Oligometastatic Prostate Adenocarcinoma. Clinical-Pathologic Study of a Histologically Under-Recognized Prostate Cancer.

The clinical parameters and the histological and immunohistochemical findings of a prospective protocolized series of 27 prostate carcinoma patients with oligometastatic disease followed homogeneously were analyzed. Lymph nodes (81.5%) and bones (18.5%) were the only metastatic sites. Local control after metastatic directed treatment was achieved in 22 (81.5%) patients. A total of 8 (29.6%) patients developed castration-resistant prostate cancer. Seventeen (63%) patients presented with non-organ confined disease. The Gleason index 8-10 was the most frequently observed (12 cases, 44.4%) combined grade. Positive immunostainings were detected with androgen receptor (100%), PGP 9.5 (74%), ERG (40.7%), chromogranin A (29.6%), and synaptophysin (18.5%) antibodies. The Ki-67 index value > 5% was observed in 15% of the cases. L1CAM immunostaining was negative in all cases. Fisher exact test showed that successful local control of metastases was associated to mild inflammation, organ confined disease, Ki-67 index < 5%, and Gleason index 3 + 3. A castration resistant status was associated with severe inflammation, atrophy, a Gleason index higher than 3 + 3, Ki-67 index ≥ 5%, and positive PGP 9.5, chromogranin A, and synaptophysin immunostainings. In conclusion, oligometastatic prostate adenocarcinoma does not have a specific clinical-pathologic profile. However, some histologic and immunohistochemical parameters of routine use may help with making therapeutic decisions.

Pretreatment Multiparametric Magnetic Resonance Imaging Findings Are More Accurate Independent Predictors of Outcome Than Clinical Variables in Localized Prostate Cancer.

PURPOSE: To prospectively determine whether multiparametric magnetic resonance imaging (mpMRI)-based staging is a more accurate independent predictor of outcome than traditional clinical variables for patients undergoing brachytherapy and external beam radiation therapy. METHODS AND MATERIALS: The primary endpoints were biochemical (nadir plus 2 ng/mL) and metastatic failure. Descriptive, univariate, and multivariate competing risks analyses were performed. The cumulative incidence rates were estimated to describe the cumulative risk of the events of interest. The magnitude of the increased risk was estimated using univariate and multivariate subdistribution hazard ratios. RESULTS: A total of 185 patients had undergone prospective treatment (123 with high risk and 62 with intermediate risk). The median age was 71 years (range 56-82). Of the patients, 20.5% had mpMRI-determined (mrT) stage mrT1-mrT2b, 37.3% had mrT2c, 31% had mrT3a, and 11.2% had mrT3b. The Gleason score was 6 in 22.2%, 7 in 49.5%, and 8 to 10 in 28.2%. The median baseline prostate-specific antigen was 11.7 ng/mL (range 2.9-153). After a median follow-up period of 46 months (range 16-70), 15 patients (8.1%) had developed biochemical failure and 9 (4.9%) had developed distant metastases. None of the traditional clinical variables (prostate-specific antigen, Gleason score, clinical stage) predicted for biochemical or metastatic failure. The multivariate competing risk analysis demonstrated that the 2 independent predictors of biochemical failure were the presence of extraprostatic extension (EPE; mrT3a; hazard ratio [HR] 4.80; P = .035) and presence of seminal vesicle invasion (SVI; mrT3b; HR 10.17; P = .003) on mpMRI. The only independent predictor of metastatic failure was the percentage of positive cores on prostate biopsy (HR 13.95; P = .014). After excluding patients with SVI, the only independent predictor of biochemical failure and metastatic failure was the presence of EPE (stage mrT3a) on mpMRI (HR 4.36; P = .042; and HR 5.76; P = .010, respectively). CONCLUSIONS: The pretreatment mpMRI findings might be more accurate independent predictors of the outcome than traditional clinical variables. In particular, the presence of EPE, SVI and a greater percentage of positive cores on biopsy predicted for a worse prognosis.

Dose escalation to dominant intraprostatic lesions with MRI-transrectal ultrasound fusion High-Dose-Rate prostate brachytherapy. Prospective phase II trial.

BACKGROUND AND PURPOSE: To demonstrate the feasibility, safety and effectiveness of dose escalation to intraprostatic lesions with MRI-transrectal ultrasound fusion High-Dose-Rate (HDR) brachytherapy. MATERIALS AND METHODS: 15 patients with intermediate-high risk prostate cancer and visible dominant intra-prostatic nodule on mpMRI have been treated. The treatment consisted of combined MRI-TRUS fusion HDR-brachytherapy (1 fraction of 1500cGy) and hypofractionated external beam (3750cGy in 15 fractions). A dose of 1875Gy was delivered to at least 98% of the DIL volume. RESULTS: Median prostate volume was 23.8cc; median number of needles was 16 (13-18). Dose escalation to DIL was feasible in 14/15 patients (93%) without violating dosimetric constraints and 1 patient presented a minimal deviation of dosimetric restrictions. With a median follow-up of 18months (17-24), none of the patients developed acute urinary retention or grade ⩾3 toxicity. In addition to standard PSA follow-up, response has been assessed by mpMRI at 12months. All patients presented adequate morphological responses on anatomical and functional sequences. CONCLUSIONS: HDR brachytherapy using MRI-transrectal ultrasound fusion for image guidance is a suitable technique for partial prostate dose escalation. Tolerance and toxicity profiles are excellent and results are encouraging in terms of biochemical, morphological and functional response.

Impact of intraoperative MRI/TRUS fusion on dosimetric parameters in cT3a prostate cancer patients treated with high-dose-rate real-time brachytherapy.

PURPOSE: The purpose of this study was to evaluate the impact of intraoperative MRI/TRUS fusion procedure in cT3a prostate cancer patients treated with high-dose-rate (HDR) real-time brachytherapy. MATERIAL AND METHODS: Prostate gland, dominant intraprostatic lesions (DILs), and extracapsular extension (ECE) were delineated in the pre-brachytherapy magnetic resonance images (MRI) of 9 consecutive patients. The pre-implant P-CTVUS (prostate clinical target volume) was defined as the prostate seen in the transrectal ultrasound (TRUS) images. The CTVMR includedthe prostate with the ECE image (ECE-CTV) as defined on the MRI. Two virtual treatment plans were performed based on the MRI/TRUS fusion images, the first one prescribing 100% of the dose to the P-PTVUS, and the second prescribing to the PTVMR. The implant parameters and dose-volume histogram (DVH) related parameters of the prostate, OARs, and ECE were compared between both plans. RESULTS: Mean radial distance of ECE was 3.6 mm (SD: 1.1). No significant differences were found between prostate V100, V150, V200, and OARs DVH-related parameters between the plans. Mean values of ECE V100, V150, and V200 were 85.9% (SD: 15.1), 18.2% (SD: 17.3), and 5.85% (SD: 7) when the doses were prescribed to the PTVUS, whereas ECE V100, V150, and V200 were 99.3% (SD: 1.2), 45.8% (SD: 22.4), and 19.6% (SD: 12.6) when doses were prescribed to PTVMR (p = 0.028, p = 0.002 and p = 0.004, respectively). CONCLUSIONS: TRUS/MRI fusion provides important information for prostate brachytherapy, allowing for better coverage and higher doses to extracapsular disease in patients with clinical stage T3a.