Karnes R. Therapeutic Value of Standard Versus Extended Pelvic Lymph Node Dissection During Radical Prostatectomy for High-Risk Prostate Cancer. Current urology reports. 2017;18:51.
14 Liss MA, Palazzi K, Stroup SP, Jabaji R, Raheem OA, Kane CJ. Outcomes and complications of pelvic lymph node dissection during robotic-assisted radical prostatectomy. World journal of urology. 2013;31:481-8.
15 Briganti A, Blute ML, Eastham JH, Graefen M, Heidenreich A, Karnes JR, et al. Pelvic lymph node dissection in prostate cancer. European urology. 2009;55:1251-65.
16 Becerra V, Avila M, Jimenez J, Cortes-Sanabria L, Pardo Y, Garin O, et al. Economic evaluation of treatments for patients with localized prostate cancer in Europe: a systematic review. BMC health services research. 2016;16:541.
17 Schroeck FR, Jacobs BL, Bhayani SB, Nguyen PL, Penson D, Hu J. Cost of New Technologies in Prostate Cancer Treatment: Systematic Review of Costs and Cost Effectiveness of Robotic-assisted Laparoscopic Prostatectomy, Intensity-modulated Radiotherapy, and Proton Beam Therapy. European urology. 2017.
18 Lester-Coll NH, Goldhaber SZ, Sher DJ, D'Amico AV. Death from high-risk prostate cancer versus cardiovascular mortality with hormonal therapy: a decision analysis. Cancer. 2013;119:1808-15.
Written by: Shingo Hatakeyama, MD, Department of Urology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan.
Read the Abstract