[Pathological findings of visible and non-visible tumors on multiparametric magnetic resonance imaging (MRI) prior to radical prostatectomy]. / Caractéristiques anatomopathologiques des tumeurs apparentes et non apparentes en IRM multiparamétrique de la prostate avant prostatectomie totale.

INTRODUCTION: As urologists are questioned about the overtreatment of localized prostate cancer, multiparametric MRI can diagnose significant prostate cancer thanks to targeted biopsies. However, some tumors cannot be detected by MRI. What are the pathological characteristics of those tumors? MATERIALS AND METHODS: We have selected 144 consecutive patients treated with radical prostatectomy for clinically localized prostate cancer diagnosed on systematic and targeted biopsies (Koelis®) according to multiparametric MRI findings. On MRI, each suspicious area was graded according to the PI-RADS score v1.0. On radical prostatectomy specimen, tumor foci with a Gleason score greater than 3+3 and/or a tumor volume greater than 0,5cm3 were considered significant. The grade-four tumoral volume was calculated by multiplying the tumoral volume by grade 4 tumoral percentage. RESULTS: Two hundred and seventy seven tumors were identified. A hundred and thirty nine were non-visible on MRI. They had a significantly lower volume (0.15cm3 versus 1.45cm3, P<0.0001) and a Gleason score significantly lower (P<0.0001) than apparent tumors. 17.3% of non-apparent tumors were significant. Moreover, the grade-four tumoral volume of significant non-apparent tumors was significantly lower than that of significant apparent tumors (0.11cm3 versus 0.66cm3, P<0.0001). CONCLUSION: Non-apparent prostate tumors on multiparametric MRI have a Gleason score, a tumor volume - and consequently - a grade 4 tumor volume significantly lower than apparent tumors. LEVEL OF PROOF: 4.

Tumor target volume for focal therapy of prostate cancer-does multiparametric magnetic resonance imaging allow for a reliable estimation?

PURPOSE: We determined whether endorectal multiparametric magnetic resonance imaging at 1.5 Tesla could predict tumor target volume in the perspective of focal therapy of prostate cancer. MATERIALS AND METHODS: A total of 84 consecutive patients underwent multiparametric magnetic resonance imaging before radical prostatectomy. The volume of each suspicious area detected on magnetic resonance imaging and of all surgical histological foci was determined by planimetry. We first used each magnetic resonance imaging sequence (T2-weighted, diffusion weighted and dynamic contrast enhanced) and then the sequence showing the largest tumor area (multiparametric volume). Finally, the largest area of any sequence was used to calculate a target volume according to the volume of a cylinder. Agreement between magnetic resonance imaging and pathological findings was assessed by linear regression and residual analysis. RESULTS: Histology revealed 99 significant tumors with a volume of greater than 0.2 cc and/or a Gleason score of greater than 6. Of the tumors 16 (16.2%) were undetected by multiparametric magnetic resonance imaging. Linear regression analysis showed that tumor volume estimated by T2-weighted or diffusion weighted imaging correlated significantly with pathological volume (r(2) = 0.82 and 0.83, respectively). Residuals from diffusion weighted imaging volume estimations did not significantly differ from 0. Nevertheless, diffusion weighted imaging underestimated pathological volume in 43 of 87 cases (49%) by a mean of 0.56 cc (range 0.005 to 2.84). Multiparametric and target volumes significantly overestimated pathological volume by a mean of 16% and 44% with underestimation in 28 (32%) and 15 cases (17%), respectively. Volume underestimation was significantly higher for tumor foci less than 0.5 cc. The percent of Gleason grade 4 did not influence tumor volume estimation. CONCLUSIONS: Magnetic resonance imaging can detect most significant tumors. However, delineating a target volume may require further adjustment before planning magnetic resonance imaging targeted focal treatment.

[Full field optical coherence tomography of prostate biopsies: a step towards pre-histological diagnosis?]. / Tomographie par cohérence optique plein champ des biopsies de la prostate: un pas vers le diagnostic pré-histologique?

OBJECTIVES: To evaluate the value of full field optical coherence tomography (FFOCT) for cancer detection on prostate biopsies PATIENTS AND METHODS: Eight consecutive patients who underwent prostate biopsies for an elevated PSA or suspicious DRE findings were included in the study. For each patient, one to three biopsy cores were imaged with FFOCT immediately after sampling. Images obtained were analyzed by a pathologist blinded to the pathological results, and classified into three categories: non-cancerous tissue, suspicion of malignancy and prostate carcinoma. A pathological correlation analysis was further performed. RESULTS: Sixteen biopsy cores were analyzed. The median FFOCT procedure time was of 4 (3-5) minutes. No artifact was noted in subsequent pathological analysis. Six cores were involved with cancer and eight cores showed no evidence of cancer. On two cores, diagnosis was uncertain, and immuno-histochemical analysis confirmed cancer involvement in one of them. The agreement rate between standard histological analysis and FFOCT evaluation was of 81% (13/16). The three cases of disagreement were due to one false positive and two false negatives of FFOCT analysis. CONCLUSIONS: FFOCT of prostate biopsy cores seemed to be feasible and to allow concordant results with those of pathological analysis in the majority of the cases.

TRUS-MRI image registration: a paradigm shift in the diagnosis of significant prostate cancer.

Accuracy of multiparametric MRI has greatly improved the ability of localizing tumor foci of prostate cancer. This property can be used to perform a TRUS-MR image registration, new technological advance, which allows for an overlay of an MRI onto a TRUS image to target a prostate biopsy toward a suspicious area Three types of registration have been developed: cognitive-based, sensor-based, and organ-based registration. Cognitive registration consists of aiming a suspicious area during biopsy with the knowledge of the lesion location identified on multiparametric MRI. Sensor-based registration consists of tracking in real time the TRUS probe with a magnetic device, achieving a global positioning system which overlays in real-time prostate image on both modalities. Its main limitation is that it does not take into account prostate and patient motion during biopsy. Two systems (Artemis and Uronav) have been developed to partially circumvent this drawback. Organ-based registration (Koelis) does not aim to track the TRUS probe, but the prostate itself to compute in a 3D acquisition the TRUS prostate shape, allowing for a registration with the corresponding 3D MRI shape. This system is not limited by prostate/patient motion and allows for a deformation of the organ during registration. Pros and cons of each technique and the rationale for a targeted biopsy only policy are discussed.

Value of multiparametric MRI in the work-up of prostate cancer.

The role of magnetic resonance imaging (MRI) in prostate cancer evaluation is controversial and likely underestimated. Technological advances over the past 5 years have demonstrated that multiparametric MRI, including diffusion-weighted imaging (DWI) and dynamic contrast-enhanced MRI, can evaluate the actual tumor burden of a newly diagnosed prostate cancer more accurately than sextant biopsy protocols. Tumor risk, defined by the D'Amico criteria, hence can be re-evaluated by multiparametric MRI. As a result, there is increasing evidence that MRI before repeat or even initial biopsy can accurately select patients who require immediate biopsies and those in whom biopsy could be deferred. Also, a relationship between apparent diffusion coefficient (ADC), calculated from DWI, and Gleason score was found. Thus, MRI before biopsy helps to detect high-grade tumors to target biopsies within areas of low ADC values. To achieve good targeting accuracy, transrectal ultrasound (TRUS)-MRI image registration is necessary. Three-dimensional deformable registration is sufficiently accurate to match TRUS and MRI volumes with a topographic precision of 1 mm. Real-time MRI-guided biopsy is another technique under evaluation. Both approaches will allow for increasing acceptance of focal therapies, should these techniques be validated in the future.

[Prebiopsy multiparametric MRI of the prostate: the end of randomized biopsies?]. / IRM mutiparamétrique de la prostate avant biopsies : la fin des biopsies systématisées ?

OBJECTIVE: To evaluate the value of multiparametric MRI-targeted prostate biopsies in patients with suspected low-risk prostate cancer. PATIENTS AND METHOD: Patients with normal digital rectal examination and a PSA level between 4 and 10 ng/mL were prospectively included. A multiparametric MRI of the prostate was performed prospectively before the biopsies. 12-core randomized biopsies were performed, with additional targeted samples in each suspicious area identified on MRI. Detected cancers and their histological characteristics were compared between those two biopsy protocols. A micro focal cancer (MFC) was defined by the presence of less than 4mm of Gleason score 3+3 cancer on a single core. RESULTS: Seventy-one consecutive patients were included. The overall detection rate was of 53% (38/71). It was of 70% (26/37) in the presence of suspicious area on MRI versus 35% (12/34) in the absence of any suspicious area (P=0.004). MRI-targeted biopsies alone detected three cancers, none of which was a MFC. 12-core biopsies alone detected 14 cancers, including ten MFC (71%). In 21 patients, prostate cancer was detected by both the MRI-targeted and 12-core biopsies. The Gleason score in the MRI-targeted area was the highest Gleason score in 90% of the cases. It was high (>6) in 76% (16/21) of the patients. CONCLUSIONS: MRI-targeted biopsies detected less micro focal cancers than randomized 12-core biopsies. They did not seem however to decrease the detection of clinically significant cancers.

[Diffusion-weighted MR imaging of the prostate]. / IRM de diffusion de la prostate.

Functional imaging complements T2-weighted imaging in the evaluation of the prostate. The most frequently used techniques are diffusion-weighted imaging and perfusion imaging following the intravenous administration of contrast material. Perfusion imaging has high sensitivity and moderate specificity, even when using a quantitative technique, because contrast kinetics in some cases of peripheral zone prostatitis and benign transition zone hyperplasia may simulate cancer. Diffusion-weighted imaging is currently under evaluation but appears to be preferable to dynamic perfusion MR imaging because of its higher specificity and simpler acquisition. Functional imaging of the prostate is performed to detect cancers missed on biopsies or evaluate the volume of a newly diagnosed clinically localized cancer to assist in therapy selection. Future applications for image-guidance of targeted therapies to the tumor are currently investigational.

[Salvage radical prostatectomy after external radiotherapy for prostate cancer: indications, morbidity and results. Review from CCAFU prostate section]. / Prostatectomie de rattrapage après échec de radiothérapie externe pour cancer de la prostate localisé : enquête de pratique, indications, morbidité et résultats. Travail du CCAFU sous-comité prostate.

Local recurrence after external radiotherapy for prostate cancer occurs in 30 to 50 % and is often diagnosed by a rising PSA. The absence of local control after radiotherapy is a risk factor of metastases and specific mortality. There are several therapeutic options to treat these patients: surveillance, hormonotherapy and salvage therapies (radical prostatectomy, cystoprostatectomy, brachytherapy, high intensity focused ultrasound [HIFU] and cryotherapy). Hormonotherapy is not a curative treatment and after a couple of years, the disease will progress again. Local salvage therapies are the only treatment to have the potential to cure these patients with the condition of very strict inclusion criteria. Among these therapies, only radical prostatectomy demonstrated his efficacity with a follow-up of 10 years on specific survival and survival without biological progression respectively from 70 to 77 % and from 30 to 43 %. During last decade, morbidity of RP has strongly decreased with a percentage of rectal and ureteral injury at 3 %. Nevertheless, percentage of urinary incontinence remains high from 29 to 50 %. Salvage mini-invasive therapies (cryotherapy, HIFU and cryotherapy) are under constant evolution due to progress of technology. Functional and oncological results are better with last generation devices but need to be evaluated and compared with radical prostatectomy.

[What's new in 2009 in prostate cancer: highlights from ASTRO, EAU, ASCO and AUA meetings]. / Les nouveautés 2009 sur le cancer de la prostate: les points forts de l'ASTRO, l'EAU, l'ASCO et l'AUA.

In 2009, prostate cancer was the subject of a large number of communications in international urologic, oncologic and radiation therapy conferences. The most interesting studies that are likely to modify physician's daily practice were selected. This year the results from the European (ERSPC) and the American (PLCO) mass screening studies. Many abstract on prevention, natural history and tumor markers such as PCa3 and fusion gene TMPRSS2 : ERG were presented. Adjuvant hormonal treatment was evaluated in high-risk patients. Hormonal and radiation therapy association reduces recurrence, specific and overall mortality in locally advanced prostate cancer. Intermittent hormonal treatment is an option in hormone sensitive metastatic patients. toremifene and denosumab were evaluated in the prevention of fracture risk in patients under androgen deprivation therapy. The mechanism of tumor proliferation in castrate resistant prostate cancer further explained and 2 new molecules abiraterone and MDV 3100 were presented.

[Quantitative dynamic MRI and localisation of non-palpable prostate cancer]. / IRM dynamique quantitative et localisation du cancer de prostate non palpable.

PURPOSE: To determine whether quantitative dynamic contrast-enhanced MRI improves the performance of T2W-MRI for the localisation of non-palpable prostate cancer (PCa) and for the estimation of tumor volume. MATERIALS AND METHODS: Twenty-three patients (PSA: 8.91+/-6.2ng/m) with a non-palpable cancer underwent endorectal MRI with T2W and dynamic contrast enhanced (DCE) imaging before radical prostatectomy. Each level of evaluation (apex, mid-portion, base) was divided in eight areas (24 areas per prostate and 552 areas for the 23 patients). Localisation and volume of tumor foci greater than 0,2cc present on the radical prostatectmoy specimens were retrospectively correlated to their MR appearance on the 552 evaluated areas. The dynamic parameters included capillary permeability (K(trans)), maximum concentration of gadolinium after 60s of perfusion ([Gd]) and wash-out (K(ep)). Uni- and multivariate analysis were performed to determine which parameters were predictive of PCa. RESULTS: Mean values of K(trans), K(ep) and [Gd] were significantly higher in the 58 tumor foci greater than 0,2 cm(3) of the PZ and the TZ (all p<0.05). Logistic regression for each zone provides provided a value of the area under the ROC curve of 0.83 for the PZ and 0.81 for the TZ (0.7 and 0.75, respectively, for the T2W imaging), only significant for the PZ (p<0.002). Sensitivity and specificity were 79 and 77% for the PZ, 62.5 and 94% for the TZ. Above 0,2 cm(3), tumor volume on dynamic MR showed a mean difference of 51+/-100% (range: -145 to +248%). CONCLUSIONS: Quantitative dynamic MRI is more accurate than T2W imaging for tumor localisation of non-palpable cancer greater than 0,2 cm(3), but the difference is only significant for the PZ. Above this volume, correlation between tumor volume measured on dynamic MRI and that on the specimen is poor.

[Fusion genes and prostate cancer. From discovery to prognosis and therapeutic perspectives]. / Gènes de fusion et cancer de la prostate. De la découverte à la valeur pronostique et aux perspectives thérapeutiques.

The identification of fusion genes provides new insights into the initial mechanisms of molecular events implicated in the prostate cancer tumorigenesis. The presence of TEMPRSS2-ETS fusion in up to half of all human prostate cancer makes it perhaps the most common genetic rearrangement in human epithelial tumors. Some data suggest that TMPRSS2-ERG fusion prostate cancers have a more aggressive phenotype, which may affect cancer progression and outcome in localized tumors treated with prostatectomy. This discovery should pave the way towards future targeted therapies.

[Analysis of anatomopathological results of radical prostatectomy specimen of patients who answer to criteria for active surveillance of prostate cancer]. / Analyse des résultats anatomopathologiques des pièces de prostatectomie radicale des patients répondant aux critères de surveillance active du cancer de prostate.

OBJECTIVE: To analyze pathological data of the radical prostatectomy specimen in patients operated for clinically-localized prostate cancer and who meet strict criteria for active surveillance. PATIENTS AND METHODS: The data of patients who underwent a radical prostatectomy by a single surgeon between 2002 and 2007 were reviewed. We only included the patients that met the usual criteria for active surveillance: clinical stage T1-2a tumor, PSA< or =10 ng/mL, biopsy Gleason sum inferior or equal to 6 with no pattern of grade 4 or 5, cancer involvement inferior or equal to two biopsy cores, inferior to 50% of malignant tissue in each positive biopsy core and a PSA density inferior or equal to 0.15 ng/ml/cc. RESULTS: Two hundred and seventy-three patients were operated, including 25 (9.2%) who met all the criteria for active surveillance. Mean age was 61 years (55-68). The mean preoperative PSA was 6.6 ng/mL (2.5-10). Clinical stage of the tumor was T1c in 84% of patients and T2a in 16%. Biopsy Gleason score was 3+3 in 92%, 2+3 in 4% and 2+2 in 4%. Pathological study of the surgical specimen showed that 28% of the tumors were pT2a, 8% pT2b, 40% pT2c and 20% pT3a. One tumor was pT0. The pathological Gleason score was 3+3 in 68% of patients and 3+4 in 28%. Surgical specimen showed a higher Gleason score in 44% of cases, but there were no cases of predominant grade 4. After a mean follow-up of 19.2 months, there was no clinical or biological recurrence. CONCLUSION: In our experience, 20% of patients who meet the criteria for active surveillance show an extracapsular extent of the tumor on pathological analysis. Active surveillance is still under evaluation. Its main risk is to underestimate the aggressiveness of the tumor at the time of diagnosis.

[Results of total prostatectomy in the elderly patient]. / Résultats de la prostatectomie totale chez le patient âgé.

Only few studies have been published regarding the results of radical Prostatectomy (RP) in elderly patients. The available data suggest that advanced age does not increase the postoperative mortality and morbidity rates, as far as reasonable selection is performed. Similarly, oncological results of RP are similar in patients aged >70 years and in younger patients. Only the risk of incontinence may be increased, with a potential impact on quality of life. There are no studies comparing the various curative treatments of Prostate cancer (RP, radiation therapy, brachytherapy, active surveillance) in the elderly population.

[Androgen suppression for the treatment of prostate cancer in the elderly]. / Le traitement hormonal du cancer de la prostate chez le patient âgé.

Prostate cancer (PaC) is a significant health problem. Elderly have the highest incidence of the disease as age is its strongest risk factor. Despite its complications, the use of androgen suppression in aging patients with prostate cancer has become extremely frequent with probable excess. However, some of these complications carry specific mortality and all of them have a negative impact on quality of life. It is critical to perform a geriatric assessment, concerning physical, mental and social items, before to consider androgen suppression in this population. Indications of androgen suppression for the treatment of prostate cancer follow the guidelines of CCAFU. Delayed treatment deserves a special attention when possible. Treatment modalities are no specific to the elderly, but complications have to be anticipated with preventive measures. Intermittent androgen suppression should be considered with caution. Close follow up will focus on the diagnosis of adverse effects of androgen suppression.

[The role and principles of radiotherapy in prostate cancer in the elderly subject]. / Place et principes de la radiothérapie dans le cancer de la prostate du sujet âgé.

The aging of the population has resulted in an increase in the number of elderly patients with prostate cancer. Among the curative treatment options in the elderly subject, external radiotherapy is the most frequently chosen option. Combined treatment including radiotherapy and hormone therapy should be preferred to hormonal therapy alone, including in elderly patients, whenever life expectancy surpasses 4-5 years. The indications for this radiotherapy should be defined in an attempt to prevent excessive or insufficient treatment, to adapt the treatment modalities to the patient's age by assessing its potential toxicity, and to discuss the possible alternatives. In cases of localized prostate cancer in men who are aging well, a standard treatment should be proposed, preferring radiotherapy possibly associated with hormone therapy in cases with negative prognostic factors. Patients with a reversible health problems can also receive standard treatment, notably in cases with aggressive prognostic factors.

[Magnetic resonance imaging and prostate cancer]. / Imagerie par résonance magnétique et cancer de la prostate.

Prostate magnetic resonance imaging (MRI) has taken advantage of recent technological developments that increase the field of its indications. Available improvements concern functional MRI based on dynamic MRI (after intravenous injection of gadolinium), diffusion-weighted imaging and, possibly, spectroscopy to localise an undiagnosed prostate cancer on a first series of biopsies and differentiate tumors of significant volume from indolent or latent tumors. The combination of dynamic MRI and diffusion-weighted imaging seems to be the most accurate for the time being. An optimal accuracy to assess local tumor staging can only be obtained with the surface endorectal coil. Future advances concern lymph node extension following an intravenous injection of iron particles and detection of bone metastases by whole-body MRI.

MR imaging-guided prostate interventional imaging: Ready for a clinical use?

Prostate interventional magnetic resonance imaging (MRI) is now routinely performed in many centers. Its more widespread acceptance is limited by the cost of the use of MRI largely related to the long duration time of the procedures. However, the benefit of a robotic assistance has generated a new interest, because it substantially shortens the procedure time, while improving the accuracy. MRI-guided biopsy is considered as an appealing alternative to transrectal ultrasound (TRUS)-guided fusion biopsy, given the limitations of TRUS-MRI image registration systems. MRI-guided focal treatment also benefits from robotic assistance and from the unique property of MRI, which allows the measurement of the temperature in real-time during tumor ablation. The transrectal and transperineal approaches can be used and the respective indications of each pathway will depend on several factors, including the location of the tumor and the examination time, which will condition the occupation time of the MR room, a major factor influencing the overall cost of MRI-guided procedures. This review addresses the current practice of prostate MRI-guided interventional procedures and potential future applications.