Prostate-specific membrane antigen (PSMA)-based imaging is an improvement in prostate cancer staging [1]. It helps discover occult metastatic disease otherwise missed by routine imaging modalities and allows better understanding of the pattern of recurrence after primary therapy. Along with the potent activity of androgen receptor signalling inhibitors, PSMA-based molecular imaging is driving a paradigm shift in the management of prostate cancer. One such a shift is the development of the concept of metastasis-directed therapy (MDT).

Prior to the advent of PSMA/positron emission tomography (PET) imaging, results of MDT in the form of ‘salvage’ lymph node dissection (LND) for pelvic/retroperitoneal nodal recurrences were disappointing. Few patients reached an undetectable PSA level in the short-term and most recurred with longer follow-up [2].

It is hoped that the incorporation of PSMA PET imaging will add more precision to salvage LND and guide the surgeon to a complete excision of all foci of cancer recurrence. Insofar, the approach utilised is a bilateral full LND including PSMA-avid and -non-avid regions [3, 4].

In September's issue of the BJUI, Knipper et al. [5] proposed a randomised clinical trial comparing unilateral salvage pelvic LND to a bilateral one in men with unilateral pelvic nodal recurrence after radical prostatectomy detected by PSMA/PET imaging (ProSTone, NCT 04271579). The primary endpoint of this non-inferiority trial is the difference in biochemical recurrence at 24 months postoperatively. In this trial, the investigators are exploring whether the negative predictive value of PSMA/PET is robust enough to pinpoint the dissection only to the PSMA-avid lesions. Thus, maintaining the oncological outcome and perhaps reducing morbidity.

This laudable objective might be too optimistic. The initial results of bilateral salvage pelvic LND removing both PSMA-avid and -non-avid nodes are not better than the salvage LND without prior PSMA PET imaging [2, 6]. This suggests that in the biochemical recurrence setting either the PSMA PET misses some nodal metastatic disease, or the concept of salvage LND as a single modality therapy is inadequate, or both.

The performance characteristics of PSMA PET imaging in detecting metastatic nodes show a nodal size dependence and a wide variation in sensitivity (24–100%). Franklin et al. [7] reported a median (range) diameter of a metastatic node detected by PSMA to be 7 (0.5–40) vs 4 (0.5–40) mm for histopathology and 11.7 (2.2–20) mm for MRI. In another study by Van Leeuwen et al. [8] the detection rates of PSMA PET were 0% for nodes of <1.9 mm in diameter, 60% for those between 2 and 4.9 mm, and 86% for nodes with a diameter >5 mm. These data reflect the superiority of PSMA PET imaging over cross-sectional imaging but also its limitations vis-à-vis histopathology. Therefore, an approach based on excision of PSMA-avid nodes only may not be sufficient. Likewise, given the overall survival advantage provided by the combination of androgen-deprivation therapy (ADT) and radiation therapy (RT) over either RT alone, or ADT alone in the management of pN1 disease [9, 10], it is likely that salvage LND performed in isolation as a single modality therapy is insufficient at halting disease progression. Therefore, if the ProSTone trial is negative, the results are to be expected; and if it is positive, both the uni- and bilateral salvage LND would be equally ineffective.

We believe that in the era of molecular imaging, the value of salvage LND as an MDT ought to be studied as a complementary intervention in concert with systemic, radiation, and other novel therapies.

基于前列腺特异性膜抗原 (PSMA) 的成像是前列腺癌分期的一种改进 [ 1 ]。它有助于发现隐匿性转移性疾病，否则常规成像方式会遗漏，并可以更好地了解主要治疗后的复发模式。随着雄激素受体信号抑制剂的强大活性，基于 PSMA 的分子成像正在推动前列腺癌管理的范式转变。其中一个转变是转移导向治疗 (MDT) 概念的发展。

在 PSMA/正电子发射断层扫描 (PET) 成像出现之前，MDT 以“挽救”淋巴结清扫 (LND) 形式治疗盆腔/腹膜后淋巴结复发的结果令人失望。很少有患者在短期内达到无法检测到的 PSA 水平，并且大多数患者在长期随访后复发 [ 2 ]。

希望 PSMA PET 成像的结合将增加挽救 LND 的精度，并指导外科医生完全切除所有癌症复发灶。到目前为止，所使用的方法是双边完整 LND，包括 PSMA 亲和和非亲和区域 [ 3, 4 ]。

在九月份的BJUI 中，Knipper等人。[ 5 ] 提出了一项随机临床试验，在 PSMA/PET 成像（ProSTone，NCT 04271579）检测到根治性前列腺切除术后单侧盆腔淋巴结复发的男性中，比较单侧挽救骨盆 LND 与双侧 LND。该非劣效性试验的主要终点是术后 24 个月生化复发的差异。在这项试验中，研究人员正在探索 PSMA/PET 的阴性预测值是否足够强大，以仅将解剖定位到 PSMA 亲和性病变。因此，保持肿瘤学结果并可能降低发病率。

这个值得称赞的目标可能过于乐观了。双侧盆腔 LND 去除 PSMA 亲和和非亲和淋巴结的初步结果并不比没有事先 PSMA PET 成像的抢救 LND 好 [ 2, 6 ]。这表明在生化复发情况下，要么 PSMA PET 错过了一些淋巴结转移性疾病，要么将挽救 LND 作为单一方式治疗的概念是不充分的，或两者兼而有之。

PSMA PET 成像在检测转移性淋巴结方面的性能特征显示出淋巴结大小依赖性和灵敏度的广泛变化（24-100%）。富兰克林等人。[ 7 ] 报告了 PSMA 检测到的转移淋巴结的中位（范围）直径，组织病理学为 7 (0.5-40) 对 4 (0.5-40) 毫米，MRI 为 11.7 (2.2-20) 毫米。在 Van Leeuwen等人的另一项研究中。[ 8] PSMA PET 的检出率对于直径 <1.9 mm 的淋巴结为 0%，对于 2 至 4.9 mm 的淋巴结为 60%，对于直径 >5 mm 的淋巴结为 86%。这些数据反映了 PSMA PET 成像优于横截面成像，但也反映了其相对于组织病理学的局限性。因此，仅基于切除 PSMA 亲和节点的方法可能是不够的。同样，考虑到雄激素剥夺疗法 (ADT) 和放射疗法 (RT) 的组合在 pN1 疾病管理中优于单独放疗或单独 ADT [ 9, 10]]，很可能单独进行的挽救性 LND 作为单一方式治疗不足以阻止疾病进展。因此，如果 ProSTone 试验是否定的，结果在意料之中；如果它是积极的，单边和双边打捞 LND 将同样无效。

我们认为，在分子成像时代，应将抢救 LND 作为 MDT 的价值作为与全身、放射和其他新疗法相配合的补充干预措施进行研究。