Volume 8, Issue 12, Pages 839-842 (December 2009)

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ABSTRACT

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Prostate Cancer: Closing the Gap Between Science and Practice — Introduction and Conclusions

published online 18 September 2009.

Take Home Message

This paper summarises the lectures held at a symposium during the European Association of Urology congress in March 2009 in Stockholm, Sweden. Different topics on prostate cancer were discussed, including neoadjuvant or adjuvant hormone therapy, intermittent hormone therapy, and patients’ quality of life.

Article Outline

• Take Home Message

• 1. Introduction

• 2. Discussion

• 2.1. Oncoforum Urology: highlights on prostate cancer

• 2.2. Who benefits from neoadjuvant or adjuvant hormone therapy?

• 2.3. Intermittent hormone therapy: What is its place in clinical practice?

• 2.4. Improving flexibility and quality of life for your patients: a must?

• Conflicts of interest

• Funding support

• Acknowledgment

• References

• Copyright

1. Introduction

Prostate cancer (PCa) is recognised as one of the most important health problems facing the male population. Worldwide, PCa is the most frequently diagnosed male cancer [1], [2]; however, a large number of cancers from the prostate are often not clinically significant or aggressive. In 2006, the number of patients who died from PCa was approximately a quarter of the number of newly diagnosed cases in Europe that year [1]. These data highlight the importance of early detection of PCa and the ongoing need to optimise and further improve the management of PCa.

Androgen deprivation therapy (ADT) has become the mainstay treatment in patients with advanced PCa (ie, locally advanced and metastatic PCa). In recent years, ADT has been used in younger patients with earlier disease stages, for instance, as adjuvant treatment with radiotherapy (RT) [3]. ADT, however, is associated with substantial adverse events, such as hot flushes, sexual problems, fatigue, psychological problems, and metabolic syndrome, that may adversely affect a patient's quality of life (QoL) [3]. Intermittent hormone therapy (IHT) has gained interest as an alternative to continuous hormone therapy for advanced PCa, with the aim of reducing adverse events and improving QoL [3], [4], [5]. Generally, physicians should carefully weigh the benefits against the potential risks of ADT in patients with PCa. Additionally, patients should be well informed about the treatment approach and its potential adverse events.

During the symposium “Prostate cancer: Closing the gap between science and practice”, five experts discussed recent findings related to PCa treatment, particularly hormone therapy. They first discussed recent data on the detection and management of PCa that were retrieved from abstracts presented at urological and oncological congresses in 2008 and were critically selected by urological experts. The current status of neoadjuvant or adjuvant hormone therapy to local treatment in the management of PCa was summarised. Scientific evidence on IHT and recommendations on how to implement IHT in clinical practice were presented. Lastly, they discussed several aspects considered important in the maintenance or improvement of the QoL of PCa patients treated with ADT. This manuscript introduces and summarises the presentations given at a satellite symposium on PCa that was held during the 24th annual congress of the European Association of Urology (EAU) in March 2009 in Stockholm, Sweden.

2. Discussion

2.1. Oncoforum Urology: highlights on prostate cancer

Many new findings on PCa were presented at the 2008 annual congresses of the EAU, the American Urological Association (AUA), the American Society of Clinical Oncology (ASCO), and the American Society for Therapeutic Radiology and Oncology (ASTRO).

Presenter Prof. Mottet summarised the highlights on PCa from these urological and oncological congresses. Pelvic lymphadenectomy is a controversial topic with regard to patients with low-risk PCa undergoing radical prostatectomy (RP). According to a study presented at the AUA annual congress, the frequency of lymph node metastases appears low in patients with low-risk PCa and the percentage positive biopsy cores can be used to predict nodal disease [6]. Hence, in patients with low-risk PCa undergoing surgery, the diagnostic benefit of extended pelvic lymph node dissection is disputed. Two studies presented at the EAU annual meeting demonstrated that appropriately selected patients with low-risk PCa might be safely managed by active surveillance [7], [8]. Furthermore, it is still unclear whether the risk of developing secondary malignancies (eg, bladder cancer) increases after primary RT of PCa [9], [10], [11]. Confounding factors such as smoking should be taken into consideration before drawing final conclusions. With regard to locally advanced PCa, the updated randomized phase 3 Southwest Oncology Group (SWOG) trial protocol 8794 confirmed that adjuvant RT to RP decreases the risk of recurrence in men with pathologic T3 PCa [12]. Moreover, adjuvant RT to surgery significantly reduced the risk of metastases and improved overall survival [12], [13]. Lastly, several phase 1/2 studies presented at the ASCO annual meeting showed that abiraterone acetate seems to be well tolerated and effective in patients with castration-resistant PCa (CRPC), even in those experiencing disease progression on ketoconazole [14], [15], [16]. Some of these interesting new data may have an impact on clinical practice, whereas other findings raise new questions that will have to be answered by further research.

2.2. Who benefits from neoadjuvant or adjuvant hormone therapy?

There is an increasing interest in the use of neoadjuvant or adjuvant hormone therapy to local treatment for the management of patients with PCa, but the issue of who may benefit from such therapy is still open. Presenter Prof. Bossi summarised evidence showing that neoadjuvant hormone therapy to RP does not provide a survival benefit over surgery alone in patients with localised or locally advanced PCa [17]. Moreover, besides biopsy Gleason grade, prostate-specific antigen, and year of surgery, neoadjuvant hormone therapy seems to have a detrimental effect on PCa-specific survival [18]. With regard to RT, neoadjuvant hormone therapy appears to statistically significantly improve treatment outcomes, except overall survival, over RT alone in patients with locally advanced PCa [19]. No differences in the risk of fatal cardiac events were observed between the treatment groups. A number of large randomised phase 3 studies have shown that adjuvant hormone therapy to RT increases overall survival compared with RT alone in patients with high-risk localised or locally advanced PCa [20], [21], [22], [23]. The added value of hormone therapy to RT, however, may pertain only to patients with no or minimal comorbidity [24]. A longer duration of adjuvant hormone therapy seems superior to short-term adjuvant hormone therapy to RT, especially in patients with high-risk PCa [25], [26]. Overall, neoadjuvant or adjuvant hormone therapy to RT may improve treatment outcomes (eg, overall survival, distant metastases, and local failure) in appropriately selected patients with PCa.

2.3. Intermittent hormone therapy: What is its place in clinical practice?

Intermittent hormone therapy, in which on-treatment periods are alternated with off-treatment periods, aims to minimise adverse events, to maintain or improve QoL, and to delay progression to CRPC [4], [5]. Questions exist about whether use of IHT is supported by scientific evidence and how it should be applied in clinical practice. Based on findings from clinical phase 2 trials [27], [28], [29] and final or preliminary results from phase 3 trials [30], [31], [32], [33], Presenter Prof. Schulman highlighted that IHT appears to have a beneficial effect on the incidence of treatment-related adverse events, QoL, and health care costs, without a negative impact on overall or progression-free survival. Further research is warranted to demonstrate that IHT prolongs the time to CRPC. Additionally, more data are needed to provide guidance on how IHT should be applied in clinical practice.

2.4. Improving flexibility and quality of life for your patients: a must?

Because ADT has a significant impact on the QoL of PCa patients, QoL is an important factor to be considered before and during the implementation of ADT. How can we make sure that the risks of ADT do not outweigh the benefits—in other words, how can we maintain or even improve QoL of patients receiving ADT? Presenter Prof. Heidenreich stressed that effective and open communication between the patient and the physician will ensure that a patient is well informed about the treatment and the potential adverse events [34], [35].

Additionally, successful patient-centred communication may enhance the patient's well-being [36]. To prevent or manage adverse events, measures should be taken before and during initiation of ADT [37], [38], [39]. Integrating the patient's expectations, preferences, and needs into daily clinical practice will ensure well-informed decisions, which may minimise future regret and improve the patient's satisfaction with treatment [36], [40]. A treatment such as the luteinising hormone-releasing hormone agonist Eligard®—available in 1-, 3-, and 6-mo depot formulations, enabling administration at different time intervals [41], [42], [43]—offers patients flexibility and is another tool for improving their QoL.

Conflicts of interest

The author has nothing to disclose.

Funding support

The publication of this review was supported by Astellas Pharma Europe Ltd.

Acknowledgements

The author is grateful to Ismar Healthcare NV for assistance in writing of the manuscript.

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doi:10.1016/j.eursup.2009.08.005

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