Cancer progresses in a stepwise fashion. Oligometastatic cancer is an intermediate stage of tumor spread between localized disease and disseminated metastases. Oligometastatic prostate cancer is defined as up to five extrapelvic lesions on conventional imaging. There are controversies surrounding the management of this malignancy, but retrospective and population-based studies suggest a role for radical prostatectomy. Despite insufficient data to draw conclusions regarding the effectiveness of aggressive therapies on overall or cancer-specific survival of patients with oligometastatic prostate cancer, current studies suggest that surgery decreases tumor burden, disease-related morbidity, and the need for palliative surgical intervention, while increasing the period of time to development of castration-resistant disease.
Introduction
The dramatic stage migration of prostate cancer toward earlier-stage, lower-grade disease at diagnosis is due to the widespread use of prostate-specific antigen (PSA) screening. In the pre-PSA era, regional or distant metastatic disease was seen in 25% of patients at diagnosis; since the introduction of PSA screening, however, fewer than 5% of men with prostate cancer are diagnosed with synchronous metastatic disease.[1] The US Preventive Services Task Force recommendation against PSA-based prostate cancer screening has resulted in an increased incidence of patients with metastatic prostate cancer at diagnosis.[2-4]
The current standard of care for men with metastatic prostate cancer targets the androgen axis (by testosterone suppression using surgical or hormonal castration). The treatment of the primary tumor in the metastatic setting is limited to patients with significant local symptoms secondary to the primary tumor, and is undertaken only as a palliative measure.[5]
Men with metastatic hormone-sensitive prostate cancer are typically treated with immediate or deferred systemic androgen deprivation therapy (ADT), with or without antiandrogen agents.[6-9] The addition of chemotherapy to hormonal therapy in the management of metastatic hormone-sensitive prostate cancer has been shown to improve survival and highlights the potential benefit of a multimodal approach in treating men with metastatic disease.[10,11] The broad, nontargeted systemic treatment of metastatic prostate cancer patients irrespective of disease burden was challenged by findings from the CHAARTED, STAMPEDE, and GETUG-AFU 15 trials.[10-12] Furthermore, recently reported results of the LATITUDE trial demonstrated improvements in both overall survival (OS) and radiographic progression-free survival (PFS) following treatment with abiraterone (plus prednisone and ADT) across all subgroups of patients with metastatic prostate cancer—including those with visceral metastasis and more than 10 bone lesions—compared with men randomized to ADT plus placebo.[13] The findings of these trials suggest that chemohormonal therapy improved survival in men with high-volume disease, whereas this treatment failed to yield a survival benefit with long-term follow-up in men with low-volume or oligometastatic disease.[10-13]
Despite the benefits observed with some of the previously mentioned therapies, metastatic prostate cancer is associated with a 5-year survival rate of only 28%, and carries a large economic burden.[14,15] This suggests the existence of a distinct phenotype of metastatic disease that may warrant distinct treatment strategies compared with the approaches used for nonmetastatic disease. Historically, radical prostatectomy (RP) and radiation therapy (RT) have been offered only to men with localized prostate cancer, and recent studies indicate that these modalities demonstrate sustained oncologic benefits in the setting of locally advanced disease.[16-21] In contrast, very few data exist to support treatment of primary prostate cancer in the metastatic setting. While the body of evidence in support of achieving local disease control to improve both the rate of response to systemic therapy and survival is well established in other malignancies (including metastatic renal cell, colon, breast, and ovarian cancers, and glioblastoma), similar evidence is lacking in the medical literature on prostate cancer.[22-28]
Extrapolating from other malignancies to metastatic prostate cancer, there is growing interest in elucidating the role of cytoreductive prostatectomy in management of low-volume metastatic or oligometastatic prostate cancer. Many theories have been proposed in support of local disease control; the leading theory is that, despite systemic therapy, the primary tumor may continue to harbor viable tumor cells with lethal molecular features and serve as a source for the seeding of new metastatic foci.[29,30]
Despite a paucity of level 1 evidence to support treatment of the primary tumor in metastatic prostate cancer, emerging data suggest improved survival with this approach in men with metastatic prostate cancer and locally advanced prostate cancer (ie, lymph node–positive disease).[20,21,31-36] The management of oligometastatic prostate cancer is complex owing to variation in the definition of oligometastatic prostate cancer and inconsistency among published data in the literature. In this review, we will examine the theories supporting treatment to achieve local disease control in oligometastatic prostate cancer, analyze the evidence supporting cytoreductive prostatectomy, and review selected relevant ongoing clinical trials.
Definition and Diagnosis of Oligometastatic Prostate Cancer
Metastatic cancer is synonymous with advanced-stage disease, where malignant cells are disseminated through the systemic circulation. Cancers are, and this dissemination is, believed to occur in a stepwise fashion. In their 1995 article, Hellman and Weichselbaum postulated an oligometastatic state with limited metastasis burden as an intermediate state in the malignancy spectrum prior to widespread metastases.[37] In their opinion, oligometastatic disease may reflect a time point in the malignant process when local therapies can potentially achieve a durable response to treatment—or even cure.[37,38]
The rise in the diagnosis of oligometastatic prostate cancer is likely multifactorial, and may result from closer monitoring of patients, improved diagnosis of low-burden disease due to advances in imaging techniques, and improved survival secondary to the use of emerging new therapies.[39,40]
Currently, the European Association of Urology and the National Comprehensive Cancer Network suggest cross-sectional studies (such as CT scan or MRI) and 99mTc-methylene diphosphonate planar or single photon emission tomography bone scan as the standard of care to evaluate for presence of metastases to lymph nodes, bone, or viscera.[7-9] The number of metastases is the most commonly used criterion to distinguish between oligometastatic and widely metastatic disease. Some clinicians additionally emphasize the anatomic location of metastasis in determining the existence of an oligometastatic state. A review of the medical literature suggests wide variability in the criteria used to define oligometastatic prostate cancer, with different levels of evidence.[41] In most studies and ongoing trials, oligometastasis is defined as the presence of disease in five or fewer sites. Tables 1 and 2 summarize selected ongoing trials and previously published studies defining oligometastatic prostate cancer.
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