Correction: von Eyben et al. A Risk Model for Patients with PSA-Only Recurrence (Biochemical Recurrence) Based on PSA and PSMA PET/CT: An Individual Patient Data Meta-Analysis. Cancers 2022, 14, 5461.

In the original publication [...].

Epigenetic Regulation of Driver Genes in Testicular Tumorigenesis.

In testicular germ cell tumor type II (TGCT), a seminoma subtype expresses an induced pluripotent stem cell (iPSC) panel with four upregulated genes, OCT4/POU5F1, SOX17, KLF4, and MYC, and embryonal carcinoma (EC) has four upregulated genes, OCT4/POU5F1, SOX2, LIN28, and NANOG. The EC panel can reprogram cells into iPSC, and both iPSC and EC can differentiate into teratoma. This review summarizes the literature on epigenetic regulation of the genes. Epigenetic mechanisms, such as methylations of cytosines on the DNA string and methylations and acetylations of histone 3 lysines, regulate expression of these driver genes between the TGCT subtypes. In TGCT, the driver genes contribute to well-known clinical characteristics and the driver genes are also important for aggressive subtypes of many other malignancies. In conclusion, epigenetic regulation of the driver genes are important for TGCT and for oncology in general.

A Risk Model for Patients with PSA-Only Recurrence (Biochemical Recurrence) Based on PSA and PSMA PET/CT: An Individual Patient Data Meta-Analysis.

An individual patient meta-analysis followed 1216 patients with PSA-only recurrence (biochemical recurrence, BCR) restaged with [68Ga]Ga-PSMA-11 PET/CT before the salvage treatment for median 3.5 years and analyzed the overall survival (OS). A new risk model included a good risk group with a prescan PSA < 0.5 ng/mL (26%), an intermediate risk group with a prescan PSA > 0.5 ng/mL and a PSMA PET/CT with 1 to 5 positive sites (65%), and a poor risk group with a prescan PSA > 0.5 ng/mL and a PSA PET/CT with > 5 positive sites (9%) (p < 0.0001, log rank test). The poor risk group had a five-year OS > 60%. Adding a BCR risk score by the European Association of Urology did not significantly improve the prediction of OS (p = 0.64). In conclusion, the restaging PSMA PET/CT markedly predicted the 5-year OS. The new risk model for patients with PSA-only relapse requires a restaging PSMA PET/CT for patients with a prescan PSA > 0.5 ng/mL and has a potential use in new trials aiming to improve the outcome for patients with PSA-only recurrence who have polysites prostate cancer detected on PSMA PET/CT.

177Lu-PSMA Radioligand Therapy Is Favorable as Third-Line Treatment of Patients with Metastatic Castration-Resistant Prostate Cancer. A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

In this systematic review and network meta-analysis (NMA), we aimed to assess the benefits and harms of third-line (L3) treatments in randomized controlled trials (RCTs) of patients with metastatic castration-resistant prostate cancer (mCRPC). Two reviewers searched for publications from 1 January 2006 to 30 June 2021. The review analyzed seven RCTs that included 3958 patients and eight treatments. Treatment with prostate-specific membrane antigen (PSMA)-based radioligand therapy (PRLT) resulted in a 1.3-times-higher rate of median PSA decline ≥50% than treatment with abiraterone, enzalutamide, mitoxantrone, or cabazitaxel (p = 0.00001). The likelihood was 97.6% for PRLT to bring about the best PSA response, out of the examined treatments. PRLT resulted in a 1.1-times-higher six-month rate of median radiographic progression-free survival. Treatment with PRLT in the VISION trial resulted in 1.05-times-higher twelve-month median overall survival than L3 treatment with cabazitaxel in other RCTs. PRLT more often resulted in severe thrombocytopenia and less often in severe leukopenia than did cabazitaxel. In conclusion, for patients with mCRPC, L3 treatment with PRLT is highly effective and safe.

68Ga-Labeled Prostate-specific Membrane Antigen Ligand Positron Emission Tomography/Computed Tomography for Prostate Cancer: A Systematic Review and Meta-analysis.

CONTEXT: 68Gallium prostate-specific membrane antigen (PSMA) ligand 68Ga-HBED-CC-PSMA (68Ga-PSMA) is a promising radiotracer for positron emission tomography (PET)/computed tomography (CT) of prostate cancer. OBJECTIVE: To conduct a meta-analysis to evaluate detection rate, diagnostic test accuracy, and adverse effects of 68Ga-PSMA PET/CT or PET/magnetic resonance imaging (MRI) for staging of prostate cancer and for restaging of rising prostate-specific antigen (PSA) after initial treatment. EVIDENCE ACQUISITION: Following the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines, our systematic review searched for articles in PubMed and EMBASE databases from 2012 to July 2016. The reference standard was pathology after biopsy or surgery. The analyses used a random effect model and a hierarchical summary receiver operating characteristic model. EVIDENCE SYNTHESIS: Fifteen 68Ga-PSMA PET/CT studies with 1256 patients met the inclusion criteria. Seven studies of staging PET/CT or PET/MRI detected a regional site of cancer for 203 of 273 patients (74%). Nine studies of restaging PET/CT detected sites of recurrence in 799 of 983 patients (81%) with a 50% detection rate (74 of 147 patients) for restaging PSA of 0.2-0.49 ng/ml and a 53% detection rate (56 of 195 patients) for restaging PSA of 0.50-0.99 ng/ml. Staging 68Ga-PSMA PET/CT in the studies had higher detection rates of sites in the prostate bed than restaging 68Ga-PSMA PET/CT (mean 57% vs 14%, p=0.031, t test). Both staging and restaging 68Ga-PSMA PET/CT found that a subgroup of the patients had metastatic sites in pelvic lymph nodes or distant organs. Eight studies of staging PET/CT undertook histologic correlations. We performed prostate-segment-based analysis specifically regarding the primary cancer lesion for four of these studies, and patient-based analysis specifically regarding pelvic lymph node metastases for four other studies. The pooled sensitivities for staging in the two groups of studies were 70% and 61%, and the pooled specificities were 84% and 97%. None of the studies reported complications from the PET/CT imaging. CONCLUSIONS: 68Ga-PSMA PET/CT has clinical relevance to detect sites of recurrence for patients with PSA recurrence after radical prostatectomy (RP) with PSA levels less than 1.0 ng/ml. PATIENT SUMMARY: Choline positron emission tomography (PET)/computed tomography (CT) can detect sites of recurrent prostate cancer in an earlier phase of prostate-specific antigen (PSA) recurrence than bone scans and CT scans, but choline PET/CT is rarely positive for patients with restaging PSA levels under 1 ng/ml. A new radiotracer called 68Ga-PSMA for PET/CT was able to detect sites of recurring cancer in up to 50% of patients who had an early rise in PSA exceeding 0.5 ng/ml after initial radical prostatectomy. The published studies did not report adverse effects of 68Ga-PSMA PET/CT imaging.

177Lu-PSMA-617 radioligand therapy for a patient with lymph node metastatic prostate cancer.

Prostate specific membrane antigen (PSMA) is expressed in unfavorable prostate cancer. PSMA is basis for new diagnostics and theranostics. PET/CT using PSMA is more sensitive than choline PET/CT. 177Lu-PSMA radioligand therapy is mainly used for patients with end-stage prostate cancer. This report describes a patient with a third recurrence in lymph nodes. The recurrence was treated with 177Lu-PSMA radioligand therapy instead of chemotherapy with docetaxel. The effect was in part evaluated relative to that of two established salvage treatments. Prior salvage radiotherapy and abiraterone of the first and second recurrence in lymph nodes had given only a partial reduction of PSA. Nevertheless within five months of follow-up, 177Lu-PSMA radioligand therapy of the third recurrence in lymph nodes reduced PSA for a period to unmeasurable levels. 177Lu-PSMA radioligand therapy gave only mild adverse effects. In conclusion, for a patient with lymph node metastatic prostate cancer, 177Lu-PSMA-617 radioligand therapy had an attractive therapeutic profile. A follow-up study of similar patients is being planned.

Acquisition with (11)C-choline and (18)F-fluorocholine PET/CT for patients with biochemical recurrence of prostate cancer: a systematic review and meta-analysis.

The objective of the systematic review and meta-analysis was to evaluate whether the choice between two radiotracers, (11)C-choline ((11)C-cho) and (18)F-fluorocholine ((18)F-FCH) for PET/CT, and different acquisition protocols contributed to detect metastases for patients with biochemical recurrence of prostate cancer after radical prostatectomy or radiotherapy. We searched in January 2016 in Pubmed and Embase for articles that had used radiolabeled choline PET/CT in restaging. The meta-analysis evaluated technical and clinical aspects. Across 18 articles 1 219 of 2 213 patients (54.9 %) had a positive radiolabeled PET/CT image. Mean of the mean/median restaging PSA levels was 3.6 ± 2.7 ng/mL (range 0.5-10.7 ng/mL). Six articles with (11)C-cho PET/CT had a radiation activity of 561 ± 122 MBq and it was 293 ± 47 MBq in 12 articles with (18)F-FCH PET/CT. The difference was significant (P = 0.007, t test). Uptake time was 5 min in articles with (11)C-cho PET/CT and it was 29 ± 24 min in articles with (18)F-FCH PET/CT. The difference was significant (P = 0.02, t test). Thereby the detection rates of metastatic sites in articles with (11)C-cho (30 ± 5 %) and (18)F-FCH (39 ± 5 %) did not differ significantly (P = 0.26, t test). In linear regression analyses of the articles, the radiation activity of (11)C-cho and (18)F-FCH was not significantly associated with the detection rate of metastatic sites (P = 0.75 and P = 0.60). Restaging with radiolabeled choline PET/CT detected metastatic sites for patients with biochemical recurrence and PSA levels of 1-10 ng/mL at clinically relevant level. The choice between the two choline radiotracers and different acquisition protocols had no significant impact on detection.

Meta-analysis of (11)C-choline and (18)F-choline PET/CT for management of patients with prostate cancer.

The aim of the study was to evaluate the diagnostic accuracy and clinical aspects of (11)C-choline and (18)F-choline PET/computed tomography (CT) in patients with prostate cancer. A meta-analysis of original studies from 1998 to September 2013 that described choline PET/CT scans for prostate cancer was conducted. We assessed the main sites of positive findings and the relationship between positive findings and histology, change of treatment and serum prostate-specific antigen (PSA) response to the changed treatment. A total of 3167 patients from 47 eligible articles were assessed with respect to their findings on choline PET/CT during staging and restaging for biochemical recurrence. We examined 661 patients at staging and 158 patients at restaging for biochemical recurrence after external beam radiotherapy. These patients had positive results in the prostate bed more often than did the 2348 patients with biochemical recurrence after radical prostatectomy (P<0.001, χ(2)-test). On assessing 609 patients, the pooled sensitivity of choline PET/CT for pelvic lymph node metastases was found to be 0.62 [95% confidence interval (CI) 0.51-0.66] and the pooled specificity was found to be 0.92 (95% CI 0.89-0.94). Head-to-head studies of 280 patients showed that more patients had positive findings with choline PET/CT than with bone scanning [127 (45%) vs. 46 (16%), odds ratio 2.8, 95% CI 1.9-4.1, P<0.0005, Wilcoxon rank test]. Choline PET/CT led to a change in treatment in 381 (41%) of 938 patients. The changes yielded complete PSA response in 101 of 404 (25%) patients. (11)C-choline or (18)F-choline PET/CT is useful as the first imaging examination for patients with prostate cancer and biochemical recurrence with PSA levels between 1.0 and 50 ng/ml.

Computed tomography scans of intra-abdominal fat, anthropometric measurements, and 3 nonobese metabolic risk factors.

The present cross-sectional study of 46 adult Danish white men and women aimed to evaluate association between intra-abdominal obesity, 4 anthropometric measurements of obesity, and combinations of 3 nonobese metabolic risk factors: systolic blood pressure of 130 mm Hg or higher, serum triglyceride concentration of more than 1.7 mmol/L, and fasting capillary blood glucose concentration of 5.6 mmol/L or more. For 80% of the subjects, intra-abdominal fat on a computed tomography scan of the abdomen using a cutoff limit of more than 144 cm(2) gave a correct classification of combinations of at least 2 of the 3 metabolic risk factors. Body mass index and waist circumference were better markers of intra-abdominal obesity than waist-to-hip ratio in receiver operating characteristic analyses (P = .0035). Body mass index of more than 26 kg/m(2) and waist circumference of more than 0.92 m classified 76% and 74% of the subjects correctly regarding combinations of the 3 nonobese metabolic risk factors. Intra-abdominal obesity was significantly stronger associated with the combinations than a raised waist-to-hip ratio (P = .016). Both body mass index and waist circumference may be used as markers of intra-abdominal obesity, whereas waist-to-hip ratio was significantly inferior. Correspondingly, both body mass index and waist circumference were better than waist-to-hip ratio to indicate combinations of the 3 nonobese metabolic risk factors.