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Open AccessEditorial

Editorial for the Special Issue on High-Risk Localized and Locally Advanced Prostate Cancer

by Kouji Izumi

Cancers 2023, 15(12), 3153; https://doi.org/10.3390/cancers15123153 - 11 Jun 2023

Viewed by 1102

Abstract

The recent development of imaging modalities, such as diffusion-weighted whole-body imaging with background suppression (DWIBS) and positron emission tomography of prostate-specific membrane antigen (PSMA-PET) with a radioactive diagnostic agent, has enabled the detection of minute metastases in patients diagnosed with high-risk localized and [...] Read more.

The recent development of imaging modalities, such as diffusion-weighted whole-body imaging with background suppression (DWIBS) and positron emission tomography of prostate-specific membrane antigen (PSMA-PET) with a radioactive diagnostic agent, has enabled the detection of minute metastases in patients diagnosed with high-risk localized and locally advanced prostate cancer by conventional modalities [...] Full article

(This article belongs to the Special Issue High-Risk Localized and Locally Advanced Prostate Cancer)

Research

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14 pages, 1881 KiB

Open AccessArticle

Differential Expression of miRNAs Contributes to Tumor Aggressiveness and Racial Disparity in African American Men with Prostate Cancer

by Richard Ottman, Kavya Ganapathy, Hui-Yi Lin, Carlos Diaz Osterman, Julie Dutil, Jaime Matta, Gilberto Ruiz-Deya, Liang Wang, Kosj Yamoah, Anders Berglund, Ratna Chakrabarti and Jong Y. Park

Cancers 2023, 15(8), 2331; https://doi.org/10.3390/cancers15082331 - 17 Apr 2023

Cited by 5 | Viewed by 1907

Abstract

Prostate cancer is the leading cancer in incidence and second leading cause of cancer mortality in US men. African American men have significantly higher incidence and mortality rates from prostate cancer than European American men. Previous studies reported that the disparity in prostate [...] Read more.

Prostate cancer is the leading cancer in incidence and second leading cause of cancer mortality in US men. African American men have significantly higher incidence and mortality rates from prostate cancer than European American men. Previous studies reported that the disparity in prostate cancer survival or mortality can be explained by different biological backgrounds. microRNAs (miRNAs) regulate gene expression of their cognate mRNAs in many cancers. Therefore, miRNAs may be a potentially promising diagnostic tool. The role of miRNAs in prostate cancer aggressiveness and racial disparity has not been fully established. The goal of this study is to identify miRNAs associated with aggressiveness and racial disparity in prostate cancer. Here we report miRNAs that are associated with tumor status and aggressiveness in prostate cancer using a profiling approach. Further, downregulated miRNAs in African American tissues were confirmed by qRT-PCR. These miRNAs have also been shown to negatively regulate the expression of the androgen receptor in prostate cancer cells. This report provides a novel insight into understanding tumor aggressiveness and racial disparities of prostate cancer. Full article

(This article belongs to the Special Issue High-Risk Localized and Locally Advanced Prostate Cancer)

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20 pages, 9749 KiB

Open AccessArticle

Leukocytic Infiltration of Intraductal Carcinoma of the Prostate: An Exploratory Study

by Mame-Kany Diop, Oscar Eduardo Molina, Mirela Birlea, Hélène LaRue, Hélène Hovington, Bernard Têtu, Louis Lacombe, Alain Bergeron, Yves Fradet and Dominique Trudel

Cancers 2023, 15(8), 2217; https://doi.org/10.3390/cancers15082217 - 9 Apr 2023

Cited by 1 | Viewed by 2176

Abstract

Intraductal carcinoma of the prostate (IDC-P) is an aggressive histological subtype of prostate cancer (PCa) detected in approximately 20% of radical prostatectomy (RP) specimens. As IDC-P has been associated with PCa-related death and poor responses to standard treatment, the purpose of this study [...] Read more.

Intraductal carcinoma of the prostate (IDC-P) is an aggressive histological subtype of prostate cancer (PCa) detected in approximately 20% of radical prostatectomy (RP) specimens. As IDC-P has been associated with PCa-related death and poor responses to standard treatment, the purpose of this study was to explore the immune infiltrate of IDC-P. Hematoxylin- and eosin-stained slides from 96 patients with locally advanced PCa who underwent RP were reviewed to identify IDC-P. Immunohistochemical staining of CD3, CD8, CD45RO, FoxP3, CD68, CD163, CD209 and CD83 was performed. For each slide, the number of positive cells per mm² in the benign tissues, tumor margins, cancer and IDC-P was calculated. Consequently, IDC-P was found in a total of 33 patients (34%). Overall, the immune infiltrate was similar in the IDC-P-positive and the IDC-P-negative patients. However, FoxP3⁺ regulatory T cells (p < 0.001), CD68⁺ and CD163⁺ macrophages (p < 0.001 for both) and CD209⁺ and CD83⁺ dendritic cells (p = 0.002 and p = 0.013, respectively) were less abundant in the IDC-P tissues compared to the adjacent PCa. Moreover, the patients were classified as having immunologically “cold” or “hot” IDC-P, according to the immune-cell densities averaged in the total IDC-P or in the immune hotspots. The CD68/CD163/CD209-immune hotspots predicted metastatic dissemination (p = 0.014) and PCa-related death (p = 0.009) in a Kaplan–Meier survival analysis. Further studies on larger cohorts are necessary to evaluate the clinical utility of assessing the immune infiltrate of IDC-P with regards to patient prognosis and the use of immunotherapy for lethal PCa. Full article

(This article belongs to the Special Issue High-Risk Localized and Locally Advanced Prostate Cancer)

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16 pages, 1013 KiB

Open AccessArticle

Comparison of Four Validated Nomograms (Memorial Sloan Kettering Cancer Center, Briganti 2012, 2017, and 2019) Predicting Lymph Node Invasion in Patients with High-Risk Prostate Cancer Candidates for Radical Prostatectomy and Extended Pelvic Lymph Node Dissection: Clinical Experience and Review of the Literature

by Giovanni Battista Di Pierro, Stefano Salciccia, Marco Frisenda, Antonio Tufano, Alessandro Sciarra, Emiliano Scarrone, Francesco Del Giudice, Vincenzo Asero, Giulio Bevilacqua, Martina Moriconi, Antonio Carbone, Antonio Pastore, Stefano Signore, Pierluigi Bove, Flavio Forte, Paolo Emiliozzi, Andrea Tubaro, Cosimo De Nunzio and Vittorio Canale

Cancers 2023, 15(6), 1683; https://doi.org/10.3390/cancers15061683 - 9 Mar 2023

Cited by 5 | Viewed by 2302

Abstract

Background: The indication for extended pelvic lymph node dissection (ePLND) at the time of radical prostatectomy (RP) is based on nomograms predicting the risk of lymph node invasion (LNI). However, limited data are available on the comparison of these predictive models in high-risk [...] Read more.

Background: The indication for extended pelvic lymph node dissection (ePLND) at the time of radical prostatectomy (RP) is based on nomograms predicting the risk of lymph node invasion (LNI). However, limited data are available on the comparison of these predictive models in high-risk prostate cancer (PC) patients. Therefore, we compared the accuracy of the most used nomograms (MSKCC, Briganti 2012, 2017, and 2019) in the setting of high-risk PC patients submitted to ePLND. Methods: 150 patients with high-risk PC disease treated from 2019 to 2022 were included. Before RP + ePLND, we assessed the MSKCC, Briganti 2012, 2017, and 2019 nomograms for each patient, and we compared the prediction of LNI with the final histopathological analysis of the ePLND using pathologic results as a reference. Results: LNI was found in 39 patients (26%), and 71.3% were cT2. The percentage of patients with estimated LNI risk above the cut-off was significantly higher in pN+ cases than in pN0 for all Briganti nomograms. The percentage of patients at risk of LNI, according to Briganti Nomogram (2012, 2017, and 2019), was significantly higher in pN+ cases than in pN0 (p < 0.04), while MSKCC prediction didn’t vary significantly between pN0 and pN+ groups (p = 0.2). All nomograms showed high sensitivity (Se > 0.90), low specificity (Sp < 0.20), and similar AUC (range: 0.526–0.573) in predicting pN+. Particularly, 74% of cases patients with MSKCC estimated risk > 7% showed pN0 compared to 71% with Briganti 2012 > 5%, 69% with Briganti 2017 > 7%, and 70% with Briganti 2019 > 7%. Conclusions: Despite the high-risk disease, in our patients treated with ePLND emerges a still high number of pN0 cases and a similar low specificity of nomograms in predicting LNI. Full article

(This article belongs to the Special Issue High-Risk Localized and Locally Advanced Prostate Cancer)

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20 pages, 2007 KiB

Open AccessArticle

Prognostic Significance of Amino Acid Metabolism-Related Genes in Prostate Cancer Retrieved by Machine Learning

by Ivana Samaržija, Koraljka Gall Trošelj and Paško Konjevoda

Cancers 2023, 15(4), 1309; https://doi.org/10.3390/cancers15041309 - 18 Feb 2023

Cited by 5 | Viewed by 3517

Abstract

Prostate cancer is among the leading cancers according to both incidence and mortality. Due to the high molecular, morphological and clinical heterogeneity, the course of prostate cancer ranges from slow growth that usually does not require immediate therapeutic intervention to aggressive and fatal [...] Read more.

Prostate cancer is among the leading cancers according to both incidence and mortality. Due to the high molecular, morphological and clinical heterogeneity, the course of prostate cancer ranges from slow growth that usually does not require immediate therapeutic intervention to aggressive and fatal disease that spreads quickly. However, currently available biomarkers cannot precisely predict the course of a disease, and novel strategies are needed to guide prostate cancer management. Amino acids serve numerous roles in cancers, among which are energy production, building block reservoirs, maintenance of redox homeostasis, epigenetic regulation, immune system modulation and resistance to therapy. In this article, by using The Cancer Genome Atlas (TCGA) data, we found that the expression of amino acid metabolism-related genes is highly aberrant in prostate cancer, which holds potential to be exploited in biomarker design or in treatment strategies. This change in expression is especially evident for catabolism genes and transporters from the solute carrier family. Furthermore, by using recursive partitioning, we confirmed that the Gleason score is strongly prognostic for progression-free survival. However, the expression of the genes SERINC3 (phosphatidylserine and sphingolipids generation) and CSAD (hypotaurine generation) can refine prognosis for high and low Gleason scores, respectively. Therefore, our results hold potential for novel prostate cancer progression biomarkers. Full article

(This article belongs to the Special Issue High-Risk Localized and Locally Advanced Prostate Cancer)

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15 pages, 1544 KiB

Open AccessArticle

Dosimetric Impact of Intrafraction Prostate Motion and Interfraction Anatomical Changes in Dose-Escalated Linac-Based SBRT

by Valeria Faccenda, Denis Panizza, Martina Camilla Daniotti, Roberto Pellegrini, Sara Trivellato, Paolo Caricato, Raffaella Lucchini, Elena De Ponti and Stefano Arcangeli

Cancers 2023, 15(4), 1153; https://doi.org/10.3390/cancers15041153 - 10 Feb 2023

Cited by 12 | Viewed by 3207

Abstract

The dosimetric impact of intrafraction prostate motion and interfraction anatomical changes and the effect of beam gating and motion correction were investigated in dose-escalated linac-based SBRT. Fifty-six gated fractions were delivered using a novel electromagnetic tracking device with a 2 mm threshold. Real-time [...] Read more.

The dosimetric impact of intrafraction prostate motion and interfraction anatomical changes and the effect of beam gating and motion correction were investigated in dose-escalated linac-based SBRT. Fifty-six gated fractions were delivered using a novel electromagnetic tracking device with a 2 mm threshold. Real-time prostate motion data were incorporated into the patient’s original plan with an isocenter shift method. Delivered dose distributions were obtained by recalculating these motion-encoded plans on deformed CTs reflecting the patient’s CBCT daily anatomy. Non-gated treatments were simulated using the prostate motion data assuming that no treatment interruptions have occurred. The mean relative dose differences between delivered and planned treatments were −3.0% [−18.5–2.8] for CTV D99% and −2.6% [−17.8–1.0] for PTV D95%. The median cumulative CTV coverage with 93% of the prescribed dose was satisfactory. Urethra sparing was slightly degraded, with the maximum dose increased by only 1.0% on average, and a mean reduction in the rectum and bladder doses was seen in almost all dose metrics. Intrafraction prostate motion marginally contributed in gated treatments, while in non-gated treatments, further deteriorations in the minimum target coverage and bladder dose metrics would have occurred on average. The implemented motion management strategy and the strict patient preparation regimen, along with other treatment optimization strategies, ensured no significant degradations of dose metrics in delivered treatments. Full article

(This article belongs to the Special Issue High-Risk Localized and Locally Advanced Prostate Cancer)

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10 pages, 893 KiB

Open AccessArticle

Three Months’ PSA and Toxicity from a Prospective Trial Investigating STereotactic sAlvage Radiotherapy for Macroscopic Prostate Bed Recurrence after Prostatectomy—STARR (NCT05455736)

by Giulio Francolini, Pietro Garlatti, Vanessa Di Cataldo, Beatrice Detti, Mauro Loi, Daniela Greto, Gabriele Simontacchi, Ilaria Morelli, Luca Burchini, Andrea Gaetano Allegra, Giulio Frosini, Michele Ganovelli, Viola Salvestrini, Emanuela Olmetto, Luca Visani, Carlotta Becherini, Marianna Valzano, Maria Grazia Carnevale, Manuele Roghi, Sergio Serni, Chiara Mattioli, Isacco Desideri and Lorenzo Livi Show full author list Hide full author list

Cancers 2023, 15(3), 992; https://doi.org/10.3390/cancers15030992 - 3 Feb 2023

Cited by 5 | Viewed by 1923

Abstract

Biochemical recurrences after radical prostatectomy (RP) can be managed with curative purpose through salvage radiation therapy (SRT). RT dose escalation, such as stereotactic RT (SSRT), may improve relapse-free survival in this setting. STARR trial (NCT05455736) is a prospective multicenter study including patients affected [...] Read more.

Biochemical recurrences after radical prostatectomy (RP) can be managed with curative purpose through salvage radiation therapy (SRT). RT dose escalation, such as stereotactic RT (SSRT), may improve relapse-free survival in this setting. STARR trial (NCT05455736) is a prospective multicenter study including patients affected by macroscopic recurrence within the prostate bed after RP treated with SSRT. Recurrence was detected with a Choline or PSMA CT-PET. In the current analysis, the early biochemical response (BR) rate and toxicity profile after three months of follow-up were assessed. Twenty-five patients were enrolled, and data about BR and toxicity at three months after treatment were available for 19 cases. Overall, BR was detected after three months in 58% of cases. Four G1–G2 adverse events were recorded; no G ≥ 3 adverse events were detected. SSRT appears feasible and safe, with more than half of patients experiencing BR and an encouraging toxicity profile. The STARR trial is one of the few prospective studies aimed at implementing this promising treatment strategy in this scenario. Full article

(This article belongs to the Special Issue High-Risk Localized and Locally Advanced Prostate Cancer)

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16 pages, 5293 KiB

Open AccessArticle

Disruption of CCL2 in Mesenchymal Stem Cells as an Anti-Tumor Approach against Prostate Cancer

by Quoc Thang Bui, Kuan-Der Lee, Yu-Ching Fan, Branwen S. Lewis, Lih-Wen Deng and Yuan-Chin Tsai

Cancers 2023, 15(2), 441; https://doi.org/10.3390/cancers15020441 - 10 Jan 2023

Cited by 6 | Viewed by 2621

Abstract

Background: MSCs are known to secrete abundant CCL2, which plays a crucial role in recruiting TAMs, promoting tumor progression. It is important to know whether disrupting MSC-derived CCL2 affects tumor growth. Methods: Murine bone marrow-derived MSCs were characterized by their surface markers and [...] Read more.

Background: MSCs are known to secrete abundant CCL2, which plays a crucial role in recruiting TAMs, promoting tumor progression. It is important to know whether disrupting MSC-derived CCL2 affects tumor growth. Methods: Murine bone marrow-derived MSCs were characterized by their surface markers and differentiation abilities. Proliferation and migration assays were performed in order to evaluate the functions of MSCs on cancer cells. CCL2 expression in MSCs was reduced by small interfering RNA (siRNA) or completely disrupted by CRISPR/Cas9 knockout (KO) approaches. An immune-competent syngeneic murine model of prostate cancer was applied in order to assess the role of tumor cell- and MSC-derived CCL2. The tumor microenvironment was analyzed to monitor the immune profile. Results: We confirmed that tumor cell-derived CCL2 was crucial for tumor growth and MSCs migration. CCL2 KO MSCs inhibited the migration of the monocyte/macrophage but not the proliferation of tumor cells in vitro. However, the mice co-injected with tumor cells and CCL2 KO MSCs exhibited anti-tumor effects when compared with those given tumor cell alone and with control MSCs, partly due to increased infiltration of CD45⁺CD11b⁺Ly6G⁻ mononuclear myeloid cells. Conclusions: Disruption of MSC-derived CCL2 enhances anti-tumor functions in an immune-competent syngeneic mouse model for prostate cancer. Full article

(This article belongs to the Special Issue High-Risk Localized and Locally Advanced Prostate Cancer)

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14 pages, 1237 KiB

Open AccessArticle

Tumor Location and a Tumor Volume over 2.8 cc Predict the Prognosis for Japanese Localized Prostate Cancer

by Haruki Baba, Shinichi Sakamoto, Xue Zhao, Yasutaka Yamada, Junryo Rii, Ayumi Fujimoto, Manato Kanesaka, Nobuyoshi Takeuchi, Tomokazu Sazuka, Yusuke Imamura, Koichiro Akakura and Tomohiko Ichikawa

Cancers 2022, 14(23), 5823; https://doi.org/10.3390/cancers14235823 - 25 Nov 2022

Cited by 5 | Viewed by 2388

Abstract

(1) Objective: Our study investigated the prognostic value of tumor volume and location in prostate cancer patients who received radical prostatectomy (RP). (2) Methods: The prognostic significance of tumor volume and location, together with other clinical factors, was studied using 557 patients who [...] Read more.

(1) Objective: Our study investigated the prognostic value of tumor volume and location in prostate cancer patients who received radical prostatectomy (RP). (2) Methods: The prognostic significance of tumor volume and location, together with other clinical factors, was studied using 557 patients who received RP. (3) Results: The receiver operating characteristic (ROC) curve identified the optimal cutoff value of tumor volume as 2.8 cc for predicting biochemical recurrence (BCR). Cox regression analysis revealed that a tumor in the posterior area (p = 0.031), peripheral zone (p = 0.0472), and tumor volume ≥ 2.8 cc (p < 0.0001) were predictive factors in univariate analysis. After multivariate analysis, tumor volume ≥ 2.8 cc (p = 0.0225) was an independent predictive factor for BCR. Among them, a novel risk model was established using tumor volume and location in the posterior area and peripheral zone. The progression-free survival (PFS) of patients who met the three criteria (unfavorable group) was significantly worse than other groups (p ≤ 0.001). Furthermore, multivariate analysis showed that the unfavorable risk was an independent prognostic factor for BCR. The prognostic significance of our risk model was observed in low- to intermediate-risk patients, although it was not observed in high-risk patients. (4) Conclusion: Tumor volume (≥2.8 cc) and localization (posterior/peripheral zone) may be a novel prognostic factor in patients undergoing RP. Full article

(This article belongs to the Special Issue High-Risk Localized and Locally Advanced Prostate Cancer)

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10 pages, 1126 KiB

Open AccessArticle

Prognostic Impact of Lymphatic Invasion in Patients with High-Risk Prostate Cancer after Robot-Assisted Radical Prostatectomy and Extended Lymph Node Dissection: A Single-Institution Prospective Cohort Study

by Shimpei Yamashita, Satoshi Muraoka, Takahito Wakamiya, Kazuro Kikkawa, Yasuo Kohjimoto and Isao Hara

Cancers 2022, 14(14), 3466; https://doi.org/10.3390/cancers14143466 - 17 Jul 2022

Cited by 5 | Viewed by 1734

Abstract

The prognostic impact of lymphatic invasion in patients with high-risk prostate cancer (PC) remains unclear. The aim of our single-institution prospective cohort study was to examine the impact of lymphatic invasion on biochemical recurrence (BCR) in patients with high-risk PC according to National [...] Read more.

The prognostic impact of lymphatic invasion in patients with high-risk prostate cancer (PC) remains unclear. The aim of our single-institution prospective cohort study was to examine the impact of lymphatic invasion on biochemical recurrence (BCR) in patients with high-risk PC according to National Comprehensive Cancer Network (NCCN) criteria who underwent robot-assisted radical prostatectomy (RARP) and extended lymph node dissection (eLND). A total of 183 patients were included who underwent RARP and eLND for NCCN high-risk PC between June 2014 and August 2019. Lymphatic invasion in resected specimens was observed in 47 patients (26%), whereas lymph node metastasis was observed in 17 patients (9%). During follow-up, BCR was observed in 48 patients (26%). The BCR rate in patients with lymphatic invasion was significantly higher than that in patients without lymphatic invasion (p < 0.01). According to multivariable Cox proportional hazards regression analyses, lymphatic invasion was a significant independent predictor of BCR in the overall patient group and was independently associated with BCR, even in patients without lymph node metastasis. In conclusion, evaluation of lymphatic invasion could be useful in predicting BCR in patients undergoing RARP and eLND for high-risk PC. Full article

(This article belongs to the Special Issue High-Risk Localized and Locally Advanced Prostate Cancer)

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14 pages, 1401 KiB

Open AccessArticle

Role of Brachytherapy Boost in Clinically Localized Intermediate and High-Risk Prostate Cancer: Lack of Benefit in Patients with Very High-Risk Factors T3b–4 and/or Gleason 9–10

by Hideya Yamazaki, Gen Suzuki, Koji Masui, Norihiro Aibe, Daisuke Shimizu, Takuya Kimoto, Kei Yamada, Koji Okihara, Takashi Ueda, Tsukasa Narukawa, Takumi Shiraishi, Atsuko Fujihara, Ken Yoshida, Satoaki Nakamura, Takashi Kato, Yasutoshi Hashimoto and Haruumi Okabe

Cancers 2022, 14(12), 2976; https://doi.org/10.3390/cancers14122976 - 16 Jun 2022

Cited by 4 | Viewed by 2300

Abstract

This study examined the role of brachytherapy boost (BT-boost) and external beam radiotherapy (EBRT) in intermediate- to high-risk prostate cancer, especially in patients with very high-risk factors (VHR: T3b–4 or Gleason score 9–10) as patients with double very high-risk factors (VHR-2: T3b–4 and [...] Read more.

This study examined the role of brachytherapy boost (BT-boost) and external beam radiotherapy (EBRT) in intermediate- to high-risk prostate cancer, especially in patients with very high-risk factors (VHR: T3b–4 or Gleason score 9–10) as patients with double very high-risk factors (VHR-2: T3b–4 and Gleason score 9–10) previously showed worst prognosis in localized prostate cancer. We retrospectively reviewed multi-institutional data of 1961 patients that were administered radiotherapy (1091 BT-boost and 872 EBRT: 593 conventional-dose RT (Conv RT: equivalent to doses of 2 Gy per fraction = EQD2 ≤ 72 Gy) and 216 dose-escalating RT (DeRT = EQD2 ≥ 74 Gy). We found that BT-boost improved PSA control and provided an equivalent overall survival rate in the intermediate- and high-risk groups, except for patients within the VHR factor group. In the VHR-1 group (single VHR), BT-boost showed a superior biochemical control rate to the Conv RT group but not to the DeRT group. In the VHR-2 group, BT-boost did not improve outcomes of either Conv RT or DeRT groups. In conclusion, BT-boost showed no benefit to modern DeRT in the patients with VHR; therefore, they are not good candidates for BT-boost to improve outcome and may be amenable to clinical trials using multimodal intensified systemic treatments. Full article

(This article belongs to the Special Issue High-Risk Localized and Locally Advanced Prostate Cancer)

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17 pages, 721 KiB

Open AccessArticle

Comparison of Clinical Outcomes of Radical Prostatectomy versus IMRT with Long-Term Hormone Therapy for Relatively Young Patients with High- to Very High-Risk Localized Prostate Cancer

by Hung-Jen Shih, Shyh-Chyi Chang, Chia-Hao Hsu, Yi-Chu Lin, Chu-Hsuan Hung and Szu-Yuan Wu

Cancers 2021, 13(23), 5986; https://doi.org/10.3390/cancers13235986 - 28 Nov 2021

Cited by 7 | Viewed by 2069

Abstract

That intensity-modulated radiotherapy (IMRT) plus antiandrogen therapy (IMRT-ADT) and radical prostatectomy (RP) are the definitive optimal treatments for relatively young patients (aged ≤ 65 years) with high- or very high-risk localized prostate cancer (HR/VHR-LPC), but remains controversial. We conducted a national population-based cohort [...] Read more.

That intensity-modulated radiotherapy (IMRT) plus antiandrogen therapy (IMRT-ADT) and radical prostatectomy (RP) are the definitive optimal treatments for relatively young patients (aged ≤ 65 years) with high- or very high-risk localized prostate cancer (HR/VHR-LPC), but remains controversial. We conducted a national population-based cohort study by using propensity score matching (PSM) to evaluate the clinical outcomes of RP and IMRT-ADT in relatively young patients with HR/VHR-LPC. Methods: We used the Taiwan Cancer Registry database to evaluate clinical outcomes in relatively young (aged ≤ 65 years) patients with HR/VHR-LPC, as defined by the National Comprehensive Cancer Network risk strata. The patients had received RP or IMRT-ADT (high-dose, ≥72 Gy plus long-term, 1.5–3 years, ADT). Head-to-head PSM was used to balance potential confounders. A Cox proportional hazards regression model was used to analyze oncologic outcomes. Results: High-dose IMRT-ADT had a higher risk of biochemical failure (adjusted hazard ratio [aHR] = 2.03, 95% confidence interval [CI] 1.56–2.65, p < 0.0001) compared with RP; IMRT-ADT did not have an increased risk of all-cause death (aHR = 1.2, 95% CI 0.65–2.24, p = 0.564), locoregional recurrence (aHR = 0.88, 95% CI 0.67–1.06, p = 0.3524), or distant metastasis (aHR = 1.03, 95% CI 0.56–1.9, p = 0.9176) compared with RP. Conclusion: In relatively young patients with HR/VHR-LPC, RP and IMRT-ADT yielded similar oncologic outcomes and RP reduced the risk of biochemical failure compared with IMRT-ADT. Full article

(This article belongs to the Special Issue High-Risk Localized and Locally Advanced Prostate Cancer)

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12 pages, 897 KiB

Open AccessArticle

Novel Prognostic Index of High-Risk Prostate Cancer Using Simple Summation of Very High-Risk Factors

by Hideya Yamazaki, Gen Suzuki, Koji Masui, Norihiro Aibe, Daisuke Shimizu, Takuya Kimoto, Kei Yamada, Takumi Shiraishi, Atsuko Fujihara, Koji Okihara, Ken Yoshida, Satoaki Nakamura and Haruumi Okabe

Cancers 2021, 13(14), 3486; https://doi.org/10.3390/cancers13143486 - 12 Jul 2021

Cited by 4 | Viewed by 2013

Abstract

This study aimed to examine the role of very high-risk (VHR) factors (T3b–4 and Gleason score 9–10) for prognosis of clinically localized high-risk prostate cancer. We reviewed multi-institutional retrospective data of 1413 patients treated with radiotherapy (558 patients treated with external beam radiotherapy [...] Read more.

This study aimed to examine the role of very high-risk (VHR) factors (T3b–4 and Gleason score 9–10) for prognosis of clinically localized high-risk prostate cancer. We reviewed multi-institutional retrospective data of 1413 patients treated with radiotherapy (558 patients treated with external beam radiotherapy (EBRT) and 855 patients treated with brachytherapy (BT) ± EBRT. We introduced an index by simple summation of the number of VHR factors—VHR-0, VHR-1, and VHR-2. With median follow-up of 69.6 months, the 5-year biochemical disease free survival rate (bDFS), prostate cancer-specific mortality (PCSM), and distant metastasis-free survival (DMSF) rates were 59.4%, 7.65%, and 83.2% for the VHR-2 group, respectively; 86.7%, 1.50%, and 95.4% for the VHR-1 group, respectively; and 93.1%, 0.12%, and 98.2% for the VHR-0 group, respectively. The VHR-2 group had significantly worse bDFS, PCSM, and DMSF than the VHR-0 (hazard ratios: 4.55, 9.607, and 7.904, respectively) and VHR-1 (hazard ratios: 1.723, 2.391, and 1.491, respectively) groups. The VHR-2 group could be identified as a super high-risk group compared with other groups, and could be a good candidate for clinical trials using multimodal intensified treatments. Simple summation of the number of VHR factors is an easy and useful predictive index for bDFS, PCSM, and DMSF. Full article

(This article belongs to the Special Issue High-Risk Localized and Locally Advanced Prostate Cancer)

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Review

Jump to: Editorial, Research

17 pages, 2124 KiB

Open AccessReview

Epithelial-to-Mesenchymal Transition-Related Markers in Prostate Cancer: From Bench to Bedside

by Samantha Gogola, Michael Rejzer, Hisham F. Bahmad, Wassim Abou-Kheir, Yumna Omarzai and Robert Poppiti

Cancers 2023, 15(8), 2309; https://doi.org/10.3390/cancers15082309 - 14 Apr 2023

Cited by 11 | Viewed by 2812

Abstract

Prostate cancer (PCa) is the second most frequent type of cancer in men worldwide, with 288,300 new cases and 34,700 deaths estimated in the United States in 2023. Treatment options for early-stage disease include external beam radiation therapy, brachytherapy, radical prostatectomy, active surveillance, [...] Read more.

Prostate cancer (PCa) is the second most frequent type of cancer in men worldwide, with 288,300 new cases and 34,700 deaths estimated in the United States in 2023. Treatment options for early-stage disease include external beam radiation therapy, brachytherapy, radical prostatectomy, active surveillance, or a combination of these. In advanced cases, androgen-deprivation therapy (ADT) is considered the first-line therapy; however, PCa in most patients eventually progresses to castration-resistant prostate cancer (CRPC) despite ADT. Nonetheless, the transition from androgen-dependent to androgen-independent tumors is not yet fully understood. The physiological processes of epithelial-to-non-epithelial (“mesenchymal”) transition (EMT) and mesenchymal-to-epithelial transition (MET) are essential for normal embryonic development; however, they have also been linked to higher tumor grade, metastatic progression, and treatment resistance. Due to this association, EMT and MET have been identified as important targets for novel cancer therapies, including CRPC. Here, we discuss the transcriptional factors and signaling pathways involved in EMT, in addition to the diagnostic and prognostic biomarkers that have been identified in these processes. We also tackle the various studies that have been conducted from bench to bedside and the current landscape of EMT-targeted therapies. Full article

(This article belongs to the Special Issue High-Risk Localized and Locally Advanced Prostate Cancer)

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19 pages, 348 KiB

Open AccessReview

Androgen Deprivation Therapy in High-Risk Localized and Locally Advanced Prostate Cancer

by Hiroaki Iwamoto, Kouji Izumi, Tomoyuki Makino and Atsushi Mizokami

Cancers 2022, 14(7), 1803; https://doi.org/10.3390/cancers14071803 - 1 Apr 2022

Cited by 8 | Viewed by 3195

Abstract

The recommended treatment for high-risk localized or locally advanced prostate cancer is radical prostatectomy plus extended pelvic lymph node dissection or radiation therapy plus long-term androgen deprivation therapy. However, some patients are treated with androgen deprivation therapy alone for various reasons. In this [...] Read more.

The recommended treatment for high-risk localized or locally advanced prostate cancer is radical prostatectomy plus extended pelvic lymph node dissection or radiation therapy plus long-term androgen deprivation therapy. However, some patients are treated with androgen deprivation therapy alone for various reasons. In this review, we will discuss the position, indications, complications, and future prospects of androgen deprivation therapy for high-risk localized and locally advanced prostate cancer. Full article

(This article belongs to the Special Issue High-Risk Localized and Locally Advanced Prostate Cancer)

17 pages, 316 KiB

Open AccessReview

Treatment Strategies for High-Risk Localized and Locally Advanced and Oligometastatic Prostate Cancer

by Tomoyuki Makino, Kouji Izumi, Hiroaki Iwamoto and Atsushi Mizokami

Cancers 2021, 13(17), 4470; https://doi.org/10.3390/cancers13174470 - 5 Sep 2021

Cited by 6 | Viewed by 3685

Abstract

Despite the significant advances in the treatment of high-risk prostate cancer, patients with very high-risk features such as being locally advanced (clinical stage T3–4 or minimal nodal involvement), having a high Gleason pattern, or with oligometastasis may still have a poor prognosis despite [...] Read more.

Despite the significant advances in the treatment of high-risk prostate cancer, patients with very high-risk features such as being locally advanced (clinical stage T3–4 or minimal nodal involvement), having a high Gleason pattern, or with oligometastasis may still have a poor prognosis despite aggressive treatment. Multidisciplinary treatment with both local and systemic therapies is thought to be effective, however, unfortunately, there is still no standard treatment. However, in recent years, local definitive therapy using a combination of radiotherapy and androgen deprivation is being supported by several randomized clinical trials. This study reviews the current literature with a focus on the definition of very high-risk prostate cancer, the role of modern imaging, and its treatment options. Full article

(This article belongs to the Special Issue High-Risk Localized and Locally Advanced Prostate Cancer)

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