Active surveillance selection and 3-year durability in intermediate-risk prostate cancer following genomic testing.

BACKGROUND: Genomic testing can add risk stratification information to clinicopathological features in prostate cancer, aiding in shared medical decision-making between the clinician and patient regarding whether active surveillance (AS) or definitive treatment (DT) is most appropriate. Here we examined initial AS selection and 3-year AS durability in patients diagnosed with localized intermediate-risk prostate cancer who underwent Prolaris testing before treatment decision-making. METHODS: This retrospective observational cohort study included 3208 patients from 10 study sites who underwent Prolaris testing at diagnosis from September 2015 to December 2018. Prolaris utilizes a combined clinical cell cycle risk score calculated at diagnostic biopsy to stratify patients by the Prolaris AS threshold (below threshold, patient recommended to AS or above threshold, patient recommended to DT). AS selection rates and 3-year AS durability were compared in patients recommended to AS or DT by Prolaris testing. Univariable and multivariable logistic regression models and Cox proportional hazard models were used with molecular and clinical variables as predictors of initial treatment decision and AS durability, respectively. RESULTS: AS selection was ~2 times higher in patients recommended to AS by Prolaris testing than in those recommended to DT (p < 0.0001). Three-year AS durability was ~1.5 times higher in patients recommended to AS by Prolaris testing than in those recommended to DT (p < 0.0001). Prolaris treatment recommendation remained a statistically significant predictor of initial AS selection and AS durability after accounting for CAPRA or Gleason scores. CONCLUSIONS: Prolaris added significant information to clinical risk stratification to aid in treatment decision making. Intermediate-risk prostate cancer patients who were recommended to AS by Prolaris were more likely to initially pursue AS and were more likely to remain on AS at 3 years post-diagnosis than patients recommended to DT.

Stockholm3 in a Multiethnic Cohort for Prostate Cancer Detection (SEPTA): A Prospective Multicentered Trial.

PURPOSE: Asian, Black, and Hispanic men are underrepresented in prostate cancer (PCa) clinical trials. Few novel prostate cancer biomarkers have been validated in diverse cohorts. We aimed to determine if Stockholm3 can improve prostate cancer detection in a diverse cohort. METHODS: An observational prospective multicentered (17 sites) clinical trial (2019-2023), supplemented by prospectively recruited participants (2008-2020) in a urology clinic setting included men with suspicion of PCa and underwent prostate biopsy. Before biopsy, sample was collected for measurement of the Stockholm3 risk score. Parameters include prostate-specific antigen (PSA), free PSA, KLK2, GDF15, PSP94, germline risk (single-nucleotide polymorphisms), age, family history, and previous negative biopsy. The primary endpoint was detection of International Society of Urological Pathology (ISUP) Grade ≥2 cancer (clinically significant PCa, csPC). The two primary aims were to (1) demonstrate noninferior sensitivity (0.8 lower bound 95% CI noninferiority margin) in detecting csPC using Stockholm3 compared with PSA (relative sensitivity) and (2) demonstrate superior specificity by reducing biopsies with benign results or low-grade cancers (relative specificity). RESULTS: A total of 2,129 biopsied participants were included: Asian (16%, 350), Black or African American (Black; 24%, 505), Hispanic or Latino and White (Hispanic; 14%, 305), and non-Hispanic or non-Latino and White (White; 46%, 969). Overall, Stockholm3 showed noninferior sensitivity compared with PSA ≥4 ng/mL (relative sensitivity: 0.95 [95% CI, 0.92 to 0.99]) and nearly three times higher specificity (relative specificity: 2.91 [95% CI, 2.63 to 3.22]). Results were consistent across racial and ethnic subgroups: noninferior sensitivity (0.91-0.98) and superior specificity (2.51-4.70). Compared with PSA, Stockholm3 could reduce benign and ISUP 1 biopsies by 45% overall and between 42% and 52% across racial and ethnic subgroups. CONCLUSION: In a substantially diverse population, Stockholm3 significantly reduces unnecessary prostate biopsies while maintaining a similar sensitivity to PSA in detecting csPC.

The Clinical Cell-Cycle Risk (CCR) Score Is Associated With Metastasis After Radiation Therapy and Provides Guidance on When to Forgo Combined Androgen Deprivation Therapy With Dose-Escalated Radiation.

PURPOSE: The clinical cell-cycle risk (CCR) score, which combines the University of California, San Francisco's Cancer of the Prostate Risk Assessment (CAPRA) and the cell cycle progression (CCP) molecular score, has been validated to be prognostic of disease progression for men with prostate cancer. This study evaluated the ability of the CCR score to prognosticate the risk of metastasis in men receiving dose-escalated radiation therapy (RT) with or without androgen deprivation therapy (ADT). METHODS AND MATERIALS: This retrospective, multi-institutional cohort study included men with localized National Comprehensive Cancer Network (NCCN) intermediate-, high-, and very high-risk prostate cancer (N = 741). Patients were treated with dose-escalated RT with or without ADT. The primary outcome was time to metastasis. RESULTS: The CCR score prognosticated metastasis with a hazard ratio (HR) per unit score of 2.22 (95% confidence interval [CI], 1.71-2.89; P < .001). The CCR score better prognosticated metastasis than NCCN risk group (CCR, P < .001; NCCN, P = .46), CAPRA score (CCR, P = .002; CAPRA, P = .59), or CCP score (CCR, P < .001; CCP, P = .59) alone. In bivariable analyses, CCR score remained highly prognostic when accounting for ADT versus no ADT (HR, 2.18; 95% CI, 1.61-2.96; P < .001), ADT duration as a continuous variable (HR, 2.11; 95% CI, 1.59-2.79; P < .001), or ADT given at or below the recommended duration for each NCCN risk group (HR, 2.19; 95% CI, 1.69-2.86; P < .001). Men with CCR scores below or above the multimodality threshold (CCR score, 2.112) had a 10-year risk of metastasis of 3.7% and 21.24%, respectively. Men with below-threshold scores receiving RT alone had a 10-year risk of metastasis of 3.7%, and for men receiving RT plus ADT, the 10-year risk of metastasis was also 3.7%. CONCLUSIONS: The CCR score accurately and precisely prognosticates metastasis and adds clinically actionable information relative to guideline-recommended therapies based on NCCN risk in men undergoing dose-escalated RT with or without ADT. For men with scores below the multimodality threshold, adding ADT may not significantly reduce their 10-year risk of metastasis.

Fluorine-18-Labeled Fluciclovine PET/CT in Clinical Practice: Factors Affecting the Rate of Detection of Recurrent Prostate Cancer.

OBJECTIVE. The purpose of this study is to show the performance and evaluate the factors influencing the positivity rate (PR) of commercially produced 18F-fluciclovine PET/CT in the detection of recurrent prostate cancer in clinical practice. MATERIALS AND METHODS. We performed a retrospective cohort study of 152 men who had suspected biochemical recurrence of prostate cancer after receiving initial treatment and underwent fluciclovine PET/CT. PRs were calculated for whole-body, prostate and prostate bed, and extraprostatic locations. The influence of different factors, such as the absolute prostate-specific antigen (PSA) level, PSA kinetics, the Gleason score, and Gleason grade groups, on the PR was evaluated. RESULTS. The overall PR was 81% (123/152) for the whole body, 61% (92/152) for the prostate and prostate bed, and 55% (83/152) for extraprostatic locations. There was a linear increase in the PR with an increasing PSA level (p < 0.001). For the whole body, the PR for PSA levels of less than 1 ng/mL, 1 to less than 2 ng/mL, 2 to less than 5 ng/mL, and 5 or more ng/mL were 58% (32/55), 87% (13/15), 100% (39/39), and 92% (35/38), respectively. No statistically significant linear trend was found between the PR and the PSA level doubling time (p > 0.05). In addition, no statistically significant linear trend was found between the PR and increasing Gleason grade group. However, for every 1-unit increase in a patient's Gleason score, the odds of a positive finding in the extraprostatic location increased by 49% (p < 0.05). CONCLUSION. Commercially produced fluciclovine PET/CT has a high PR for detection of prostate cancer recurrence and is positively correlated with increasing PSA levels. For extraprostatic disease, the PR increases with higher Gleason scores.

Metastatic Male Breast Cancer With Increased Uptake on 18F-Fluciclovine PET/CT Scan.

Prostate imaging with F-labeled 1-amino-3-fluorocyclobutane-1-carboxylic acid (FACBC, F-fluciclovine) PET/CT scan (Axumin) was recently approved by the US Food and Drug Administration for men with suspected prostate cancer recurrence based on elevated blood prostate-specific antigen levels following prior treatment. We present a rare case of a 77-year-old man with suspected recurrent prostate cancer with an incidental finding of advanced-stage breast cancer showing different degrees of F-fluciclovine uptake.

Small Cell Carcinoma of the Prostate: A Case Report and Brief Review of the Literature.

Small cell carcinoma of the prostate (SCCP) is a rare disorder. We present here a case of SCCP exhibiting multiple unique clinical findings, demonstrating the variability of SCCP at presentation.

Radiation exposure to the corporeal bodies during 3-dimensional conformal radiation therapy for prostate cancer.

PURPOSE: Radiation therapy for prostate cancer is associated with the development of post-treatment erectile dysfunction. Use of 3-dimensional (D) conformal delivery techniques has reduced delivery of radiation to periprostatic tissues. However, the exact magnitude of radiation that the corporeal bodies are exposed to using this delivery technique is currently unknown. This study was undertaken to calculate the radiation dose delivered to the corporeal bodies during 3-D conformal radiotherapy. MATERIALS AND METHODS: Ten patients with proven prostate adenocarcinoma who underwent pre-therapy computerized tomography simulation and radiation delivery planning had the proximal corporeal bodies outlined on axial computerized tomography. The dose to the proximal penile tissues was then calculated using computer modeling. RESULTS: The total dose of radiation administered to the prostate and seminal vesicles was 73.8 Gy. Mean radiation delivered to the most proximal 2 cm. of the corporeal bodies was 31 +/- 12.8 Gy., equating to 43% of the total dose of radiation delivered to the prostate and seminal vesicles. CONCLUSIONS: These data indicate that large doses of radiation are being delivered to erectile tissue in the proximal penis despite careful pretreatment planning for 3-D conformal radiation therapy for prostate cancer. These data should encourage the development of radiation delivery strategies that minimize corporeal tissue exposure.