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A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Pathophysiology".

Deadline for manuscript submissions: closed (25 October 2023) | Viewed by 6286

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Dr. Isabel Heidegger-Pircher

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Guest Editor

Department of Urology, Medical University Innsbruck, 6020 Innsbruck, Austria
Interests: metastatic prostate cancer; hormonal therapy; chemotherapy; immunotherapy; PARP inhibition; combination therapies; emerging (pre)clinical mCRPC treatment options; biomarkers
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Special Issue Information

Dear Colleagues,

Prostate cancer (PC) is one of the most prevalent malignancies of the present day. While most cases are diagnosed at a localized stage, a considerable number of patients with intermediate or high-risk localized, locally advanced or metastatic cancer die from the disease itself each year. Although therapeutic advances have been introduced in the field of metastatic PC in recent years, androgen deprivation therapy (ADT) remains the leading therapeutic backbone for metastatic PC. However, most patients develop castration resistance. The exact mechanisms driving the progression from androgen-dependent PC to castration-resistant prostate cancer (CRPC) are not completely understood.In recent years, the treatment landscape of metastatic CRPC (mCRPC) has substantially improved due to the availability of different agents. However, fast tumor progression, cross-resistance, the use of these substances in earlier (hormone-sensitive) stages of the disease, and patient-related factors should be taken into account when assessing which is the optimal treatment sequencing in the setting of mCRPC. This Special Issue aims, on one hand, to better understand the biological mechanisms of tumor progression and, on the other hand, to elucidate recent clinical developments in the treatment of both localized and metastatic disease.

Dr. Isabel Heidegger-Pircher
Guest Editor

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Keywords

prostate cancer
localized disease
metastatic prostate cancer
novel therapies
combination therapies
biomarkers
biology
clinical research
translational research
basic research

Published Papers (6 papers)

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Research

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20 pages, 2361 KiB

Open AccessArticle

Renal Function Parameters in Distinctive Molecular Subtypes of Prostate Cancer

Andrei Daniel Timofte

and

Cancers 2023, 15(20), 5013; https://doi.org/10.3390/cancers15205013 - 16 Oct 2023

Viewed by 555

Abstract

Prostate cancer is a prevalent malignancy in male patients, having diverse clinical outcomes. The follow-up of patients diagnosed with prostate cancer involves the evaluation of renal function, because its impairment reduces patient survival rates and adds complexity to their treatment and clinical care. This study aimed to investigate the relationship between renal function parameters and distinctive molecular subtypes of prostate adenocarcinomas, defined by the immunoexpression of the SPINK1, ERG, HOXB13, and TFF3 markers. The study group comprised 72 patients with prostate cancer and associated chronic kidney disease (CKD) who underwent radical prostatectomy. Histopathological, molecular, and renal parameters were analyzed. Patients were categorized based on ERG/SPINK1 and HOXB13/TFF3 status, and correlations with renal function and prognostic grade groups were assessed. The ERG+/SPINK1+ subgroup exhibited significantly higher postoperative CKD stages and serum creatinine levels compared to the ERG+/SPINK1− subgroup. This suggests an intricate relationship between SPINK1 overexpression and renal function dynamics. The HOXB13−/TFF3+ subgroup displayed higher preoperative serum creatinine levels and CKD stages than the HOXB13−/TFF3− subgroup, aligning with TFF3’s potential role in renal function. Furthermore, the study revealed associations between CKD stages and prognostic grade groups in different molecular subtypes, pointing out an intricate interplay between renal function and tumor behavior. Although the molecular classification of prostate acinar ADK is not yet implemented, this research underscores the variability of renal function parameters in different molecular subtypes, offering potential insights into patient prognosis. Full article

(This article belongs to the Special Issue Prostate Cancer Progression)

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12 pages, 2482 KiB

Open AccessArticle

Characterization of Lymph Node Tumor Burden in Node-Positive Prostate Cancer Patients after Robotic-Assisted Radical Prostatectomy with Extended Pelvic Lymph Node Dissection

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Cancers 2023, 15(14), 3707; https://doi.org/10.3390/cancers15143707 - 21 Jul 2023

Viewed by 579

Abstract

Background: Prostate cancer (PCa) nodal staging does not account for lymph node (LN) tumor burden. The LN anatomical compartment involved with the tumor or the quantified extent of extranodal extension (ENE) have not yet been studied in relation to biochemical recurrence-free survival (BRFS). Methods: Histopathological slides of 66 pN1 PCa patients who underwent extended pelvic lymph node dissection were reviewed. We recorded metrics to quantify LN tumor burden. We also characterized the LN anatomical compartments involved and quantified the extent of ENE. Results: The median follow-up time was 38 months. The median number of total LNs obtained per patient was 30 (IQR 23–37). In the risk-adjusted cox regression model, the following variables were associated with BRFS: mean size of the largest LN deposit per patient (log2: adjusted hazard ratio (aHR) = 1.91, p < 0.001), the mean total span of all LN deposits per patient (2.07, p < 0.001), and the mean percent surface area of the LN involved with the tumor (1.58, p < 0.001). There was no significant BRFS association for the LN anatomical compartment or the quantified extent of ENE. Conclusion: LN tumor burden is associated with BRFS. The LN anatomical compartments and the quantified extent of ENE did not show significant association with BRFS. Full article

(This article belongs to the Special Issue Prostate Cancer Progression)

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13 pages, 5109 KiB

Open AccessArticle

Theranostics of Primary Prostate Cancer: Beyond PSMA and GRP-R

Romain Schollhammer

Marie-Laure Quintyn Ranty

Henri de Clermont Gallerande

and

Cancers 2023, 15(8), 2345; https://doi.org/10.3390/cancers15082345 - 18 Apr 2023

Cited by 3 | Viewed by 1080

Abstract

The imaging of Prostate-Specific Membrane Antigen (PSMA) is now widely used at the initial staging of prostate cancers in patients with a high metastatic risk. However, its ability to detect low-grade tumor lesions is not optimal. Methods: First, we prospectively performed neurotensin receptor-1 (NTS₁) IHC in a series of patients receiving both [⁶⁸Ga]Ga-PSMA-617 and [⁶⁸Ga]Ga-RM2 before prostatectomy. In this series, PSMA and GRP-R IHC were also available (n = 16). Next, we aimed at confirming the PSMA/GRP-R/NTS₁ expression profile by retrospective autoradiography (n = 46) using a specific radiopharmaceuticals study and also aimed to decipher the expression of less-investigated targets such as NTS₂, SST₂ and CXCR4. Results: In the IHC study, all samples with negative PSMA staining (two patients with ISUP 2 and one with ISUP 3) were strongly positive for NTS₁ staining. No samples were negative for all three stains—for PSMA, GRP-R or NTS₁. In the autoradiography study, binding of [¹¹¹In]In-PSMA-617 was high in all ISUP groups. However, some samples did not bind or bound weakly to [¹¹¹In]In-PSMA-617 (9%). In these cases, binding of [¹¹¹n]In-JMV 6659 and [¹¹¹In]In-JMV 7488 towards NTS₁ and NTS₂ was high. Conclusions: Targeting PSMA and NTS₁/NTS₂ could allow for the detection of all intraprostatic lesions. Full article

(This article belongs to the Special Issue Prostate Cancer Progression)

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10 pages, 836 KiB

Open AccessArticle

Prognostic Impact and Clinical Implications of Unfavorable Upgrading in Low-Risk Prostate Cancer after Robot-Assisted Radical Prostatectomy: Results of a Single Tertiary Referral Center

Cancers 2022, 14(24), 6055; https://doi.org/10.3390/cancers14246055 - 09 Dec 2022

Viewed by 1098

Abstract

Objective: to evaluate predictors and the prognostic impact of favorable vs. unfavorable tumor upgrading among low-risk prostate cancer (LR PCa) patients treated with robot-assisted radical prostatectomy (RARP). Methods: From January 2013 to October 2020, LR PCa patients treated with RARP at our institution were identified. Unfavorable tumor upgrading was defined as the presence of an International Society of Urological Pathology (ISUP) grade group at final pathology > 2. Disease relapse was coded as biochemical recurrence and/or local recurrence and/or presence of distant metastases. Regression analyses tested the association between clinical and pathological features and the risk of unfavorable tumor upgrading and disease relapse. Results: Of the 237 total LR PCa patients, 60 (25.3%) harbored unfavorable tumor upgrading. Disease relapse occurred in 20 (8.4%) patients. Unfavorable upgrading represented an independent predictor of disease relapse, even after adjustment for other clinical and pathological variables. Conversely, favorable tumor upgrading did not show any statistically significant association with PCa relapse. Unfavorable tumor upgrading was associated with tumors being larger (OR: 1.03; p = 0.031), tumors extending beyond the gland (OR: 8.54, p < 0.001), age (OR: 1.07, p = 0.009), and PSA density (PSAD) ≥ 0.15 ng/mL/cc (OR: 1.07, p = 0.009). Conclusions: LR PCa patients with unfavorable upgrading at final pathology were more likely to be older, to have PSAD ≥ 0.15 ng/mL/cc, and to experience disease relapse. Unfavorable tumor upgrading is an issue to consider when counseling these patients to avoid delayed treatments, which may impair cancer-specific survival. Full article

(This article belongs to the Special Issue Prostate Cancer Progression)

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Review

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17 pages, 1660 KiB

Open AccessReview

Castration-Resistant Prostate Cancer: From Uncovered Resistance Mechanisms to Current Treatments

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Cancers 2023, 15(20), 5047; https://doi.org/10.3390/cancers15205047 - 19 Oct 2023

Cited by 2 | Viewed by 860

Abstract

Prostate cancer (PC) is the second most common cancer in men worldwide. Despite recent advances in diagnosis and treatment, castration-resistant prostate cancer (CRPC) remains a significant medical challenge. Prostate cancer cells can develop mechanisms to resist androgen deprivation therapy, such as AR overexpression, AR mutations, alterations in AR coregulators, increased steroidogenic signaling pathways, outlaw pathways, and bypass pathways. Various treatment options for CRPC exist, including androgen deprivation therapy, chemotherapy, immunotherapy, localized or systemic therapeutic radiation, and PARP inhibitors. However, more research is needed to combat CRPC effectively. Further investigation into the underlying mechanisms of the disease and the development of new therapeutic strategies will be crucial in improving patient outcomes. The present work summarizes the current knowledge regarding the underlying mechanisms that promote CRPC, including both AR-dependent and independent pathways. Additionally, we provide an overview of the currently approved therapeutic options for CRPC, with special emphasis on chemotherapy, radiation therapy, immunotherapy, PARP inhibitors, and potential combination strategies. Full article

(This article belongs to the Special Issue Prostate Cancer Progression)

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12 pages, 1264 KiB

Open AccessReview

The Impact of PSMA PET/CT on Modern Prostate Cancer Management and Decision Making—The Urological Perspective

Azik Hoffman

and

Gilad E. Amiel

Cancers 2023, 15(13), 3402; https://doi.org/10.3390/cancers15133402 - 29 Jun 2023

Cited by 2 | Viewed by 1443

Abstract

Prostate-specific membrane antigen (PSMA) PET use in prostate cancer treatment has recently become a routinely used imaging modality by urologists. New, established data regarding its performance in different stages of prostate cancer, as well as gaining clinical knowledge with new tracers, drives the need for urologists and other clinicians to improve the utilization of this tool. While the use of PSMA PET/CT is more common in metastatic disease, in which it outperforms classical imaging modalities and drives treatment decisions and adjustments, recently, it gained ground in localized prostate cancer as well, especially in high-risk disease. Still, PSMA PET/CT might reveal lesions within the prostate or possibly locoregional or metastatic disease, not always representing true cancer when utilized in earlier stages of the disease, potentially adding diagnostic burden and changing treatment decisions. As urological treatment options advance toward focal treatments in localized organ-confined prostate cancer, recent reports suggest the utilization of PSMA PET/CT in treatment planning and follow-up and even when choosing active surveillance. This review aims to reveal the current perspective of urologists regarding its daily use. Full article

(This article belongs to the Special Issue Prostate Cancer Progression)

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