Kendi, Ayse T

Abstract The American Joint Committee on Cancer (AJCC) staging system for all cancer sites, including gastroenteropancreatic neuroendocrine tumors (GEP‐NETs), is meant to be dynamic, requiring periodic updates to optimize AJCC staging definitions. This entails the collaboration of experts charged with evaluating new evidence that supports changes to each staging system. GEP‐NETs are the second most prevalent neoplasm of gastrointestinal origin after colorectal cancer. Since publication of the AJCC eighth edition, the World Health Organization has updated the classification and separates grade 3 GEP‐NETs from poorly differentiated neuroendocrine carcinoma. In addition, because of major advancements in diagnostic and therapeutic technologies for GEP‐NETs, AJCC version 9 advocates against the use of serum chromogranin A for the diagnosis and monitoring of GEP‐NETs. Furthermore, AJCC version 9 recognizes the increasing role of endoscopy and endoscopic resection in the diagnosis and management of NETs, particularly in the stomach, duodenum, and colorectum. Finally, T1NXM0 has been added to stage I in these disease sites as well as in the appendix.

Metastatic prostate cancer continues to be an incurable disease. Despite all the novel therapies approved in the past two decades, overall patient outcomes remain relatively poor, and these patients die on a regular basis. Clearly, improvements in current therapies are needed. Prostate-specific membrane antigen (PSMA) is a target for prostate cancer given its increased expression on the surface of the prostate cancer cells. PSMA small molecule binders include PSMA-617 and PSMA-I&T and monoclonal antibodies such as J591. These agents have been linked to different radionuclides including beta-emitters such as lutetium-177 and alpha-emitters such as actinium-225. The only regulatory-approved PSMA-targeted radioligand therapy (PSMA-RLT) to date is lutetium-177–PSMA-617 in the setting of PSMA-positive metastatic castration-resistant prostate cancer that has failed androgen receptor pathway inhibitors and taxane chemotherapy. This approval was based on the phase III VISION trial. Many other clinical trials are evaluating PSMA-RLT in various settings. Both monotherapy and combination studies are underway. This article summarizes pertinent data from recent studies and provides an overview of human clinical trials in progress. The field of PSMA-RLT is rapidly evolving, and this therapeutic approach will likely play an increasingly important role in the years to come.

AbstractBackgroundProstatic specific antigen (PSA) has well‐recognized limitations as a marker for treatment response and disease progression. Post hoc analysis of the PREVAIL trial reported 24.5% of chemotherapy naïve metastatic castration‐resistant prostate cancer (mCRPC) patients on enzalutamide had radiographic progression on conventional imaging with nonrising PSA. In this study, we sought to study the discordance of imaging with PSA kinetics in mCRPC patients on second generation anti‐androgens (SGA) post‐chemotherapy using combined conventional imaging, and new generation imaging in the form of C‐11 choline positron emission tomography/computed tomography (C[11] choline PET/CT) scan.MethodsWe retrospectively reviewed the medical records of 123 patients with mCRPC treated with SGA (Abiraterone or Enzalutamide) after docetaxel between 2016 and 2019. Patients underwent PSA testing, and C[11] choline PET/CT scan at baseline level before starting treatment with SGA, then every 3–6 months as part of their follow up evaluation. Loss of response to SGA was defined by increase in corrected maximum standardized uptake value (SUVmax) of pretreatment lesions on C‐11 Choline PET/CT, and/or development of new lesions. Suspicious new lesions were confirmed by biopsy and/or conventional imaging.ResultsWe identified 123 mCRPC patients who received SGA (Abiraterone, n = 106; Enzalutamide, n = 17) after docetaxel. Median duration of therapy was 13.9 months (interquartile range: 8.75–21.14). Approximately 43% (n = 53) of subjects in this study exhibited an increase in choline avidity while on SGA. Of this group, 60.4% of patients experienced a parallel rise in PSA (Group‐A), whereas 39.6% displayed a paradoxical response (PR) (Group‐B), defined as increased choline avidity combined with stable or down‐trending PSA. Median PSA at time of increase in choline avidity was 3.1 ng/ml for Group‐A, and 1.3 ng/ml for Group‐B (p = 0.0176). Median SUVmax was similar in both groups (4.9 for Group‐A, 4.6 for Group‐B; p = 0.6072). The median time for increase in choline avidity was 9.5 versus 3.9 months for Group‐A versus Group‐B, respectively (Log‐Rank = 0.0063).ConclusionNearly 40% of mCRPC patients placed on SGA post docetaxel chemotherapy will exhibit paradoxical responses to therapy, therefore, warranting close follow up with imaging. C‐11 choline PET/CT imaging is a useful tool that can help in early predication of disease progression or treatment failure.

Abstract Background Radium (Ra)‐223 is an established treatment option for patients with metastatic castrate‐resistant prostate cancer (mCRPC) who have symptomatic bone metastases without soft tissue disease. Studies have indicated genetic aberrations that regulate DNA damage response (DDR) in prostate cancer can increase susceptibility to treatments such as poly ADP‐ribose polymerase inhibitors and platinum‐based therapies. This study aims to evaluate mCRPC response to Ra‐223 stratified by tumor genomics. Methods This is a retrospective study of mCRPC patients who received Ra‐223 and genetic testing within the Mayo Clinic database (Arizona, Florida, and Minnesota) and Tulane Cancer Center. Patient demographics, genetic aberrations, treatment responses in terms of alkaline phosphatase (ALP) and prostate‐specific antigen (PSA), and survival were assessed. Primary end points were ALP and PSA response. Secondary end points were progression‐free survival (PFS) and overall survival (OS) from time of first radium treatment. Results One hundred and twenty‐seven mCRPC patients treated with Ra‐223 had germline and/or somatic genetic sequencing. The median age at time of diagnosis and Ra‐223 treatment was 61.0 and 68.6 years, respectively. Seventy‐nine (62.2%) had Gleason score ≥ 8 at time of diagnosis. 50.4% received prior docetaxel, and 12.6% received prior cabazitaxel. Notable alterations include TP53 (51.7%), BRCA 1/2 (15.0%), PTEN (13.4%), ATM (11.7%), TMPRSS2‐ERG (8.2%), RB deletion (3.4%), and CDK12 (1.9%). There was no significant difference in ALP or PSA response among the different genetic aberrations. Patients with a TMPRSS2‐ERG mutation exhibited a trend toward lower OS 15.4 months (95% confidence interval [CI] 10.0−NR) versus 26.8 months (95% CI 20.9−35.1). Patients with an RB deletion had a lower PFS 6.0 months (95% CI 1.28−NR) versus 9.0 months (95% CI 7.3−11.1) and a lower OS 13.9 months (95% CI 5.2−NR) versus 26.5 months (95% CI 19.8−33.8). Conclusions Among mCRPC patients treated with Ra‐223 at Mayo Clinic and Tulane Cancer Center, we did not find any clear negative predictors of biochemical response or survival to treatment. TMPRSS2‐ERG and RB mutations were associated with a worse OS. Prospective studies and larger sample sizes are needed to determine the impact of genetic aberrations in response to Ra‐223.

AbstractBackgroundWe sought to assess the prognostic utility of 11C‐choline positron emission tomography/computed tomography (PET/CT) in patients with metastatic castrate resistant prostate cancer (mCRPC) undergoing primary docetaxel chemotherapy.MethodsWe performed a single institution retrospective analysis of 77 mCRPC patients who were treated with 6 cycles of docetaxel chemotherapy, and who also underwent 11C‐choline PET/CT scans at baseline (before chemotherapy), mid‐course (after 3 cycles), and posttherapy (after 6 cycles). We evaluated treatment response based on percent change in blood pool‐corrected maximum standardized uptake value (SUVmax) of the target lesion on PET/CT, as well as percent change in serum prostate specific antigen (PSA). Logistic regression analysis was used to identify factors associated with complete treatment response. Progression free survival (PFS) analysis was performed using log‐rank test and shown on Kaplan–Meier plot.ResultsPercent change in blood pool‐corrected SUVmax on mid‐course scan was a significant predictor of complete response (odds ratio [OR]: 0.98, 95% confidence interval [CI]: 0.96–0.99, p = .0003), whereas percent change in PSA was not (OR: 0.99, 95% CI: 0.99–1.01, p = .6025). 57 of 77 patients (74%) achieved ≥20% reduction in blood pool‐corrected SUVmax on mid‐course; these patients were 3.6 times more likely to achieve complete response after full 6 cycles of docetaxel chemotherapy, compared to patients with <20% reduction in blood pool‐corrected SUVmax (OR: 3.56, 95% CI: 1.04–16.52, p = .0420). Median PFS in the complete response group was 35.1 months (95% CI: 26.0–52.7 months), compared to 9.4 months (95% CI: 6.9–13.0 months) in the incomplete response group (p = .0005).ConclusionsOur study showed that mid‐course and posttherapy 11C‐choline PET/CT evaluation for mCRPC patients undergoing primary docetaxel chemotherapy can predict full course treatment response and PFS, respectively. 11C‐choline PET/CT imaging may provide valuable prognostic information to guide treatment choices for patients with mCRPC.