Differences in early diagnosis and management of patients with high-risk localized disease can play an important role in cancer outcomes, says Christine Geffriaud-Ricouard, MD, Medical Director, Sanofi Oncology
Prostate cancer is the most frequently diagnosed cancer in men in Europe . Despite screening efforts with PSA testing, its mortality remains the third highest (after lung and colon) and is only marginally decreasing . Moreover, registries consistently highlight significant disparities in cancer outcomes across Europe, Eastern countries such as Bulgaria, Latvia, Poland and Slovakia showing the worst prostate cancer survival rate at 5 years .
This is linked to differences in access to quality care and resources allocated to it – lower mortality rates being observed in countries with the highest health care expenditure [4-5] and lack of Comprehensive National Cancer Control Plan. Differences in early diagnosis and management of patients with high-risk localized disease also play an important role in cancer outcomes. Hence, survival at 5-years appears related to an early diagnosis – at a stage it is still curable – and treatment with curative intent (radical prostatectomy or radiation therapy) of patients with high-risk disease .
Undertreatment of high-risk disease appears even more pronounced in senior adults (ie men aged ≥ 70 years). This is mainly due to the fact that many physicians still consider the age of the patients rather that their health status (mainly driven by comorbidities) in their decision making process . With the increasing life expectancy and an ageing population in all European countries, it is important to keep in mind the SIOG recommendations that fit and vulnerable senior adults (ie who have a chance of surviving for 10 years) diagnosed with high-risk localized prostate cancer are likely to benefit from treatment with curative intent . At an advanced stage of the disease, inequities in availability and access to life-extending therapies are also an issue since survival increases with the number of such therapies received.
Hence, in randomized controlled studies, median overall survival of patients with metastatic castration-resistant prostate cancer (mCRPC) has progressively increased from 12.6 months with prednisone alone in the 1990s  to 18.9 months with docetaxel plus prednisone in 2004  and approximately 30 months in 2010-2011 when a second life-extending therapy was prescribed after docetaxel (either cabazitaxel or an new androgen-receptor (AR)-targeted tagent) [10-11]. According to a recent retrospective registry, overall survival may be even more impressive in patients receiving 2 consecutive life-extending therapies (cabazitaxel AR-targeted agent or vice versa) after docetaxel .
Recently, two large cooperative group studies have demonstrated that the benefit of chemotherapy on survival is even more pronounced when it is given at an earlier stage, in newly diagnosed, hormone naïve, metastatic patients [13-14]. Compared to androgen deprivation therapy alone (ADT), the combination of ADT plus docetaxel (6 cycles) prolonged survival by a median of 14 months in CHAARTED  and 22 months in STAMPEDE . his unprecedented survival benefit was observed despite the fact that a majority of patients received life-extending therapies at progression in both arms. The rationale is that prostate cancer is highly heterogeneous with coexistence of tumor cells who respond and others who do not respond to ADT.
Adding chemotherapy to ADT allows blocking proliferation of lethal clones which do not respond to ADT resulting in a prolonged survival.
Docetaxel (6 cycles) plus ADT is now recommended as first-line treatment of metastatic, hormone-naïve disease in men fit enough for chemotherapy by European guidelines (level 1 evidence) . Docetaxel is available as a generic in all European countries at a low cost.
However, since these trials were conducted by cooperative groups and thus were not specifically designed to fulfill registration requirements, many Eastern Europe countries will not be able to prescribe docetaxel in this off-label setting. Moreover, multidisciplinary team (MDT) management of patients is not a standard and may slowdown the introduction of these important data in the clinic.
Management of prostate cancer is complex
Therefore involvement of all appropriate specialties in a multidisciplinary team (including but not restricted to medical, radiation, surgical oncologists, imaging experts, pathologists, psycho-oncologists, social workers, nurses, and palliative care specialists) is crucial to ensure that patients get the right treatment at the right time, in agreement with the best level of evidence and improve cancer outcomes .
MDT has been identified as a key element in cancer care by the European Partnership for Action Against Cancer (EPAAC), launched by the European Commission in 2009. It contributes to improve quality of disease management, from diagnosis to follow-up, making cancer care more tailored to individuals and subsequently more effective in addressing patient needs and improving outcomes .
In February 2014, a Bill of Rights for patients with cancer in Europe was launched at the European Parliament on World Cancer Day, in partnership with European cancer patient organizations and Members of the European Parliament Against Cancer (MEPs Against Cancer) .
The aim of this Bill of Rights is to enable each European citizen to receive an optimum standard of care across the cancer continuum and includes 3 key principles: (1) the right of every European citizen to receive accurate information and be involved in their own care; (2) the right of every European citizen to access specialised cancer care underpinned by research and innovation; and (3) the right of every European citizen to cost-effective health systems that ensure optimum cancer outcomes
The Thalinn Charter signed in 2008 by member states of the WHO in the European region committed to improve health care systems in Europe and clearly stipulated that high performing health systems contribute to economic development and wealth by saving lives .
We do hope politicians will empower this European Cancer Patient’s Bill of Rights and make Thalinn charter commitments effectively happen to reduce cancer care inequities across Europe
1. Ferlay J et al. Cancer incidence and mortality patterns in Europe: Estimates for 40 countries in 2012. Eur J Cancer 2013; 49: 1374-1403
2. Malvezzi M et al. European cancer mortality predictions for the year 2015: does lung cancer have the highest death rate in EU women? Ann. Oncol. 2015: 26: 779–786.
3. De Angelis et al. Cancer survival in Europe 1999–2007 by country and age: results of EUROCARE-5—a population-based study. Lancet Oncol 2014; 15: 23–34
4. Ades F et al. Discrepancies in cancer incidence and mortality and its relationship to health expenditure in the 27 EuropeanUnion member states. Annals Oncol 2013; 24: 2897-902
5. Gatta G et al. Variations in cancer survival and patterns of care across Europe: Roles of wealth and health-care organization. J Natl Cancer Inst Monogr 2013;46:79–87
6. De Camargo Cancela M et al. Age remains the major predictor of curative treatment non-receipt for localised prostate cancer: a population-based study. Br J. Cancer 2013; 109, 272–279.
7. Droz JP et al. Management of prostate cancer in older patients: updated recommendations of a working group of the International Society of Geriatric Oncology. Lancet Oncol 2014; 15: e404–14.
8. Kantoff PW et al. Hydrocortisone with or without mitoxantrone in men with hormone-refractory prostate cancer: results of the Cancer and Leukemia Group B 9182 study. J Clin Oncol 1999; 17: 2506-2513
9. Tannock IF et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med 2004; 351: 1502-12
10. Sartor O et al. Survival benefit from first docetaxel treatment for cabazitaxel plus prednisone compared with mitoxantrone plus prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC) enrolled in the TROPIC trial. J Clin Oncol 2011; 29 (suppl); abstr 4525
11. Fizazi K et al. Abiraterone acetate for treatment of metastatic castration-resistant prostate cancer: final overall survival analysis of the COU-AA-301 randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol 2012;13:983-92
12. Oudard S et al. Updated results of the FLAC European database of metastatic castration resistant prostate cancer (mCRPC) patients treated with life extending therapies in post-docetaxel setting. Eur J Cancer 2015; 51 (suppl); abstract 2541.
13. Sweeney C et al. Chemohormonal therapy in hormone-sensitive metastatic prostate cancer: An ECOG-led phase III randomized trial. N Engl J Med 2015 (epub ahead of print).
14. James N et al Docetaxel and/or zoledronic acid for hormone-naïve prostate cancer: First overall survival results from STAMPEDE (NCT00268476). J Clin Oncol 2015; 33 (suppl): abstract 5001.
15. C. Parker et al. Cancer of the prostate: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2015 (epub ahead of print). doi: 10.1093/annonc/mdv222
16. European Partnership Action Against Cancer consensus group. Policy statement on multidisciplinary cancer care. Eur J Cancer 2014; 50: 475– 480
17. Mark Lawler et al. A Bill of Rights for patients with cancer in Europe. Lancet 2014; 15: 258-60
18. WHO. The Tallinn Charter: health systems for health and wealth. Tallinn: WHO Regional Office for Europe, 2008. http://www.euro.who.int/__data/assets/pdf_file/0008/88613/E91438.pdf (access July 30 2015)