PSMA Response Could Point out Higher Metastasis Management in Oligometastatic CSPC

Prostate-specific membrane antigen (PSMA) response following stereotactic ablative radiation (SABR) could point out an enchancment in metastasis-free survival (MFS) in sufferers with oligometastatic castration-sensitive prostate most cancers (CSPC) in contrast with those that didn’t have a PSMA response, based on information from a retrospective examine.

Findings printed in Advances in Radiation Oncology demonstrated that the median MFS was 39.9 months in sufferers who had a PSMA response (n = 92) in contrast with 12 months in those that didn’t have a PSMA response (n = 39; P = .001). The three-year MFS charges have been 51% and 33% for PSMA responders and PSMA non-responders, respectively. Within the general cohort, the median MFS was 35.4 months (95% CI, 23.6-47.2), and the 3-year MFS fee was 46%.

Moreover, a multivariable Cox regression evaluation confirmed that PSMA response, as a steady variable, was related to MFS when accounting for complete PSMA consolidation, illness timing, Gleason grade group, androgen-deprivation remedy (ADT), pre–metastasis-directed remedy (MDT) prostate-specific antigen (PSA) stage, and staging imaging (HR, 1.003; 95% CI, 1.001-1.004; P <.001).

“These findings counsel that PSMA-PET response could also be an efficient radiographic biomarker for distant management following MDT in oligometastatic CSPC. The identification of a PSMA PET response biomarker that correlates with MFS following MDT in oligometastatic CSPC is of explicit curiosity, as MFS has been proven to be a powerful surrogate for general survival [OS] in localized CSPC,” lead examine creator Philip Sutera, MD, and colleagues, wrote within the journal. Sutera is a radiation oncology resident within the Division of Radiation Oncology and Molecular Radiation Sciences at Johns Hopkins College College of Drugs in Baltimore, Maryland.

The retrospective examine included sufferers with newly recognized oligometastatic CSPC who obtained metastasis-directed SABR and underwent PSMA-PET/CT imaging earlier than and after remedy. Oligometastatic illness was outlined as not more than 3 metastases per typical or PSMA-targeted imaging. Notably, the examine included sufferers who had oligometastatic illness per typical imaging and polymetastatic illness with 4 to 25 lesions per PET imaging. Concurrent remedy with ADT didn’t preclude sufferers from inclusion. Investigators additionally included sufferers handled at Johns Hopkins Hospital within the conventionally staged cohort of the section 2 ORIOLE trial (NCT02680587), in addition to sufferers handled within the PSMA-PET staged cohort of ORIOLE at Baskent College in Ankara, Turkey.

All sufferers obtained PET or CT utilizing 68Ga-PSMA-HBED-CC or 18F-DCFPyL-PSMA previous to MDT. SABR was given at doses starting from 16 to 60 Gy in 1 to five fractions; 1 affected person obtained hypofractionated radiation in 15 fractions. Following SABR, sufferers obtained follow-up PSMA-PET/CT imaging to judge illness response. Except concurrent ADT, no different remedy was given till proof of illness development.

Lesion response was categorized as a whole response (CR; no residual PSMA exercise), a partial response (PR; ≥30% discount in most standardized uptake worth [SUVmax]), steady illness (SD; <30% discount or <20% improve in SUVmax), or progressive illness (PD; ≥20% improve in SUVmax). The first goal of the examine was MFS after SABR in PSMA responders (sufferers with all lesions in CR/PR) and non-responders (sufferers with at the least 1 lesion categorized as SD/PD).

Amongst all sufferers included within the examine (n = 131), the median age was 66 years (IQR, 60.75-66), and the median PSA at oligometastasis was 4.5 ng/mL (IQR, 1.Sep 11.8). Seventy-four p.c of sufferers had metachronous illness, and 25.2% had synchronous/de novo illness. Staging was accomplished by way of typical (26.7%) or PSMA-PET (73.3%) imaging. The variety of PSMA lesions included 1 (47.3%), 2 (32.1%), 3 (9.2%), or at the least 4 (11.5%). Moreover, 87.8% of sufferers had complete PSMA consolidation, and 65.6% of sufferers obtained concurrent ADT with MDT. The median period of ADT was 2 months (IQR, 1.0-3.75).

Moreover, 48.9% of sufferers have been disease-free long run after remedy, 24.4% skilled oligoprogression, and 26.7% had polyprogression.

The placement of the 261 lesions evaluated throughout 131 sufferers included node (45.2%), bone (52.5%), visceral (1.1%), and prostate/native recurrence (0.4%). The median SUVmax previous to MDT was 8.7 (IQR, 4.0-16.7) for all lesions, 9.1 (IQR, 4.0-18.5) for nodal lesions, 8.6 (IQR, 4.2-15.7) for bone lesions, and seven.8 (IQR, 6.2-10.2) for visceral lesions. The median biologically efficient dose (BED3) was 116.7 Gy (IQR, 90-126) for all lesions, 116.7 Gy (IQR, 90-124) for nodal lesions, 116.7 Gy (IQR, 90-126) for bone lesions, and 378 Gy (IQR, 234-419) for visceral lesions.

Put up-treatment PSMA-PET imaging was performed at a median of 6.2 months (IQR, 4.6-8.7; vary, 2.4-10.9) following MDT. PSMA responses included CR (27.6% of lesions), PR (51.7%), SD (14.2%), and PD (6.5%). Notably, 90.7% of untreated lesions (n = 54) have been categorized as SD or PD. A multivariable logistic regression confirmed that concurrent ADT was related to an elevated likelihood of PSMA response in a lesion (odds ratio, 3.04; 95% CI, 1.38-6.70; P = .006).

Further information confirmed that the 3-year lesion native management (LLC) fee was 87% for all sufferers, and the median LLC was not reached. PSMA responders skilled a 3-year LLC fee of 92% in contrast with 66% for PSMA non-responders. The multivariable Cox regression mannequin confirmed that as a steady variable, PSMA response was linked to LLC after accounting for BED3 of SABR, lesion location, ADT, and pre-MDT SUVmax (HR, 1.003; 95% CI, 1.001-1.006; P = .016).

For the reason that retrospective examine’s cohort included sufferers with various staging imaging, timing of illness, use of ADT, and metastatic places, the affiliation between PSMA response and MFS was evaluated in numerous subsets of sufferers. A major affiliation between PSMA response and MFS was present in sufferers handled with and with out ADT; these with metachronous illness; these staged with typical imaging and PSMA-PET imaging; sufferers with complete PSMA consolidation; and people with lymph node solely and bone/visceral metastases. There was not a big affiliation between PSMA response and MFS in sufferers with synchronous illness and people with subtotal PSMA consolidation.

Sutera and colleagues famous that the examine was restricted by its retrospective nature and the heterogeneous cohort of sufferers. Moreover, various occasions of post-MDT imaging may have affected the diploma of PSMA responses noticed. Additionally they defined that PSA kinetics weren’t obtainable for these sufferers, stopping the analysis of its relationship with PSMA response. Additionally they defined that though MFS has been strongly correlated with OS in localized CSPC, the affiliation between MFS and OS within the oligometastatic setting has not been decided.

“Pending potential validation, our findings counsel that PSMA-PET needs to be thought-about for MDT focusing on, evaluating remedy response, and guiding subsequent intervention. Future work is required to additional refine our understanding of when post-SABR PSMA-PET imaging needs to be carried out and the way greatest to characterize the PSMA response,” examine authors concluded.

Reference

Sutera P, Deek MP, Deek RA, et al. Prostate-specific membrane antigen PET response associates with metastasis-free survival after stereotactic ablative radiation in oligometastatic prostate most cancers. Adv Radiat Oncol. 2024;9(7):101507. doi:10.1016/j.adro.2024.101507