Response Evaluation Criteria in PSMA PET/CT (RECIP 1.0) in Metastatic Castration-resistant Prostate Cancer

Abstract

Background Response Evaluation Criteria in Prostate-specific Membrane Antigen (PSMA) PET/CT (RECIP 1.0) initially integrated software-based quantitative assessment of PSMA-positive total tumor volume (TTV). Clinical implementation of such software is not expected soon, limiting the use of RECIP in practice. Purpose To assess the agreement of RECIP determined using tumor segmentation software (quantitative RECIP) with RECIP determined by qualitative reads by nuclear medicine physicians (visual RECIP) for response evaluation in metastatic castration-resistant prostate cancer. Materials and Methods This multicenter retrospective study at three academic centers included men who received lutetium 177 (¹⁷⁷Lu) PSMA treatment between December 2014 and July 2019. PSMA PET/CT images at baseline and 12 weeks were assessed qualitatively by five readers for changes in TTV and for new lesions. Quantitative changes in TTV were also measured using tumor segmentation software. The status of new lesions was combined with qualitative changes in TTV to determine visual RECIP and with quantitative changes in TTV to determine quantitative RECIP. The primary outcomes were the agreement between visual and quantitative RECIP and the interreader reliability of visual RECIP according to the Fleiss κ. The secondary outcome was the association of visual RECIP with overall survival according to Cox regression. Results A total of 124 men (median age, 73 years [IQR, 67-76 years]) were included. Forty (32%) and 84 (68%) men had quantitative RECIP progressive disease (PD) and non-PD, respectively. Agreement between visual versus quantitative RECIP was excellent (κ = 0.89; 118 of 124 men [95%]). Agreement among readers in classifying visual RECIP PD versus non-PD was excellent (κ = 0.81; 103 of 124 men [83%]). RECIP PD was associated with significantly shorter overall survival compared with non-PD (hazard ratio, 2.6 [95% CI: 1.7, 3.8]; P < .001). Conclusion Qualitatively assessed RECIP demonstrated excellent agreement with quantitative RECIP and excellent interreader reliability and can be readily implemented in clinical practice for response evaluation in men with metastatic castration-resistant prostate cancer undergoing ¹⁷⁷Lu-PSMA therapy. © RSNA, 2023 Supplemental material is available for this article.

Graphical abstract

Figure 1:

Study flowchart. In total, 287 men were screened at three academic centers. Of these, 156 (54%) did not meet inclusion criteria and were excluded. A total of 131 men (46%) met inclusion criteria and were considered for analyses. Seven of 131 men (5%) were lost to follow-up and excluded from the final analysis. Finally, 124 of 287 men (43%) were included in this study. ¹⁷⁷Lu = lutetium 177, mCRPC = metastatic castration-resistant prostate cancer, PSMA = prostate-specific membrane antigen.

Figure 2:

Pictorial representation of visual Response Evaluation Criteria in Prostate-specific Membrane Antigen (PSMA) PET/CT (RECIP) and quantitative RECIP. RECIP combines changes in PSMA-positive total tumor volume (TTV) and the occurrence of new lesions. Changes in TTV can be determined quantitatively by using tumor segmentation software and combined with the occurrence of new lesions to calculate quantitative RECIP. Changes in TTV can be determined qualitatively by nuclear medicine physicians and combined with the occurrence of new lesions to calculate visual RECIP.

Figure 3:

Patient examples of agreement between visual Response Evaluation Criteria in Prostate-specific Membrane Antigen (PSMA) PET/CT (RECIP) and quantitative RECIP. (A) Baseline and interim fluorine 18 rhPSMA-7.3 PET maximum intensity projection images in a 53-year-old man with metastatic castration-resistant prostate cancer previously treated with docetaxel, abiraterone, enzalutamide, and radium 223. The serum prostate-specific antigen value at baseline was 1457 ng/mL and increased after two cycles of lutetium 177 (¹⁷⁷Lu) PSMA to 2598 ng/mL (78% increase). ¹⁷⁷Lu-PSMA was discontinued after two cycles. All five readers detected at least one new lesion at the interim PET examination and classified this patient as having progression in PSMA-positive total tumor volume (TTV) and progressive disease (PD) according to visual RECIP. Quantitative analysis of TTV also showed progression in TTV from 1222 mL at baseline to 2158 mL at interim PET (77% increase). The tumor lesions were annotated using qPSMA software, version 1.0, and are highlighted in red on the maximum intensity projection images. Overall survival was 9.2 months. (B) Baseline and interim gallium 68 PSMA-11 PET maximum intensity projection images in a 78-year-old man with metastatic castration-resistant prostate cancer previously treated with docetaxel, abiraterone, and enzalutamide. The serum prostate-specific antigen level at baseline was 24 ng/mL and declined after two cycles of ¹⁷⁷Lu-PSMA to 11 ng/mL (55% decrease). All five readers detected no new lesions at the interim PET examination and classified this as nonprogression in TTV and non-PD according to visual RECIP. Quantitative analysis of TTV showed a decline from 256 mL at baseline to 87 mL at interim PET (66% decrease) and non-PD according to quantitative RECIP. The tumor lesions delineated after tumor segmentation are highlighted in red on the maximum intensity projection images. A total of six cycles of ¹⁷⁷Lu-PSMA were administered. Overall survival was 21.7 months.

Figure 4:

Patient examples of disagreement between visual Response Evaluation Criteria in Prostate-specific Membrane Antigen (PSMA) PET/CT (RECIP) and quantitative RECIP. (A) Fluorine 18 rhPSMA-7.3 PET maximum intensity projection images in a 77-year-old man with metastatic castration-resistant prostate cancer previously treated with docetaxel, abiraterone, and enzalutamide. The serum prostate-specific antigen level at baseline was 2547 ng/mL and declined after two cycles of lutetium 177 (¹⁷⁷Lu) PSMA to 1866 ng/mL (27% decrease). All readers detected at least one new lesion at the interim PET examination. Three of five readers classified disease in this patient as nonprogression in PSMA-positive total tumor volume (TTV) (majority rule), which resulted in non–progressive disease (PD) according to visual RECIP. Quantitative analysis of TTV showed an increase from 1978 mL at baseline to 2567 mL at interim PET (30% increase; progression), and it was classified as PD according to quantitative RECIP. The tumor lesions were annotated using qPSMA software, version 1.0, and are highlighted in red on the maximum intensity projection images. A total of four cycles of ¹⁷⁷Lu-PSMA were applied. Overall survival was 13.1 months. (B) Gallium 68 PSMA-11 PET maximum intensity projection images in a 69-year-old man with metastatic castration-resistant prostate cancer previously treated with abiraterone and enzalutamide and unfit for chemotherapy. The serum prostate-specific antigen level at baseline was 89 ng/mL and increased after two cycles of ¹⁷⁷Lu-PSMA to 138 ng/mL (55% increase). All readers detected at least one new lesion at the interim PSMA PET/CT examination. Four of five readers classified this patient as having progression in TTV (majority rule), which resulted in PD according to visual RECIP. Quantitative analysis of TTV showed an increase from 351 mL at baseline to 373 mL on interim PET (6% increase; nonprogression), which resulted in non-PD according to quantitative RECIP. The tumor lesions are highlighted in red on the maximum intensity projection images. The treatment with ¹⁷⁷Lu-PSMA was discontinued after two cycles. The overall survival in this patient was 20.5 months.

Figure 5:

Bar graphs show results of independent reads (A) for visual Response Evaluation Criteria in Prostate-specific Membrane Antigen PET/CT (RECIP) progressive disease (PD) versus non-PD (nPD) and (B) for classifying disease into visual RECIP PD, RECIP stable disease (SD), or RECIP partial response (PR).

Figure 6:

Kaplan-Meier plots show the association of overall survival with (A, B) visual Response Evaluation Criteria in Prostate-specific Membrane Antigen PET/CT (RECIP) and (C, D) quantitative RECIP determined by the readers’ majority rule. PD = progressive disease, PR = partial response, SD = stable disease.