Brachytherapy 14 (2015) 753e755
Point/Counterpoint
Point: Surgery is the most cost-effective option for prostate cancer needing treatment Ahmed A. Hussein1,2, Matthew R. Cooperberg1,3,* 1
Department of Urology, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 2 Department of Urology, Cairo University, Egypt 3 Department of Epidemiology & Biostatistics, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA
For most men with localized prostate cancer (PCa), options include active surveillance, radical prostatectomy (RP), and radiation therapy (RT) in the form of brachytherapy (BT) and/or one of a variety of external beam radiation therapy (EBRT) techniques (1e3). Treatment should be tailored to each patient, considering the patient’s overall health, life expectancy, and the disease risk (prostate specific antigen [PSA], tumor extent, and grade). Clinicians’ skill and experience, and the patients’ preference to tradeoff potential benefits, side effects, and complications are other crucial factors guiding the treatment decision (1). Men must face treatment decisions in the face of a relative dearth of high-quality evidence comparing these options. Indeed, the effectiveness of the management strategies for localized PCa was considered among the highest initial national priorities for comparative effectiveness research by the Institute of Medicine in 2009 (4). Although randomized controlled trials (RCTs) are still sorely lacking, however, in recent years, increasingly high-quality retrospective evidence regarding oncologic efficacy, side effects, and health-related quality of life (HRQOL), and cost has become available to inform these decisions.
Oncologic efficacy Comparative effectiveness research addressing oncologic outcomes for localized PCa is not straightforward given the long natural history of the disease, a myriad of definitions of ‘‘recurrence,’’ and the varying impact and time course of different treatments on tumor cells. Specifically, the various treatments have markedly different effects on PSA and PSA kinetics, and the definitions of biochemical recurrence * Corresponding author. Department of Urology, Helen Diller Family Comprehensive Cancer Center, University of California, 1600 Divisadero St, Box 1695, San Francisco, CA 94143-1695. Tel.: þ415-885-3660; fax: þ415-353-7093. E-mail address: [email protected] (M.R. Cooperberg).
vary from one treatment to another. Disease recurrence/progression rates may vary up to 35% depending on the definition used even within a given modality (5e8). Between surgery and radiation, moreover, biochemical recurrence definitions are completely noncomparable. Postsurgical recurrence definitions are intended to identify the earliest signs of persistent/recurrent tumor, whereas the radiation definitions are intended to predict clinical progression and mortality (8, 9). In one example analysis, using the Phoenix ‘‘nadirþ2’’ recurrence definition rather than a O0.2 surgical threshold definition shifted out the median time to recurrence by over 5 years. Therefore, despite the continued publication of articles making claims regarding comparative efficacy between surgery and radiation based on biochemical recurrence (10), these analyses are quite simply not valid. Only clinical endpoints (metastasis, cancer-specific mortality, and overall mortality) are interpretable for comparisons of oncologic efficacy between surgery and radiation. For higher-risk PCa, RCTs have shown the superiority of surgery over watchful waiting and EBRT with androgen ablation therapy (ADT) over either EBRT or ADT alone (11e15). No RCT in the contemporary era has reported outcomes between RP and RT, although the prostate testing for cancer and treatment study (ProtecT) has accrued and is expected to report initial findings next year. Even prostate testing for cancer and treatment, although, includes few men with high-risk PCa (16). In the meantime, no fewer than 10 studies have been published in the past 8 years, across a range of contextsdacademic, community, and population based; American; and Europeandcomparing metastasis and cancer-specific and/or overall mortality outcomes after RP vs. EBRT. With one exception, all these have consistently shown roughly twofold risk-adjusted survival advantages favoring RP over EBRT (Table 1); no study has found better survival after RT compared with RP. Only one study to date has included a BT arm; BT seemed intermediate between RP and EBRT in terms of efficacy (23).
1538-4721/$ - see front matter Ó 2015 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.brachy.2015.02.393
754
A.A. Hussein, M.R. Cooperberg / Brachytherapy 14 (2015) 753e755
Table 1 Outcomes of observational studies comparing the outcomes of radical prostatectomy and radiation therapy for localized prostate cancer Author
Year
Site/data
Conclusions
Tewari et al. (17) Albertsen et al. (18) Zelefsky et al. (19) Cooperberg et al. (20) Stattin et al. (21) Boorjian et al. (22) Kibel et al. (23) Hoffman et al. (24) Sun et al. (25) Sooriakumaran et al. (26)
2007 2007 2010 2010 2010 2011 2012 2013 2014 2014
Henry Ford CT registry MSKCC/Baylor CaPSURE NPCR Sweden Mayo/Fox Chase WashU/CCF PCOS SEER PCBaSe
CSM CSM CSM CSM CSM CSM CSM CSM CSM CSM
HR 0.5 (0.3e1.0) favoring RP over EBRT RR 2.5 (1.7e3.5) favoring RP over EBRT HR 2.9 (1.3e7.7) favoring RP over EBRT HR 2.2 (1.5e3.2) favoring RP over EBRT; ADT 3.2 (2.2e4.8)a RR 1.4 (0.9e2.0) favoring RP over EBRT HR 1.1 (0.7e1.9) NS for RP vs. EBRTa HR 1.5 (1.0e2.3) favoring RP over EBRT; brachy 1.3 (0.7e2.4)a HR 2.9 (2.0e3.8) favoring RP over EBRTa HR 2.5 (1.5e4.2) favoring RP over EBRT HR 1.8 (1.5e2.1) favoring RP over EBRT
CSM 5 cancer-specific mortality; HR 5 hazards ratio; RP 5 radical prostatectomy; EBRT 5 external beam radiation therapy; CT 5 Connecticut; RR 5 risk ratio; MSKCC 5 Memorial Sloan Kettering Cancer Centre; CaPSURE 5 Cancer of the Prostate Strategic Urologic Research Endeavor; ADT 5 androgen deprivation therapy; NPCR 5 National Program of Cancer Registries; NS 5 nonsignificant; CCF 5 Cleveland Clinic Foundation; brachy 5 brachytherapy; PCOS 5 Prostate Cancer Outcomes Study; SEER 5 Surveillance, Epidemiology, and End Results; PCBaSe 5 Prostate Cancer Database of Sweden. a Also showed benefit for RP in terms of overall survival.
Two studiesdfrom the community-based Cancer of the Prostate Strategic Urologic Research Endeavor registry and from a two-center academic cohortdused multiple, particularly robust strategies to optimize risk adjustment, which is critical given well-documented differences in cancer risk parameters between RP and RT patients (19, 20). Of further key importance is the fact that both studies found the greatest differences in outcomes for men with high-risk disease; for those with low-risk disease, very few men experience clinical progression and differences between treatments were minimal. Comparing HRQOL Side effects, toxicities, and HRQOL impacts of different treatment modalities are all well documented and relatively noncontroversial. It should be stressed, however, that for outcomes such as urinary and sexual function, outcomes must be reported by patients, using validated questionnaires, as physician report and coding data do not accurately reflect symptom burden (27, 28). During the first years after treatment, RP patients generally have worse incontinence and sexual function and experience improvement over the first 1e2 years postoperatively. RT patients generally have worse urinary and bowel irritative symptoms (29). RT patients have less early erectile dysfunction, although adding ADT to radiation significantly worsens outcomes in this domain (30). For the most part, differences across modalities tend to attenuate with long-term followup (31, 32). Although these effects are all well characterized and can be reliably expressed in terms of unit functional declines using instruments like the Expanded Prostate Index Composite (33), what is less clear is the translation of these functional HRQOL outcomes to subjective utilities. Optimally weighing, in other words, the impact of persistent single-pad incontinence vs. persistent every-two-hour urinary frequencydor the impact of severe incontinence vs. a rectourinary fistuladhas not been standardized. Patients therefore are guided
by the nature and quality of the counseling they receive (both by clinicians and by friends and family) about what are usually to them hypothetical outcomes. Comparing costs: who pays? The economic burden of PCa management on the health care system is growing, owing to an aging population, increased detection and treatment of localized disease, and the advent of newer and more costly treatments. Emerging technologies have affected RP and RT costs very differently; for reasons that are largely political, robot-assisted surgery is reimbursed essentially equivalently with open surgery, whereas treatments such as intensity-modulated radiation therapy (IMRT) and proton-beam therapy are reimbursed much more generously than earlier treatments. A large national analysis of Medicare claims found that minimally invasive RP increased from 1.5% in 2002 to 28.7% in 2005, whereas for RT, the use of IMRT increased from 29% to 82%. This resulted in substantial increase in expenditure, accounting for an additional $341 million for IMRT compared with $4 million for minimally invasive RP (34). A comprehensive decision analysis using a Markov model incorporating oncologic and HRQOL outcomes of both primary and subsequent treatments showed that among all risk groups, surgical options were consistently less expensive than radiation options and often more effective. Regarding RT, BT was the most effective radiation modality among low-risk patients, whereas a combination of EBRT þ BT was the most effective for intermediate- and high-risk patients. IMRT monotherapy was more expensive and not more effective than RP or brachytherapy and should not be used as monotherapy, particularly for low-risk disease (35). Conclusions Although RCTs are still lacking, a growing body of highquality evidence supports a greater role for active
A.A. Hussein, M.R. Cooperberg / Brachytherapy 14 (2015) 753e755
surveillance for low-risk PCa and for surgery in the management of higher-risk PCa. It should be stressed, although that for men with high-risk PCa, the debate may be a false one. For other aggressive malignanciesdbreast cancer, rectal cancer, and so forthdthe question is not surgery, radiation, or systemic therapy, but rather how these modalities should be optimally combined. In the era of stage migration and a growing controversy regarding PCa screening, it is essential that management decisions be tailored to individual patient’s cancer risk and overall health. References [1] Guideline for the management of clinically localized prostate cancer. Available at: http://www.auanet.org/education/guidelines/prostatecancer.cfm 2007;. Accessed April 30, 2014. [2] Carter HB, Albertsen PC, Barry MJ, et al. Early detection of prostate cancer: AUA Guideline. J Urol 2013;190:419e426. [3] Heidenreich A, Bastian PJ, Bellmunt J, et al. EAU guidelines on prostate cancer. part 1: screening, diagnosis, and local treatment with curative intent-update 2013. Eur Urol 2014;65:124e137. [4] Potosky AL, Knopf K, Clegg LX, et al. Quality-of-life outcomes after primary androgen deprivation therapy: results from the Prostate Cancer Outcomes Study. J Clin Oncol 2001;19:3750e3757. [5] Amling CL, Bergstralh EJ, Blute ML, et al. Defining prostate specific antigen progression after radical prostatectomy: what is the most appropriate cut point? J Urol 2001;165:1146e1151. [6] Gretzer MB, Trock BJ, Han M, Walsh PC. A critical analysis of the interpretation of biochemical failure in surgically treated patients using the American Society for Therapeutic Radiation and Oncology criteria. J Urol 2002;168:1419e1422. [7] Kuban DA, Thames HD, Shipley WU. Defining recurrence after radiation for prostate cancer. J Urol 2005;173:1871e1878. [8] Cookson MS, Aus G, Burnett AL, et al. Variation in the definition of biochemical recurrence in patients treated for localized prostate cancer: the American Urological Association Prostate Guidelines for Localized Prostate Cancer Update Panel report and recommendations for a standard in the reporting of surgical outcomes. J Urol 2007;177:540e545. [9] Roach M 3rd, Hanks G, Thames H Jr, et al. Defining biochemical failure following radiotherapy with or without hormonal therapy in men with clinically localized prostate cancer: recommendations of the RTOG-ASTRO Phoenix Consensus Conference. Int J Radiat Oncol Biol Phys 2006;65:965e974. [10] Grimm P, Billiet I, Bostwick D, et al. Comparative analysis of prostate-specific antigen free survival outcomes for patients with low, intermediate and high risk prostate cancer treatment by radical therapy. Results from the Prostate Cancer Results Study Group. BJU Int 2012;109(Suppl. 1):22e29. [11] Bill-Axelson A, Holmberg L, Garmo H, et al. Radical prostatectomy or watchful waiting in early prostate cancer. N Engl J Med 2014;370: 932e942. [12] Wilt TJ, Brawer MK, Jones KM, et al. Radical prostatectomy versus observation for localized prostate cancer. N Engl J Med 2012;367: 203e213. [13] Warde P, Mason M, Ding K, et al. Combined androgen deprivation therapy and radiation therapy for locally advanced prostate cancer: a randomised, phase 3 trial. Lancet 2011;378:2104e2111. [14] Denham JW, Steigler A, Lamb DS, et al. Short-term neoadjuvant androgen deprivation and radiotherapy for locally advanced prostate cancer: 10-year data from the TROG 96.01 randomised trial. Lancet Oncol 2011;12:451e459. [15] Jones CU, Hunt D, McGowan DG, et al. Radiotherapy and short-term androgen deprivation for localized prostate cancer. N Engl J Med 2011;365:107e118.
755
[16] Lane JA, Donovan JL, Davis M, et al. Active monitoring, radical prostatectomy, or radiotherapy for localised prostate cancer: study design and diagnostic and baseline results of the ProtecT randomised phase 3 trial. Lancet Oncol 2014;15:1109e1118. [17] Tewari A, Divine G, Chang P, et al. Long-term survival in men with high grade prostate cancer: a comparison between conservative treatment, radiation therapy and radical prostatectomyda propensity scoring approach. J Urol 2007;177:911e915. [18] Albertsen PC, Hanley JA, Penson DF, et al. 13-year outcomes following treatment for clinically localized prostate cancer in a population based cohort. J Urol 2007;177:932e936. [19] Zelefsky MJ, Eastham JA, Cronin AM, et al. Metastasis after radical prostatectomy or external beam radiotherapy for patients with clinically localized prostate cancer: a comparison of clinical cohorts adjusted for case mix. J Clin Oncol 2010;28:1508e1513. [20] Cooperberg MR, Vickers AJ, Broering JM, Carroll PR. Comparative risk-adjusted mortality outcomes after primary surgery, radiotherapy, or androgen-deprivation therapy for localized prostate cancer. Cancer 2010;116:5226e5234. [21] Stattin P, Holmberg E, Johansson JE, et al. Outcomes in localized prostate cancer: national Prostate Cancer Register of Sweden follow-up study. J Natl Cancer Inst 2010;102:950e958. [22] Boorjian SA, Karnes RJ, Viterbo R, et al. Long-term survival after radical prostatectomy versus external-beam radiotherapy for patients with high-risk prostate cancer. Cancer 2011;117:2883e2891. [23] Kibel AS, Ciezki JP, Klein EA, et al. Survival among men with clinically localized prostate cancer treated with radical prostatectomy or radiation therapy in the prostate specific antigen era. J Urol 2012;187:1259e1265. [24] Hoffman RM, Koyama T, Fan KH, et al. Mortality after radical prostatectomy or external beam radiotherapy for localized prostate cancer. J Natl Cancer Inst 2013;105:711e718. [25] Sun M, Sammon JD, Becker A, et al. Radical prostatectomy vs radiotherapy vs observation among older patients with clinically localized prostate cancer: a comparative effectiveness evaluation. BJU Int 2014;113:200e208. [26] Sooriakumaran P, Nyberg T, Akre O, et al. Comparative effectiveness of radical prostatectomy and radiotherapy in prostate cancer: observational study of mortality outcomes. BMJ 2014;348:g1502. [27] Litwin MS, Lubeck DP, Henning JM, Carroll PR. Differences in urologist and patient assessments of health related quality of life in men with prostate cancer: results of the CaPSURE database. J Urol 1998; 159:1988e1992. [28] Sonn GA, Sadetsky N, Presti JC, Litwin MS. Differing perceptions of quality of life in patients with prostate cancer and their doctors. J Urol 2013;189(1 Suppl.):S59eS65. [29] Sanda MG, Dunn RL, Michalski J, et al. Quality of life and satisfaction with outcome among prostate-cancer survivors. N Engl J Med 2008;358:1250e1261. [30] Wu AK, Cooperberg MR, Sadetsky N, Carroll PR. Health related quality of life in patients treated with multimodal therapy for prostate cancer. J Urol 2008;180:2415e2422. [31] Resnick MJ, Koyama T, Fan KH, et al. Long-term functional outcomes after treatment for localized prostate cancer. N Engl J Med 2013;368: 436e445. [32] Punnen S, Cowan JE, Chan JM, et al. Long-term health-related quality of life after primary treatment for localized prostate cancer: results from the CaPSURE registry. Eur Urol 2014. [33] Wei JT, Dunn RL, Litwin MS, et al. Development and validation of the expanded prostate cancer index composite (EPIC) for comprehensive assessment of health-related quality of life in men with prostate cancer. Urology 2000;56:899e905. [34] Nguyen PL, Gu X, Lipsitz SR, et al. Cost implications of the rapid adoption of newer technologies for treating prostate cancer. J Clin Oncol 2011;29:1517e1524. [35] Cooperberg MR, Ramakrishna NR, Duff SB, et al. Primary treatments for clinically localised prostate cancer: a comprehensive lifetime cost-utility analysis. BJU Int 2013;111:437e450.
Point/Counterpoint
Point: Surgery is the most cost-effective option for prostate cancer needing treatment Ahmed A. Hussein1,2, Matthew R. Cooperberg1,3,* 1
Department of Urology, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 2 Department of Urology, Cairo University, Egypt 3 Department of Epidemiology & Biostatistics, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA
For most men with localized prostate cancer (PCa), options include active surveillance, radical prostatectomy (RP), and radiation therapy (RT) in the form of brachytherapy (BT) and/or one of a variety of external beam radiation therapy (EBRT) techniques (1e3). Treatment should be tailored to each patient, considering the patient’s overall health, life expectancy, and the disease risk (prostate specific antigen [PSA], tumor extent, and grade). Clinicians’ skill and experience, and the patients’ preference to tradeoff potential benefits, side effects, and complications are other crucial factors guiding the treatment decision (1). Men must face treatment decisions in the face of a relative dearth of high-quality evidence comparing these options. Indeed, the effectiveness of the management strategies for localized PCa was considered among the highest initial national priorities for comparative effectiveness research by the Institute of Medicine in 2009 (4). Although randomized controlled trials (RCTs) are still sorely lacking, however, in recent years, increasingly high-quality retrospective evidence regarding oncologic efficacy, side effects, and health-related quality of life (HRQOL), and cost has become available to inform these decisions.
Oncologic efficacy Comparative effectiveness research addressing oncologic outcomes for localized PCa is not straightforward given the long natural history of the disease, a myriad of definitions of ‘‘recurrence,’’ and the varying impact and time course of different treatments on tumor cells. Specifically, the various treatments have markedly different effects on PSA and PSA kinetics, and the definitions of biochemical recurrence * Corresponding author. Department of Urology, Helen Diller Family Comprehensive Cancer Center, University of California, 1600 Divisadero St, Box 1695, San Francisco, CA 94143-1695. Tel.: þ415-885-3660; fax: þ415-353-7093. E-mail address: [email protected] (M.R. Cooperberg).
vary from one treatment to another. Disease recurrence/progression rates may vary up to 35% depending on the definition used even within a given modality (5e8). Between surgery and radiation, moreover, biochemical recurrence definitions are completely noncomparable. Postsurgical recurrence definitions are intended to identify the earliest signs of persistent/recurrent tumor, whereas the radiation definitions are intended to predict clinical progression and mortality (8, 9). In one example analysis, using the Phoenix ‘‘nadirþ2’’ recurrence definition rather than a O0.2 surgical threshold definition shifted out the median time to recurrence by over 5 years. Therefore, despite the continued publication of articles making claims regarding comparative efficacy between surgery and radiation based on biochemical recurrence (10), these analyses are quite simply not valid. Only clinical endpoints (metastasis, cancer-specific mortality, and overall mortality) are interpretable for comparisons of oncologic efficacy between surgery and radiation. For higher-risk PCa, RCTs have shown the superiority of surgery over watchful waiting and EBRT with androgen ablation therapy (ADT) over either EBRT or ADT alone (11e15). No RCT in the contemporary era has reported outcomes between RP and RT, although the prostate testing for cancer and treatment study (ProtecT) has accrued and is expected to report initial findings next year. Even prostate testing for cancer and treatment, although, includes few men with high-risk PCa (16). In the meantime, no fewer than 10 studies have been published in the past 8 years, across a range of contextsdacademic, community, and population based; American; and Europeandcomparing metastasis and cancer-specific and/or overall mortality outcomes after RP vs. EBRT. With one exception, all these have consistently shown roughly twofold risk-adjusted survival advantages favoring RP over EBRT (Table 1); no study has found better survival after RT compared with RP. Only one study to date has included a BT arm; BT seemed intermediate between RP and EBRT in terms of efficacy (23).
1538-4721/$ - see front matter Ó 2015 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.brachy.2015.02.393
754
A.A. Hussein, M.R. Cooperberg / Brachytherapy 14 (2015) 753e755
Table 1 Outcomes of observational studies comparing the outcomes of radical prostatectomy and radiation therapy for localized prostate cancer Author
Year
Site/data
Conclusions
Tewari et al. (17) Albertsen et al. (18) Zelefsky et al. (19) Cooperberg et al. (20) Stattin et al. (21) Boorjian et al. (22) Kibel et al. (23) Hoffman et al. (24) Sun et al. (25) Sooriakumaran et al. (26)
2007 2007 2010 2010 2010 2011 2012 2013 2014 2014
Henry Ford CT registry MSKCC/Baylor CaPSURE NPCR Sweden Mayo/Fox Chase WashU/CCF PCOS SEER PCBaSe
CSM CSM CSM CSM CSM CSM CSM CSM CSM CSM
HR 0.5 (0.3e1.0) favoring RP over EBRT RR 2.5 (1.7e3.5) favoring RP over EBRT HR 2.9 (1.3e7.7) favoring RP over EBRT HR 2.2 (1.5e3.2) favoring RP over EBRT; ADT 3.2 (2.2e4.8)a RR 1.4 (0.9e2.0) favoring RP over EBRT HR 1.1 (0.7e1.9) NS for RP vs. EBRTa HR 1.5 (1.0e2.3) favoring RP over EBRT; brachy 1.3 (0.7e2.4)a HR 2.9 (2.0e3.8) favoring RP over EBRTa HR 2.5 (1.5e4.2) favoring RP over EBRT HR 1.8 (1.5e2.1) favoring RP over EBRT
CSM 5 cancer-specific mortality; HR 5 hazards ratio; RP 5 radical prostatectomy; EBRT 5 external beam radiation therapy; CT 5 Connecticut; RR 5 risk ratio; MSKCC 5 Memorial Sloan Kettering Cancer Centre; CaPSURE 5 Cancer of the Prostate Strategic Urologic Research Endeavor; ADT 5 androgen deprivation therapy; NPCR 5 National Program of Cancer Registries; NS 5 nonsignificant; CCF 5 Cleveland Clinic Foundation; brachy 5 brachytherapy; PCOS 5 Prostate Cancer Outcomes Study; SEER 5 Surveillance, Epidemiology, and End Results; PCBaSe 5 Prostate Cancer Database of Sweden. a Also showed benefit for RP in terms of overall survival.
Two studiesdfrom the community-based Cancer of the Prostate Strategic Urologic Research Endeavor registry and from a two-center academic cohortdused multiple, particularly robust strategies to optimize risk adjustment, which is critical given well-documented differences in cancer risk parameters between RP and RT patients (19, 20). Of further key importance is the fact that both studies found the greatest differences in outcomes for men with high-risk disease; for those with low-risk disease, very few men experience clinical progression and differences between treatments were minimal. Comparing HRQOL Side effects, toxicities, and HRQOL impacts of different treatment modalities are all well documented and relatively noncontroversial. It should be stressed, however, that for outcomes such as urinary and sexual function, outcomes must be reported by patients, using validated questionnaires, as physician report and coding data do not accurately reflect symptom burden (27, 28). During the first years after treatment, RP patients generally have worse incontinence and sexual function and experience improvement over the first 1e2 years postoperatively. RT patients generally have worse urinary and bowel irritative symptoms (29). RT patients have less early erectile dysfunction, although adding ADT to radiation significantly worsens outcomes in this domain (30). For the most part, differences across modalities tend to attenuate with long-term followup (31, 32). Although these effects are all well characterized and can be reliably expressed in terms of unit functional declines using instruments like the Expanded Prostate Index Composite (33), what is less clear is the translation of these functional HRQOL outcomes to subjective utilities. Optimally weighing, in other words, the impact of persistent single-pad incontinence vs. persistent every-two-hour urinary frequencydor the impact of severe incontinence vs. a rectourinary fistuladhas not been standardized. Patients therefore are guided
by the nature and quality of the counseling they receive (both by clinicians and by friends and family) about what are usually to them hypothetical outcomes. Comparing costs: who pays? The economic burden of PCa management on the health care system is growing, owing to an aging population, increased detection and treatment of localized disease, and the advent of newer and more costly treatments. Emerging technologies have affected RP and RT costs very differently; for reasons that are largely political, robot-assisted surgery is reimbursed essentially equivalently with open surgery, whereas treatments such as intensity-modulated radiation therapy (IMRT) and proton-beam therapy are reimbursed much more generously than earlier treatments. A large national analysis of Medicare claims found that minimally invasive RP increased from 1.5% in 2002 to 28.7% in 2005, whereas for RT, the use of IMRT increased from 29% to 82%. This resulted in substantial increase in expenditure, accounting for an additional $341 million for IMRT compared with $4 million for minimally invasive RP (34). A comprehensive decision analysis using a Markov model incorporating oncologic and HRQOL outcomes of both primary and subsequent treatments showed that among all risk groups, surgical options were consistently less expensive than radiation options and often more effective. Regarding RT, BT was the most effective radiation modality among low-risk patients, whereas a combination of EBRT þ BT was the most effective for intermediate- and high-risk patients. IMRT monotherapy was more expensive and not more effective than RP or brachytherapy and should not be used as monotherapy, particularly for low-risk disease (35). Conclusions Although RCTs are still lacking, a growing body of highquality evidence supports a greater role for active
A.A. Hussein, M.R. Cooperberg / Brachytherapy 14 (2015) 753e755
surveillance for low-risk PCa and for surgery in the management of higher-risk PCa. It should be stressed, although that for men with high-risk PCa, the debate may be a false one. For other aggressive malignanciesdbreast cancer, rectal cancer, and so forthdthe question is not surgery, radiation, or systemic therapy, but rather how these modalities should be optimally combined. In the era of stage migration and a growing controversy regarding PCa screening, it is essential that management decisions be tailored to individual patient’s cancer risk and overall health. References [1] Guideline for the management of clinically localized prostate cancer. Available at: http://www.auanet.org/education/guidelines/prostatecancer.cfm 2007;. Accessed April 30, 2014. [2] Carter HB, Albertsen PC, Barry MJ, et al. Early detection of prostate cancer: AUA Guideline. J Urol 2013;190:419e426. [3] Heidenreich A, Bastian PJ, Bellmunt J, et al. EAU guidelines on prostate cancer. part 1: screening, diagnosis, and local treatment with curative intent-update 2013. Eur Urol 2014;65:124e137. [4] Potosky AL, Knopf K, Clegg LX, et al. Quality-of-life outcomes after primary androgen deprivation therapy: results from the Prostate Cancer Outcomes Study. J Clin Oncol 2001;19:3750e3757. [5] Amling CL, Bergstralh EJ, Blute ML, et al. Defining prostate specific antigen progression after radical prostatectomy: what is the most appropriate cut point? J Urol 2001;165:1146e1151. [6] Gretzer MB, Trock BJ, Han M, Walsh PC. A critical analysis of the interpretation of biochemical failure in surgically treated patients using the American Society for Therapeutic Radiation and Oncology criteria. J Urol 2002;168:1419e1422. [7] Kuban DA, Thames HD, Shipley WU. Defining recurrence after radiation for prostate cancer. J Urol 2005;173:1871e1878. [8] Cookson MS, Aus G, Burnett AL, et al. Variation in the definition of biochemical recurrence in patients treated for localized prostate cancer: the American Urological Association Prostate Guidelines for Localized Prostate Cancer Update Panel report and recommendations for a standard in the reporting of surgical outcomes. J Urol 2007;177:540e545. [9] Roach M 3rd, Hanks G, Thames H Jr, et al. Defining biochemical failure following radiotherapy with or without hormonal therapy in men with clinically localized prostate cancer: recommendations of the RTOG-ASTRO Phoenix Consensus Conference. Int J Radiat Oncol Biol Phys 2006;65:965e974. [10] Grimm P, Billiet I, Bostwick D, et al. Comparative analysis of prostate-specific antigen free survival outcomes for patients with low, intermediate and high risk prostate cancer treatment by radical therapy. Results from the Prostate Cancer Results Study Group. BJU Int 2012;109(Suppl. 1):22e29. [11] Bill-Axelson A, Holmberg L, Garmo H, et al. Radical prostatectomy or watchful waiting in early prostate cancer. N Engl J Med 2014;370: 932e942. [12] Wilt TJ, Brawer MK, Jones KM, et al. Radical prostatectomy versus observation for localized prostate cancer. N Engl J Med 2012;367: 203e213. [13] Warde P, Mason M, Ding K, et al. Combined androgen deprivation therapy and radiation therapy for locally advanced prostate cancer: a randomised, phase 3 trial. Lancet 2011;378:2104e2111. [14] Denham JW, Steigler A, Lamb DS, et al. Short-term neoadjuvant androgen deprivation and radiotherapy for locally advanced prostate cancer: 10-year data from the TROG 96.01 randomised trial. Lancet Oncol 2011;12:451e459. [15] Jones CU, Hunt D, McGowan DG, et al. Radiotherapy and short-term androgen deprivation for localized prostate cancer. N Engl J Med 2011;365:107e118.
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