Between Pathological Prostate Cancer Lymph Nodes and Sentinel Nodes: Which Information Is the Leader?

PURPOSE: On the basis of the concept of sentinel lymph node biopsy (SLNB), SLNs should contain decisive information for clinical outcomes. In localized prostate cancer patients, this study assessed retrospectively clinical outcome after radical laparoscopic prostatectomy associated with SLNB and extensive pelvic lymph node dissection. METHODS: A total of 231 consecutive patients of intermediate to high risk were analyzed. Recurrence-free survival (RFS) was assessed with Kaplan-Meier curves. Various pathological parameters were analyzed using univariable and multivariable analyses through Cox regression analysis. The study was approved and registered under 2007-R41. RESULTS: The median follow-up was 7.1 years (95% confidence interval, 6.6-7.5). In total, 38/231 (16.5%) patients were pN1. Of these 38 patients, 27 had only SLN involvement (SLNI), 10 patients had both SLN and non-SLNI, and 1 patient had isolated non-SLNI, indicating a false-negative (FN). If the updated Briganti nomogram threshold set at >7% for recommending extensive pelvic lymph node dissection had been applied to these patients, we would have missed 44% (12/27) of patients with SLNI and 50% (5/10) of patients with SLNI and non-SLNI, as well as the FN patient. At the time of final follow-up, 84/231 (36.5%) patients had recurrence. In multivariable analysis, and regarding node status, the most significant prognostic factor was SLN with macrometastases and/or micrometastases, respectively, P = 10-3 and P < 10-3. No more information was obtained with non-SLN status. Probabilities of RFS between negative and positive SLN patients presented a major significant difference (P < 10-15) with a risk of event 8.75 times more frequent if SLN was involved than if it was metastasis-free. CONCLUSIONS: SLNB seems to contain decisive information for the clinical outcome of patients with localized intermediate- and high-risk prostate cancer patients. The question raised is thus whether immediate additional postoperative treatment should be offered to patients with metastatic SLN.

Laparoscopic sentinel lymph node dissection in prostate cancer patients: the additional value depends on preoperative data.

AIM: In intermediate- or high-risk prostate cancer (PC) patients, to avoid extended pelvic lymph node dissection (ePLND), the updated Briganti nomogram is recommended with the cost of missing 1.5 % of patients with lymph node invasion (LNI). Is it possible to reduce the percentage of unexpected LNI patients (nomogram false negative)? We used the isotopic sentinel lymph node (SLN) technique systematically associated with laparoscopic ePLND to assess the potential value of isotopic SLN method to adress this point. METHODS: Two hundred and two consecutive patients had procedures with isotopic SLN detection associated with laparoscopic ePLND for high or intermediate risk of PC. The area under the curve (AUC) of the receiver operating characteristics (ROC) analysis was used to quantify the accuracy of different models as: the updated Briganti nomogram, the percentage of positive cores, and an equation of the best predictors of LNI. We tested the model cutoffs associated with an optimal negative predictive value (NPV) and the best cutoff associated with avoiding false negative SLN detection, in order to assist the clinician's decision of when to spare ePLND. RESULTS: LNI was detected in 35 patients (17.2 %). Based on preoperative primary Gleason grade and percentage of positive cores, a bivariate model was built to calculate a combined score reflecting the risk of LNI. For the Briganti nomogram, the 5 % probability cutoff avoided ePLND in 53 % (108/202) of patients, missing three LNI patients (8.6 %), but all were detected by the SLN technique. For our bivariate model, the best cutoff was <10, leaving no patient with LNI due to positive SLN detection (four patients = 11.4 %), and avoiding ePLND in 52 % (105/202) of patients. CONCLUSION: For patients with a low risk of LNI determined using the updated Briganti nomogram or bivariate model, SLN technique could be used alone for lymph node staging in intermediate- or high-risk PC patients.

The accuracy of different biopsy strategies for the detection of clinically important prostate cancer: a computer simulation.

PURPOSE: The true accuracy of different biopsy strategies for detecting clinically significant prostate cancer is unknown, given the positive evaluation bias required for verification by radical prostatectomy. To evaluate how well different biopsy strategies perform at detecting clinically significant prostate cancer we used computer simulation in cystoprostatectomy cases with cancer. MATERIALS AND METHODS: A computer simulation study was performed on prostates acquired at radical cystoprostatectomy. A total of 346 prostates were processed and examined for prostate cancer using 3 mm whole mount slices. The 96 prostates that contained cancer were digitally reconstructed. Biopsy simulations incorporating various degrees of random localization error were performed using the reconstructed 3-dimensional prostate computer model. Each biopsy strategy was simulated 500 times. Two definitions of clinically significant prostate cancer were used to define the reference standard, including definition 1--Gleason score 7 or greater, and/or lesion volume 0.5 ml or greater and definition 2--Gleason score 7 or greater, and/or lesion volume 0.2 ml or greater. RESULTS: A total of 215 prostate cancer foci were present. The ROC AUC to detect and rule out definition 1 prostate cancer was 0.69, 0.75, 0.82 and 0.91 for 12-core transrectal ultrasound biopsy with a random localization error of 15 and 10 mm, 14-core transrectal ultrasound biopsy and template prostate mapping using a 5 mm sampling frame, respectively. CONCLUSIONS: To our knowledge our biopsy simulation study is the first to evaluate the performance of different sampling strategies to detect clinically important prostate cancer in a population that better reflects the demographics of a screened cohort. Compared to other strategies standard transrectal ultrasound biopsy performs poorly for detecting clinically important cancer. Marginal improvement can be achieved using additional cores placed anterior but the performance attained by template prostate mapping is optimal.

Focal laser ablation of prostate cancer: definition, needs, and future.

Current challenges and innovations in prostate cancer management concern the development of focal therapies that allow the treatment of only the cancer areas sparing the rest of the gland to minimize the potential morbidity. Among these techniques, focal laser ablation (FLA) appears as a potential candidate to reach the goal of focusing energy delivery on the identified targets. The aim of this study is to perform an up-to-date review of this new therapeutic modality. Relevant literature was identified using MEDLINE database with no language restrictions (entries: focal therapy, laser interstitial thermotherapy, prostate cancer, FLA) and by cross-referencing from previously identified studies. Precision, real-time monitoring, MRI compatibility, and low cost of integrated system are principal advantages of FLA. Feasibility and safety of this technique have been reported in phase I assays. FLA might eventually prove to be a middle ground between active surveillance and radical treatment. In conclusion, FLA may have found a role in the management of prostate cancer. However, further trials are required to demonstrate the oncologic effectiveness in the long term.

A biopsy simulation study to assess the accuracy of several transrectal ultrasonography (TRUS)-biopsy strategies compared with template prostate mapping biopsies in patients who have undergone radical prostatectomy.

UNLABELLED: What's known on the subject? and What does the study add? Transrectal ultrasonography (TRUS)-guided biopsies can miss prostate cancer and misclassify risk in a diagnostic setting; the exact extent to which it does so in a repeat biopsy strategy in men with low-intermediate risk prostate cancer is unknown. A simulation study of different biopsy strategies showed that repeat 12-core TRUS biopsy performs poorly. Adding anterior sampling improves on this but the highest accuracy is achieved using transperineal template prostate mapping using a 5 mm sampling frame. OBJECTIVE: To determine the effectiveness of two sampling strategies; repeat transrectal ultrasonography (TRUS)-biopsy and transperineal template prostate mapping (TPM) to detect and exclude lesions of ≥0.2 mL or ≥0.5 mL using computer simulation on reconstructed three-dimensional (3-D) computer models of radical whole-mount specimens. PATIENTS AND METHODS: Computer simulation on reconstructed 3-D computer models of radical whole-mount specimens was used to evaluate the performance characteristics of repeat TRUS-biopsy and TPM to detect and exclude lesions of ≥0.2 mL or ≥0.5 mL. In all, 107 consecutive cases were analysed (1999-2001) with simulations repeated 500 times for each biopsy strategy. TPM and five different TRUS-biopsy strategies were simulated; the latter involved a standard 12-core sampling and incorporated variable amounts of error, as well as the addition of anterior cores. Sensitivity, specificity, negative and positive predictive values for detection of lesions with a volume of ≥0.2 mL or ≥0.5 mL were calculated. RESULTS: The mean (SD) age and PSA concentration were 61 (6.4) years and 8.5 (5.9) ng/mL, respectively.In all, 53% (57/107) had low-intermediate risk disease. In all, 665 foci were reconstructed; there were 149 foci ≥0.2 mL and 97 ≥ 0.5 mL in the full cohort and 68 ≥ 0.2 mL and 43 ≥ 0.5 mL in the low-intermediate risk group. Overall, TPM accuracy (area under the receiver operating curve, AUC) was ≈0.90 compared with AUC 0.70-0.80 for TRUS-biopsy. In addition, at best, TRUS-biopsy missed 30-40% of lesions of ≥0.2 mL and ≥0.5 mL whilst TPM missed 5% of such lesions. CONCLUSION: TPM under simulation conditions appears the most effective re-classification strategy, although augmented TRUS-biopsy techniques are better than standard TRUS-biopsy.

Focal laser interstitial thermotherapy (LITT) at 980 nm for prostate cancer: treatment feasibility in Dunning R3327-AT2 rat prostate tumour.

OBJECTIVE: To examine the feasibility and reproducibility of laser interstitial thermotherapy (LITT) as a minimally invasive method for the treatment of prostate cancer. MATERIALS AND METHODS: Heterotopic tumours of prostatic adenocarcinoma (Dunning R3327-AT2) were induced in 10 male Copenhagen rats. After preoperative magnetic resonance imaging (MRI), a 10-mm cylindrical diffusing fibre developed by our research department was inserted under ultrasonographic guidance into the tumour. LITT was performed with a 980-nm diode laser (power 5 W) for 75 s (fluence rate of 1145 J/cm(2)). Non-enhanced T2-weighted and dynamic gadolinium-enhanced T1-weighted MRI examinations were performed at baseline, 1 and 48 h after the procedure and correlated with histological findings. RESULTS: The necrosis lesions induced by LITT were visible on MRI. The mean (SD) ellipsoid necrosis volumes were 0.748 (0.075) mL at 1 h and 0.982 (0.052) mL at 48 h after the LITT procedure, and significantly different (P < 0.001). Histological analysis showed a strong correlation (r = 0.87) with the mean necrosis volume obtained by MRI at 48 h after LITT. CONCLUSIONS: In a prostatic adenocarcinoma model, 980-nm LITT induces reproducible necrosis volumes. Further characterization of the response to LITT in an animal model and in human tissues will be important in establishing the efficacy of the procedure for prostate cancer focal therapy.

Quantitative tissue analyses of prostate cancer foci in an unselected cystoprostatectomy series.

UNLABELLED: What's known on the subject? and What does the study add? Much of our understanding of the pathological basis of prostate cancer comes from our analysis of radical prostatectomy specimens. Prostate cancer diagnosed by transrectal ultrasonography-guided biopsy is more likely to be posterior and basal in orientation rather than anterior or apical. Quantitative tissue analyses have not been undertaken both with details and in an unselected population, e.g. prostate specimens from autopsy cystoprostatectomy series from bladder cancer. Quantitative tissue analysis of incidentally detected prostate cancer such as largest cancer surface area, volume, site of origin, multifocality and laterality could be of paramount importance when trying to understand the findings of screen-detected programmes and focal therapy. Cancers were found in 30% of prostates. In the 96 prostates, 215 cancer foci were identified (mean 2.24). Prostate cancer was multifocal in 60% and bilateral in 80% of cases. The site of origin was in the peripheral and transition zone (TZ) in 75% and 25%, respectively. Overall, 90% of cancer foci were clinically insignificant with volume of <0.5 mL and no grades 4-5. In all, 75% of the cancer foci were in the peripheral zone, the remainder were within the TZ. One third of cancer foci were anteriorly located beyond the area sampled by posterior biopsies. One fifth of cancer foci were ≤ 6 mm of the apex. OBJECTIVE: • To describe multifocality, volume and location of prostate cancers incidentally found in cystoprostatectomy specimens. Quantitative tissue analysis of prostate cancer in a population free of the evaluation bias associated with prostate-specific antigen level and biopsy is important as some men are likely to be offered tissue-preserving therapeutic strategies in the future. PATIENTS AND METHODS: • Cystoprostatectomy specimens for bladder cancer from 345 consecutive patients without clinically manifest prostate cancer were included. • Cancers were found in 104/345 (30%) of prostates. Cases with largest cancer >2 mL (eight patients) were excluded from morphometric study. Quantitative tissue analysis of 3-mm step-sectioned glands included largest cancer surface area, volume, site of origin, multifocality and laterality. RESULTS: • In the 96 prostates, 215 cancer foci were identified (mean 2.24). Prostate cancer was multifocal in 58% and bilateral in 79% of cases. • Of the 215 cancers, 90% were <0.5 mL and 79% <0.2 mL. Overall, 88% of cancer foci were clinically insignificant with a volume of <0.5 mL and no grades 4-5. • In all, 75% of the cancer foci were in the peripheral zone, the remainder were within the transition zone. • One third of cancer foci were anteriorly located beyond the area sampled by posterior biopsies. One fifth of cancer foci were ≤ 6 mm of the apex. • Limitations include the fact that cystoprostatectomy cancer foci are at an earlier stage than screened-detected cancers. CONCLUSION: • This detailed morphometric analysis of prostate cancer foci in a population that is free from the selection bias associated with screening can help inform our diagnostic and treatment strategies.

Combined multiparametric MRI and targeted biopsies improve anterior prostate cancer detection, staging, and grading.

OBJECTIVES: To assess the efficacy of magnetic resonance imaging (MRI) in detection of suspicious anterior prostate lesions, and its role in staging and grading of anterior prostate cancer (APC). METHODS: Between January 2008 and August 2009, 243 patients had prostate cancer diagnosed at 12-cores posterior systematic biopsies and additional 2-cores transrectal ultrasound-guided, free-hand-targeted biopsy at any area suspicious for malignancy at prebiopsy multiparametric MRI. We conducted a retrospective study of 45 of 243 (19%) patients with an area suspicious for malignancy at MRI predominantly located in the anterior part of the gland, for which targeted biopsies were positive. Targeted vs systematic biopsy cancer detection rate and upgrading based on length of cancer in the most involved core and Gleason score were measured. RESULTS: Of the 45 patients, 46 separate APCs were identified at MRI with positive targeted biopsies. APC was not detected by systematic biopsies in 21 (46%) cases and detected in 25 (54%) cases. For these 25 cases, median cancer length of the most involved core in targeted compared with systematic biopsies was 8 mm vs 1 mm (P <.001), respectively. Significant Gleason score upgrading was observed in 11 of 25 (44%) cases. Correlation coefficient between the cancer length on targeted biopsies and the antero-posterior diameter of the area suspicious for malignancy on MRI was r(2) = .6 (P <.001). Separate posterior cancer was diagnosed in 26 patients. CONCLUSIONS: Targeted biopsies based on a prebiopsy MRI-detected lesion improved detection rate, volume, and grade of APC compared with currently used 12-cores systematic biopsies.

Focal laser ablation of prostate cancer: numerical simulation of temperature and damage distribution.

BACKGROUND: The use of minimally invasive ablative techniques in the management of patients with low grade and localized prostate tumours could represent a treatment option between active surveillance and radical therapy. Focal laser ablation (FLA) could be one of these treatment modalities. Dosimetry planning and conformation of the treated area to the tumor remain major issues, especially when, several fibers are required. An effective method to perform pre-treatment planning of this therapy is computer simulation. In this study we present an in vivo validation of a mathematical model. METHODS: The simulation model is based on finite elements method (FEM) to solve the bio-heat and the thermal damage equations. Laser irradiation was performed with a 980 nm laser diode system (5 W, 75 s). Light was transmitted using a cylindrical diffusing fiber inserted inside a preclinical animal prostate cancer model induced in Copenhagen rats. Non-enhanced T2-weighted and dynamic gadolinium-enhanced T1-weighted MR imaging examinations were performed at baseline and 48 hours after the procedure. The model was validated by comparing the simulated necrosis volume to the results obtained in vivo on (MRI) and by histological analysis. 3 iso-damage temperatures were considered 43° C, 45° C and 50° C. RESULTS: The mean volume of the tissue necrosis, estimated from the histological analyses was 0.974 ± 0.059 cc and 0.98 ± 0.052 cc on the 48 h MR images. For the simulation model, volumes were: 1.38 cc when T = 43° C, 1.1 cc for T = 45°C and 0.99 cc when T = 50 C°. CONCLUSIONS: In this study, a clear correlation was established between simulation and in vivo experiments of FLA for prostate cancer.Simulation is a promising planning technique for this therapy. It needs further more evaluation to allow to FLA to become a widely applied surgical method.

[Photodynamic therapy and urothelial carcinoma]. / Thérapie photodynamique et carcinomes urothéliaux.

PURPOSE: Photodynamic therapy (PDT) is an innovative therapeutic modality in urologic oncology. MATERIAL AND METHODS: We reviewed the current literature on principles and modalities of PDT in urothelial and penile oncology. RESULTS: PDT has been tested for the treatment recurrent superficial bladder tumors and in situ carcinoma. Carcinologic efficacy has been observed with first generation photosensitizer. The lack of selectivity for tumoral cells was responsible of serious adverse events. Development of selective photosensitizers has reduced the importance of side effects. Data concerning PDT for upper urinary tract and urethra carcinoma are still limited. CONCLUSION: First PDT clinical applications in urothelial oncology have shown some effectiveness at the cost of significant morbidity. The development of selective photosensitizers should help to reduce side effects.

Varicocele repair: does it still have a role in infertility treatment?

PURPOSE OF REVIEW: To review the role of varicocele repair in the treatment of male infertility. RECENT FINDINGS: Since the advent of technologies bypassing boundaries of natural selection, this question may seem outdated. Over the past 20 years, fertility has decreased, and testicular damage (cryptorchidism, tumors) has increased. Thus the exploration of the infertile male is still unavoidable. However, what should be done and assigned to the discovery of a varicocele?The issue raised is whether varicocele found during the review of the infertile couple should be treated or 'ignored'.This study will update significant findings with regards to the pathophysiology of varicocele-induced infertility, such as oxidative stress and role of varicocele in bilaterality of testicular damage. Benefits of varicocele repair in semen analysis and simplifications of assisted reproductive techniques are reported. But reviews of randomized clinical trials have raised doubts about the benefit of varicocele treatment in infertile men. SUMMARY: We conclude that varicocele repair may be effective in men with subnormal semen analysis, a clinical varicocele and otherwise unexplained infertility. Deleterious cofactors, like obesity or smoking, could also be reduced for the benefit of general health and fertility.

Celiac axis and superior mesenteric artery: danger zone for left nephrectomy.

We report two cases of iatrogenic occlusion of the superior mesenteric artery (SMA) and celiac axis (CA) during left nephrectomy. A patient with a urothelial carcinoma (open surgery) and one with coralliform calculi (laparoscopy) experienced injury to both the SMA and/or CA due to bulky perihilar adenopathy and kidney adherence to surrounding tissue. The cancer patient survived after fast repair. Repair was delayed in the second patient who subsequently died. It is essential to identify each arterial branch carefully on the preoperative CT-scan to identify any duplicate renal arteries and avoid mistaking the SMA and/or CA for the renal artery.