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Serum prostate-specific antigen (PSA) needs to be monitored with ultrasensitive PSA assays (uPSAs) for oncologists to be able to start salvage radiotherapy (SRT) while PSA is <0.5 µg/L for patients with prostate cancer (PCa) relapsing after a radical prostatectomy (RP). Our systematic review (SR) aimed to summarize uPSAs for patients with localized PCa. The SR was registered as InPLASY2023110084. We searched for studies on Google Scholar, PUBMED and reference lists of reviews and studies. We only included studies on uPSAs published in English and excluded studies of women, animals, sarcoidosis and reviews. Of the 115 included studies, 39 reported PSA assay methods and 76 reported clinical findings. Of 67,479 patients, 14,965 developed PSA recurrence (PSAR) and 2663 died. Extremely low PSA nadir and early developments of PSA separated PSAR-prone from non-PSAR-prone patients (cumulative p value 3.7 × 1012). RP patients with the lowest post-surgery PSA nadir and patients who had the lowest PSA at SRT had the fewest deaths. In conclusion, PSA for patients with localized PCa in the pre-PSAR phase of PCa is strongly associated with later PSAR and survival. A rising but still exceedingly low PSA at SRT predicts a good 5-year overall survival.

To broaden our understanding of baseline PSA variations over the last decades in men under 40 years old. We analysed the baseline total PSA of 48,896 men below the age of 40 years, grouped into 3 age groups: <30 (n = 6,123), 30-35 (n = 16,118), and >35 (n = 25,351) years old. Multiple linear regression model predicted the average LogPSA per month as a function of time, age, and testing rate during the 16-year period of the data (2003-2018). The average age and standard deviation were 34.5 ±4.6 years, and the median PSA ± interquartile range was 0.63 ±0.46 ng/dl with a leftward skew towards zero (81% of results below 1 ng/dl) in all years. The average LogPSA was steadily rising over time, independent of age and testing rate in all 3 age groups: multiple R = 0.40, estimate = 1.211e-05, p <0.0001. Mean/median PSA and age were 0.69/0.57 ng/dl and 35.6/37.2 years in 2003 and 1.04/0.66 ng/dl and 33.6/35.8 years in 2018. The average baseline PSA is rising in young men. Changes in medical routine practice (e.g. reserving the test for those with higher suspicion) and a true rise in benign or pathological prostate conditions are possible reasons.

Background The majority of men referred with a raised PSA for suspected prostate cancer will receive unnecessary tertiary investigations including MRI and biopsy. Here, we compared different types of biomarkers to refine tertiary referrals and when different definitions of clinically significant cancer were used. Methods Data and samples from 798 men referred for a raised PSA (≥ 3 ng/mL) and investigated through an MRI-guided biopsy pathway were accessed for this study. Bloods were acquired pre-biopsy for liquid biomarkers and germline DNA. Variables explored included PSA + Age (base model), free/total PSA (FTPSA), Prostate Health Index ( phi ), PSA density (PSAd), polygenic risk score (PRS) and MRI (≥ LIKERT 3). Different diagnostic endpoints for significant cancer (≥ grade group 2 [GG2], ≥ GG3, ≥ Cambridge Prognostic Group 2 [CPG2], ≥ CPG3) were tested. The added value of each biomarker to the base model was evaluated using logistic regression models, AUC and decision curve analysis (DCA) plots. Results The median age and PSA was 65 years and 7.13 ng/mL respectively. Depending on definition of clinical significance, ≥ grade group 2 (GG2) was detected in 57.0% (455/798), ≥ GG3 in 27.5% (220/798), ≥ CPG2 in 61.6% (492/798) and ≥ CPG3 in 42.6% (340/798). In the pre-MRI context, the PSA + Age (base model) AUC for prediction of ≥ GG2, ≥ GG3, ≥ CPG2 and ≥ CPG3 was 0.66, 0.68, 0.70 and 0.75 respectively. Adding phi and PSAd to base model improved performance across all diagnostic endpoints but was notably better when the composite CPG prognostic score was used: AUC 0.82, 0.82, 0.83, 0.82 and AUC 0.74, 0.73, 0.79, 0.79 respectively. In contrast, neither FTPSA or PRS scores improved performance especially in detection of ≥ GG3 and ≥ CPG3 disease. Combining biomarkers did not alter results. Models using phi and PSAd post-MRI also improved performances but again benefit varied with diagnostic endpoint. In DCA analysis, models which incorporated PSAd and phi in particular were effective at reducing use of MRI and/or biopsies especially for ≥ CPG3 disease. Conclusion Incorporating phi or PSAd can refine and tier who is referred for tertiary imaging and/or biopsy after a raised PSA test. Incremental value however varied depending on the definition of clinical significance and was particularly useful when composite prognostic endpoints are used.

Abstract Objectives To provide a mathematical background for understanding the phenomenon of analyte hemodilution using a kinetic analysis. Methods The first assumption for this analysis is that change in concentration of any analyte, such as prostate-specific antigen (PSA), is due to the flux of the analyte from an organ into the blood minus its flux from the blood. What results is a relatively simple differential equation that emphasizes the importance of plasma volume, organ mass, and two rate constants. Results The analyses demonstrate how serum PSA can be affected by plasma volume as well as body mass and how hemodilution due to obesity can be at least partly corrected for by expressing PSA in units of total mass or total mass density. Conclusions At a time when obesity is prevalent, expressing analytes in units of total mass may make them relate more closely to disease status and prognosis.

Prostate cancer is one of the malignancies that affects men and significantly contributes to increased mortality rates in men globally. Patients affected with prostate cancer present with either a localized or advanced disease. In this review, we aim to provide a holistic overview of prostate cancer, including the diagnosis of the disease, mutations leading to the onset and progression of the disease, and treatment options. Prostate cancer diagnoses include a digital rectal examination, prostate-specific antigen analysis, and prostate biopsies. Mutations in certain genes are linked to the onset, progression, and metastasis of the cancer. Treatment for localized prostate cancer encompasses active surveillance, ablative radiotherapy, and radical prostatectomy. Men who relapse or present metastatic prostate cancer receive androgen deprivation therapy (ADT), salvage radiotherapy, and chemotherapy. Currently, available treatment options are more effective when used as combination therapy; however, despite available treatment options, prostate cancer remains to be incurable. There has been ongoing research on finding and identifying other treatment approaches such as the use of traditional medicine, the application of nanotechnologies, and gene therapy to combat prostate cancer, drug resistance, as well as to reduce the adverse effects that come with current treatment options. In this article, we summarize the genes involved in prostate cancer, available treatment options, and current research on alternative treatment options.

Purpose To examine the relationship between the extent of disease determined by [ 68 Ga]PSMA-HBED-CC-PET/CT and the important clinical measures prostate-specific antigen (PSA), PSA doubling time (PSAdt) and Gleason score. Methods We retrospectively studied the first 155 patients with recurrent prostate cancer (PCA) referred to our university hospital for [ 68 Ga]PSMA-HBED-CC PET/CT. Results PET/CT was positive in 44 %, 79 % and 89 % of patients with PSA levels of ≤1, 1 – 2 and ≥2 ng/ml, respectively. Patients with high PSA levels showed higher rates of local prostate tumours ( p  < 0.001), and extrapelvic lymph node ( p  = 0.037) and bone metastases ( p  = 0.013). A shorter PSAdt was significantly associated with pelvic lymph node ( p  = 0.026), extrapelvic lymph node ( p  = 0.001), bone ( p  < 0.001) and visceral ( p  = 0.041) metastases. A high Gleason score was associated with more frequent pelvic lymph node metastases ( p  = 0.039). In multivariate analysis, both PSA and PSAdt were independent determinants of scan positivity and of extrapelvic lymph node metastases. PSAdt was the only independent marker of bone metastases ( p  = 0.001). Of 20 patients with a PSAdt <6 months and a PSA ≥2 ng/ml, 19 (95 %) had a positive scan and 12 (60 %) had M1a disease. Of 14 patients with PSA <1 ng/ml and PSAdt >6 months, only 5 (36 %) had a positive scan and 1 (7 %) had M1a disease. Conclusion [ 68 Ga]PSMA-HBED-CC PET/CT will identify PCA lesions even in patients with very low PSA levels. Higher PSA levels and shorter PSAdt are independently associated with scan positivity and extrapelvic metastases, and can be used for patient selection for [ 68 Ga]PSMA-HBED-CC PET/CT.

Previous studies suggest that North Pacific extratropical atmospheric variability influences ENSO via the seasonal footprinting mechanism (SFM). This study confirms that quadrapole sea surface temperature (SST) variability in the extratropical South Pacific triggered by mid-latitude South Pacific atmospheric variability may also have an additional influence on ENSO. The response of the evolution of the ENSO-related zonal wind and SST anomalies in the tropics to the South Pacific extratropical forcing is consistent with the SFM hypothesis. That is, the Pacific–South American (PSA) pattern of the South Pacific extratropical sea level pressure (SLP) anomalies imparts an SST footprint (i.e., a quadrapole SST pattern) onto the ocean during austral summer. This SST footprint subsequently forces the zonal wind anomalies along the equator in the following austral winter that ultimately result in ENSO events during the following austral summer via ocean–atmosphere coupling in the tropics. The present study demonstrates that the influences of extratropical atmospheric variability in the South Pacific and North Pacific on ENSO are different and relatively independent. It is possible that they may, together or separately, influence the occurrence of ENSO events, and the importance of the South Pacific forcing in initiating ENSO events is comparable with that of the North Pacific forcing. An empirical model was established to predict the Niño3.4 index based on the combined South Pacific and North Pacific signals, and results show that it can be used to produce skillful forecasts of the Niño3.4 index with a leading time of up to 1 year.

Prostate cancer (PC) is the second most diagnosed cancer among men. It was observed that early diagnosis of disease is highly beneficial for the survival of cancer patients. Therefore, the extension and increasing quality of life of PC patients can be achieved by broadening the cancer screening programs that are aimed at the identification of cancer manifestation in patients at earlier stages, before they demonstrate well-understood signs of the disease. Therefore, there is an urgent need for standard, sensitive, robust, and commonly available screening and diagnosis tools for the identification of early signs of cancer pathologies. In this respect, the “Holy Grail” of cancer researchers and bioengineers for decades has been molecular sensing probes that would allow for the diagnosis, prognosis, and monitoring of cancer diseases via their interaction with cell-secreted and cell-associated PC biomarkers, e.g., PSA and PSMA, respectively. At present, most PSA tests are performed at centralized laboratories using high-throughput total PSA immune analyzers, which are suitable for dedicated laboratories and are not readily available for broad health screenings. Therefore, the current trend in the detection of PC is the development of portable biosensors for mobile laboratories and individual use. Phage display, since its conception by George Smith in 1985, has emerged as a premier tool in molecular biology with widespread application. This review describes the role of the molecular evolution and phage display paradigm in revolutionizing the methods for the early diagnosis and monitoring of PC.

Epigenetic “clocks” can now surpass chronological age in accuracy for estimating biological age. Here, we use four such age estimators to show that epigenetic aging can be reversed in humans. Using a protocol intended to regenerate the thymus, we observed protective immunological changes, improved risk indices for many age‐related diseases, and a mean epigenetic age approximately 1.5 years less than baseline after 1 year of treatment (−2.5‐year change compared to no treatment at the end of the study). The rate of epigenetic aging reversal relative to chronological age accelerated from −1.6 year/year from 0–9 month to −6.5 year/year from 9–12 month. The GrimAge predictor of human morbidity and mortality showed a 2‐year decrease in epigenetic vs. chronological age that persisted six months after discontinuing treatment. This is to our knowledge the first report of an increase, based on an epigenetic age estimator, in predicted human lifespan by means of a currently accessible aging intervention. Epigenetic aging—an accurate measure of biological aging in humans—can run in reverse. A thymus regeneration protocol has enabled estimated biological age to decrease in healthy 51‐ to 65‐year‐old men by 1.5 years after 1 year of treatment (or by 2.5 years compared to chronological age). This significantly exceeds the heretofore theoretical concept of “longevity escape velocity,” wherein biological age is reduced by 1 year for every 1 year of chronological age.

Objective: To assess the influence of biochemical recurrence (BCR) risk groups and PSA kinetics on the outcomes of radioguided surgery against prostate-specific membrane antigen (PSMA-RGS). Currently, neither BCR risk group nor PSA doubling time (PSA-DT), or PSA velocity (PSA-V) are actively assigned or relevant for counseling prior to PSMA-RGS. Methods: We retrospectively analyzed PSMA-RGS cases for oligorecurrent prostate cancer between 2014 and 2023. BCR risk groups, PSA-DT, and PSA-V were analyzed as predictors for complete biochemical response (cBR, PSA < 0.2 ng/mL), BCR-free, and therapy-free survival (BCRFS, TFS). Results: Of 374 included patients, only 21/374 (6%) and 201/374 (54%) were classified as low- and high-risk BCR (no group assignment possible in 152/374, 41%). A total of 13/21 (62%) patients with low- and 120/201 (60%) with high-risk BCR achieved cBR (p = 1.0). BCR classification was no predictor for BCRFS (HR:1.61, CI: 0.70–3.71, p = 0.3) or subsequent TFS (HR:1.07, CI: 0.46–2.47, p = 0.9). A total of 47/76 (62%) patients with PSA-DT ≤ 6 mo and 50/84 (60%) with PSA-DT > 6 mo achieved cBR (p = 0.4). PSA-DT was not associated with cBR (OR: 0.99, CI: 0.95–1.03, p = 0.5), BCRFS (HR: 1.00, CI: 0.97–1.03, p = 0.9), or TFS (HR: 1.02, CI: 0.99–1.04, p = 0.2). Consistent negative findings were recorded for PSA-V. Conclusions: The BCR risk groups and PSA kinetics do not predict the oncological success of PSMA-RGS performed at low absolute PSA values. Indolent low-risk BCR is rarely treated by PSMA-RGS.