Highlighting Unmet Needs: Real Patients, Difficult Choices

Size: px
Start display at page:

Download "Highlighting Unmet Needs: Real Patients, Difficult Choices"

Transcription

1 european urology supplements 8 (2009) 4 12 available at journal homepage: Highlighting Unmet Needs: Real Patients, Difficult Choices Massimo Maffezzini * Department of Urology, S. C. Urologia, E. O. Ospedali Galliera, Mura delle Cappuccine, 14, Genova, Italy Article info Keywords: Hormone-resistant prostate cancer Toxicity Treatment decisions Unmet needs Abstract Context: Prostate cancer is a heterogeneous disease with several different stages necessitating a broad range of therapies to treat patients diagnosed at different points in the disease course. Androgen deprivation therapy (ADT) is commonly used to treat all stages of prostate cancer but is associated with toxicities that limit its use, particularly in patients with asymptomatic disease or existing comorbidities for whom such toxicity is not justified. The absence of a standard approach to ADT leads to significant variation in treatment regimens and extensive debate about timing of initiation and duration of therapy. Evidence acquisition: A nonsystematic review of the literature including PubMed and congress abstracts was performed in Evidence synthesis: Most prostate cancer patients eventually progress to develop hormone-resistant prostate cancer (HRPC). Frequent prostatespecific antigen monitoring is detecting an increasing number of patients who have asymptomatic HRPC for whom the toxicity of currently available chemotherapy treatments cannot always be justified. In these cases, watchful waiting with a background of continuing castration therapy (with or without antiandrogen) is often the treatment paradigm. The majority of patients, however, receive additional secondline hormonal manipulations despite the associated toxicity and the lack of data to support the efficacy of this approach. Although there is currently no standard of care or approved treatment for nonmetastatic HRPC, docetaxel has been licensed for metastatic HRPC in many countries. The observed improvement in overall survival (2.4 mo) is considered by some to be marginal, and the toxicity profile can be problematic. Further studies are also required to address the ongoing debate regarding timing of initiation and duration of docetaxel therapy. Conclusions: Effective treatments are lacking for patients with HRPC, especially those with asymptomatic, nonmetastatic disease. The treatments that are available are limited by lack of data, suboptimal efficacy, and toxicity. There is clearly a significant requirement for new, welltolerated, efficacious therapies for the treatment of HRPC, and extensive efforts are under way to identify new agents. # 2008 European Association of Urology. Published by Elsevier B.V. All rights reserved. * Tel address: massimo.maffezzini@galliera.it /$ see front matter # 2008 European Association of Urology. Published by Elsevier B.V. All rights reserved. doi: /j.eursup

2 european urology supplements 8 (2009) Introduction Recent research efforts have greatly improved the understanding of the pathophysiology of prostate cancer, and it is hoped that these breakthroughs can be translated into the development of novel and effective treatment modalities. The biologic heterogeneity that characterises prostate cancer complicates diagnosis, prognosis and treatment; there are many different stages of this disease, and the point in the disease course at which patients are diagnosed can vary widely. This variation necessitates use of a range of treatments at different points in the disease course, the exact combination and sequence of which varies significantly between patients. Although radical prostatectomy is utilised for localised disease, alternatives are required for advanced and metastatic disease. Similarly, hormone therapy, which can be effective initially, becomes less valuable as the disease progresses and resistance becomes evident (hormone-resistant prostate cancer [HRPC]). This review aims to provide an overview of the limitations of current treatment practices, considering the most frequently encountered clinical scenarios when treating patients with advanced prostate cancer. 2. Limitations of current treatment practices Androgen deprivation therapy (ADT) has been used for the treatment of prostate cancer for >65 yr, following the initial report by Huggins and Hodges that androgen deprivation via surgical castration was beneficial to men with metastatic disease [1]. Androgen deprivation is generally achieved by surgical castration (bilateral orchiectomy), by medical castration with luteinising hormone-releasing hormone (LHRH) agonists/antagonists, and by steroidal or nonsteroidal antiandrogen blockade of the androgen receptor. American Society of Clinical Oncology (ASCO) guidelines recommend ADT as first-line therapy for metastatic disease, and it is also widely used to treat other stages of prostate cancer [2,3]. Despite its recognised utility, ADT is associated with a number of side-effects which vary depending on the exact treatment used [4 8]. Common treatment-related adverse effects include hot flushes, erectile dysfunction, loss of bone density, metabolic syndrome, and cardiovascular disease. These potential adverse effects, combined with the diverse array of patient profiles in terms of both disease severity and progression, complicates clinical decisions regarding initiation of ADT. One outcome of this complication is significant variation in prescribing practices among urologists depending on their experience, knowledge, and preference [9]. Although treatment practices have remained the same over time, the characteristics of prostate cancer patients have evolved. Implementation of widespread prostate-specific antigen (PSA) screening initiatives has greatly increased detection of early asymptomatic (initial) disease; however, it has not always been straightforward to adapt treatment approaches in parallel. Some physicians utilise watchful waiting to monitor patients with asymptomatic, nonmetastatic disease [10]. In many cases, however, physicians implement the approach that they have previously employed for patients presenting with symptomatic disease and initiate ADT immediately. A number of studies have been conducted to investigate the most appropriate timing for initiation of ADT. European Organisation for Research and Treatment of Cancer (EORTC) was a randomised trial which investigated immediate hormonal treatment versus deferred treatment at symptomatic disease progression in 985 patients with asymptomatic T0-4 N0-2 M0 prostate cancer [11]. After a median follow-up of 7.8 yr, there was an increase in mortality rate of 6.9% at 5 yr and of 11.1% at 10 yr for the deferred treatment group versus the immediate treatment group; however, this difference was not statistically significant. Another study by the Swiss Group for Clinical Cancer Research (SAKK 08/88) enrolled 196 patients, primarily with M1 prostate cancer [12]. A large proportion of patients in the deferred group in this study never required treatment, and there was no difference in overall survival or time to symptoms (after orchiectomy) between the groups. This study did report a significant improvement in overall median time to onset of first symptoms (+2.8 yr; p < 0.01) in those patients given immediate treatment. The Early Prostate Cancer Program (EPCP) consisted of three randomised controlled trials in which 1114 patients were randomly assigned to receive immediate treatment while treatment was deferred for 1170 patients [13]. After a median follow-up of 7.4 yr, 41.1% of the immediate treatment group had died (all causes) versus 39.5% of the deferred treatment group (odds ratio [OR]: 1.02; 95% CI, ). Objective progression-free survival was improved in the immediate treatment group (OR: 0.77; 95% CI, ); however, gynaecomastia (68.8% vs 7.6%) and breast pain (73.6% vs 7.6%) were reported more frequently. Meta-analyses of these and a number of other studies (Medical Research Council [MRC] PR03 [14], Veterans Administration Cooperative Urological Research Group [VACURG] 1 [15], EORTC [16], Eastern Coop-

3 6 european urology supplements 8 (2009) 4 12 erative Oncology Group [ECOG] [17]) have also been conducted. All of these data were analysed in the recent update to the ASCO guidelines, in which it was concluded that based on the available data, immediate treatment of patients following diagnosis, rather than treatment at onset of symptoms, did not offer a significant survival advantage [2]. Importantly, none of the trials analysed in the ASCO guidelines included prognostic factors which are now being used to aid clinical decision-making processes. The most robust of these is PSA doubling time (PSA DT); shorter PSA DT predicts shorter overall survival, cause-specific survival, and time to metastatic disease [18 21]. It is not only the optimal timing of ADT initiation that is unclear but also the duration for which therapy should be continued. Although several detrimental side-effects are associated with ADT, the toxicity profile of chemotherapy is much more severe; therefore, clinicians are often keen to delay its implementation [22]. This information is of particular concern to prostate cancer patients, many of whom are elderly with significant comorbidities; therefore, physicians frequently prolong treatment with ADT. 3. Clinical experience: a case study The limited therapeutic options currently available and their various shortcomings affect the clinical decisions that are made when treating patients with prostate cancer. This clinical case study demonstrates the course of action taken in the treatment of a 68-yr-old male patient who presented with mild lower urinary tract symptoms (Table 1). The patient Table 1 Patient status at presentation and prostatectomy Age (yr) 68 Medical history Mild hypertension, controlled Nocturia Two episodes per night Stable for 3 4 yr PSA 12.7 ng/ml Biopsy Left: 2/6 cores positive for adenocarcinoma Right: 3/6 cores positive for adenocarcinoma Gleason sum Prostatectomy Radical retropubic prostatectomy pt3a Margin positive (m+), unifocal right apex pn0 (6 + 5) nodes PSA = prostate-specific antigen. underwent a PSA test in which his levels were found to be elevated (12.7 ng/ml), and a subsequent biopsy confirmed clinically localised prostate cancer G7 (4 + 3). The patient had controlled hypertension and mild obstructive airways disease, but as he was relatively young, he was referred for surgery and underwent a radical retropubic prostatectomy. The patient was monitored after surgery using PSA measurements to track disease status (Fig. 1). After 2.5 yr following prostatectomy, PSA levels began to rise (PSA DT estimated at 4 mo) and ADT was initiated with bicalutamide. Although this treatment did initially offer some benefit, within 12 mo the patient s PSA was rising again and total androgen blockade was implemented by the addition of LHRH analogues and a switch from bicalutamide to flutamide; however, no major benefit was observed from this change. Subsequent flutamide withdrawal had little impact and effects of estra- Fig. 1 Treatment profile of a prostate cancer patient. The changing prostate-specific antigen (PSA) profile of the patient following radical prostatectomy. A range of different androgen deprivation therapy (ADT) approaches were used sequentially in attempts to control disease with limited success. LHRH = luteinising hormone-releasing hormone; PET = positron emission tomography.

4 european urology supplements 8 (2009) mustine were also transient. At 63 mo, with PSA still rising, the patient underwent restaging. Disease was identified in at least three spots in the spine and aortic bifurcation was found, confirming disease progression; his obstructive airways disease had also deteriorated somewhat and he was keen to avoid chemotherapy if possible. Introduction of a 5a-reductase inhibitor, however, did little to control PSA levels, and eventually, the patient did undergo chemotherapy with docetaxel. This therapy appeared to have an impact on the disease, but it followed 6 mo of treatment with different forms of ADT after metastasis had already occurred. This case study highlights the limited effective treatment options for prostate cancer which led the treating clinicians to implement multiple forms of ADT in repeated attempts to control this patient s disease, which eventually metastasised despite these interventions. It is likely that chemotherapy was delayed to spare the patient from its severe side-effect profile; however, this delay meant that by the time docetaxel treatment was initiated, the disease was advanced. Had a less toxic therapy been available, it would have provided an earlier alternative to the multiple rounds of ADT. 4. Clinical management of nonmetastatic hormone-resistant prostate cancer Although ADT can be an effective preliminary treatment for prostate cancer, responses are normally short-lived (median duration of mo) with most patients becoming hormone resistant [23,24]. Historically, HRPC was diagnosed when metastasis was detected; however, the introduction of PSA monitoring in the 1980 s has resulted in earlier identification of hormone resistance. Hormone resistance is defined as a rise in PSA levels during or following ADT, with serum testosterone remaining at castrate levels and without obvious clinical disease progression. The consequence of earlier detection is that there are now several forms of HRPC associated with different patient characteristics and median survival times, which necessitate alternative treatment approaches. In particular, some of the aggressive therapies utilised for metastatic disease are deemed inappropriate for patients who remain asymptomatic. The broad spread of disease states makes it essential that therapeutic regimens are tailored to the individual case and consider a number of factors including prior therapy, current rate of disease progression, symptoms, and evidence of metastatic disease. Consequently, there is no standard of treatment for asymptomatic HRPC and treatment protocols vary significantly among hospitals, physicians, and patients. In some cases, physicians opt to withdraw or withhold treatment and to simply monitor patients for signs of disease progression. Watchful waiting is generally employed for elderly patients at low risk of metastasis [10]. Such patients are often experiencing significant comorbidities, and the negative impact that the toxicities associated with further treatment would have on their quality of life is not considered to be justified. The limited evidence of efficacy with currently available treatments further supports watchful waiting as a valid treatment option for these patients. Close follow-up is essential to ensure that any disease progression is detected as early as possible, so that treatment can be initiated. In many cases, however, watchful waiting is discounted due to patient anxiety about doing nothing, and treatment is initiated despite the potential side-effects and limited efficacy. Second-line hormonal manipulation is widely employed to treat patients with localised HRPC and utilises a range of modalities all based on the theme of androgen deprivation [25 30] (Table 2). It is difficult, however, to predict which subset of patients will respond to secondary hormone treatments. For those patients who have not previously undergone maximum androgen blockade, using a combination of a LHRH agonist and an antiandrogen, such therapy can be initiated [31]; however, only a modest survival advantage has been demonstrated from combined therapy. Furthermore, the cost, the toxicity, and the minimal survival benefit can discourage physicians from implementing this approach. Antiandrogen withdrawal is another approach often used for patients who have previously received maximum androgen blockade, but this approach is effective in only about one-third of patients. Antiandrogen withdrawal has been demonstrated to induce PSA declines, but these responses are generally biochemical only and shortlived, with no demonstrated survival advantage [32]. For patients who do not respond to antiandrogen withdrawal or in whom it has failed, the next step generally consists of initiation of alternative forms of hormonal manipulation including oestrogens, adrenal suppressants, or corticosteroids. Historically, oestrogens, such as the oral synthetic compound diethylstilbestrol (DES), have been shown to decrease PSA levels. These act by decreasing LHRH secretion and directly inhibiting luteinising hormone (LH) secretion, thereby decreasing testosterone levels. In two recent studies of DES, PSA responses of 43% and 80% were achieved; however,

5 8 european urology supplements 8 (2009) 4 12 Table 2 Second-line hormonal manipulation for nonmetastatic hormone-resistant prostate cancer Approach Example Limitation(s) Reference Withdrawal response Antiandrogens Responses biochemical only and short-lived Small et al (1995) [28] Oestrogens Oral diethylstilbestrol Gynaecomastia, fluid retention, Smith et al (1998) [25] cardiovascular effects, thromboembolic events Adrenal suppressants Ketoconazole Skin toxicity, liver function, nausea, vomiting Wilkinson and Chodak (2004) [26] Aminogluthethimide Lethargy, skin rash Kruit et al (2004) [27] Corticosteroids Prednisone Addisonian crisis, short-lived effects Sartor et al (1995) [29] DES was associated with significant cardiovascular toxicities, including myocardial infarction and pulmonary embolism. Approximately 10% of circulating androgen is secreted by the adrenal glands; therefore, adrenal suppressants can be used to manipulate the hormonal balance in prostate cancer patients. Ketoconazole inhibits steroidogenesis in the testes and the adrenal gland. Trials of this drug in combination with corticosteroids and/or antiandrogen withdrawal have demonstrated PSA reductions. Although inclusion of corticosteroids in the treatment regimen reduces the toxicity of adrenal suppression, adverse effects including gastrointestinal disturbances, fatigue, and liver function abnormalities still occur [33]. It is recommended that patients receiving ketoconazole undergo monthly liver function tests. Aminogluthethimide is another adrenal suppressant that has been shown to yield a PSA reduction in patients with advanced prostate cancer [34]. Toxicities are similar to those observed with ketoconazole. As indicated, corticosteroids are commonly used as a supportive therapy to adrenal suppression; however, they may also have some anticancer activity [35]. PSA declines and improvement of symptoms have been reported in patients treated with low-dose prednisone or dexamethasone [36,37]. The side-effect profile of corticosteroids can limit their utility, and in some cases, withdrawal of treatment includes potentially fatal Addisonian crisis. Importantly, all of the data available to support use of these treatments have been generated by small phase 2 studies with short-term follow-up periods. Large, randomised trials are required to elucidate the true utility of second-line hormonal manipulation for localised advanced prostate cancer. All of these treatments are also associated with toxicities that limit their potential in the clinic. Novel therapies are clearly required for patients with nonmetastatic HRPC who are generally asymptomatic and need to have access to treatments with a minimal impact on quality of life. 5. Clinical management of metastatic hormone-resistant prostate cancer Further androgen manipulation following antiandrogen withdrawal used to be the standard of care for patients with metastatic HRPC despite the lack of Fig. 2 Overall survival (OS) of hormone-refractory prostate cancer patients in docetaxel trials [24,43]: (a) OS in March 2007 after 867 deaths had occurred in the TAX327 population of 1006 patients randomly assigned to receive three-weekly (q3w) docetaxel, weekly (q1w) docetaxel, or mitoxantrone. (Reprinted with permission # 2008 American Society of Clinical Oncology. All rights reserved.); (b) OS after a median follow-up of 32 mo when 452 deaths had occurred in the Southwest Oncology Group (SWOG) population of 674 patients randomly assigned to receive docetaxel plus estramustine or mitoxantrone plus prednisone. (Reprinted with permission # 2004 Massachusetts Medical Society. All rights reserved.)

6 european urology supplements 8 (2009) any phase 3 randomised controlled trials demonstrating a survival advantage from this practice. Two major prospective randomised studies, TAX327 and Southwest Oncology Group (SWOG) 99-16, have demonstrated a survival benefit for patients with metastatic HRPC receiving docetaxel-based therapy [23,24] (Fig. 2), so chemotherapy may now be considered as the first option following androgen withdrawal in cases where the patient is fit enough to tolerate this treatment. The TAX327 study demonstrated that three-weekly docetaxel versus mitoxantrone could yield a significant improvement in patient survival (Fig. 2a), whereas SWOG showed a benefit of docetaxel plus estramustine versus mitoxantrone plus prednisone (Fig. 2b). Improvements in the quality of life of HRPC patients were demonstrated in the TAX327 study. These results led to the approval of three-weekly docetaxel in combination with prednisone for treatment of metastatic HRPC in many countries. Although docetaxel is being increasingly used to treat patients with metastatic HRPC, there are a number of important considerations relating to its use. First, although TAX327 and SWOG demonstrated efficacy, the improvement in median overall survival was only 2.4 mo, which some physicians view as marginal. This efficacy must be balanced against the toxicities of treatment. Up to 45% of patients in these studies experienced grade 3 or 4 adverse events, an important factor in an elderly population with many comorbidities. Moreover, most of the patients in the TAX327 and SWOG studies had good performance status, which is not always the case in everyday practice. Another consideration is the necessity for hospital visits, which are not only inconvenient for patients but also have major cost implications. Because chemotherapy may not be appropriate for all patients, a surrogate marker for survival that could be used to identify the patients most likely to benefit would be advantageous. PSA DT, is known to be a surrogate for survival in earlier stages of prostate cancer [19], and Semeniuk et al demonstrated that this is also the case in patients with HRPC [38]. They reviewed 224 HRPC patients with evidence of metastasis and calculated the PSA DT at diagnosis. They demonstrated that patients with a PSA DT <70 d survived for 11 mo compared with 19 mo for those with a PSA DT of >70 d (relative risk [RR]: 1.79; p < ). This finding confirmed that PSA DT can serve as an independent prognostic marker for survival in patients with metastatic HRPC. Although TAX327 and SWOG were clearly milestone studies for the treatment of metastatic HRPC, two key questions about the use of chemotherapy in this setting remain unanswered. First, it has not been established exactly when in the disease course chemotherapy should be initiated. The studies described in this paper have indicated that chemotherapy should be administered when disease has metastasised; however, there are currently very limited data available regarding therapeutic efficiency of docetaxel given early (ie, following a rise in PSA level but prior to metastasis). Some physicians believe treatment should be started early, whereas others feel that because no clinical benefit has been conclusively demonstrated, treatment should be withheld to minimise the impact of the toxic side-effects of docetaxel. The second uncertainty is how long treatment with docetaxel should be continued when considering the limited tolerance for this agent. Further studies are required to address both of these important issues to ensure that chemotherapy is used in the most efficacious manner in patients with prostate cancer. In addition to disease-modifying treatments, supportive care options are also available to alleviate symptoms associated with HRPC, although they do not limit disease progression. A lot of the pain associated with prostate cancer occurs in the bone, where formation of metastases leads to significant discomfort. Bisphosphonates, including zoledronic acid, have been demonstrated to yield a clinically significant reduction in bone pain and to prevent skeletal complications in patients with metastatic HRPC [39]. External-beam radiation can also provide palliation for painful focal lesions, but repeated courses are typically required for effective treatment in those patients with systemic disease. Radioisotope therapy is another treatment indicated as supportive care for HRPC. Strontium-89 is a b- emitting radioisotope that can decrease bone pain in up to 70% of patients; however, early use can affect subsequent utility of chemotherapy due to issues with myelosuppression [40]. Further research is ongoing to establish the best docetaxel regimens and other treatment modalities for metastatic HRPC. Investigational therapies include immunotherapies, highly potent antiandrogens, and targeted agents are also in development (for further details see Miller [41], this issue). 6. Patient perceptions and the role of the physician The complexity and uncertainty associated with prostate cancer can be daunting for its sufferers. Patients are faced with a series of difficult treatment

7 10 european urology supplements 8 (2009) 4 12 decisions in which they must carefully consider the trade-off between the probability of curing their disease and the desire to avoid the range of toxicities associated with all of the currently available therapeutic options. The lack of definitive evidence to indicate which treatments offer the greatest chance of long-term survival makes these decisions very difficult. A study by Denberg et al [42] investigated the influences that affect treatment decisions in patients with localised prostate cancer through a series of interviews with recently diagnosed patients. Three key factors influencing the decision-making process were apparent: Emotion, primarily fuelled by fear and uncertainty, and a desire for rapid treatment drives a lot of patient choices; misconceptions about the available treatments were also common and many patients relied on anecdotes from other prostate cancer sufferers, even if their clinical circumstances were different. In addition to the influences that exist at this early stage following diagnosis, there are also patient preconceptions about the progression of their disease. Many patients become heavily reliant on their PSA measurements as an indicator of their disease state. This value provides them with a tangible measure of their condition and can therefore be very important in their decision-making process. Despite the numerous information sources available to patients when making their treatment decisions, the physician remains the most direct influence on patient choice; therefore, physicians have a responsibility to fully inform patients about their disease and the available treatment options. It is important to explain not only the potential benefits in terms of disease control but also the negative impact that many of the treatments can have on the patient s ongoing quality of life. By ensuring that patients are fully informed and educated, physicians support their patients ability to make informed treatment decisions. This partnership between patients and physicians extends beyond initial treatment decisions throughout the course of the disease. Prostate cancer has a long natural course and patients often experience uncertainty and a loss of confidence in their initial treatment decisions as their cancer progresses. They rely on their physicians to support them in the decisions that they have made. This role of the physician will be particularly important as new therapies emerge that challenge existing patient perceptions. Physicians will be responsible for educating patients about the novel mechanisms of action of the new agents and how these will affect the disease. In particular, patients may require education about the role of PSA and its utility in their disease monitoring because the impact of targeted therapies on this parameter will not be the same as with previous treatments. 7. Conclusions: unmet needs of the hormoneresistant prostate cancer patient The current treatment landscape for patients with prostate cancer is complex and highly variable. The resulting lack of clarity about the best treatment approaches for each stage of the disease means there is currently no standard of care for most patients. The lack of predictability regarding treatment outcomes means that patients are presented with a multitude of treatment options but lack definitive guidance about which will be the most effective. Faced with this uncertainty, patients often opt for more aggressive therapy to feel that they are doing something to fight their disease. It is vital that physicians educate and support their patients so that the best treatment decisions are made. The major factors affecting current treatment decisions for all stages of disease are limited by data availability, suboptimal efficacy, and toxicity of existing treatments. All of the therapeutic approaches described in this paper are restricted by one or more of these factors. The lack of clinical evidence to support current treatments can affect clinicians confidence in their use and reduce uptake of particular therapies. In the case of HRPC, the absence of data to answer key questions about timing and duration of chemotherapy results in a lack of clarity for clinicians and highly variable treatment practices. Suboptimal efficacy of existing agents is also a significant issue limiting the effective treatment of HRPC. Although docetaxel is now an established treatment for metastatic disease, there is debate about the clinical significance of the limited improvement in overall survival that it offers. Clearly, an alternative with greater efficacy would be highly advantageous for patients with this advanced stage of the disease. Finally, toxicity is a major issue associated with virtually all current treatments for prostate cancer, particularly in this susceptible population. Identifying new treatments with greater tolerability will both improve quality of life for patients who are currently enduring unpleasant side-effects of existing treatments and open up the possibility of therapy to a new group of patients who are currently unable to tolerate treatment. It is clear from the data presented that there is a significant requirement for new, well-tolerated, efficacious therapies with minimal impact on quality of life for the treatment of HRPC. Extensive

8 european urology supplements 8 (2009) efforts are under way to identify new agents, and these will be discussed in the subsequent manuscripts in this supplement. Conflicts of interest The author has nothing to disclose. Funding support AstraZeneca provided funding for editorial assistance. Acknowledgements Editorial assistance was provided by Sarah Jane Mason from Mudskipper Bioscience. References [1] Huggins C, Hodges CV. Studies on prostatic cancer. I. The effect of castration, of estrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate. Cancer Res 1941;1: [2] Loblaw DA, Virgo KS, Nam R, et al. Initial hormonal management of androgen-sensitive metastatic, recurrent, or progressive prostate cancer: 2007 update of an American Society of Clinical Oncology practice guideline. J Clin Oncol 2007;25: [3] Basch EM, Somerfield MR, Beer TM, et al. American Society of Clinical Oncology endorsement of the Cancer Care Ontario practice guideline on nonhormonal therapy for men with metastatic hormone-refractory (castration-resistant) prostate cancer. J Clin Oncol 2007;25: [4] Keating NL, O Malley AJ, Smith MR. Diabetes and cardiovascular disease during androgen deprivation therapy for prostate cancer. J Clin Oncol 2006;24: [5] Saigal CS, Gore JL, Krupski TL, Hanley J, Schonlau M, Litwin MS. Androgen deprivation therapy increases cardiovascular morbidity in men with prostate cancer. Cancer 2007;110: [6] Bylow K, Mohile SG, Stadler WM, Dale W. Does androgendeprivation therapy accelerate the development of frailty in older men with prostate cancer?: a conceptual review. Cancer 2007;110: [7] Higano CS. Androgen-deprivation-therapy-induced fractures in men with nonmetastatic prostate cancer: what do we really know? Nat Clin Pract Urol 2008;5: [8] Smith MR, Lee H, McGovern F, et al. Metabolic changes during gonadotropin-releasing hormone agonist therapy for prostate cancer: differences from the classic metabolic syndrome. Cancer 2008;112: [9] Cooperberg MR, Grossfeld GD, Lubeck DP, Carroll PR. National practice patterns and time trends in androgen ablation for localized prostate cancer. J Natl Cancer Inst 2003;95: [10] Holmberg L, Bill-Axelson A, Helgesen F, et al. A randomized trial comparing radical prostatectomy with watchful waiting in early prostate cancer. N Engl J Med 2002;347: [11] Studer UE, Hauri D, Hanselmann S, et al. Immediate versus deferred hormonal treatment for patients with prostate cancer who are not suitable for curative local treatment: results of the randomized trial SAKK 08/88. J Clin Oncol 2004;22: [12] Studer UE, Whelan P, Albrecht W, et al. Immediate or deferred androgen deprivation for patients with prostate cancer not suitable for local treatment with curative intent: European Organisation for Research and Treatment of Cancer (EORTC) Trial J Clin Oncol 2006;24: [13] McLeod DG, Iversen P, See WA, Morris T, Armstrong J, Wirth MP. Bicalutamide 150 mg plus standard care vs standard care alone for early prostate cancer. BJU Int 2006;97: [14] Kirk D. Timing and choice of androgen ablation. Prostate Cancer Prostatic Dis 2004;7: [15] Byar DP. Proceedings: The Veterans Administration Cooperative Urological Research Group s studies of cancer of the prostate. Cancer 1973;32: [16] Schroder FH, Kurth KH, Fossa SD, et al. Early versus delayed endocrine treatment of pn1-3 M0 prostate cancer without local treatment of the primary tumor: results of European Organisation for the Research and Treatment of Cancer a phase III study. J Urol 2004;172: [17] Messing EM, Manola J, Sarosdy M, Wilding G, Crawford ED, Trump D. Immediate hormonal therapy compared with observation after radical prostatectomy and pelvic lymphadenectomy in men with node-positive prostate cancer. N Engl J Med 1999;341: [18] Maffezzini M, Bossi A, Collette L. Implications of prostatespecific antigen doubling time as indicator of failure after surgery or radiation therapy for prostate cancer. Eur Urol 2007;51: [19] D Amico AV, Kantoff P, Loffredo M, Renshaw AA, Loffredo B, Chen MH. Predictors of mortality after prostate-specific antigen failure. Int J Radiat Oncol Biol Phys 2006;65: [20] Kim-Sing C, Pickles T. Intervention after PSA failure: examination of intervention time and subsequent outcomes from a prospective patient database. Int J Radiat Oncol Biol Phys 2004;60: [21] Pound CR, Partin AW, Eisenberger MA, Chan DW, Pearson JD, Walsh PC. Natural history of progression after PSA elevation following radical prostatectomy. JAMA 1999; 281: [22] Shelley M, Harrison C, Coles B, Stafforth J, Wilt T, Mason M. Chemotherapy for hormone-refractory prostate cancer. Cochrane Database Syst Rev 2006:CD Available at:

9 12 european urology supplements 8 (2009) 4 12 [23] Tannock IF, de Wit R, Berry WR, et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med 2004;351: [24] Petrylak DP, Tangen CM, Hussain MH, et al. Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med 2004;351: [25] Smith DC, Redman BG, Flaherty LE, Li L, Strawderman M, Pienta KJ. A phase II trial of oral diethylstilbesterol as a second-line hormonal agent in advanced prostate cancer. Urology 1998;52: [26] Wilkinson S, Chodak G. An evaluation of intermediatedose ketoconazole in hormone refractory prostate cancer. Eur Urol 2004;45: [27] Kruit WH, Stoter G, Klijn JG. Effect of combination therapy with aminoglutethimide and hydrocortisone on prostatespecific antigen response in metastatic prostate cancer refractory to standard endocrine therapy. Anticancer Drugs 2004;15: [28] Small EJ, Srinivas S. The antiandrogen withdrawal syndrome. Experience in a large cohort of unselected patients with advanced prostate cancer. Cancer 1995;76: [29] Sartor O, Weinberger M, Moore A, Li A, Figg WD. Effect of prednisone on prostate-specific antigen in patients with hormone-refractory prostate cancer. Urology 1998;52: [30] Fizazi K, Le MA, Hudes G, et al. Addition of estramustine to chemotherapy and survival of patients with castrationrefractory prostate cancer: a meta-analysis of individual patient data. Lancet Oncol 2007;8: [31] Labrie F, Cusan L, Gomez JL, Belanger A, Candas B. Longterm combined androgen blockade alone for localized prostate cancer. Mol Urol 1999;3: [32] Sartor AO, Tangen CM, Hussain MH, et al. Antiandrogen withdrawal in castrate-refractory prostate cancer: a Southwest Oncology Group trial (SWOG 9426). Cancer 2008;112: [33] Ryan CJ, Weinberg V, Rosenberg J, et al. Phase II study of ketoconazole plus granulocyte-macrophage colony-stimulating factor for prostate cancer: effect of extent of disease on outcome. J Urol 2007;178: [34] Lam JS, Leppert JT, Vemulapalli SN, Shvarts O, Belldegrun AS. Secondary hormonal therapy for advanced prostate cancer. J Urol 2006;175: [35] Schmid HP, Gregorin J, Altwein JE. Growth hormone inhibitors in prostate cancer: a systematic analysis. Urol Int 2008;81: [36] Keith BD. Systematic review of the clinical effect of glucocorticoids on nonhematologic malignancy. BMC Cancer 2008;8:84. [37] Heng DY, Chi KN. Prednisone monotherapy in asymptomatic hormone refractory prostate cancer. Can J Urol 2006;13: [38] Semeniuk RC, Venner PM, North S. Prostate-specific antigen doubling time is associated with survival in men with hormone-refractory prostate cancer. Urology 2006;68: [39] Sciarra A, Salciccia S. New treatment strategies in the management of hormone refractory prostate cancer (HRPC): only chemotherapy? Eur Urol 2007;52: [40] Tu SM, Lin SH. Current trials using bone-targeting agents in prostate cancer. Cancer J 2008;14:35 9. [41] Miller K. Challenges and opportunities in hormone-resistant prostate cancer. Eur Urol Suppl 2009;8: [42] Denberg TD, Melhado TV, Steiner JF. Patient treatment preferences in localized prostate carcinoma: The influence of emotion, misconception, and anecdote. Cancer 2006;107: [43] Berthold DR, Pond GR, Soban F, de Wit R, Eisenberger M, Tannock IF. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer: updated survival in the TAX 327 study. J Clin Oncol 2008;26:

Definition Prostate cancer

Definition Prostate cancer Prostate cancer 61 Definition Prostate cancer is a malignant neoplasm that arises from the prostate gland and the most common form of cancer in men. localized prostate cancer is curable by surgery or radiation

More information

LONDON CANCER NEW DRUGS GROUP RAPID REVIEW

LONDON CANCER NEW DRUGS GROUP RAPID REVIEW LONDON CANCER NEW DRUGS GROUP RAPID REVIEW Abiraterone for the treatment of metastatic castration-resistant prostate cancer that has progressed on or after a docetaxel-based chemotherapy regimen Disease

More information

Hormonotherapy of advanced prostate cancer

Hormonotherapy of advanced prostate cancer Annals of Oncology 16 (Supplement 4): iv80 iv84, 2005 doi:10.1093/annonc/mdi913 Hormonotherapy of advanced prostate cancer P. Pronzato & M. Rondini Department of Oncology, Felettino Hospital, La Spezia,

More information

Recent Progress in Management of Advanced Prostate Cancer

Recent Progress in Management of Advanced Prostate Cancer Review Article [1] April 15, 2005 By Philip W. Kantoff, MD [2] Androgen-deprivation therapy, usually with combined androgen blockade, is standard initial treatment for advanced prostate cancer. With failure

More information

Session 4 Chemotherapy for castration refractory prostate cancer First and second- line chemotherapy

Session 4 Chemotherapy for castration refractory prostate cancer First and second- line chemotherapy Session 4 Chemotherapy for castration refractory prostate cancer First and second- line chemotherapy October- 2015 ESMO 2004 October- 2015 Fyraftensmøde 2 2010 October- 2015 Fyraftensmøde 3 SWOG 9916 OS

More information

J Clin Oncol 25: by American Society of Clinical Oncology INTRODUCTION

J Clin Oncol 25: by American Society of Clinical Oncology INTRODUCTION VOLUME 25 NUMBER 12 APRIL 20 2007 JOURNAL OF CLINICAL ONCOLOGY A S C O S P E C I A L A R T I C L E Initial Hormonal Management of Androgen-Sensitive Metastatic, Recurrent, or Progressive Prostate Cancer:

More information

Initial Hormone Therapy

Initial Hormone Therapy Initial Hormone Therapy Alan Horwich Institute of Cancer Research and Royal Marsden Hospital, London, UK Alan.Horwich@icr.ac.uk MANAGEMENT OF PROSTATE CANCER Treatment windows Subclinical Localised PSA

More information

Hormone Therapy for Prostate Cancer: Guidelines versus Clinical Practice

Hormone Therapy for Prostate Cancer: Guidelines versus Clinical Practice european urology supplements 5 (2006) 362 368 available at www.sciencedirect.com journal homepage: www.europeanurology.com Hormone Therapy for Prostate Cancer: Guidelines versus Clinical Practice Antonio

More information

Naviga2ng the Adverse Effects of ADT: Improving Pa2ent Outcomes

Naviga2ng the Adverse Effects of ADT: Improving Pa2ent Outcomes Naviga2ng the Adverse Effects of ADT: Improving Pa2ent Outcomes E. David Crawford, M.D. Professor of Surgery/ Urology/ Radiation Oncology University of Colorado Greetings from Colorado Disclosures Consultant:

More information

Initial Hormone Therapy

Initial Hormone Therapy Initial Hormone Therapy Alan Horwich Institute of Cancer Research and Royal Marsden Hospital, London, UK Alan.Horwich@icr.ac.uk MANAGEMENT OF PROSTATE CANCER Treatment windows Subclinical Localised PSA

More information

Modern Screening and Treatment of Advanced Prostate Cancer John Tuckey

Modern Screening and Treatment of Advanced Prostate Cancer John Tuckey Modern Screening and Treatment of Advanced Prostate Cancer John Tuckey Commonest male cancer - 2939 per year Third male cancer death 670 per year More die with it than of it but More people die of prostate

More information

Hormone therapy works best when combined with radiation for locally advanced prostate cancer

Hormone therapy works best when combined with radiation for locally advanced prostate cancer Hormone therapy works best when combined with radiation for locally advanced prostate cancer Phichai Chansriwong, MD Ramathibodi Hospital, Mahidol University Introduction Introduction 1/3 of patients

More information

Medical Treatments for Prostate Cancer

Medical Treatments for Prostate Cancer Medical Treatments for Prostate Cancer Ian F Tannock MD, PhD Daniel E Bergsagel Professor of Medical Oncology, Princess Margaret Hospital and University of Toronto March 17, 2005 Brampton 1 A hypothetical

More information

reviews LHRH Agonists in the Treatment of Advanced Carcinoma of the Prostate therapy

reviews LHRH Agonists in the Treatment of Advanced Carcinoma of the Prostate therapy reviews therapy LHRH Agonists in the Treatment of Advanced Carcinoma of the Prostate Martin I. Resnick, MD, Lester Persky Professor and Chief, Department of Urology, Case Western Reserve University School

More information

majority of the patients. And taking an aggregate of all trials, very possibly has a modest effect on improved survival.

majority of the patients. And taking an aggregate of all trials, very possibly has a modest effect on improved survival. Hello. I am Farshid Dayyani. I am Assistant Professor in Genitourinary Medical Oncology at The University of Texas MD Anderson Cancer Center. We will be talking today about prostate cancer for survivorship

More information

Timing of Androgen Deprivation: The Modern Debate Must be conducted in the following Contexts: 1. Clinical States Model

Timing of Androgen Deprivation: The Modern Debate Must be conducted in the following Contexts: 1. Clinical States Model Timing and Type of Androgen Deprivation Charles J. Ryan MD Associate Professor of Clinical Medicine UCSF Comprehensive Cancer Center Timing of Androgen Deprivation: The Modern Debate Must be conducted

More information

Metastatic prostate carcinoma. Lee Say Bob July 2017

Metastatic prostate carcinoma. Lee Say Bob July 2017 Metastatic prostate carcinoma Lee Say Bob July 2017 Scenario A 58 year old gentleman presents with PSA 200 ng/ml with hard prostate and bone mets. LUTS but upper tracts are normal with normal RP. history

More information

Maximal androgen blockade versus castration alone in patients with metastatic prostate cancer*

Maximal androgen blockade versus castration alone in patients with metastatic prostate cancer* Chinese-German J Clin Oncol DOI 10.1007/s10330-014-0037-9 September 2014, Vol. 13, No. 9, P417 P421 Maximal androgen blockade versus castration alone in patients with metastatic prostate cancer* Abeer

More information

When exogenous testosterone therapy is. adverse responses can be induced.

When exogenous testosterone therapy is. adverse responses can be induced. Theoretical tips It has been reasoned that discontinuation of ADT in nonorchiectomized patients may have detrimental effect on patients with CRPC as discontinuation of ADT can result in renewed release

More information

Advanced Prostate Cancer. November Jose W. Avitia, M.D

Advanced Prostate Cancer. November Jose W. Avitia, M.D Advanced Prostate Cancer November 4 2017 Jose W. Avitia, M.D In 2017 161,000 new cases of prostate cancer diagnosed in US, mostly with elevated PSA 5-10% will present with metastatic disease In 2017: 26,000

More information

Policy. not covered Sipuleucel-T. Considerations Sipuleucel-T. Description Sipuleucel-T. be medically. Sipuleucel-T. covered Q2043.

Policy. not covered Sipuleucel-T. Considerations Sipuleucel-T. Description Sipuleucel-T. be medically. Sipuleucel-T. covered Q2043. Cellular Immunotherapy forr Prostate Cancer Policy Number: 8.01.53 Origination: 11/2010 Last Review: 11/2014 Next Review: 11/2015 Policy BCBSKC will provide coverage for cellular immunotherapy for prostate

More information

Management of castration resistant prostate cancer after first line hormonal therapy fails

Management of castration resistant prostate cancer after first line hormonal therapy fails Management of castration resistant prostate cancer after first line hormonal therapy fails Simon Crabb Senior Lecturer in Medical Oncology University of Southampton WHAT ARE THE AIMS OF TREATMENT? Cure?

More information

Published on The YODA Project (

Published on The YODA Project ( Principal Investigator First Name: David Last Name: Lorente Degree: MD Primary Affiliation: Medical Oncology Service, Hospital Provincial de Castellón E-mail: lorente.davest@gmail.com Phone number: +34

More information

Prostate cancer update: Dr Robert Huddart Cancer Clinic London

Prostate cancer update: Dr Robert Huddart Cancer Clinic London Prostate cancer update: 2013 Dr Robert Huddart Cancer Clinic London Recent developments Improved imaging New radiotherapy technologies Radiotherapy for advanced disease Intermittent hormone therapy New

More information

The Natural History of Noncastrate Metastatic Prostate Cancer after Radical Prostatectomy

The Natural History of Noncastrate Metastatic Prostate Cancer after Radical Prostatectomy european urology 51 (2007) 940 948 available at www.sciencedirect.com journal homepage: www.europeanurology.com Prostate Cancer The Natural History of Noncastrate Metastatic Prostate Cancer after Radical

More information

Management of castrate resistant disease: after first line hormone therapy fails

Management of castrate resistant disease: after first line hormone therapy fails Management of castrate resistant disease: after first line hormone therapy fails Rob Jones Consultant in Medical Oncology Beatson Cancer Centre Glasgow Relevant Disclosure I have received research support

More information

Prostate Cancer 2009 MDV Anti-Angiogenesis. Anti-androgen Radiotherapy Surgery Androgen Deprivation Therapy. Docetaxel/Epothilone

Prostate Cancer 2009 MDV Anti-Angiogenesis. Anti-androgen Radiotherapy Surgery Androgen Deprivation Therapy. Docetaxel/Epothilone Prostate Cancer 2009 Anti-Angiogenesis MDV 3100 Anti-androgen Radiotherapy Surgery Androgen Deprivation Therapy Docetaxel/Epothilone Abiraterone DC therapy Bisphosphonates Denosumab Secondary Hormonal

More information

MOLECULAR AND CLINICAL ONCOLOGY 4: , 2016

MOLECULAR AND CLINICAL ONCOLOGY 4: , 2016 MOLECULAR AND CLINICAL ONCOLOGY 4: 839-844, 2016 Clinical outcomes of anti androgen withdrawal and subsequent alternative anti-androgen therapy for advanced prostate cancer following failure of initial

More information

Eligard W 6: A New Form of Treatment for Prostate Cancer

Eligard W 6: A New Form of Treatment for Prostate Cancer european urology supplements 5 (2006) 905 910 available at www.sciencedirect.com journal homepage: www.europeanurology.com Eligard W 6: A New Form of Treatment for Prostate Cancer Oliver Sartor * Dana

More information

X, Y and Z of Prostate Cancer

X, Y and Z of Prostate Cancer X, Y and Z of Prostate Cancer Dr Tony Michele Medical Oncologist Prostate cancer Epidemiology Current EUA (et al) guidelines on Advanced Prostate Cancer Current clinical management in specific scenarios

More information

Medical management in locally advanced and metastatic prostate cancer: Does changes in treatment policy have any specific effect on PSA levels?

Medical management in locally advanced and metastatic prostate cancer: Does changes in treatment policy have any specific effect on PSA levels? ORIGINAL PAPER DOI: 10.4081/aiua.2017.4.282 Medical management in locally advanced and metastatic prostate cancer: Does changes in treatment policy have any specific effect on PSA levels? Murat Bagcioglu

More information

Lower Baseline PSA Predicts Greater Benefit From Sipuleucel-T

Lower Baseline PSA Predicts Greater Benefit From Sipuleucel-T Lower Baseline PSA Predicts Greater Benefit From Sipuleucel-T Schelhammer PF, Chodak G, Whitmore JB, Sims R, Frohlich MW, Kantoff PW. Lower baseline prostate-specific antigen is associated with a greater

More information

Division of Urologic Surgery and Duke Prostate Center (DPC), Duke University School of Medicine, Durham, NC

Division of Urologic Surgery and Duke Prostate Center (DPC), Duke University School of Medicine, Durham, NC LHRH AGONISTS: CONTEMPORARY ISSUES The Evolving Definition of Advanced Prostate Cancer Judd W. Moul, MD, FACS Division of Urologic Surgery and Duke Prostate Center (DPC), Duke University School of Medicine,

More information

BIOCHEMICAL RECURRENCE POST RADICAL PROSTATECTOMY

BIOCHEMICAL RECURRENCE POST RADICAL PROSTATECTOMY BIOCHEMICAL RECURRENCE POST RADICAL PROSTATECTOMY AZHAN BIN YUSOFF AZHAN BIN YUSOFF 2013 SCENARIO A 66 year old man underwent Robotic Radical Prostatectomy for a T1c Gleason 4+4, PSA 15 ng/ml prostate

More information

Updates in Prostate Cancer Treatment 2018

Updates in Prostate Cancer Treatment 2018 Updates in Prostate Cancer Treatment 2018 Mountain States Cancer Conference Elaine T. Lam, MD November 3, 2018 Learning Objectives Understand the difference between hormone sensitive and castration resistant

More information

The Return of My Cancer -Emerging Effective Therapies Jianqing Lin, MD

The Return of My Cancer -Emerging Effective Therapies Jianqing Lin, MD Februray, 2013 The Return of My Cancer -Emerging Effective Therapies Jianqing Lin, MD Why/How my cancer is back after surgery and/or radiation? Undetected micro-metastatic disease (spreading) before local

More information

Hormonal Treatment and other Options in men with locally Advanced Prostate Cancer. Seoul Veterans Hospital Department of Urology Tae Young Jung

Hormonal Treatment and other Options in men with locally Advanced Prostate Cancer. Seoul Veterans Hospital Department of Urology Tae Young Jung Hormonal Treatment and other Options in men with locally Advanced Prostate Cancer Seoul Veterans Hospital Department of Urology Tae Young Jung Introduction Watchful waiting / Androgen deprivation therapy

More information

2. The effectiveness of combined androgen blockade versus monotherapy.

2. The effectiveness of combined androgen blockade versus monotherapy. Relative effectiveness and cost-effectiveness of methods of androgen suppression in the treatment of advanced prostate cancer Blue Cross and Blue Shield Association, Aronson N, Seidenfeld J Authors' objectives

More information

www.drpaulmainwaring.com Figure 1 Androgen action Harris W P et al. (2009) Nat Clin Pract Urol doi:10.1038/ncpuro1296 Figure 2 Mechanisms of castration resistance in prostate cancer Harris W P et al. (2009)

More information

Management of castrate resistant disease: after first line hormone therapy fails

Management of castrate resistant disease: after first line hormone therapy fails Management of castrate resistant disease: after first line hormone therapy fails Rob Jones Consultant in Medical Oncology Beatson Cancer Centre Glasgow Rhona McMenemin Consultant in Clinical Oncology The

More information

High Risk Localized Prostate Cancer Treatment Should Start with RT

High Risk Localized Prostate Cancer Treatment Should Start with RT High Risk Localized Prostate Cancer Treatment Should Start with RT Jason A. Efstathiou, M.D., D.Phil. Assistant Professor of Radiation Oncology Massachusetts General Hospital Harvard Medical School 10

More information

Incorporating New Agents into the Treatment Paradigm for Prostate Cancer

Incorporating New Agents into the Treatment Paradigm for Prostate Cancer Incorporating New Agents into the Treatment Paradigm for Prostate Cancer Dr. Celestia S. Higano FACP, Professor, Medicine and Urology, Uni. of Washington Member, Fred Hutchinson Cancer Research Center

More information

Prostate Cancer: 2010 Guidelines Update

Prostate Cancer: 2010 Guidelines Update Prostate Cancer: 2010 Guidelines Update James L. Mohler, MD Chair, NCCN Prostate Cancer Panel Associate Director for Translational Research, Professor and Chair, Department of Urology, Roswell Park Cancer

More information

New Hope for Patients with Metastatic Hormone-Refractory Prostate Cancer

New Hope for Patients with Metastatic Hormone-Refractory Prostate Cancer european urology supplements 5 (2006) 817 823 available at www.sciencedirect.com journal homepage: www.europeanurology.com New Hope for Patients with Metastatic Hormone-Refractory Prostate Cancer Ronald

More information

When exogenous testosterone therapy is. adverse responses can be induced.

When exogenous testosterone therapy is. adverse responses can be induced. Theoretical tips It has been reasoned that discontinuation of ADT in non orchiectomized patients may have detrimental effect on patients with CRPC as discontinuation of ADT can result in renewed release

More information

New Treatment Modalities and Clinical Trials for HRPC 계명의대 김천일

New Treatment Modalities and Clinical Trials for HRPC 계명의대 김천일 New Treatment Modalities and Clinical Trials for HRPC 계명의대 김천일 Castrate-Resistant Prostate Cancer (CRPC) Current standard therapy Androgen receptor (AR) in CRPC New systemic therapies Hormonal therapy

More information

Name of Policy: Cellular Immunotherapy for Prostate Cancer

Name of Policy: Cellular Immunotherapy for Prostate Cancer Name of Policy: Cellular Immunotherapy for Prostate Cancer Policy #: 432 Latest Review Date: July 2014 Category: Medical Policy Grade: A Background/Definitions: As a general rule, benefits are payable

More information

Risk of renal side effects with ADT. E. David Crawford University of Colorado, Aurora, CO, USA

Risk of renal side effects with ADT. E. David Crawford University of Colorado, Aurora, CO, USA Risk of renal side effects with ADT E. David Crawford University of Colorado, Aurora, CO, USA ADT: A key treatment for advanced prostate cancer John Hunter 1780-castration 1904: First RP 1938: Acid Phos.

More information

Saad et al [12] Metastatic CRPC. Bhoopalam et al [14] M0 PCa on ADT <1 yr vs >1 yr ADT

Saad et al [12] Metastatic CRPC. Bhoopalam et al [14] M0 PCa on ADT <1 yr vs >1 yr ADT Evolution of Treatment Options for Patients with and Bone Metastases Trials of Treatments for Castration-Resistant Prostrate Cancer Mentioned in This Review Bisphosphonates (Zometa) 4 mg IV 8 mg IV ( to

More information

When PSA fails. Urology Grand Rounds Alexandra Perks. Rising PSA after Radical Prostatectomy

When PSA fails. Urology Grand Rounds Alexandra Perks. Rising PSA after Radical Prostatectomy When PSA fails Urology Grand Rounds Alexandra Perks Rising PSA after Radical Prostatectomy Issues Natural History Local vs Metastatic Treatment options 1 10 000 men / year in Canada 4000 RRP 15-year PSA

More information

METASTATIC PROSTATE CANCER MANAGEMENT K I R U B E L T E F E R A M. D. T R I H E A LT H C A N C E R I N S T I T U T E 0 1 / 3 1 /

METASTATIC PROSTATE CANCER MANAGEMENT K I R U B E L T E F E R A M. D. T R I H E A LT H C A N C E R I N S T I T U T E 0 1 / 3 1 / METASTATIC PROSTATE CANCER MANAGEMENT K I R U B E L T E F E R A M. D. T R I H E A LT H C A N C E R I N S T I T U T E 0 1 / 3 1 / 2 0 1 8 Prostate Cancer- Statistics Most common cancer in men after a skin

More information

17/07/2014. Prostate Cancer Watchful Waiting New Treatments Andrew Williams Urologist and Urological Oncologist ADHB, CMDHB and 161 Gillies Ave, Epsom

17/07/2014. Prostate Cancer Watchful Waiting New Treatments Andrew Williams Urologist and Urological Oncologist ADHB, CMDHB and 161 Gillies Ave, Epsom My Biases Prostate Cancer Watchful Waiting New Treatments Andrew Williams Urologist and Urological Oncologist ADHB, CMDHB and 161 Gillies Ave, Epsom I am a member of the specialist group of the Prostate

More information

Challenging Cases. With Q&A Panel

Challenging Cases. With Q&A Panel Challenging Cases With Q&A Panel Case Studies Index Patient #1 Jeffrey Wieder, MD Case # 1 72 year old healthy male with mild HTN Early 2011: Preop bone scan and pelvic CT = no mets Radical prostatectomy

More information

SESSIONE PLATINUM SERIES (Best Papers Poster o Abstract on Prostate Cancer) In Oncologia

SESSIONE PLATINUM SERIES (Best Papers Poster o Abstract on Prostate Cancer) In Oncologia SESSIONE PLATINUM SERIES (Best Papers Poster o Abstract on Prostate Cancer) In Oncologia Divisione di Oncologia Medica Unità Tumori Genitourinari SESSIONE PLATINUM SERIES (Best Papers Poster o Abstract

More information

National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) Trial design:

National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) Trial design: Open clinical uro-oncology trials in Canada Eric Winquist, MD, Mary J. Mackenzie, MD, George Rodrigues, MD London Health Sciences Centre, London, Ontario, Canada BLADDER CANCER A PHASE III STUDY OF IRESSA

More information

GUIDELINEs ON PROSTATE CANCER

GUIDELINEs ON PROSTATE CANCER GUIDELINEs ON PROSTATE CANCER (Text update March 2005: an update is foreseen for publication in 2010. Readers are kindly advised to consult the 2009 full text print of the PCa guidelines for the most recent

More information

2014 Treatment Paradigms in mcrpc Docetaxel in hormone sensitive PC

2014 Treatment Paradigms in mcrpc Docetaxel in hormone sensitive PC Ronald de Wit Erasmus MC Cancer Institute The Netherlands 2014 Treatment Paradigms in mcrpc Docetaxel in hormone sensitive PC Disclosures Sanofi ; research grant support, consultancy and speaker fees Astellas;

More information

The Prognostic Importance of Prostate-Specific Antigen in Monitoring Patients Undergoing Maximum Androgen Blockage for Metastatic Prostate Cancer

The Prognostic Importance of Prostate-Specific Antigen in Monitoring Patients Undergoing Maximum Androgen Blockage for Metastatic Prostate Cancer Research Article TheScientificWorldJOURNAL (005) 5, 8 4 ISSN 57-744X; DOI 0.00/tsw.005.9 The Prognostic Importance of Prostate-Specific Antigen in Monitoring Patients Undergoing Maximum Androgen Blockage

More information

ADT vs chemo + ADT as initial treatment for advanced prostate cancer

ADT vs chemo + ADT as initial treatment for advanced prostate cancer ADT vs chemo + ADT as initial treatment for advanced prostate cancer By Hussein Khaled Prof. Medical Oncology Cairo University Possible Levels of Prostate Cancer At Diagnosis Local-Regional Disease Spread

More information

Management Options in Advanced Prostate Cancer: What is the Role for Sipuleucel-T?

Management Options in Advanced Prostate Cancer: What is the Role for Sipuleucel-T? Clinical Medicine Insights: Oncology Consise Review Open Access Full open access to this and thousands of other papers at http://www.la-press.com. Management Options in Advanced Prostate Cancer: What is

More information

J Clin Oncol 23: by American Society of Clinical Oncology INTRODUCTION

J Clin Oncol 23: by American Society of Clinical Oncology INTRODUCTION VOLUME 23 NUMBER 28 OCTOBER 1 2005 JOURNAL OF CLINICAL ONCOLOGY O R I G I N A L R E P O R T Predictors of Prostate Cancer Specific Mortality After Radical Prostatectomy or Radiation Therapy Ping Zhou,

More information

Manipulating Hormones: Androgen Suppression in Prostate Cancer Patients

Manipulating Hormones: Androgen Suppression in Prostate Cancer Patients Focus on CME at the University of Queen s ManitobaUniversity Manipulating Hormones: Androgen Suppression in ostate Cancer Patients By D. Robert Siemens, MD, FRCSC Case A 62-year old man presents with complaints

More information

Radical Prostatectomy: Management of the Primary From Localized to Oligometasta:c Disease

Radical Prostatectomy: Management of the Primary From Localized to Oligometasta:c Disease Radical Prostatectomy: Management of the Primary From Localized to Oligometasta:c Disease Disclosures I do not have anything to disclose Sexual function causes moderate to severe distress 2 years after

More information

Cost-effectiveness of androgen suppression therapies in advanced prostate cancer Bayoumi A M, Brown A D, Garber A M

Cost-effectiveness of androgen suppression therapies in advanced prostate cancer Bayoumi A M, Brown A D, Garber A M Cost-effectiveness of androgen suppression therapies in advanced prostate cancer Bayoumi A M, Brown A D, Garber A M Record Status This is a critical abstract of an economic evaluation that meets the criteria

More information

Initial hormone therapy (and more) for metastatic prostate cancer

Initial hormone therapy (and more) for metastatic prostate cancer Initial hormone therapy (and more) for metastatic prostate cancer Silke Gillessen, MD Medical Oncology Kantonsspital St.Gallen Switzerland silke.gillessen@kssg.ch Conflicts of interest Speakers Bureau

More information

Since the beginning of the prostate-specific antigen (PSA) era in the. Characteristics of Insignificant Clinical T1c Prostate Tumors

Since the beginning of the prostate-specific antigen (PSA) era in the. Characteristics of Insignificant Clinical T1c Prostate Tumors 2001 Characteristics of Insignificant Clinical T1c Prostate Tumors A Contemporary Analysis Patrick J. Bastian, M.D. 1 Leslie A. Mangold, B.A., M.S. 1 Jonathan I. Epstein, M.D. 2 Alan W. Partin, M.D., Ph.D.

More information

TREATMENT OPTIONS FOR LOCALIZED PROSTATE CANCER: QUALITY-ADJUSTED LIFE YEARS AND THE EFFECTS OF LEAD-TIME

TREATMENT OPTIONS FOR LOCALIZED PROSTATE CANCER: QUALITY-ADJUSTED LIFE YEARS AND THE EFFECTS OF LEAD-TIME ADULT UROLOGY TREATMENT OPTIONS FOR LOCALIZED PROSTATE CANCER: QUALITY-ADJUSTED LIFE YEARS AND THE EFFECTS OF LEAD-TIME VIBHA BHATNAGAR, SUSAN T. STEWART, WILLIAM W. BONNEY, AND ROBERT M. KAPLAN ABSTRACT

More information

Efficacy of Taxotere, Thalidomide, and Prednisolone in Patients with Hormone- Resistant Metastatic Prostate Cancer

Efficacy of Taxotere, Thalidomide, and Prednisolone in Patients with Hormone- Resistant Metastatic Prostate Cancer Efficacy of Taxotere, Thalidomide, and Prednisolone in Patients with Hormone- Resistant Metastatic Prostate Cancer Hamid Rezvani, Shirin Haghighi, Mojtaba Ghadyani, Hamid Attarian UROLOGICAL ONCOLOGY Taleghani

More information

To treat or not to treat: When to treat! A case presentation

To treat or not to treat: When to treat! A case presentation To treat or not to treat: When to treat! A case presentation Filip Ameye, MD,Phd Universitary Hospitals Leuven, Belgium Departement of Urology Prostate Center A case presentation Pt. 76 y. Mild LUTS (07/1999)

More information

Intermittent Androgen Suppression - A standard of care or a good second choice?

Intermittent Androgen Suppression - A standard of care or a good second choice? Intermittent Androgen Suppression - A standard of care or a good second choice? Dr Nicholas Buchan Uro-oncology Fellow Olympic Medal Standings Gold Silver Bronze USA 9 15 13 Germany 10 13 7 Canada 14 7

More information

Joelle Hamilton, M.D.

Joelle Hamilton, M.D. Joelle Hamilton, M.D. www.urologycentersalabama.com Case Presentation: CRPC, Rising PSA 70 yo healthy, fit, active man post RALP 8 years prior with rising PSA Rising PSA from 0.02 nadir to 3.4 thus ADT

More information

SIMPOSIO. Radioterapia stereotassica e nuovi farmaci nel tumore e della prostata metastatico

SIMPOSIO. Radioterapia stereotassica e nuovi farmaci nel tumore e della prostata metastatico SIMPOSIO Radioterapia stereotassica e nuovi farmaci nel tumore e della prostata metastatico Definition of Oligometastatic PCa 1-3 synchronous metastases (bone and/or lymph nodes) 2-5 synchronous metastases

More information

Preoperative Gleason score, percent of positive prostate biopsies and PSA in predicting biochemical recurrence after radical prostatectomy

Preoperative Gleason score, percent of positive prostate biopsies and PSA in predicting biochemical recurrence after radical prostatectomy JBUON 2013; 18(4): 954-960 ISSN: 1107-0625, online ISSN: 2241-6293 www.jbuon.com E-mail: editorial_office@jbuon.com ORIGINAL ARTICLE Gleason score, percent of positive prostate and PSA in predicting biochemical

More information

Open clinical uro-oncology trials in Canada George Rodrigues, MD, Mary J. Mackenzie, MD, Eric Winquist, MD

Open clinical uro-oncology trials in Canada George Rodrigues, MD, Mary J. Mackenzie, MD, Eric Winquist, MD Open clinical uro-oncology trials in Canada George Rodrigues, MD, Mary J. Mackenzie, MD, Eric Winquist, MD London Health Sciences Centre, London, Ontario, Canada BLADDER CANCER A MULTICENTRE, RANDOMIZED

More information

Philip Kantoff, MD Dana-Farber Cancer Institute

Philip Kantoff, MD Dana-Farber Cancer Institute CHEMOTHERAPY FOR MCRPC Philip Kantoff, MD Dana-Farber Cancer Institute Harvard Medical School 1 Disclosure of Financial Relationships With Any Commercial Interest Name Nature of Financial Commercial Interests

More information

Sequencing Strategies in Metastatic Castration Resistant Prostate Cancer (MCRPC)

Sequencing Strategies in Metastatic Castration Resistant Prostate Cancer (MCRPC) Sequencing Strategies in Metastatic Castration Resistant Prostate Cancer (MCRPC) Amit Bahl Consultant Oncologist Bristol Cancer Institute Clinical Director Spire Specialist Care Centre UK Disclosures Advisory

More information

Management of Prostate Cancer

Management of Prostate Cancer Management of Prostate Cancer An ESMO Perspective Alan Horwich Conflicts of Interest Disclosure Alan Horwich I have no personal conflicts of interest relating to prostate cancer. European Incidence and

More information

Radiation with oral hormonal manipulation for non-metastatic, intermediate or high risk prostate cancer in men 70 and older or with comorbidities

Radiation with oral hormonal manipulation for non-metastatic, intermediate or high risk prostate cancer in men 70 and older or with comorbidities Radiation with oral hormonal manipulation for non-metastatic, intermediate or high risk prostate cancer in men 70 and older or with comorbidities Prostate cancer is predominately a disease of older men,

More information

Cabazitaxel (XRP-6258) for hormone refractory, metastatic prostate cancer second line after docetaxel

Cabazitaxel (XRP-6258) for hormone refractory, metastatic prostate cancer second line after docetaxel Cabazitaxel (XRP-6258) for hormone refractory, metastatic prostate cancer second line after docetaxel April 2009 This technology summary is based on information available at the time of research and a

More information

January Abiraterone pre-docetaxel for patients with asymptomatic or minimally symptomatic metastatic castration resistant prostate cancer

January Abiraterone pre-docetaxel for patients with asymptomatic or minimally symptomatic metastatic castration resistant prostate cancer LONDON CANCER NEW DRUGS GROUP RAPID REVIEW Abiraterone pre-docetaxel for asymptomatic/minimally symptomatic metastatic castration resistant prostate cancer Abiraterone pre-docetaxel for patients with asymptomatic

More information

Open clinical uro-oncology trials in Canada Eric Winquist, MD, George Rodrigues, MD

Open clinical uro-oncology trials in Canada Eric Winquist, MD, George Rodrigues, MD Open clinical uro-oncology trials in Canada Eric Winquist, MD, George Rodrigues, MD London Health Sciences Centre, London, Ontario, Canada BLADDER CANCER A MULTICENTRE, RANDOMIZED PLACEBO-CONTROLLED, DOUBLE-BLIND

More information

HOW I DO IT. Introduction. BARKIN J. How I Do It: Managing bone health in patients with prostate cancer. Can J Urol 2014;21(4):

HOW I DO IT. Introduction. BARKIN J. How I Do It: Managing bone health in patients with prostate cancer. Can J Urol 2014;21(4): HOW I DO IT How I Do It: Managing bone health in patients with prostate cancer Jack Barkin, MD Department of Surgery, University of Toronto, Humber River Hospital, Toronto, Ontario, Canada BARKIN J. How

More information

In autopsy, 70% of men >80yr have occult prostate ca

In autopsy, 70% of men >80yr have occult prostate ca Prostate Cancer UpToDate: Introduction: Risk Factors: Biology: Symptoms: Diagnosis: Two randomized trials showed survival benefit of adding docetaxol to ADT in fit man with very high localized disease

More information

Elsevier Editorial System(tm) for European Urology Manuscript Draft

Elsevier Editorial System(tm) for European Urology Manuscript Draft Elsevier Editorial System(tm) for European Urology Manuscript Draft Manuscript Number: EURUROL-D-13-00306 Title: Post-Prostatectomy Incontinence and Pelvic Floor Muscle Training: A Defining Problem Article

More information

Sequencing treatment for metastatic prostate cancer

Sequencing treatment for metastatic prostate cancer 11 Sequencing treatment for metastatic prostate cancer SOPHIE MERRICK, STYLIANI GERMANOU, ROGER KIRBY AND SIMON CHOWDHURY In the past 10 years there have been significant advances in the understanding

More information

Guidelines for the Management of Prostate Cancer West Midlands Expert Advisory Group for Urological Cancer

Guidelines for the Management of Prostate Cancer West Midlands Expert Advisory Group for Urological Cancer Guidelines for the Management of Prostate Cancer West Midlands Expert Advisory Group for Urological Cancer West Midlands Clinical Networks and Clinical Senate Coversheet for Network Expert Advisory Group

More information

Prostate-specific antigen half-life: a new predictor of progressionfree survival and overall survival in Chinese prostate cancer patients

Prostate-specific antigen half-life: a new predictor of progressionfree survival and overall survival in Chinese prostate cancer patients Original Article Asian Journal of Andrology (2009) 11: 443 450 2009 AJA, SIMM & SJTU All rights reserved 1008-682X/09 $ 32.00 www.nature.com/aja npg 443 : a new predictor of progressionfree survival and

More information

Challenges in the management of metastatic prostate cancer

Challenges in the management of metastatic prostate cancer Oncology 323 Challenges in the management of metastatic prostate cancer A significant number of men with prostate cancer will be elderly. Although some of the issues they face will be the same as their

More information

Edward P. Gelmann, MD

Edward P. Gelmann, MD Prostate Cancer Edward P. Gelmann, MD Prostate Cancer Etiology and Ep pidemiology Screening Pathology Staging Localized Disease Metastatic Disease normal prostate epithelium GSTP1 CpG island hypermethylation

More information

Impact of Adjuvant Androgen-Deprivation Therapy on Disease Progression in Patients with Node-Positive Prostate Cancer

Impact of Adjuvant Androgen-Deprivation Therapy on Disease Progression in Patients with Node-Positive Prostate Cancer www.kjurology.org http://dx.doi.org/10.4111/kju.2011.52.11.741 Urological Oncology Impact of Adjuvant Androgen-Deprivation Therapy on Disease Progression in Patients with Node-Positive Prostate Cancer

More information

Adjuvant Docetaxel and Abbreviated Androgen Deprivation Therapy in Patients with High Risk Prostate Cancer

Adjuvant Docetaxel and Abbreviated Androgen Deprivation Therapy in Patients with High Risk Prostate Cancer The Open Prostate Cancer Journal, 21, 3, 9914 99 Open Access Adjuvant Docetaxel and Abbreviated Androgen Deprivation Therapy in Patients with High Risk Prostate Cancer Jose G. Bazan, Christopher R. King,

More information

PSA Screening and Prostate Cancer. Rishi Modh, MD

PSA Screening and Prostate Cancer. Rishi Modh, MD PSA Screening and Prostate Cancer Rishi Modh, MD ABOUT ME From Tampa Bay Went to Berkeley Prep University of Miami for Undergraduate - 4 years University of Miami for Medical School - 4 Years University

More information

Early Chemotherapy for Metastatic Prostate Cancer

Early Chemotherapy for Metastatic Prostate Cancer Early Chemotherapy for Metastatic Prostate Cancer Daniel P. Petrylak, MD Professor of Medicine and Urology Smilow Cancer Center Yale University Medical Center Disclosure Consultant: Sanofi Aventis, Celgene,

More information

Outcomes of Radical Prostatectomy in Thai Men with Prostate Cancer

Outcomes of Radical Prostatectomy in Thai Men with Prostate Cancer Original Article Outcomes of Radical Prostatectomy in Thai Men with Prostate Cancer Sunai Leewansangtong, Suchai Soontrapa, Chaiyong Nualyong, Sittiporn Srinualnad, Tawatchai Taweemonkongsap and Teerapon

More information

Changes in prostate-specific antigen and hormone levels following withdrawal of prolonged androgen ablation for prostate cancer

Changes in prostate-specific antigen and hormone levels following withdrawal of prolonged androgen ablation for prostate cancer Changes in prostate-specific antigen and hormone levels following withdrawal of prolonged androgen ablation for prostate cancer S Egawa 1 *, H Okusa 1, K Matsumoto 1, K Suyama 1 & S Baba 1 1 Department

More information

Castrate resistant prostate cancer: the future of anti-androgens.

Castrate resistant prostate cancer: the future of anti-androgens. Castrate resistant prostate cancer: the future of anti-androgens. Dmitri Pchejetski 1,2*, Heba Alshaker 3, Justin Stebbing 3,4* 1. Department of Medicine, Imperial College, London, UK 2. School of Medicine,

More information

Prostate Cancer UK Best Practice Pathway: ACTIVE SURVEILLANCE

Prostate Cancer UK Best Practice Pathway: ACTIVE SURVEILLANCE Prostate Cancer UK Best Practice Pathway: ACTIVE SURVEILLANCE Low risk localised PSA < 10 ng/ml and Gleason score 6, and clinical stage T1 - T2a Intermediate risk localised PSA 10-20 ng/ml, or Gleason

More information

Early detection the key to prostate cancer

Early detection the key to prostate cancer Early detection the key to prostate cancer Kirby R. Early detection the key to prostate cancer. The Practitioner 2009;253 (1715):17 22 Professor Roger Kirby MA MD FRCS Director, The Prostate Centre, London

More information

Prostate Cancer UK s Best Practice Pathway

Prostate Cancer UK s Best Practice Pathway Prostate Cancer UK s Best Practice Pathway TREATMENT Updated August 2018 To be updated in vember Active surveillance What is the patient s stage of disease? Low risk localised PSA < 10 ng/ml and Gleason

More information

Subject Index. Androgen antiandrogen therapy, see Hormone ablation therapy, prostate cancer synthesis and metabolism 49

Subject Index. Androgen antiandrogen therapy, see Hormone ablation therapy, prostate cancer synthesis and metabolism 49 OOOOOOOOOOOOOOOOOOOOOOOOOOOOOO Subject Index Androgen antiandrogen therapy, see Hormone ablation therapy, synthesis and metabolism 49 Bacillus Calmette-Guérin adjunct therapy with transurethral resection

More information