S. Joniau MD, PhD

Appropriateness of treatment options in patients with metastatic castrationresistant prostate cancer with a focus on radium-223: outcomes of a Belgian multidisciplinary Consensus Meeting

SUMMARY

The treatment landscape for metastatic castration-resistant prostate cancer (mCRPC) has changed dramatically with the approval of a variety of therapeutic agents including abiraterone acetate, cabazitaxel, docetaxel, enzalutamide and radium-223 dichloride and the introduction of docetaxel and abiraterone acetate in combination with androgen deprivation therapy in newly diagnosed metastatic prostate cancer. Evidence on the optimal sequence of these therapies is scarce. In practice, the most appropriate treatment (sequence) depends on patient and disease characteristics. This article summarises the recommendations of a multidisciplinary group of Belgian experts in sequencing treatments for patients with mCRPC, with a focus on radium-223 dichloride.

(BELG J MED ONCOL 2019;13(6): 240–250)

Multimodality treatment for high-risk prostate cancer: New perspectives

High-risk prostate cancer represents the most aggressive form of the disease worldwide. In the past it was largely treated without curative intent but during the last years there has been a paradigm shift with an increase of curative procedures (particularly radical prostatectomy) for high-risk patients and, vice versa, active surveillance for low-risk disease. For this reason the high-risk group represents the novel target for contemporary research. The pre-operative risk groups are considered homogeneous in terms of prognosis and therapeutic response but there are grey zones within each group that have not been adequately studied. The main hypothesis of this PhD thesis (ISBN-NUMBER: 9789082757606 for the printed version and 9789082757613 for the e-version) is that not all high-risk prostate cancer patients have the same outcomes after surgery and also not the same response to multimodality therapies. In this context, novel treatments or their combinations should be tested. We analysed the largest high-risk database in the world demonstrating that not all high-risk patients after surgery have the same outcome according to their postoperative pathologic features. The European Multicentre Prostate Cancer Clinical and Translational Research group classifier was then defined as three different prognostic groups to predict cancer specific death. Interestingly, patients in these groups did not respond homogenously to adjuvant radiotherapy and/or androgen deprivation therapy. We also analysed the survival impact of neoadjuvant hormonal therapy before surgery, showing that patients who need adjuvant radiotherapy and were exposed to neoadjuvant hormonal therapy have the best prognosis. This outcome opens new perspectives for neoadjuvant treatment with or without other treatment combinations. The ARNEO trial is a phase II randomised, double blind, placebo controlled trial to study the association of apalutamide and degarelix before surgery for intermediate and high-risk disease.

(BELG J MED ONCOL 2018:12(3):130–132)

Highlights of Scientific Summits Meeting

Summary

Since last year a board of respectively three urologists and one radiation oncologist created the ‘Scientific Summits’. This is a scientifically independent Belgian congress for urologists, radiation oncologists, medical oncologists and radiologists with special interest in urology and more specifically in urologic oncology. The aim of Scientific Summits is providing up-to-date scientific information based on the highlights of the most recent international congresses. The 4^th edition took place in the charming city of Durbuy, Belgium.

The first day of the meeting focussed on the treatment and prevention of side effects of various anticancer treatments in urologic oncology. Experts in the field shared practical tips and tricks, based on interactive case discussions. They illustrated difficult situations and how to deal with them. On the second day of the meeting, interactive state-of-the-art lectures provided us with up-to-date information on how to evaluate and manage advanced and recurrent prostate cancer.

(BELG J MED ONCOL 2018;12(2):82–85)

BRCA2 gene mutation and risk of aggressive prostate cancer

Summary

BRCA2 mutation carriers generally present with prostate cancer at a younger age, with more aggressive disease and with a higher risk of nodal involvement or distant metastases at diagnosis. We present a patient with metastatic castrate resistant prostate cancer with a BRCA2 gene mutation and its clinical significance for daily practice.

(BELG J MED ONCOL 2016;10(6):223–227)

Genomic analysis of high-risk prostate cancer

Summary

Whole exome sequencing was performed on 38 high-risk prostate cancer samples. We confirmed recurrent mutations in prostate cancer-specific genes, but also identified genes not reported to be mutated, like TET1. This DNA hydroxymethylase converts methylcytosines to hydroxymethylcytosines as a first step in DNA demethylation. By immunohistochemistry, we detected decreased TET1 protein levels in tumour compared to surrounding non-tumour tissue. DNA hydroxymethylation followed the same course. Furthermore, TET1 mRNA expression levels are an independent predictor of metastasis-free survival in a larger retrospective cohort, indicating an important role for TET1 and hydroxymethylation in prostate cancer.
The LNCaP and C4-2B cell lines form an excellent preclinical model to study the development of metastatic castration-resistant prostate cancer. Both exome and transcriptome sequencing was performed: more than half of the mutations found in the exomes were confirmed in the RNA-sequencing data. Combining C4-2B-specific mutations with differentially expressed genes allowed the detection of changes in focal adhesion and ECM-receptor interactions, which might contribute to the metastatic potential of C4-2B cells.

(BELG J MED ONCOL 2016;10(4):139–142)

Prostatopubic fistula and osteomyelitis of the pubic bone as severe complication after salvage high intensity focused ultrasound for prostate cancer: report of two cases

Summary

High-intensity focused ultrasound has been used as an alternative treatment for prostate cancer, as both primary or salvage treatment. It is considered a minimally invasive treatment modality. We recently needed to care for two patients with severe osteomyelitis of the pubic bone as a result of a prostatopubic fistula, after they underwent salvage high-intensity focused ultrasound treatment post-radiotherapy.

(BELG J MED ONCOL 2015;9(7):290–95)

Resection of two metachronous solitary pulmonary metastases of prostate cancer after radical prostatectomy: an exceptional case

A solitary pulmonary metastasis of prostate cancer is not considered a surgical lesion. However, growing evidence supports that highly selected patients could benefit from metastasectomy of a solitary pulmonary metastasis. We present an exceptional case of resection of two metachronous pulmonary metastases of prostate cancer after previous radical prostatectomy, resulting in nearly undetectable prostate-specific antigen (0.04 ng/ml).

(BELG J MED ONCOL 2014;8(5):217–9)