Low- and High-Volume Disease in Metastatic Hormone-Sensitive Prostate Cancer: From CHAARTED to PSMA PET—An International Multicenter Retrospective Study

Lena M. Unterrainer, Thomas A. Hope, Wolfgang P. Fendler, Tristan Grogan, Honest Ndlovu, Wesley Armstrong, Francesco Barbato, Matthias R. Benz, Matthew B. Rettig, Amar U. Kishan, Mike Sathekge, Ken Herrmann, Johannes Czernin, Jeremie Calais
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Abstract

High-volume disease (HVD) and low-volume disease (LVD) definitions in metastatic hormone-sensitive prostate cancer (mHSPC) patients are based on conventional imaging (CI) (CT/MRI with bone scan [BS]) according to CHAARTED criteria. HVD and LVD definitions are associated with overall survival and are used for treatment decisions. It remains unknown how these definitions transfer to prostate-specific membrane antigen (PSMA) PET imaging. The aim of this retrospective multicenter study was to compare the CI-based disease volume criteria to PSMA PET–based volume definitions in a CHAARTED-like cohort. Methods: mHSPC patients from 5 international sites who underwent PSMA PET/CT or PSMA PET/MRI and BS within a time interval of 100 d and without initiation of a new therapy between the 2 scans were retrospectively included in the analysis. CHAARTED HVD and LVD criteria were applied to BS, CT, MRI, and PSMA PET. HVD was defined by the presence of visceral metastases or at least 4 bone metastases (with ≥1 beyond the spine or pelvis). Whole-body (WB) tumor burden was estimated with the automated bone scan index (aBSI, EXINI v2.0) on BS and with the WB PSMA PET–positive tumor volume (PSMA-TV) on PSMA PET, respectively. Results: Sixty-seven patients with paired PSMA PET and BS were included. The median prostate-specific antigen level was 54.9 ng/mL (interquartile range [IQR], 10.4–191.0 ng/mL). On the basis of CI, it was determined that 17 of 67 patients had HVD-CI (25.4%) and 50 of 67 patients had LVD-CI (74.6%). On the basis of PSMA PET, it was determined that 27 of 67 patients had HVD-PET (40.3%) and 24 of 67 patients had LVD-PET (35.8%). In total, 16 of 67 patients (22.4%) had no visible lesion or only locoregional pelvic disease (M0) with PSMA PET (M0-PET). Stage migration between CI and PSMA PET occurred in 27 of 67 patients (40.3%) by both upstaging and downstaging: 11 of 50 (22%) LVD-CI patients were HVD-PET, whereas 1 of 17 (5.9%) HVD-CI and 15 of 50 (30%) of LVD-CI patients were M0-PET. The median WB PSMA-TV and automated BS index were 248.0 mL (IQR, 54.6–1,427.0 mL) and 3.4% (IQR, 1,0–7.2%) for HVD-CI, 25.1 mL (IQR, 6.6–74.6 mL) and 0.1% (IQR, 0.0–0.2%) for LVD-CI, 141.0 mL (IQR, 47.5–458.0 mL) and 0.9% (IQR, 0.04–4.1%) for HVD-PET, and 31.5 mL (IQR, 10.1–67.9 mL) and 0% (IQR, 0–0.1%) for LVD-PET, respectively. The optimal WB PSMA-TV to stratify CI-based CHAARTED LVD-CI versus HVD-CI was 107 mL with a misclassification of 21.9%. Conclusion: Compared with CI, addition of PSMA PET leads to M0 downstaging in every third and LVD to HVD upstaging in every fifth mHSPC patient. Future HVD and LVD definitions based on PSMA PET/CT should be adjusted based on patient outcome.

转移性激素敏感前列腺癌的低容量和高容量疾病:从charted到PSMA pet——一项国际多中心回顾性研究
转移性激素敏感性前列腺癌(mHSPC)患者的高容量疾病(HVD)和低容量疾病(LVD)定义是基于传统影像学(CI) (CT/MRI伴骨扫描[BS])根据CHAARTED标准确定的。HVD和LVD的定义与总生存率相关,并用于治疗决策。目前尚不清楚这些定义如何转移到前列腺特异性膜抗原(PSMA) PET成像。这项回顾性多中心研究的目的是比较基于ci的疾病体积标准和基于PSMA pet的疾病体积定义。方法:回顾性分析了来自5个国家的mHSPC患者,这些患者在间隔100 d的时间内接受了PSMA PET/CT或PSMA PET/MRI和BS检查,并且在两次扫描之间没有开始新的治疗。对BS、CT、MRI和PSMA PET进行HVD和LVD诊断。HVD的定义是存在内脏转移或至少4个骨转移(≥1个在脊柱或骨盆以外)。分别使用BS上的自动骨扫描指数(aBSI, EXINI v2.0)和PSMA PET上的WB PSMA PET阳性肿瘤体积(PSMA- tv)来估计全身(WB)肿瘤负荷。结果:纳入67例PSMA PET和BS配对患者。前列腺特异性抗原水平中位数为54.9 ng/mL(四分位数范围[IQR], 10.4 ~ 191.0 ng/mL)。根据CI, 67例患者中HVD-CI为17例(25.4%),LVD-CI为50例(74.6%)。根据PSMA PET, 67例患者中HVD-PET 27例(40.3%),LVD-PET 24例(35.8%)。67例患者中有16例(22.4%)未见明显病变或仅局部盆腔病变(M0), PSMA PET (M0-PET)。67例患者中有27例(40.3%)出现了pci和PSMA PET之间的分期转移:50例LVD-CI患者中有11例(22%)为HVD-PET,而17例HVD-CI患者中有1例(5.9%)和50例LVD-CI患者中有15例(30%)为M0-PET。HVD-CI的中位WB pma - tv和自动BS指数分别为248.0 mL (IQR, 54.6 - 1427.0 mL)和3.4% (IQR, 1,0 - 7.2%), LVD-CI为25.1 mL (IQR, 6.6-74.6 mL)和0.1% (IQR, 0.0-0.2%), HVD-PET为141.0 mL (IQR, 47.5-458.0 mL)和0.9% (IQR, 0.04-4.1%), LVD-PET为31.5 mL (IQR, 10.1-67.9 mL)和0% (IQR, 0-0.1%)。区分基于ci的charted LVD-CI与HVD-CI的最佳WB PSMA-TV为107 mL,误分类率为21.9%。结论:与CI相比,添加PSMA PET可导致三分之一的mHSPC患者M0降期,五分之一的mHSPC患者LVD向HVD上升。未来基于PSMA PET/CT的HVD和LVD定义应根据患者结果进行调整。
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