Nomograms May Aid Patient Selection for 177Lu-PSMA Therapy in Metastatic Castration-Resistant Prostate Cancer

New nomograms can predict survival outcomes for patients with metastatic castration-resistant prostate cancer (mCRPC) treated with lutetium-177 prostate-specific membrane antigen (^177-Lu-PSMA), according to a study published in The Lancet Oncology.

To create the nomograms, researchers screened patients with mCRPC who had received ^177-Lu-PSMA from 2014 to 2019 as part of 2 phase 2 trials (trial identifiers: NCT03042312 and ACTRN12615000912583) or compassionate access programs.

There were 270 eligible patients who had received ^177-Lu-PSMA once every 6 to 8 weeks for a maximum of 4 to 6 cycles. The researchers divided these patients into a development cohort (n=196) and 2 validation cohorts (n=74).

One of the nomograms was designed to predict the probability of overall survival (OS). Predictors selected for the OS model were time since diagnosis, chemotherapy status, baseline hemoglobin, bone involvement, liver involvement, number of metastatic lesions, and mean tumor standardized uptake value (SUV_mean).

The C-index of the OS model was 0.71 (95% CI, 0.69-0.73) for the development cohort, 0.71 (95% CI, 0.69-0.73) for the internal validation cohort, and 0.72 (95% CI, 0.68-0.76) for the external validation cohort.

The researchers used the OS nomogram to stratify patients into low- and high-risk groups, and OS outcomes were consistently superior in the low-risk groups.

In the development cohort, the median OS was 19.1 months for low-risk patients and 8.4 months for high-risk patients (P <.0001). In the validation cohort (internal and external together), the median OS was 24.9 months and 7.4 months, respectively (P <.0001). In all eligible patients, the median OS was 19.9 months and 8.2 months, respectively (P <.0001).

The researchers also created a nomogram for prostate-specific antigen (PSA) progression-free survival (PFS). The predictors selected were time since diagnosis, chemotherapy status, pelvic nodal status, bone involvement, liver involvement, and tumor SUV_mean.

The C-index of the PSA-PFS model was 0.70 (95% CI, 0.68-0.72) for the development cohort, 0.70 (95% CI, 0.68-0.72) for the internal validation cohort, and 0.71 (95% CI, 0.68-0.74) for the external validation cohort.

As with OS, PSA-PFS outcomes were superior in low-risk patients.

In the development cohort, the median PSA-PFS was 9.4 months for low-risk patients and 3.3 months for high-risk patients (P <.0001). In the validation cohort, the median PSA-PFS was 6.6 months and 2.5 months, respectively (P =.022). In all eligible patients, the median PSA-PFS was 8.8 months and 3.3 months, respectively (P <.0001).

“Our nomograms for outcomes after ¹⁷⁷Lu-PSMA in late-stage mCRPC could help in trial design and provide guidance for clinicians,” the researchers wrote. “Robust and accurate risk assessment might aid physician decision-making regarding treatment plans and clinical trial patient stratification.”

The researchers noted that these models can be updated as new clinical trial data become available.

Disclosures: This research was supported by the Prostate Cancer Foundation and others. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

Gafita A, Calais J, Grogan TR, et al. Nomograms to predict outcomes after ¹⁷⁷Lu-PSMA therapy in men with metastatic castration-resistant prostate cancer: an international, multicentre, retrospective study. Lancet Oncol. Published online July 8, 2021. doi:10.1016/S1470-2045(21)00274-6