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13 pages, 1327 KiB

Open AccessArticle

The Effect of Adverse Surgical Margins on the Risk of Biochemical Recurrence after Robotic-Assisted Radical Prostatectomy

by Enric Carbonell, Roger Matheu, Maria Muní, Joan Sureda, Mónica García-Sorroche, María José Ribal, Antonio Alcaraz and Antoni Vilaseca

Biomedicines 2022, 10(8), 1911; https://doi.org/10.3390/biomedicines10081911 - 7 Aug 2022

Cited by 6 | Viewed by 2289

Abstract

Positive surgical margins (PSM) after radical prostatectomy are associated with a greater risk of biochemical recurrence (BCR). However, not all PSM harbour the same prognosis for recurrence. We aim to determine the impact of different PSM characteristics and their coexistence on the risk [...] Read more.

Positive surgical margins (PSM) after radical prostatectomy are associated with a greater risk of biochemical recurrence (BCR). However, not all PSM harbour the same prognosis for recurrence. We aim to determine the impact of different PSM characteristics and their coexistence on the risk of BCR. This retrospective study included 333 patients that underwent robotic-assisted radical prostatectomy for prostate cancer between 2015–2020 at a single institution. The effect of PSM and their adverse characteristics on the risk of BCR was assessed using Cox proportional hazard models. Kaplan–Meier was used to represent BCR-free survival stratified by margin status. With a median follow-up of 34.5 months, patients with PSM had a higher incidence of BCR, higher risk of relapse and lower BCR-free survival than negative margins (p < 0.001). We established as adverse characteristics: PSM length ≥ 3 mm, multifocality and Gleason at margin > 3. PSM ≥ 3 mm or multifocal PSM were associated with an increased risk for BCR compared to favourable margins (HR 3.50; 95% CI 2.05–5.95, p < 0.001 and HR 2.18; 95% CI 1.09–4.37, p = 0.028, respectively). The coexistence of these two adverse features in the PSM also conferred a higher risk for biochemical relapse and lower BCR-free survival. Adverse Gleason in the margin did not confer a higher risk for BCR than non-adverse margins in our models. We concluded that PSM are an independent predictor for BCR and that the presence of adverse characteristics, such as length and focality, and their coexistence in the PSM are associated with a greater risk of recurrence. Nevertheless, subclassifying PSM with adverse features did not enhance the model’s predictive performance in our cohort. Full article

(This article belongs to the Special Issue Implementation of New Imaging Techniques, Biomarkers and New Treatments in Prostate Cancer)

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9 pages, 1004 KiB

Open AccessArticle

The Usefulness of Adaptative Radiotherapy in Prostate Cancer: How, When, and Who?

by Rodrigo Muelas-Soria, Rafael García-Mollá, Virginia Morillo-Macías, Jorge Bonaque-Alandí, Patricia Sorribes-Carreras, Francisco García-Piñón and Carlos Ferrer-Albiach

Biomedicines 2022, 10(6), 1401; https://doi.org/10.3390/biomedicines10061401 - 13 Jun 2022

Cited by 4 | Viewed by 2184

Abstract

The aim of this study was to develop a deformable image registration (DIR)-based offline ART protocol capable of identifying significant dosimetric changes in the first treatment fractions to determine when adaptive replanning is needed. A total of 240 images (24 planning CT (pCT) [...] Read more.

The aim of this study was to develop a deformable image registration (DIR)-based offline ART protocol capable of identifying significant dosimetric changes in the first treatment fractions to determine when adaptive replanning is needed. A total of 240 images (24 planning CT (pCT) and 216 kilovoltage cone-beam CT (CBCT)) were prospectively acquired from 24 patients with prostate adenocarcinoma during the first three weeks of their treatment (76 Gy in 38 fractions). This set of images was used to plan a hypofractionated virtual treatment (57.3 Gy in 15 fractions); correlation with the DIR of pCT and each CBCT allowed to translate planned doses to each CBCT, and finally mapped back to the pCT to compare with those actually administered. In 37.5% of patients, doses administered in 50% of the rectum (D50) would have exceeded the dose limitation to 50% of the rectum (R50). We first observed a significant variation of the planned rectal volume in the CBCTs of fractions 1, 3, and 5. Then, we found a significant relationship between the D50 accumulated in fractions 1, 3, and 5 and the lack of compliance with the R50. Finally, we found that a D50 variation rate [100 × (administered D50 − planned D50/planned D50)] > 1% in fraction three can reliably identify variations in administered doses that will lead to exceeding rectal dose constraint. Full article

(This article belongs to the Special Issue Implementation of New Imaging Techniques, Biomarkers and New Treatments in Prostate Cancer)

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9 pages, 845 KiB

Open AccessArticle

Intraoperative Neurovascular Bundle Preservation with Hyaluronic Acid during Radical Brachytherapy for Localized Prostate Cancer: Technique and MicroMosfet In Vivo Dosimetry

by Pedro J. Prada, María Ferri, Juan Cardenal, Ana García Blanco, Elisabeth Arrojo, Javier Anchuelo, Ivan Diaz de Cerio, Pedro Lastra, Alejandro Fernández, Andrés Vázquez and Samuel Ruiz Arrebola

Biomedicines 2022, 10(5), 959; https://doi.org/10.3390/biomedicines10050959 - 21 Apr 2022

Cited by 1 | Viewed by 2160

Abstract

Purpose: To evaluate the reduction in the absorbed dose delivered to the neurovascular bundle (NB) in patients with localized prostate cancer treated with only HDR brachytherapy and NB protection with hyaluronic acid (HA) on the side of the prostate to increase the distance [...] Read more.

Purpose: To evaluate the reduction in the absorbed dose delivered to the neurovascular bundle (NB) in patients with localized prostate cancer treated with only HDR brachytherapy and NB protection with hyaluronic acid (HA) on the side of the prostate to increase the distance from NB to the radioactive sources. Methods: This is the first published report in the medical literature that studies a new approach to decrease neurovascular bundle toxicity and improve quality of life for patients with prostate cancer treated with radical brachytherapy as monotherapy. Transperineal HA injection on the side of the prostate into the lateral aspect of the prostate fat was used to consistently displace several autonomic fibers and vessels on the lateral wall of the prostate away from radiation sources. Results: When a protection in the form of an HA layer is placed, the reduction effect at the maximum dose is between 46% and 54% (calculated values), which means that the method for protection is highly recommended. The values of the absorbed dose calculated in this project have been compared with the ones given by the treatment planning system. Conclusions: This newly created space decreases absorbed dose in the NB, calculated with the TPS and measured by microMOSFET due to the thickness of HA. Full article

(This article belongs to the Special Issue Implementation of New Imaging Techniques, Biomarkers and New Treatments in Prostate Cancer)

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15 pages, 1006 KiB

Open AccessArticle

Raloxifene Suppresses Tumor Growth and Metastasis in an Orthotopic Model of Castration-Resistant Prostate Cancer

by Hannah Palmer, Mhairi Nimick, Aloran Mazumder, Sebastien Taurin, Zohaib Rana and Rhonda J. Rosengren

Biomedicines 2022, 10(4), 853; https://doi.org/10.3390/biomedicines10040853 - 5 Apr 2022

Cited by 1 | Viewed by 2363

Abstract

Androgen receptor (AR)-castrate-resistant prostate cancer (CRPC) is an aggressive form of prostate cancer that does not have clinically approved targeted treatment options. To this end, the cytotoxic potential of raloxifene and the synthetic curcumin derivative 2,6-bis (pyridin-4-ylmethylene)-cyclohexanone (RL91) was examined in AR-(PC3 and [...] Read more.

Androgen receptor (AR)-castrate-resistant prostate cancer (CRPC) is an aggressive form of prostate cancer that does not have clinically approved targeted treatment options. To this end, the cytotoxic potential of raloxifene and the synthetic curcumin derivative 2,6-bis (pyridin-4-ylmethylene)-cyclohexanone (RL91) was examined in AR-(PC3 and DU145) cells and AR+ (LnCaP) CRPC cells. The results showed that both raloxifene and RL91 elicited significant cytotoxicity across three cell lines with the lowest EC₅₀ values in PC3 cells. Additionally, the two drugs were synergistically cytotoxic toward the PC3, DU-145 and LNCaP cell lines. To determine the effect of the drug combination in vivo, an orthotopic model of CRPC was used. Male mice were injected with PC3 prostate cancer cells and then treated with vehicle (5 mL/kg), raloxifene (8.5 mg/kg, po), RL91 (8.5 mg/kg, po) or a combination of raloxifene and RL91 for six weeks. Sham animals were subjected to the surgical procedure but were not implanted with PC3 cells. The results showed that raloxifene decreased tumor size and weight as well as metastasis to renal lymph nodes. However, combination treatment reversed the efficacy of raloxifene as tumor volume and metastasis returned to control levels. The results suggest that raloxifene has tumor suppressive and anti-metastatic effects and has potential for further clinical use in AR-CRPC. Full article

(This article belongs to the Special Issue Implementation of New Imaging Techniques, Biomarkers and New Treatments in Prostate Cancer)

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Review

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17 pages, 327 KiB

Open AccessReview

Necessity of Pelvic Lymph Node Irradiation in Patients with Recurrent Prostate Cancer after Radical Prostatectomy in the PSMA PET/CT Era: A Narrative Review

by Naeim Nabian, Reza Ghalehtaki and Felipe Couñago

Biomedicines 2023, 11(1), 38; https://doi.org/10.3390/biomedicines11010038 - 24 Dec 2022

Cited by 1 | Viewed by 2332

Abstract

The main prostate cancer (PCa) treatments include surgery or radiotherapy (with or without ADT). However, none of the suggested treatments eliminates the risk of lymph node metastases. Conventional imaging methods, including MRI and CT scanning, are not sensitive enough for the diagnosis of [...] Read more.

The main prostate cancer (PCa) treatments include surgery or radiotherapy (with or without ADT). However, none of the suggested treatments eliminates the risk of lymph node metastases. Conventional imaging methods, including MRI and CT scanning, are not sensitive enough for the diagnosis of lymph node metastases; however, the novel imaging method, PSMA PET/CT scanning, has provided valuable information about the pelvic LN involvement in patients with recurrent PCa (RPCa) after radical prostatectomy. The high sensitivity and negative predictive value enable accurate N staging in PCa patients. In this narrative review, we summarize the evidence on the treatment and extent of radiation in prostate-only or whole-pelvis radiation in patients with positive and negative LN involvement on PSMA PET/CT scans. Full article

(This article belongs to the Special Issue Implementation of New Imaging Techniques, Biomarkers and New Treatments in Prostate Cancer)

14 pages, 1551 KiB

Open AccessReview

Theragnostic Radionuclide Pairs for Prostate Cancer Management: ⁶⁴Cu/⁶⁷Cu, Can Be a Budding Hot Duo

by Anupriya Chhabra and Mathew L. Thakur

Biomedicines 2022, 10(11), 2787; https://doi.org/10.3390/biomedicines10112787 - 2 Nov 2022

Cited by 6 | Viewed by 3302

Abstract

Prostate cancer (PCa) is one of the preeminent causes of mortality in men worldwide. Theragnostic, a combination of therapy and diagnostic, using radionuclide pairs to diagnose and treat disease, has been shown to be a promising approach for combating PCa. In PCa patients, [...] Read more.

Prostate cancer (PCa) is one of the preeminent causes of mortality in men worldwide. Theragnostic, a combination of therapy and diagnostic, using radionuclide pairs to diagnose and treat disease, has been shown to be a promising approach for combating PCa. In PCa patients, bone is one of the most common sites of metastases, and about 90% of patients develop bone metastases. This review focuses on (i) clinically translated theragnostic radionuclide pairs for the management of PCa, (ii) radionuclide therapy of bone metastases in PCa, and (iii) a special emphasis on emerging theragnostic radionuclide pair, Copper-64/Copper-67 (⁶⁴Cu/⁶⁷Cu) for managing the disease. Full article

(This article belongs to the Special Issue Implementation of New Imaging Techniques, Biomarkers and New Treatments in Prostate Cancer)

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22 pages, 3843 KiB

Open AccessReview

PARP Inhibitors: A New Horizon for Patients with Prostate Cancer

by Belén Congregado, Inés Rivero, Ignacio Osmán, Carmen Sáez and Rafael Medina López

Biomedicines 2022, 10(6), 1416; https://doi.org/10.3390/biomedicines10061416 - 15 Jun 2022

Cited by 28 | Viewed by 4033

Abstract

The introduction of PARP inhibitors (PARPi) in prostate cancer is a milestone and provides a pathway to hope in fighting this disease. It is the first time that drugs, based on the concept of synthetic lethality, have been approved for prostate cancer. In [...] Read more.

The introduction of PARP inhibitors (PARPi) in prostate cancer is a milestone and provides a pathway to hope in fighting this disease. It is the first time that drugs, based on the concept of synthetic lethality, have been approved for prostate cancer. In addition, it is also the first time that genetic mutation tests have been included in the therapeutic algorithm of this disease, representing a significant step forward for precision and personalized treatment of prostate cancer. The objectives of this review are: (1) understanding the mechanism of action of PARPi in monotherapy and combinations; (2) gaining insights on patient selection for PARPi; (3) exposing the pivotal studies that have allowed its approval, and; (4) offering an overview of the ongoing trials. Nevertheless, many unsolved questions remain, such as the number of patients who could potentially benefit from PARPi, whether to use PARPi in monotherapy or in combination, and when is the best time to use them in advanced or localized disease. To answer these and other questions, many clinical trials are underway. Some of them have recently demonstrated promising results that may favor the introduction of new combinations in metastatic castration-resistant prostate cancer. Full article

(This article belongs to the Special Issue Implementation of New Imaging Techniques, Biomarkers and New Treatments in Prostate Cancer)

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18 pages, 1154 KiB

Open AccessReview

Immunotherapy in Advanced Prostate Cancer: Current Knowledge and Future Directions

by Fernando López-Campos, Pablo Gajate, Nuria Romero-Laorden, Juan Zafra-Martín, Manel Juan, Susana Hernando Polo, Antonio Conde Moreno and Felipe Couñago

Biomedicines 2022, 10(3), 537; https://doi.org/10.3390/biomedicines10030537 - 24 Feb 2022

Cited by 11 | Viewed by 3666

Abstract

The advent of immunotherapy has revolutionized cancer treatment. Unfortunately, this has not been the case for metastatic castration-resistant prostate cancer (mCRPC), likely due to the heterogeneous and immune-suppressive microenvironment present in prostate cancer. The identification of molecular biomarkers that could predict response to [...] Read more.

The advent of immunotherapy has revolutionized cancer treatment. Unfortunately, this has not been the case for metastatic castration-resistant prostate cancer (mCRPC), likely due to the heterogeneous and immune-suppressive microenvironment present in prostate cancer. The identification of molecular biomarkers that could predict response to immunotherapy represents one of the current challenges in this clinical scenario. The management of advanced castration-resistant prostate cancer is rapidly evolving and immunotherapy treatments, mostly consisting of immune checkpoint inhibitors combinations, BiTE^® (bispecific T-cell engager) immune therapies, and chimeric antigen receptors (CAR) are in development with promising results. This review analyses the current evidence of immunotherapy treatments for mCRPC, evaluating past failures and promising approaches and discussing the directions for future research. Full article

(This article belongs to the Special Issue Implementation of New Imaging Techniques, Biomarkers and New Treatments in Prostate Cancer)

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