The Prognostic Role of Preoperative PSMA PET/CT in cN0M0 pN+ Prostate Cancer: A Multicenter Study.

CONTEXT: Despite negative preoperative conventional imaging, up to 10% of patients with prostate cancer (PCa) harbor lymph-node involvement (LNI) at radical prostatectomy (RP). The advent of more accurate imaging modalities such as PET/CT improved the detection of LNI. However, their clinical impact and prognostic value are still unclear. We aimed to investigate the prognostic value of preoperative PET/CT in patients node positive (pN+) at RP. EVIDENCE SYNTHESIS: We retrospectively identified cN0M0 patients at conventional imaging (CT and/or MRI, and bone scan) who had pN+ PCa at RP at 17 referral centers. Patients with cN+ at PSMA/Choline PET/CT but cN0M0 at conventional imaging were also included. Systemic progression/recurrence was the primary outcome; Cox proportional hazards models were used for multivariate analysis. EVIDENCE ACQUISITION: We included 1163 pN+ men out of whom 95 and 100 had preoperative PSMA and/or Choline PET/CT, respectively. ISUP grade ≥4 was detected in 66.6%. Overall, 42% of patients had postoperative PSA persistence (≥0.1 ng/mL). Postoperative management included initial observation (34%), ADT (22.7%) and adjuvant RT+/-ADT (42.8%). Median follow-up was 42 months. Patients with cN+ on PSMA PET/CT had an increased risk of systemic progression (52.9% vs. 13.6% cN0 PSMA PET/CT vs. 21.5% cN0 at conventional imaging; P < .01). This held true at multivariable analysis: (HR 6.184, 95% CI: 3.386-11-295; P < .001) whilst no significant results were highlighted for Choline PET/CT. No significant associations for both PET types were found for local progression, BCR, and overall mortality (all P > .05). Observation as an initial management strategy instead of adjuvant treatments was related with an increased risk of metastases (HR 1.808; 95% CI: 1.069-3.058; P < .05). CONCLUSIONS: PSMA PET/CT cN+ patients with negative conventional imaging have an increased risk of systemic progression after RP compared to their counterparts with cN0M0 disease both at conventional and/or molecular imaging.

New technologies and techniques for prostate cancer focal therapy.

INTRODUCTION: The aim of this study was to review the oncological and functional outcomes of new and established primary focal treatments (FT) for localized prostate cancer (PCa). EVIDENCE ACQUISITION: We performed a systematic search of published studies on FT for localized PCa using electronic databases (Medline and Embase). These studies included reports on hemi-ablation, focal ablation and target-ablation. We excluded salvage focal therapy studies and limited the search to those with a minimum of 12 months of follow-up. EVIDENCE SYNTHESIS: We selected 20 studies with a total of 2523 patients who were treated in the primary setting. The energy sources used were cryotherapy (8), high-intensity focused ultrasound (9), irreversible electroporation (1), photodynamic therapy (1) and focused laser ablation (1), with 65% hemiablation, 25% focal ablation and 10% target-ablation. The median follow-ups ranged from 6 to 44.4 months. Mean age was 60.4-70 years and mean prostate-specific antigen was 4.4-<10 ng/dL; 26-100% had a Gleason Score of 6, and 0-65% had a Gleason Score of 7. Patient selection was carried out by TRUS biopsy in 9 studies, while transperineal template mapping biopsy and mp-MRI were employed in six and 13 studies, respectively. The overall post-treatment positive biopsy rate was 1.2-51% with 1.6-32% patients having a residual disease in the treated area. The post-treatment continence rates were 90-100%, and the rates of erectile dysfunction ranged from 0-53.2%. CONCLUSIONS: Reliable evidence for the partial-gland treatment of PCa is increasing, and encouraging mid-term oncologic outcomes with the preservation of sexual and urinary functions have been reported. Accurate patient selection at the outset of treatment and careful follow-up seem key attributes to achieve excellent functional results and encouraging oncological outcomes.

Tratamiento Focal del cáncer de próstata localizado: Modelo "À la carte” / Localized prostate cancer Focal Therapy: "A la carte" Model

La terapia focal se ha instaurado como una alternativa al tratamiento radical en casos seleccionados de cáncer de próstata localizado. La selección de pacientes candidatos a terapia focal se basa en un diagnóstico por imagen apoyado en la resonancia magnética multiparamétrica y las técnicas de fusión de imagen. Debido a los resultados oncológicos y los perfiles de seguridad de series iniciales, se han desarrollado distintas fuentes de energía en los últimos años. La disponibilidad de múltiples tipos de energía para el tratamiento focal, nos compromete a evaluar qué tipo de energía será la óptima según el perfil de paciente y el tipo de lesión. Una energía única para el tratamiento focal sería el ideal, pero ante la investigación de los diversos tipos de energías debemos identificar cuál es la recomendada para cada lesión. Con la experiencia de nuestro centro en distintos abordajes de terapia focal, proponemos el MODELO "À LA CARTE" basado en la localización de la lesión. Presentamos los criterios en los que se basa el modelo "à la carte", apoyados por la evidencia publicada en el uso de distintos tratamientos ablativos para el tratamiento de cáncer de próstata localizado. Tanto la localización de la lesión, las características técnicas de cada tipo de energía, el perfil del paciente y los efectos secundarios, han de contemplarse en toda elección de tratamiento focal

Focal therapy has settled as an alternative to radical treatment in selected cases of localized prostate cancer. The selection of patients who are candidates for focal therapy is based on imaging diagnosis relying on multiparametric MRI and image fusion techniques. Thanks to the oncological results and safety profiles of initial series, various energy sources have been developed over the last years. The availability of multiple types of energy sources for focal therapy, commits us to evaluate what type of energy would be the optimal depending on patient's profile and type of lesion. A unique energy for focal therapy would be ideal, but facing the research of the various types of energy we must identify which one is recommended for each lesion. With the experience of our center in different approaches of focal therapy we propose the "A LA CARTE" MODEL based on localization of the lesion. We present the criteria the "a la carte" model is based on, supported by the published evidence on the use of different ablative therapies for the treatment of localized prostate cancer. Lesion localization, technical characteristics of each type of energy, patient's profile and secondary effects must be considered in every choice of focal therapy

One-step customized transurethral resection of the prostate and permanent implant brachytherapy for selected prostate cancer patients: technically feasible but too toxic.

INTRODUCTION: Patients with prominent median lobe hyperplasia and/or high International Prostate Symptom Score (IPSS) are often contraindicated for prostate brachytherapy, mainly because of the risk of post-implant urinary retention. We evaluated an approach combining in the same operative step a limited transurethral resection (TURP) of the median lobe, immediately followed by permanent implant-free seed brachytherapy. METHODS AND MATERIALS: From January 2007 to November 2008, 22 patients underwent a customized limited TURP of their median lobe immediately before brachytherapy. All patients fulfilled our criteria for permanent implant brachytherapy, but presented with a more or less prominent median lobe and/or a high IPSS. RESULTS: The procedure appeared to be technically feasible, with only 0.3% of migrating seeds, a mean post-implant D90 of 173.4 Gy and a mean post-implant V100 of 96.6%. However, 5 patients (23%) experienced a urinary retention, with two patients having to undergo a complementary post-implant TURP. Moreover, urinary toxicity was more pronounced than in our current experience, with high IPSS at 2 months (mean 19.2) and 6 months (mean 15.8). CONCLUSION: Although technically feasible, with relatively few migrating seeds and satisfactory post-implant dosimetric parameters, one-step TURP and brachytherapy was found to be poorly tolerated, with higher than usual urinary retention and urinary toxicity rates. Considering those results, our group is presently evaluating a two-step procedure, with a customized TURP followed after 4-6 months by brachytherapy.

Surgical outcomes for men undergoing laparoscopic radical prostatectomy after transurethral resection of the prostate.

PURPOSE: We reviewed outcomes for men with a history of transurethral prostate resection who underwent laparoscopic radical prostatectomy for prostate cancer. MATERIALS AND METHODS: Between January 26, 1998 and December 2006, 3,061 men underwent laparoscopic radical prostatectomy at our institution. A retrospective review showed that 119 had a history of transurethral prostate resection. These men were compared to randomized matched controls with regard to operative and postoperative outcomes. The matching criteria used to randomly select patients were clinical stage, preoperative prostate specific antigen and biopsy Gleason score. RESULTS: Mean +/- SD age in the groups with and without transurethral prostate resection was 66.2 +/- 5.6 and 60.7 +/- 7.0 years, respectively (p <0.01). Mean estimated blood loss, transfusion rate, pathological prostate volume and reoperation rate were statistically similar between the groups. Mean length of stay for the groups with and without transurethral prostate resection was 6.5 +/- 3.0 and 5.29 +/- 2.3 days, respectively (p <0.01). Mean operative time for the groups with and without transurethral prostate resection was 179 +/- 44 and 171 +/- 38 minutes, respectively (p = 0.02). Positive margins were seen in 21.8% and 12.6% of the patients with and without transurethral prostate resection, respectively (p = 0.02). A total of 64 complications were seen in patients with a history of transurethral prostate resection compared to 34 in those without such a history (p <0.01). CONCLUSIONS: We report that patients with a history of transurethral prostate resection who undergo laparoscopic radical prostatectomy have worse outcomes with respect to operative time, length of stay, positive margin rate and overall complication rate. This subset of patients should be made aware of these potential risks before undergoing laparoscopic radical prostatectomy.

Molecular detection of localized prostate cancer using quantitative methylation-specific PCR on urinary cells obtained following prostate massage.

PURPOSE: The diagnosis of localized prostate cancer is difficult due to a lack of cancer-specific biomarkers. Many patients require repeat prostate biopsies to diagnose the disease. We investigated whether aberrant promoter hypermethylation in prostatic fluid could reliably detect prostate cancer. EXPERIMENTAL DESIGN: Urine samples were collected after prostate massage from 95 patients with localized prostate cancer undergoing radical prostatectomy (63 pT(1), 31 pT(2), and 1 pT(3)) and from 38 control patients. Ten genes (GSTP1, RASSF1a, ECDH1, APC, DAPK, MGMT, p14, p16, RARbeta2, and TIMP3) were investigated using quantitative real-time methylation-specific PCR. Receiver operator curves were generated. RESULTS: The frequency of gene methylation ranged from 6.3% (p14) to 83.2% (GSTP1) in prostate cancer patients. At least one gene was hypermethylated in 93% of cancer patients. The specificity of methylation was 0.74. Methylation was significantly more frequent (P < 0.05) in cancer than control patients for all genes except p14 and p16. According to receiver operator curve analysis, the four-gene combination of GSTP1 (0.86), RASSF1a (0.85), RARbeta2 (0.80), and APC (0.74) best discriminated malignant from nonmalignant cases. The sensitivity and accuracy of this four-gene set were 86% and 89%, respectively. CONCLUSIONS: The presence of aberrant methylation in urinary cells obtained after prostate massage is significantly associated with prostate cancer. A panel of four genes could stratify patients into low and high risk of having prostate cancer and optimize the need for repeat prostatic biopsies.

Transrectal focused ultrasound combined with transurethral resection of the prostate for the treatment of localized prostate cancer: feasibility study.

PURPOSE: We studied the feasibility of combined treatment with high intensity focused ultrasound (HIFU) and transurethral resection or incision of the prostate for localized prostate cancer to decrease the risk of posttreatment prolonged urinary retention. MATERIALS AND METHODS: Included in this feasibility study were 30 patients fulfilling certain criteria, namely localized prostate cancer indicated for HIFU, age 60 years or older, prostate volume 45 cc or less, no more than 4 positive samples at sextant biopsy, baseline prostate specific antigen (PSA) 10 ng/ml or less and no evidence of cancer extension. They received the combined treatment under general anesthesia using an Ablatherm HIFU device (EDAP SA, Lyon, France). RESULTS: The enrolled patients were a mean of 72 years old and presented with a median prostate volume of 30 cc. Median Gleason score was 6, median PSA was 7 ng/ml and pretreatment sextant biopsies provided a median of 2 positive samples. Mean operative time was 2 hours 48 minutes, including resection and HIFU. An average of 616 HIFU shots were delivered. The urinary catheter was removed at day 2 after treatment. Median hospital stay was 3 days. Only a few complications were observed. In regard to the oncological aspects at a mean of 20 months of followup 86% of the patients had negative biopsies after HIFU. Median PSA was 0.9 ng/ml. At 1 year of followup the mean International Prostate Symptom Score was 8. Regarding sexual function, 73% of previously potent patients reported preserved sexual activity. CONCLUSIONS: The combination of endoscopic resection or incision of the prostate with HIFU treatment decreases urinary catheterization time and improves posttreatment urinary status without additional morbidity.