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Home » EU Health, Health, Prostate Cancer

Towards a paradigm shift in diagnosis and management

Submitted by on 31 Mar 2016 – 10:00

Over the past years, there has been a fundamental change in the way prostate cancer has been diagnosed and treated, with patients having a greater variety of options to choose from. Prof Ronald Van Velthoven, Head of Urology, Institut Jules Bordet, says the trend is set to continue and the future appears even brighter, particularly in molecular and genetic understandings of tumors

Van velthoven - copie 2

The last few decades were marked by a widespread use of PSA-based prostate cancer screening and hence by an exponential rise in the number of prostate biopsies, in terms of patients and of biopsies per patient. Some of these biopsies were unnecessarily performed while others missed significant prostate cancers. In addition, more men with low-risk prostate cancer were diagnosed and some were thus unnecessarily treated.

The limited specificity of PSA and the low detection rate of prostate cancer on TRUS-guided biopsy generated much of the controversy existing about prostate cancer screening. Furthermore, the poor sampling of cancers under 2D TRUS and the underestimation of Gleason score widely opened the door for the development of more accurate strategies for the diagnosis of prostate cancer.

In this context, we had already reported, in a previous study of biopsy-naïve men, higher detection rate using the 3D system of Koelis Urostation® without MRI fusion compared to standard protocol (50% vs. 33%, p < 0.05) ) (1). Our results reflected a wider distribution of prostate cores inside the prostate and thus better sampling. Afterwards, we integrated MRI-targeted biopsy using the same system into our practice. This yielded an overall cancer detection rate of 62.7%, which is higher than most of the studies reporting on standard biopsy (2). In addition, in our study, TAR protocol improved prostate cancer detection rate compared to STD protocol and demonstrated higher detection rate of clinically significant disease with fewer tissue samples removed from lesions.

In addition, we have used a combined localisation strategy based on a complete match between multiparametric MRI and transrectal ultrasound (TRUS) guided systematic biopsy to assess feasibility, safety, and short-to-medium-term oncological and functional outcomes of hemiablation HIFU. Results were promising as hemi-ablation HIFU of an entire lobe, delivered with the intention to treat, was a feasible and safe procedure.(3) Functional and oncological outcomes were also encouraging at 3-years of follow up as demonstrated in our recently published updated series.(4) This is a timely issue given the recent concerns about the quality of life of prostate cancer survivors.

The principal rationale of such an approach is harm reduction without compromising cancer control: early self-resolving LUTS were the most common complications but no rectal toxicities were reported and the strategy was well tolerated in the genitourinary functional domains. The procedure can also be delivered in an ambulatory care setting. This treatment strategy was associated with a good medium-term cancer control in well-selected patients (unilateral low- to Intermediate-risk prostate cancer). Furthermore, patients with bilateral significant prostate cancer can also be safely treated by whole gland ablation with good outcomes (5). In our match cohort analysis, functional and oncologic outcomes were similar between patients treated by brachytherapy and those offered whole gland HIFU (6). However, the earlier decrease of PSA in the HIFU group compared to the brachytherapy group allowed better stratification of responders.

In parallel, recent developments of molecular and clinical imaging with better specificity and sensitivity than anatomic imaging provided clinicians with the opportunity to detect lymphatic and/or haematogenous prostatic metastases at an earlier point in the disease progression, resulting in a treatment window for what was called oligo-metastatic disease(7). Since then, a paradigm shift toward more aggressive local control of primary tumor and/or small number of metastatic lesions has gained interest in the oncologic centres of excellence.

In our institution, we have implemented such an approach based on the most accurate metabolic imaging for prostate cancer that is PSMA- PET. In our experience, inherited from our routine practice of large cohorts of robot assisted laparoscopic prostatectomy for organ confined prostate cancer, radical prostatectomy remains safe, feasible and offers good local control in well-selected oligo-metastatic patients. Apart from the debatable oncologic effect of local control – at present the primary endpoint was to delay ADT – the main advantage is the symptomatic loco-regional improvement. Several complications encountered in the late stages of metastatic prostate cancer could be avoided. This could translate into an improvement in the quality of life of many patients.

Actually, one should bear in mind that treating the primary tumor in such patients remains outside of all urologic guidelines and should be preferably offered under the umbrella of clinical trials. Of note, some of the patients already treated with primary radiation therapy are accurately diagnosed with PSMA-PET showing an isolated organ confined recurrence. In the same way, these patients are offered a curative treatment instead of palliative ADT, a common mistake in the current practice of urology. These patients were treated by salvage whole gland HIFU or hemiablation according to the results of MRI and MRI targeted biopsies. Our results with both strategies are encouraging, keeping in mind the morbidity of salvage radical prostatectomy in this setting. Finally, we are witnessing at the moment, a paradigm shift in the diagnosis and management of prostate cancer. The future appears even brighter when we see the enormous efforts and advances in molecular and genetic understanding of prostate cancer tumors. The development of new accurate biomarkers will lead cancer revolution and personalized care in men with prostate cancer

References:
1. Peltier et al., Prostate Cancer 2014
2. Peltier et al., BioMed Research International 2015
3. van Velthoven et al., Prostate Cancer 2014
4. van Velthoven et al., Prostate Cancer Prostate Disease 2015
5. Limani et al., Prostate Cancer 2014
6. Aoun et al., Advances in Urology 2015
7. Aoun et al, BioMed Research International 2015