Veterans Affairs seamless phase II/III randomized trial of STAndard systemic theRapy with or without PET-directed local therapy for OligoRecurrenT prostate cancer (VA STARPORT)

前列腺癌是退伍军人中最常见的癌症，占30%。 退伍军人事务部新的癌症诊断85%的局限性前列腺患者 cer，通常采用积极监测或手术或局部治疗进行治疗， 放射治疗不幸的是，百分之二十的退伍军人接受治疗性局部治疗， 会出现转移性复发这些人通常接受姑息性全身激素 治疗以控制疾病。尽管如此，超过一半的男性将有癌症进展 在1-2年内死亡，一半在5年内死亡。 近年来研究了两种不同的范式，以提高男性的生存率， 复发转移性前列腺癌首先，一部分患者患有复发性疾病， 以1-5个转移灶为标准。这些患者被假设有一个中间临床- 在这种状态下，对所有转移部位进行手术或放射的消融性局部治疗， 转移导向治疗（MDT）可以导致持久的疾病控制， 在特定患者中治愈。最近的II期随机试验表明， 无全身治疗情况下MDT的长期无进展生存期。 然而，75%的接受MDT治疗的少复发性癌症患者在新的领域出现进展， 认为需要全身治疗来治疗隐匿性转移。这是有数据支持的 这表明早期姑息性激素治疗与生存率提高有关。在 事实上，近年来研究的第二种方法是， 通过添加新的雄激素受体轴靶向药物或化疗的治疗改善了 是转移性前列腺癌患者多项III期随机试验证明 使用这些新型治疗剂的激素治疗可以改善无进展 生存率和总体生存率都有很大的提高。因此，这些代理已被整合为 选择进入今天的标准全身治疗（SST）转移复发。 考虑到MDT诱导长期癌症控制的前景和SST的有效性， 预防癌症进一步进展，迫切需要确定是否增加MDT SST可进一步改善疾病结局。我们研究的主要目的是确定是否添加- 与SST单独治疗相比，MDT可改善患有少复发性前列腺癌的退伍军人的疾病控制 泰特癌症。我们将进行一项多机构II期随机试验，比较SST与 或者没有MDT。这项研究的其他目标是确定癌症模式的任何差异 进展，生存，生活质量，以及每种方法的成本效益。我们也将 确定RNA转录组学分析和DNA测序如何从原发性肿瘤 最初的前列腺癌诊断可以帮助确定哪些退伍军人受益最多 数据终端我们还将利用VA国家精确肿瘤学计划对转移进行测序。 该试验是与VA合作研究合作开发的， 计划（CSP），并代表了前列腺癌专家的多学科合作， MDT专家、临床试验设计专家和退伍军人。 如果MDT能改善FFS，我们的研究将作为制定明确的III期随机- 有把握度确定MDT是否改善总体生存率的标准化试验-确定 新的护理标准。

Prostate Cancer is the most commonly diagnosed cancer among Veterans, comprising 30% of new cancer diagnoses in the VA. Eighty-five percent of men present with localized prostate can- cer, which is typically treated with active surveillance or curative local therapy using surgery or radiation therapy. Unfortunately, twenty percent of Veterans undergoing curative local therapy will develop metastatic recurrence. These men typically receive palliative systemic hormonal therapy to control their disease. Despite this, over half of men will have cancer progression within 1-2 years and half will die within 5 years. Two diverging paradigms have been studied in recent years to improve the survival of men with recurrent metastatic prostate cancer. First, a subset of patients has oligorecurrent disease, de- fined as 1-5 sites of metastases. These patients are hypothesized to have an intermediate clini- cal state in which ablative local therapy with surgery or radiation to all metastatic sites of dis- ease (metastasis-directed therapy; MDT) can lead to durable disease control and potentially cure in select patients. Recent Phase II randomized trials have demonstrated improved long- term progression-free survival with MDT in the absence of systemic therapy. Yet, 75% of patients receiving MDT for oligorecurrent cancer develop progression in new areas, arguing that systemic therapy is needed to treat occult metastases. This is supported by data demonstrating that earlier palliative hormonal therapy is associated with improved survival. In fact, the second approach that has been studied in recent years, is whether escalating hormonal therapy by adding novel androgen receptor axis targeted agents or chemotherapy improves out- comes in men with metastatic prostate cancer. Multiple phase III randomized trials demonstrate that escalating hormonal therapy with these novel therapeutic agents improves progression-free survival and overall survival dramatically. Therefore, these agents have been integrated as an option into today’s standard systemic therapy (SST) for metastatic recurrence. Given the promise of MDT to induce long-term cancer control and the effectiveness of SST to prevent further cancer progression, there is an urgent need to determine whether adding MDT to SST improves disease outcomes further. The primary goal of our study is to determine if add- ing MDT improves disease control compared to SST alone in Veterans with oligorecurrent pros- tate cancer. We will conduct a multi-institutional phase II randomized trial comparing SST with or without MDT. Other goals of the study are to determine any differences in patterns of cancer progression, survival, quality of life, and the cost-effectiveness of each approach. We also will determine how RNA transcriptomic analysis and DNA sequencing of the primary tumor from the original prostate cancer diagnosis can help determine which Veterans benefit the most from MDT. We will also utilize the VA National Precision Oncology Program to sequence metastases. The trial was developed and will be conducted in collaboration with the VA Cooperative Studies Program (CSP), and represents the multidisciplinary collaboration of prostate cancer experts, MDT experts, clinical trial design experts, and Veterans. If MDT improves FFS, our study will serve as the basis to develop a definitive phase III random- ized trial that will be powered to determine if MDT improves overall survival—establishing the new standard of care.