Adjuvant Androgen Deprivation Therapy Augments Cure
Adjuvant Androgen Deprivation Therapy Augments Cure
Historically, adjuvant androgen deprivation therapy has been viewed as a palliative treatment option for patients with poor-prognosis non-metastatic prostate cancer. In addition, guidelines from bodies such as the European Association of Urology and American Society for Clinical Oncology do not specifically categorize adjuvant hormonal therapy as being curative in intent. We propose that adjuvant androgen deprivation therapy should now be classified as a treatment of curative intent in patients with poor-prognosis, non-metastatic prostate cancer. By applying a carefully considered definition of cure (based on long-term (10- to 15-year) disease-free survival curves) to the findings from randomized controlled clinical trials that have studied adjuvant hormonal treatments in non-metastatic prostate cancer, we challenged whether this viewpoint should now be considered redundant. According to our review of relevant studies and our definition of cure, goserelin appears to augment cure in a sizeable proportion of men with poor-prognosis non-metastatic prostate cancer when given adjuvant to radical prostatectomy or radiotherapy. Across several trials, the relevant survival curves for the goserelin-treated population became indefinitely flat after long-term follow-up. This indicates that these patients have a mortality risk comparable to the general population without prostate cancer. On the basis of the evidence presented within this review, we believe that, given it can control disease for a long period of time, adjuvant goserelin should be reclassified as a treatment of curative intent for patients with poor-prognosis non-metastatic prostate cancer.
Physicians managing patients with cancer seek to permanently rid their patients of the disease. However, current technology makes it difficult to determine whether a patient is entirely free of cancer. Although physical signs of the tumor, including imaging tests and biological markers, may be negative, it is usually impossible to determine if all remnants of the disease have been eradicated. Because of these uncertainties, oncologists are very reluctant to use the term 'cure'. As the understanding of cancer biology continues to evolve, it is increasingly evident that the concept of cure is somewhat nave. Patients may live with existing cancer cells for decades and increasingly sensitive markers are identifying residual or recurrent disease many years prior to clinical manifestation. Many patients with treated, but not cured cancers, die of other diseases, rendering the concept even more confusing. This may lead to a situation where long-term control of disease is of clinical importance.
In the 1970s, Frei and Gehan outlined a definition of cure in the setting of cancer, which proposed that cure exists among a group of disease-free survivors whose progressive death rate from all causes is similar to that of an age- and sex-matched population. This concept first led to 5-year survival rates becoming widely accepted as an indication of the success of a cancer treatment. However, over the past 30 years, earlier detection, improved therapies and better data acquisition have made the 5-year survival concept obsolete for many cancers. This is particularly evident with relatively slow-growing tumors such as prostate cancer, when life may not be threatened by the disease for 10-20 years. In these cases, a longer-term view is required to establish whether treatment results in adequate long-term control, leading to cure of the disease.
In contrast to physicians, many patients with cancer have high expectations of treatment and are desirous to know whether a given treatment will offer them cure. Although 'cure' may be too definitive a word to use in discussions with patients, it is nonetheless referred to in the lay literature and in patient/patient and patient/family discussions.
For certain stages of some cancers including genitourinary cancers, cure is becoming a reality. Although general opinion is that patients with poor-prognosis non-metastatic prostate cancer cannot be cured, results from recent studies have prompted re-evaluation of this belief. The aim of this review is to examine the concept of cure in genitourinary cancers and focus on the role of adjuvant hormonal therapy in prostate cancer, with reference to re-examining the historical treatment paradigm, which considers androgen deprivation a palliative option.
Historically, adjuvant androgen deprivation therapy has been viewed as a palliative treatment option for patients with poor-prognosis non-metastatic prostate cancer. In addition, guidelines from bodies such as the European Association of Urology and American Society for Clinical Oncology do not specifically categorize adjuvant hormonal therapy as being curative in intent. We propose that adjuvant androgen deprivation therapy should now be classified as a treatment of curative intent in patients with poor-prognosis, non-metastatic prostate cancer. By applying a carefully considered definition of cure (based on long-term (10- to 15-year) disease-free survival curves) to the findings from randomized controlled clinical trials that have studied adjuvant hormonal treatments in non-metastatic prostate cancer, we challenged whether this viewpoint should now be considered redundant. According to our review of relevant studies and our definition of cure, goserelin appears to augment cure in a sizeable proportion of men with poor-prognosis non-metastatic prostate cancer when given adjuvant to radical prostatectomy or radiotherapy. Across several trials, the relevant survival curves for the goserelin-treated population became indefinitely flat after long-term follow-up. This indicates that these patients have a mortality risk comparable to the general population without prostate cancer. On the basis of the evidence presented within this review, we believe that, given it can control disease for a long period of time, adjuvant goserelin should be reclassified as a treatment of curative intent for patients with poor-prognosis non-metastatic prostate cancer.
Physicians managing patients with cancer seek to permanently rid their patients of the disease. However, current technology makes it difficult to determine whether a patient is entirely free of cancer. Although physical signs of the tumor, including imaging tests and biological markers, may be negative, it is usually impossible to determine if all remnants of the disease have been eradicated. Because of these uncertainties, oncologists are very reluctant to use the term 'cure'. As the understanding of cancer biology continues to evolve, it is increasingly evident that the concept of cure is somewhat nave. Patients may live with existing cancer cells for decades and increasingly sensitive markers are identifying residual or recurrent disease many years prior to clinical manifestation. Many patients with treated, but not cured cancers, die of other diseases, rendering the concept even more confusing. This may lead to a situation where long-term control of disease is of clinical importance.
In the 1970s, Frei and Gehan outlined a definition of cure in the setting of cancer, which proposed that cure exists among a group of disease-free survivors whose progressive death rate from all causes is similar to that of an age- and sex-matched population. This concept first led to 5-year survival rates becoming widely accepted as an indication of the success of a cancer treatment. However, over the past 30 years, earlier detection, improved therapies and better data acquisition have made the 5-year survival concept obsolete for many cancers. This is particularly evident with relatively slow-growing tumors such as prostate cancer, when life may not be threatened by the disease for 10-20 years. In these cases, a longer-term view is required to establish whether treatment results in adequate long-term control, leading to cure of the disease.
In contrast to physicians, many patients with cancer have high expectations of treatment and are desirous to know whether a given treatment will offer them cure. Although 'cure' may be too definitive a word to use in discussions with patients, it is nonetheless referred to in the lay literature and in patient/patient and patient/family discussions.
For certain stages of some cancers including genitourinary cancers, cure is becoming a reality. Although general opinion is that patients with poor-prognosis non-metastatic prostate cancer cannot be cured, results from recent studies have prompted re-evaluation of this belief. The aim of this review is to examine the concept of cure in genitourinary cancers and focus on the role of adjuvant hormonal therapy in prostate cancer, with reference to re-examining the historical treatment paradigm, which considers androgen deprivation a palliative option.