Search

Oligometastatic disease was originally defined by Hellman and Weichselbaum as an intermediate-state existing between locally confined and widely disseminated malignancy, whose natural history could be positively impacted with systemic and importantly local therapies such as radiation. Currently oligometastatic prostate cancer (OPCa) is defined clinically by lesion enumeration and several subgroups exist: de novo (synchronous) oligometastatic disease present at initial diagnosis, oligorecurrent (metachronous) disease arising after definitive therapy to the prostate, and oligoprogressive disease where isolated lesions progress in a background of otherwise stable disease. In this review we highlight current knowledge and the potential future of local therapies, such as radiation to the primary prostate and metastasis-directed therapy (MDT), in the disease management of OPCa for all 3 subgroups. In addition, we examine more recent studies classifying the patterns of failure and natural history of OPCa following treatment with local therapies. Finally, while current clinical definitions of OPCa dominate, we introduce studies attempting to elucidate a more biological definition of OPCa to allow for improved selection of patients to treat with local therapies and to better inform precision combination approaches with systemic therapy., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Disseminated tumor cells (DTCs) have been reported in the bone marrow (BM) of patients with localized prostate cancer (PCa). However, the existence of these cells continues to be questioned, and few methods exist for viable DTC isolation. Therefore, we sought to develop novel approaches to identify and, if detected, analyze localized PCa patient DTCs., Methods: We used fluorescence-activated cell sorting (FACS) to isolate a putative DTC population, which was negative for CD45, CD235a, alkaline phosphatase, and CD34, and strongly expressed EPCAM. We examined tumor cell content by bulk cell RNA sequencing (RNA-Seq) and whole-exome sequencing after whole genome amplification. We also enriched for BM DTCs with α-EPCAM immunomagnetic beads and performed quantitative reverse trancriptase polymerase chain reaction (qRT-PCR) for PCa markers., Results: At a threshold of 4 cells per million BM cells, the putative DTC population was present in 10 of 58 patients (17%) with localized PCa, 4 of 8 patients with metastatic PCa of varying disease control, and 1 of 8 patients with no known cancer, and was positively correlated with patients' plasma PSA values. RNA-Seq analysis of the putative DTC population collected from samples above (3 patients) and below (5 patients) the threshold of 4 putative DTCs per million showed increased expression of PCa marker genes in 4 of 8 patients with localized PCa, but not the one normal donor who had the putative DTC population present. Whole-exome sequencing also showed the presence of single nucleotide polymorphisms and structural variants in the gene characteristics of PCa in 2 of 3 localized PCa patients. To examine the likely contaminating cell types, we used a myeloid colony formation assay, differential counts of cell smears, and analysis of the RNA-Seq data using the CIBERSORT algorithm, which most strongly suggested the presence of B-cell lineages as a contaminant. Finally, we used EPCAM enrichment and qRT-PCR for PCa markers to estimate DTC prevalence and found evidence of DTCs in 21 of 44 samples (47%)., Conclusion: These data support the presence of DTCs in the BM of a subset of patients with localized PCa and describe a novel FACS method for isolation and analysis of viable DTCs., (© 2019 Wiley Periodicals, Inc.)

Purpose: Several studies have documented that increased biopsy sampling, that is 6 versus 12 biopsy cores, can detect more prostate cancer. It is unknown whether increased sampling of the prostate will detect a higher number of potentially insignificant tumors., Materials and Methods: We searched the surgical pathology files at The Johns Hopkins Hospital for patients in whom prostate needle biopsy was performed by a single urologist between April 1993 and April 2000, and subsequently underwent radical prostatectomy. Patients who underwent radical prostatectomy and had 8 core biopsies or less between March 1994 and August 1999 were also studied. Clinically significant tumors were defined as those with volume greater than 0.5 cc, Gleason score 7 or greater or nonorgan confined disease., Results: A total of 297 patients with a mean age of 60 years (range 36 to 75) were evaluated. Group 1 consisted of 107 men with 8 core biopsies or less, including 51 with 6, and group 2 comprised 190 men with 9 cores or greater, including 145 with 12. The 2 groups were equal in regard to prostate specific antigen, age, digital rectal examination and transrectal ultrasound gland volume at biopsy. The only difference between the groups was a higher number of cores with cancer in group 2 (mean 2.8 versus 2.1, p = 0.0006). Of the patients who underwent radical prostatectomy 59.6% had Gleason score 6 or less, 26.3% 3+4, 6.7% 4+3 and 7.4% 8 to 9. There were 12.4% of patients with positive margins, 36.4% extraprostatic extension, and 5.4% seminal vesicle invasion and/or lymph node metastasis. Tumor volumes averaged 1.1 cc (range 0.01 to 10.7) and 60.9% of tumors were greater than 0.5 cc. Clinically significant tumors were seen in 77.4% of patients in group 1 and 74.6% in group 2. There was no significant difference in Gleason score, margin status, tumor volume, seminal vesicle invasion, or lymph node metastasis between groups 1 and 2, or in a subset analysis of men with 6 versus 12 core biopsies. However, patients in whom cancer was diagnosed with 9 core biopsies or greater were more likely to have organ confined disease (p = 0.02)., Conclusions: Although increased sampling of the prostate does not increase the detection of potentially insignificant tumors, it does appear to detect earlier stage cancer.