PSA and PSA Kinetics as Predictors for 18F-Fluciclovine PET/CT Positivity in Biochemically Recurrent Prostate Cancer

<b><i>Introduction:</i></b> ¹⁸F-Fluciclovine PET/CT is one of the imaging techniques currently employed to restage prostate cancer (PCa). Due to the conflicting results reported in the literature, it is not yet known at what PSA threshold ¹⁸F-fluciclovine PET/CT could reliably demonstrate the presence of recurring disease. We explored the association between ¹⁸F-fluciclovine PET/CT positivity and prescan PSA, PSA doubling time, and PSA velocity in patients with biochemical recurrence (BCR) of PCa after curative-intent treatment. <b><i>Methods:</i></b> Data from 59 patients who underwent ¹⁸F-fluciclovine PET/CT for BCR after radical prostatectomy or radiotherapy were retrieved from a single institution database. Patients already undergone salvage treatments at the time of PET/CT, with newly diagnosed PCa or with initial diagnosis of metastatic PCa were excluded. A 2-sided independent samples Bayesian <i>t</i> test and Bayesian Mann-Whitney U test were used to assess the association between PET/CT and prescan PSA, PSA doubling time, and PSA velocity. <b><i>Results:</i></b> Evidence for no difference between PET/CT-positive and -negative patients for log-transformed PSA was found (BF₀₁ 3.61, % error: 0.01). Robustness check and sequential analysis showed stability across a wide range of prior distribution specifications. The hypothesis of no difference in terms of PSA-dt and for PSA-vel between groups was found to be more likely compared to the alternative hypothesis (BF₀₁ of 3.44 and 3.48, respectively). <b><i>Conclusion:</i></b> PSA and PSA kinetics are unlikely to be associated with ¹⁸F-fluciclovine PET/CT positivity in patients with BCR, and none of these serum biomarkers might be used as single predictors of PET/CT detection. Larger studies might be needed to evaluate the role of different predictors.

Prostate Specific Antigen Dynamics and Features in Prostate Cancer

Despite the common use of the prostate-specific antigen (PSA) serum level as a tumour marker in diagnosis of prostate cancer, it seems that the PSA doubling time (PSADT) and PSA velocity (PSAV) could be more useful indicators of tumour behaviour and prognosis for patients. The aim of the study was to evaluate the value of PSAV and PSADT in the diagnosis of prostate cancer and their relationship with prostate cancer histopathological characteristics. Eighty-six patients undergoing radical prostatectomy were enrolled in the study. Based on the PSA measurements the PSA dynamic values were calculated: PSADT and PSAV. In addition, clinical and histo-pathological characteristics, including disease stage and prognostic groups were evaluated. The obtained results showed that the first PSA value was 4.29 ng/ml (1.28–13.56), the second PSA value was 7.76 ng/ml (7.60–47.60), and the third PSA value was 9.67 ng/ml (2.56–98.50). The median PSADT was 51.01 months (7.80–311.81) and the median PSAV was 2.66 ng/ml/per year (0.22–4.66). In addition, significant correlations between PSAV and pre- and post-operative Gleason score, and prognostic groups were observed. Significant correlation between PSADT and pre- and pos-toperative Gleason score and prognostic risk groups was demonstrated. This study demonstrated that PSAV and PSADT were significantly correlated with postoperative Gleason score and prognostic risk groups, demonstrating its role in the diagnosis of prostate cancer progression.

Parameters predicting [18F]PSMA-1007 scan positivity and type and number of detected lesions in patients with biochemical recurrence of prostate cancer

Background Detection of the site of recurrence using PSMA-PET/CT is important to guide treatment in patients with biochemical recurrence of prostate cancer (PCa). The aim of this study was to evaluate the positivity rate of [18F]PSMA-1007-PET/CT in patients with biochemically recurrent PCa and identify parameters that predict scan positivity as well as the type and number of detected lesions. This monocentric retrospective study included 137 PCa patients with biochemical recurrence who underwent one or more [18F]PSMA-1007-PET/CT scans between August 2018 and June 2019. PET-positive malignant lesions were classified as local recurrence, lymph node (LN), bone or soft tissue lesions. The association between biochemical/paraclinical parameters, as PSA value, PSA doubling time, PSA velocity, Gleason score (GS) and androgen deprivation therapy (ADT), and scan positivity as well as type and number of detected lesions was evaluated using logistic regression analysis (binary outcomes) and Poisson models (count-type outcomes). Results We included 175 [18F]PSMA-1007-PET/CT scans after radical prostatectomy (78%), external beam radiation therapy (8.8%), ADT (7.3%), brachytherapy (5.1%) and high intensity focused ultrasound (0.7%) as primary treatment (median PSA value 1.6 ng/ml). Positivity rate was 80%. PSA value and PSA velocity were significant predictors of scan positivity as well as of the presence of bone and soft tissue lesions and number of bone, LN and soft tissue lesions, both in uni- and/or multivariable analysis. Multivariable analysis also showed prior ADT as predictor of bone and soft tissue lesions, GS as predictor of the number of bone lesions and ongoing ADT as predictor of the number of LN lesions. Conclusion [18F]PSMA-1007-PET/CT showed a high positivity rate in patients with biochemically recurrent PCa. PSA value and PSA velocity were significant predictors of scan positivity as well as of the presence and number of bone and soft tissue lesions and the number of LN lesions. Our findings can guide clinicians in optimal patient selection for [18F]PSMA-1007-PET/CT and support further research leading to the development of a prediction nomogram.

Evaluation of heterogeneous factors of low-grade prostate cancer in patients before and after radical prostatectomy

Objective: to determine the degree of heterogeneity of prostate cancer Gleason 6 (3 + 3) by assessing: long-term oncological results, mismatch of pre- and postoperative degree of prostate cancer aggressiveness, preoperative clinical component.Materials and methods. 528 patients with clinically localized prostate cancer and Gleason»s preoperative score of 6 (3 + 3). All patients were divided into 3 groups: group 1 (n = 151) — Gleason 6, prostate specific antigen (PSA) density <0.15ng/ml/cm3, ≤4 positive biopsy cores, <50 % lesion of the biopsy cores, group 2 (n = 229) — Gleason 6, PSA <10 ng/ml and group 3 (n = 148) — Gleason 6, PSA >10 ng/ml.Results. Statistically significant differences between group 1 and group 2 were observed only when assessing PSA velocity (p <0.017). The median time to the development of biochemical relapse (BCR) in the study population was 12 (3—77) months. BCR in group 1 was observed in 1.98 % of patients, in group 2 and 3 — 7.86 and 14.19 %, respectively. Statistically significant differences in the time of onset of BCR within 2 years after surgery were found between groups 1 and 2 (p = 0.002) and group 1 and 3 (p = 0.0001). An increase in the degree of malignancy after surgery in group 1 was determined only in 13 % of patients, in group 2 in 27 %, in group 3 in 43 % of patients. The contribution of a greater postoperative degree of malignancy of prostate cancer to the development of BCR in group 1 was 1.32 % (2 out of 3 patients). Thus, in group 1 in the case of true Gleason 6 (3 + 3), the probability of BCR was 0.66 %.Conclusion. PSA velocity before surgery showed a statistical difference between groups 1 and 2. Based on long-term oncological results after surgery, heterogeneous behavior of the tumor is observed among the study groups. Group 1 in comparison with group 2 and 3 showed the lowest frequency of increase in the Gleason score and the likelihood of developing BCR after surgery. These results may be useful in planning an individual patient treatment plan.

A prospective study of 68Ga-RM2 PET/MRI in patients with biochemically recurrent prostate cancer and negative conventional imaging.

e17536 Background: 68Ga-RM2 is a synthetic bombesin receptor antagonist targeting gastrin-releasing peptide receptors (GRPr) that are overexpressed in several human tumors, including prostate cancer (PC). Methods: We enrolled 114 men with BCR PC, 45-83-year-old (mean±SD: 68.2±7.0). Imaging started at 40-89 minutes (mean±SD: 51.3±9.2 after injection of 113.8-152.6 MBq (mean±SD: 140.7±6.4) of 68Ga-RM2 using a time-of-flight (TOF)-enabled simultaneous positron emission tomography (PET) / magnetic resonance imaging (MRI) scanner. Twenty-four and 23 patients also underwent 68Ga-PSMA11 and 18F-DCFPyL PET/CT, respectively. Results: All patients had rising PSA and negative conventional imaging prior to enrollment. 68Ga-RM2 PET identified recurrent PC in 78 of the 114 participants, while the simultaneous MRI was positive for PC in 45 of the 103 patients. Positivity rate of 68Ga-RM2 PET was: 31.8% for PSA < 0.5 ng/dl ( n= 22), 60% for PSA 0.5 – 1.0 ng/dl ( n= 15), 64.7% for PSA 1.0 – 2.0 ng/dl ( n= 17), 81.8% for PSA 2.0 – 5.0 ng/dl ( n= 22) and 87.2% for PSA > 5.0 ng/dl ( n= 38). PSA velocity values were 1.9±2.7 ng/ml/year (range: 0-9.1) in patients with negative PET scans and 5.8±9 ng/ml/year (range: 0.2-45.4) in patients with positive PET scans ( P: 0.01). Twenty-eight and 34 lesions were detected by 68Ga-RM2 PET and 68Ga-PSMA11 PET, respectively, while 25 lesions in 13 patients were identified by both radio-pharmaceuticals. The mean SUVmax ranged 1.6-51.2 (mean±SD:14.7±12.5) for PSMA and ranged 2.5-52.5 (mean±SD: 10.7±11.6) for RM2 ( P= 0.096). Three lesions in 2 patients were RM2-avid only (all lymph nodes) and 9 lesions in 7 patients were PSMA avid only (7 lymph nodes, 1 skeletal and 1 lung nodule). 32 and 48 lesions were detected by 68Ga-RM2 PET and 18F-DCFPyL PET, respectively. 28 lesions in 12 patients were identified by both radio-pharmaceuticals. The mean SUVmax ranged 1.7-79.3 (mean±SD: 22.2±23) for DCFPyL and ranged 1.7-46.8 (mean±SD: 7±9.2) for RM2 (P < 0.01). Four lesions in 2 patients were RM2 avid only (1 adrenal and 3 skeletal); 17 lesions in 6 patients were DCFPyL avid only (7 lymph nodes, 9 skeletal and 1 prostate). Conclusions: 68Ga-RM2 may identify higher risk patients given the highly statistically significant difference PSA velocity values between patients with negative and positive scans and may be a complementary radiopharmaceutical to the PSMA-targeting tracers to ultimately allow for personalized medicine. Clinical trial information: NCT02624518 .

Exploratory study of prognostic factors in mCRPC patients who administered enzalutamide focusing on early PSA decline and PSA kinetics at PSA progression: Results of retrospective multicenter study.

292 Background: Recent studies have shown that an early PSA response to AR-targeting agents in mCRPC is associated with a better prognosis. We analyzed the early PSA response to enzalutamide (ENZ) by measuring the PSA doubling time (PSADT) and PSA Velocity while monitoring oncologic outcomes and survival in Japanese patients. Methods: A total of 241 patients with mCRPC treated with ENZ were analyzed. Patients’ median age is 75±7.9 (range 53-93). The patients pre-docetaxel settings were 171 cases (71 %), post-docetaxel settings were 70 cases (29 %). The PSA-PFS and OS were assessed according to PCWG2 criteria. This study was approved by the institutional review board of Gunma University Hospital (No.1595). Results: A case where PSA did not decline at all was defined as Primary Resistance (PR). A case in which PSA once declined after treatment but then progressed was defined as Acquired Resistance (AR). Those in which PSA remained low after treatment were defined as Good Response (GR). We observed 77 PR cases (31.9 %), 125 AR cases (51.9 %) and 39 GR cases (16.2 %).PSA-PFS and OS pre-docetaxel were significantly increased as compared to patients’ post-docetaxcel (PSA-PFS; 47.0 wks vs. 13.4 wks p < 0.001, OS; Not Yet Reached vs. 80.7 wks p < 0.001). Multivariate analysis of prognostic factors, including the PSA response at 4 weeks, was performed using a Cox regression analysis. The PS (0 or 1-2), Hb (≧11.4 or < 11.4), time to CRPC(≧12 m or < 12 m), docetaxel treatment history (none or done) and a PSA decrease of 50% at 4 weeks were all significant factors for the prediction of OS (all variables, p < 0.05). In cases of acquired resistance (n = 125), a multivariate analysis using PSA kinetics factors such as PSADT and PSA Velocity (ng/mL/month) at PSA progression, Hb, time to CRPC(≧12 m or < 12 m), PSADT (≧2 months or < 2 months) and PSA Velocity ( < 20 ng/mL/month or≧20 ng/mL/month), were all factors predicting OS following PSA progression (p < 0.05). Conclusions: Our study has demonstrated that PSA dynamics after ENZ administration may be a useful prognostication factor for mCRPC patients.