Circulating Tumor DNA (ctDNA):   In cancer patients fragments of DNA from tumor cells are found in the blood along with short stretches of DNA from healthy cells (cell-free DNA, cfDNA) shed during cell turnover. In early-stage disease the ctDNA fraction of total cfDNA (circulating free DNA) may be <0.1%; in locally advanced disease, 0.1 to 1.0%; and in patients with advanced stage cancer the ctDNA fraction (ctDNA divided by cfDNA) may rise to 10% or substantially more. These DNA snippets are cleared rapidly from the blood with an estimate half-life of 30 – 120 minutes. (Da ..read more

Question: Why not be treated at initial diagnosis of prostate cancer— and hope for cure? Answer: Because all treatments are associated with unwelcome adverse effects that most men would prefer to avoid. Who should receive immediate treatment, and which men may safely delay treatment, preserving quality of life, — and with careful monitoring and timely intervention experience a similar outcome as if treated initially. That is the subject of this Commentary: patient selection for active surveillance (AS) and new techniques for monitoring for progression during AS.  Currently, eligibil ..read more

Oligometastatic prostate cancer (omPC) designates the status of having 3 to 5 metastatic lesions at diagnosis with an untreated primary or a similar extent of spread at recurrence after primary therapy. Metastasis directed therapy (MDT) focuses radiation to those several lesions. This situation is increasingly prevalent due to the more frequent use of PSMA PET imaging and in 2018 the incidence of hormone sensitive metastatic PC prostate cancer (mHSPC) at diagnosis was 8.2% (Vandenberg et al. Prostate Cancer and Prostatic Diseases, 2023), occurring mainly in men with high-risk cancer. Metastat ..read more

  Some men with low- or intermediate-risk localized prostate cancer will present on MRI imaging with a lesion sufficiently small and apparently well-delineated to warrant targeted focused therapy. This is termed “focal therapy” and can be accomplished with heat probes (laser ablation), radioactive seeds (brachytherapy), freezing (cryotherapy) or highly focused radiation (stereotactic ablative radiotherapy with, i.e., CyberKnife). The goal is total eradication of the cancer with the associated benefit in quality of life by better preservation of erectile function and urinary continence as ..read more

A forceful sea change is roiling in the management of this disease: artificial intelligence (AI) is coming into prominence benefiting cancer diagnosis, risk stratification and the prediction of response to therapy for individual patients. Multimodal AI (using deep learning) draws upon increasingly large stores of clinical and outcome data and digital histopathology to identify patterns that can predict therapeutic benefit for personalized treatment. The reference datasets might be extensive information generated from large clinical trials, a repository of annotated pathology specimens or imag ..read more

With the increased use of PSMA PET/CT scanning both at initial diagnosis of advanced prostate cancer and at disease recurrence, a substantial number of men will be found to have some extent of metastatic disease — either metastatic hormone sensitive prostate cancer (mHSPC) or castration-resistant prostate cancer (CRPC). The second of these states will have arisen in what is termed ‘non-metastatic’ castration resistant cancer (rising PSA despite castrate level of testosterone), in which, upon PET scanning, metastases are frequently identified. There is no current consensus regarding the a ..read more

Background:  The function of initial staging of prostate cancer is to accurately estimate the risk of progression in order to guide optimal therapy. The influential National Comprehensive Cancer Network (NCCN) recommends a PSMA PET/CT as part of initial staging for men in the risk categories of intermediate- and high-risk cancer as defined by clinicopathologic features: PSA, Gleason score, clinical tumor stage and number of positive biopsy cores. For men with a life expectancy of >10 years molecular analysis (i.e., Decipher, Prolaris or OncotypeDx Prostate) is suggested by the NC ..read more

Background:  Ever since 1675 when the Dutch lens maker, Leeuwenhoek, looked down the newly invented microscope at rainwater and reported seeing ‘animalcules – tiny dancing creatures” (bacteria), pathologists have been similarly looking down their scopes and guiding prostate management by applying their expertise in pattern recognition. In the 1960’s Dr. Donald Gleason organized those patterns into doublets of 3, 4 (i.e., 3+4) and 5 to create the prognostic Gleason Score — now further refined.  Anthony D’Amico, professor of Radiation Oncology a ..read more

 Background: Although neuroendocrine cancer (NEPC) infrequently (<2%) presents elusively in the prostate,  much more commonly it develops late in the course of disease admixed in varying extent in metastatic lesions with standard adenocarcinoma. In this situation it is termed “treatment emergent t-NEPC” postulated to have “transdifferentiated” from adenocarcinoma. Its development is thought to be induced by mutations that have occurred during treatment due to increased therapeutic pressure from androgen suppressive therapy on the androgen signaling pathway. The genomic characteri ..read more

The outcome of the VISION trial, the first reported study of radioligand therapy (RLT) with the radionuclide 177-Lutetium-PSMA-617 targeting the PSMA antigen now serves as the baseline for further development of this promising treatment. The VISION trial studied 831 heavily pretreated men with metastatic castration-resistant prostate cancer (mCRPC) (Sartor et el., NEJM  2021) with at least one PSMA positive lesion. RLT plus standard of care (SOC) was administered in     6-wk cycles x 4 and was compared to SOC. Men who had lesions seen on the accompanying CAT scan ..read more