EAU 2024: PSA Persistence After Radical Prostatectomy: Optimal Treatment in the Case of PSA Persistence
EAU 2024：根治性前列腺切除术后PSA持续存在：最佳疗法
The 2024 European Association of Urology (EAU) annual congress held in Paris, France between April 5th and 8th was host to a joint session of the EAU and the Advanced Prostate Cancer Consensus (APCCC). Professor Nick James discussed the optimal treatment in the case of PSA persistence following radical prostatectomy.
2024年欧洲泌尿外科学会（EAU）年会于4月5日-8日在法国巴黎举行，年会召开了EAU晚期前列腺癌共识（APCC）会议。Nick James教授讨论了根治性前列腺切除术（RP）后PSA持续存在患者的最佳治疗方法。
Which of these patients should be treated? Professor James argued that this depends on the prior surgical history (i.e., whether prior lymph node dissection was performed and how extensive), surgical pathology, and availability of imaging.
这类患者中哪些患者应该接受治疗？James教授认为，这取决于既往手术史（即是否接受过淋巴结清扫术以及清扫范围如何）、手术病理学检查结果和成像的可用性。
辅助放疗vs挽救性放疗
There is some evidence to inform the timing of treatment administration. The RADICALS-RT trial randomized post-prostatectomy patients with a post-operative PSA ≤0.2 ng/ml with ≥1 worrisome clinicopathologic feature to either adjuvant radiotherapy or salvage radiotherapy at the time of PSA failure.
目前有证据显示了治疗时机。RADICALS-RT试验纳入了前列腺切除术后PSA≤0.2 ng/ml且具有≥1个令人担忧的临床病理特征的患者，患者随机接受辅助放疗或在PSA失败时接受挽救性放疗。
While the RADICALS-RT trial did not necessarily include patients with persistent levels post-operatively, Professor James argued that the results of this trial likely can be generalized to this patient population. As summarized below, the urinary (and bowel) toxicity outcomes are significantly worse for patients who undergo adjuvant radiotherapy, as opposed to salvage radiotherapy. As such, Professor James argued that there may be value in delaying radiotherapy in this cohort of patients until there is clear evidence of disease progression.
虽然RADICALS-RT试验不一定纳入了术后PSA持续存在的患者，但James教授认为，该试验的结果可能适用于RP术后PSA持续存在的患者群体。该试验发现，辅助放疗组的泌尿系统（和肠道）毒性反应结局不如挽救性放疗组。因此，James教授认为，在有明确的疾病进展证据之前，推迟此类患者的放疗可能对患者有益。
术后放疗时是否应同时给予激素治疗
The next question is whether hormone therapy should be added concurrently at time of post-operative radiotherapy. The RADICALS-HD trial evaluated the role of ADT, including duration (6 or 24 months) concurrently with radiotherapy in this setting.
下一个问题是，术后放疗时是否应同时给予激素治疗。RADICALS-HD试验评估了ADT的作用，包括与放疗同时进行的激素治疗的持续时间（6或24个月）。
There was no difference in metastasis-free survival among patients who received short-term versus no ADT with post-operative radiotherapy.
结果发现，在接受术后放疗的患者中，短期ADT组和不接受ADT组的无转移生存率没有差异。
In the second pairwise comparison, patients receiving long-term ADT had significantly superior metastasis-free survival compared to those receiving short-term ADT (HR: 0.77, 95% CI: 0.61–0.97).
在第二次配对比较中，接受长期ADT的患者无转移生存率显著优于接受短期ADT的患者（HR:0.77，95%CI:0.61-0.97）。
既往淋巴结清扫术的影响
How does prior surgical status, namely relating to prior performance of a lymph node dissection, alter treatment decision making? In patients with no prior node dissection, the morbidity of radiotherapy is likely to be less, but pathologic staging would be less certain. While patients with a prior node dissection are likely to have better pathologic staging, PET data often shows 'atypical’ relapse patterns/sites.
既往手术史，即淋巴结清扫术，会对治疗决策有哪些影响？在既往没有接受淋巴结清扫术的患者中，放疗的不良事件发生率可能较低，但病理分期不太确定。虽然既往接受淋巴结清扫术的患者可能有更好的病理分期结果，但PET通常显示其为“非典型”复发模式/部位。
To date, the extent of nodal dissection has not been demonstrated to significantly impact oncologic outcomes. The randomized clinical trial of extended versus limited nodal dissection failed to reach its primary endpoint of biochemical recurrence-free survival improvement with an extended nodal dissection.
迄今为止，尚无研究证明淋巴结清扫术的清扫范围对肿瘤学结局有显著影响。比较扩大的淋巴结清扫术和有限淋巴结清扫术的随机临床试验未能实现其主要终点——扩大淋巴结清扫术可提高无生化复发生存率。
如何利用术后病理检查结果
What about surgical pathology? This information can be used to guide the disease site likelihood in patients with biochemical persistence. If resection margins are clear, then prostatic fossa disease is less likely. Conversely, if resection margins are positive, the opposite scenario becomes more likely. In either case, distant disease cannot be excluded. If patients are node positive and the PSA is still persistently elevated, the disease also remains unpredictable. One thing to note is that as the PSA level rises, the likelihood of PSMA PET imaging detecting the exact site of disease spread/persistence increases.
那手术病理检查结果的影响如何？结论便是，病理结果可用于提示RP术后PSA持续存在的患者的疾病复发部位。如果切缘阴性，那么前列腺窝复发的可能性较小。但是，如果切缘阳性，则前列腺窝复发的可能性较大。无论哪种情况，都不能排除远处疾病复发。如果患者淋巴结阳性，PSA仍持续升高，疾病也仍然不可预测。需要注意的一点是，随着PSA水平的升高，PSMA PET成像会更容易检测到疾病扩散/持续存在的确切部位。
For patients who undergo adjuvant or salvage radiotherapy post-radical prostatectomy, it is important to note that relapses mainly occur outside the radiotherapy field.
对于根治性前列腺切除术后接受辅助放疗或挽救性放疗的患者，需要注意的是，复发主要发生在未接受放疗的部位。
With regards to imaging, PSMA PET is more sensitive than CT, MRI, or bone scan for the detection of nodal relapse. However, at low PSA values (<1 ng/ml), there are significant false-negative rates for pelvic lymph nodes. At higher PSA values, sensitivity improves but is more likely to be low volume M1.
就成像而言，PSMA PET在检测淋巴结复发方面的敏感度优于CT、MRI和骨扫描。然而，在PSA值较低（<1 ng/ml）时，盆腔淋巴结的假阴性率较高。当PSA值较高时，敏感度提高，但最终结果可能是低负荷M1期疾病。
总结
Professor James concluded with the following take home messages regarding PSA persistence and relapse:
·The patterns of relapse are complex and unpredictable.
·The sites of relapse may be influenced by prior surgery, but more extensive surgery is probably best viewed as a staging rather than a therapeutic procedure
·Relapses can occur in the surgical field, but rare inside the radiotherapy field
·The current literature supports more limited surgery and more frequent imaging to best define sites for radiotherapy in the relapse setting
关于PSA持续存在和疾病复发，James教授给出了如下总结：
·复发的模式复杂、不可预测。
·复发的部位可能会受到先前淋巴结清扫术的影响，但建议最好将更广泛的清扫术视为一种分期手段，而不是一种治疗方式。
·复发部分可能位于手术切除区域，放疗区域内的复发较为罕见。
·目前的文献支持更有限的淋巴结清扫术和更频繁的成像，以更好地确定复发患者接受放疗的部位。
Presented by: Professor Nick James, MBBS, PhD, Professor of Prostate and Bladder Cancer Research at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London, UK
Written by: Rashid Sayyid, MD, MSc - Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @rksayyid on Twitter during the 2024 European Association of Urology (EAU) annual congress, Paris, France, April 5th - April 8th, 2024
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