Identification of Morphologic Criteria Associated with Biochemical Recurrence in Intraductal Carcinoma of the Prostate

Intraductal carcinoma of the prostate (IDC-P) is an aggressive subtype of prostate cancer strongly associated with an increased risk of biochemical recurrence (BCR). However, approximately 40% of men with IDC-P remain BCR-free five years after radical prostatectomy. In this retrospective multicenter study, we aimed to identify histologic criteria associated with BCR for IDC-P lesions. A total of 108 first-line radical prostatectomy specimens were reviewed. In our test cohort (n = 39), presence of larger duct size (>573 µm in diameter), cells with irregular nuclear contours (CINC) (≥5 CINC in two distinct high-power fields), high mitotic score (>1.81 mitoses/mm2), blood vessels, and comedonecrosis were associated with early BCR (<18 months) (p < 0.05). In our validation cohort (n = 69), the presence of CINC or blood vessels was independently associated with an increased risk of BCR (hazard ratio [HR] 2.32, 95% confidence interval [CI] 1.09–4.96, p = 0.029). When combining the criteria, the presence of any CINC, blood vessels, high mitotic score, or comedonecrosis showed a stronger association with BCR (HR 2.74, 95% CI 1.21–6.19, p = 0.015). Our results suggest that IDC-P can be classified as low versus high-risk of BCR. The defined morphologic criteria can be easily assessed and should be integrated for clinical application following validation in larger cohorts.

Correlation between serum PSA, gleason score and histopathological grading of adenocarcinoma of prostate in patients undergoing TRUS guided prostatic biopsy in a tertiary care centre of Southern India

Background Prostate cancer is the second most common cancer and the fifth leading cause of cancer deaths worldwide. Serum psa, a glycoprotein and a serine protease, which is increased in all prostatic diseases but markedly elevated levels are indicative of carcinoma prostate. The present study was done to evaluate the histopathologyof carcinoma of prostate in trus guided prostatic biopsy specimens and correlate serum psa levels with gleason score and grade groups. Methods A hundred patients presented with luts and suspicious of carcinoma prostate underwent trus guided 16 core prostatic biopsy. Histopathological examination, gleason scores and grades of biopsies were obtained. Based on the gleason scores, patients with carcinoma of the prostate were divided into five-grade groups. Mean serum psa levels were calculated and correlated with gleason score and grade groups. Results Malignancy was found in 69 per cent of cases, of which 68 patients were found to have adenocarcinoma of the prostate, one patient found to have undifferentiated carcinoma of the prostate. The total number of patients in each gleason grade groups were obtained, and the mean serum psa levels of these patients in each group were calculated. Mean serum psa levels in each group are group 1 (21.3 ng/ml), group 2 (58.4 ng/ml), group 3 (73.6 ng/ml), group 4 (118.4 ng/ml), group 5 (96.3 ng/ml). Conclusion Serum psa is a highly sensitive tumour marker with low specificity, and its levels are increased in many benign and iatrogenic conditions. Psa has a high negative predictive value which is essential in ruling out malignancy. In our study, higher serum psa levels were correlated with higher gleason score and grades.

Genomic Features and Clinical Implications of Intraductal Carcinoma of the Prostate

Intraductal carcinoma of the prostate (IDC-P) is a rare and unique form of aggressive prostate carcinoma, which is characterized by an expansile proliferation of malignant prostatic epithelial cells within prostatic ducts or acini and the preservation of basal cell layers around the involved glands. The vast majority of IDC-P tumors result from adjacent high-grade invasive cancer via the retrograde spreading of tumor cells into normal prostatic ducts or acini. A subset of IDC-P tumors is rarely derived from the de novo intraductal proliferation of premalignant cells. The presence of IDC-P in biopsy or surgical specimens is significantly associated with aggressive pathologic features, such as high Gleason grade, large tumor volume, and advanced tumor stage, and with poor clinical courses, including earlier biochemical recurrence, distant metastasis, and worse survival outcomes. These architectural and behavioral features of IDC-P may be driven by specific molecular properties. Notably, IDC-P possesses distinct genomic profiles, including higher rates of TMPRSS2–ERG gene fusions and PTEN loss, increased percentage of genomic instability, and higher prevalence of germline BRCA2 mutations. Considering that IDC-P tumors are usually resistant to conventional therapies for prostate cancer, further studies should be performed to develop optimal therapeutic strategies based on distinct genomic features, such as treatment with immune checkpoint blockades or poly (adenosine diphosphate–ribose) polymerase inhibitors for patients harboring increased genomic instability or BRCA2 mutations, as well as genetic counseling with genetic testing. Patient-derived xenografts and tumor organoid models can be the promising in vitro platforms for investigating the molecular features of IDC-P tumor.

Modern principles of diagnosis and treatment of patients with neuroendocrine carcinoma of the prostate

Background. Prostate cancer (PCa) is well-known as the 2nd leading cause of death from malignant neoplasms among the males from developed countries. One of the variants of the disease - neuroendocrine carcinoma of the prostate (NECP) -manifests itself as the form of castration-resistant PCa. Distinctive manifestations of NECP include a low level of serum prostate specific antigen (PSA), a high potential rate of metastasis, and resistance to hormone replacement therapy. There are very few medical publications on the possibilities of diagnosis and therapy of this type of tumor.The objective of the study is to review the current foundations of pathogenesis, methods of diagnosis and treatment of patients with NECP.Materials and methods. The data of modern medical literature from the PubMed/Crossref archives, from the Elsevier and Scopus databases for 1991-2020 were studied. The materials on the epidemiology and pathogenesis of NECP, as well as the methods of diagnosis and treatment of patients with this pathology are summarized. A comparative analysis of the levels of neuroendocrine markers in castration-resistant and localized forms of PCa was carried out. The schemes of combination therapy of NECP with the use of somatostatin analogs are considered.Results. The detection rate of NECP is reduced due to the blurred clinical picture and morphological characteristics similar to poorly differentiated carcinoma. The basis for the diagnosis of NECP is the determination of the levels of neuronal markers - chromogranin A, neuron-specific enolase, and a number of potentially mitogenic hormones, including PTHrP, NT, serotonin, bombesin, calcitonin, and thyroid-stimulating hormone. The worst prognosis was observed in patients with initially high levels of chromogranin A, which emphasizes the high significance of this indicator for monitoring NECP. The drug of choice in the treatment of patients with this pathology is the somatostatin analogue octreotide-depot, the use of which in combination with hormone replacement therapy leads to stabilization of PCa in 50 % of cases. During therapy with an analogue of somatostatin alone or in cases of tumor progression against the background of chemotherapy, a decrease in PSA level is noted in 50-60 % of cases, and PSA level stabilization - in 41.7-53.3 %.Conclusion. We founded an insufficient number of randomized clinical trials of NECP, therefore, the prognosis of the development of this pathology remains completely unclear. The use of somatostatin analogues, along with targeted therapy, is the main choice of therapy for NECP, but requires further study in the program of randomized trials. If a positive result is obtained, it will be possible to use somatostatin analogs more widely to improve the quality and increase the life expectancy of patients with NECP.

Genomic analysis of circulating tumor cells in adenosquamous carcinoma of the prostate: a case report

Background Adenosquamous carcinoma of the prostate (ASCP) is an extremely rare and aggressive prostate cancer variant, whose genomic characteristics have not been elucidated. Although liquid biopsy of circulating tumor cells (CTCs) is an emerging topic in oncology, no study has assessed CTCs in patients with ASCP. Case presentation. A 76-year-old man presented with discomfort in his urethra. His prostate-specific antigen (PSA) level was 13.37 ng/mL. A computed tomography (CT) scan indicated a prostate mass with multiple lymph node and lung metastases. The patient underwent transurethral resection of the prostate and prostatic needle biopsy; both specimens demonstrated Gleason grade group 5 acinar adenocarcinoma of the prostate. Bone scintigraphy indicated bone metastasis in the ischium. Combined androgen blockade was implemented, and his serum PSA level rapidly decreased to 0.01 ng/mL. However, a CT scan 6 months after the initial diagnosis revealed worsening of the disease. The patient therefore underwent repeated prostatic needle biopsy; its specimen demonstrated prostatic adenocarcinoma together with squamous carcinoma components. As immunohistochemical analyses showed the tumor cells to be negative for CD56, chromogranin A, synaptophysin, and PSA, the definitive diagnosis was ASCP. Although the patient underwent chemotherapy (docetaxel and cabazitaxel), he died of the disease 3 months after the diagnosis of ASCP, or 13 months after the initial diagnosis of prostatic adenocarcinoma. His PSA values remained ≤ 0.2 ng/mL. CTCs from the patient’s blood (collected before starting docetaxel) were analyzed and genomically assessed. It showed 5 cytokeratin (CK)+ CTCs, 14 CK− CTCs, and 8 CTC clusters, per 10 mL. Next-generation sequencing identified a total of 14 mutations in 8 oncogenes or tumor suppressor genes: PIK3CB, APC, CDKN2A, PTEN, BRCA2, RB1, TP53, and CDK12. Of 14 mutations, 9 (64%) were detected on CK− CTCs and 5 (36%) were detected on CK+ CTCs. Conclusions This is the first report of CTC analysis and genomic assessment in ASCP. Although the prognosis of ASCP is dismal due to lack of effective treatment, genomic analysis of CTCs might lead to effective treatment options and improved survival.