18F-PSMA-1007 PET/CT Performance on Risk Stratification Discrimination and Distant Metastases Prediction in Newly Diagnosed Prostate Cancer

ObjectiveTo evaluate the prediction performance of 18F-PSMA-1007 PET/CT and clinicopathologic characteristics on prostate cancer (PCa) risk stratification and distant metastatic prediction.Materials and MethodsA retrospective analysis was performed on 101 consecutively patients with biopsy or radical prostatectomy proved PCa who underwent 18F-PSMA-1007 PET/CT. The semi-quantitative analysis provided minimum, maximum and mean standardized uptake (SUVmin, SUVmax and SUVmean) of PCa. Association between clinicopathologic characteristics (total prostate-specific antigen, tPSA and Gleason Score, GS) and PET/CT indexes were analyzed. The diagnostic performance of distant metastatic on PET/CT parameters, tPSA and GS was evaluated using logistic regression analyses. A path analysis was conducted to evaluate the mediating effect of tPSA level on the relation between semi-quantitative parameters of primary tumors and metastatic lesions.ResultsThe PET/CT parameters were all higher in high risk stratification subgroups (tPSA>20 ng/mL, GS ≥ 8, and tPSA>20 ng/mL and/or GS ≥ 8, respectively) with high sensitivity (86.89%, 90.16% and 83.61%, respectively). The SUVmax, tPSA and GS could effectively predict distant metastatic with high sensitivity of SUVmax (90.50%) compared with tPSA (57.14%) and GS (55.61%). With a cutoff value of 29.01ng/mL for tPSA, the detection rate of distant metastasis between low and high prediction tPSA group had statistical differences (50.00% vs. 76.60%, respectively; P = 0.006) which was not found on guideline tPSA level (P>0.05). 6/15 (40%) patients tPSA between 20ng/mL to 29.01ng/mL without distant metastases may change the risk stratification. Finally, tPSA had a partial mediating effect on SUVmax of primary tumors and metastases lesions.ConclusionThe 18F-PSMA-1007 PET/CT SUVmax has a higher sensitivity and can be an “imaging biomarker” for primary PCa risk stratification. The prediction tPSA level (29.01 ng/mL) is more conducive to the assessment of distant metastasis and avoid unnecessary biopsy.

18F-PSMA-1007 PET/CT in Primary Prostate Cancer: Using tPSA to Detect Distant Metastasis and Incorporating SUVmax to Characterize Primary Prostate Cancer and Distant Metastasis

PurposeTo evaluate the diagnostic performance of total prostate-specific antigen (tPSA) for primary prostate cancer (PCa) distant metastasis in 18F-PSMA-1007 PET/CT, and the potential mediation role of tPSA level on the maximum standardized uptake value (SUVmax) of different metastasis stages.MethodsRetrospective analysis was performed on 101 patients admitted consecutively between March 2019 and June 2020 with biopsy proven PCa who were referred for PET/CT. The diagnostic performance of tPSA to detect distant metastasis was evaluated using receiver operating characteristic curve (ROC) and logistic regression analyses. SUVmax was compared across different metastatic stages with either low or high tPSA level using analysis of variance (ANOVA). A path analysis was conducted to evaluate the mediating effect of tPSA level on the relation between SUVmax of primary PCa and SUVmax of metastatic foci.ResultsAt a value of 29.01, the prediction tPSA demonstrated a sensitivity of 57.14% and a specificity of 73.68% for detecting distant metastasis with an area under the curve of 0.656 (P = 0.004). The prediction tPSA level was the only significant predictive variable in a logistic regression model (P = 0.008, odds ratio = 3.273). SUVmax was significantly different between primary prostate tissue with metastasis and metastasis foci only when tPSA ≥ 29.01 (P = 0.001). In addition, for those with metastasis foci, SUVmax was significantly higher in those with tPSA ≥ 29.01 than those with tPSA < 29.01 (P = 0.034). Both tPSA and SUVmax associated with risk of metastasis (P = 0.008, P = 0.014), and tPSA was found to have a partial mediating effect on SUVmax of primary PCa and metastases foci (P < 0.05). ConclusionA prediction tPSA level of 29.01 can help predict the distant metastases in primary PCa. The incorporation of 18F-PSMA-1007 PET/CT in PCa evaluation may better characterize the metastasis lesions.

Genomic Profiling in ctDNA Revealing Complicated Resistance Mechanism of Olaparib and Abiraterone as Salvage Therapy in Prostate Cancer: A Case Report

Background: PARP inhibitor, e.g. Olaparib, displayed superior clinical effect in metastatic castration prostate cancer (mCRPC) patients with deleterious mutations of DNA damage repair genes (DDR) as reported recently. Besides, for mCRPC patients without DDR alterations, a combination of Olaparib and abiraterone may achieve an acceptable clinical outcome as indicated by researches. However, these previous clinical studies involved patients strictly following inclusion criteria. In real-world situations, where the situation of patients is more complicated, the efficacy of salvage treatment of Olaparib with or without abiraterone-prednisone remains to be unclear. Case presentation: The present case displayed a 61-year-old man who was initially diagnosed with metastatic hormone-sensitive prostate cancer(mHSPC) and proceeding into mCRPC after several kinds of standard therapies. Surprisingly, the patient had a well TPSA response and remission of symptoms for four months by taking Olaparib combined with abiraterone-prednisone, basing on androgen-deprivation therapy (ADT). The resistance of Olaparib was occurred with slowly increasing serum TPSA level again.Conclusion: Resistance mechanism as discovered by comprehensive genomics profiling. The major concern was that two somatic reversion mutations occurred in PALB2 recovering its reading framer storing the function of the primary PALB2 mutation and caused the resistance to a PARP inhibitor.

Long-Term Prediction of Prostate Cancer: Prostate-Specific Antigen (PSA) Velocity Is Predictive but Does Not Improve the Predictive Accuracy of a Single PSA Measurement 15 Years or More Before Cancer Diagnosis in a Large, Representative, Unscreened Population

PurposeWe tested whether total prostate-specific antigen velocity (tPSAv) improves accuracy of a model using PSA level to predict long-term risk of prostate cancer diagnosis.MethodsDuring 1974 to 1986 in a preventive medicine study in Sweden, 5,722 men aged ≤ 50 gave two blood samples about 6 years apart. We measured free (fPSA) and total PSA (tPSA) in archived plasma samples from 4,907 participants. Prostate cancer was subsequently diagnosed in 443 (9%) men. Cox proportional hazards regression was used to evaluate tPSA and tPSAv as predictors of prostate cancer. Predictive accuracy was assessed by the concordance index.ResultsThe median time from second blood draw to cancer diagnosis was 16 years; median follow-up for men without prostate cancer was 21 years. In univariate models, tPSA level at second assessment and tPSAv between first and second assessments were associated with prostate cancer (both P < .001). tPSAv was highly correlated with tPSA level (r = 0.93). Twenty-year probabilities of cancer for men at 50th, 90th, and 95th percentile of tPSA and tPSAv were 10.6%, 17.1%, and 21.2% for tPSA, and 9.1%, 11.8%, and 14.1% for tPSAv, respectively. The concordance index for tPSA level was 0.771. Adding tPSAv, fPSA, %fPSA or velocities of fPSA and %fPSA did not importantly increase accuracy of tPSA to predict prostate cancer. Results were unchanged if the analysis was restricted to patients with advanced cancer at diagnosis.ConclusionAlthough PSA velocity is significantly increased in men with prostate cancer up to two decades before diagnosis, it does not aid long-term prediction of prostate cancer.