Oligometastases in prostate cancer: restaging stage IV cancers and new radiotherapy options

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Oligometastases in prostate cancer: restaging stage IV cancers and new radiotherapy options Antonio José Conde Moreno*, Carlos Ferrer Albiach, Rodrigo Muelas Soria, Verónica González Vidal, Raquel García Gómez and María Albert Antequera

Abstract There are various subgroups of patients with metastatic prostate cancer: polymetastatic, oligometastatic, or oligo-recurrent cancers whose progression follows different courses and for whom there are different treatment options. Knowledge of tumor dissemination pathways and different genetic and epigenetic tumor profiles, as well as their evolution during disease progression, along with new diagnostic and therapeutic advances has allowed us to address these situations with local ablative treatments such as stereotactic body radiation therapy or stereotactic radiosurgery. These treatments provide high rates of local control with low toxicity in metastatic spread for primary cancers including those of pulmonary, digestive, and renal origin, while these types of treatments are still emerging for cancers of prostatic origin. There are several retrospective studies showing the effectiveness of such treatments in prostate cancer metastases, which has led to the emergence of prospective studies on the issue and even some phase II studies intended to prevent or delay systemic treatments such as chemotherapy. Here we collect together and review these past experiences and the studies currently underway. These types of radiotherapy treatments redefine how we approach extracranial metastatic disease and open up new possibilities for combination therapy with new systemic treatment agents. Keywords: SBRT, SRS, Prostate metastases

Introduction Restaging stage IV cancer

Beginning with Halsted [1] in 1907 various theories for tumor dissemination have been proposed. The first important theory involved the locoregional lymphatic pathway and hypothesized that the disease could be cured if diagnosed at an early stage and if aggressively surgically managed. More than 70 years later, a second model became popular in oncological practice: using the breast cancer model (also used by Halsted), this model proposed that cancer is a systemic disease that always metastasizes and thus will already have done so early in the disease course, meaning that local therapies are less important than the tumor microenvironment or systemic therapies [2-4]. Later a third theory was proposed based in the "Spectrum hypothesis" [5] according to which the disease ranges between local and disseminated at the time of diagnosis. However, none of these theories has * Correspondence: [email protected] Servicio de Oncología Radioterápica, Instituto Oncológico de Castellón “Dr. Altava”, Consorcio Hospitalario Provincial de Castellón, Av. Dr. Clarà N 19, 12002 Castellón de la Plana, Castellón, Spain

been tested in randomized clinical trials at the biological level [6]. Progression describes the cause of cancer as the accumulation of acquired somatic mutations and chromosomal rearrangements which g