Alexander Winter

First results of [11C]choline PET/CT-guided secondary lymph node surgery in patients with PSA failure and single lymph node recurrence after radical retropubic prostatectomy.

Introduction: [11C]choline PET/CT provides the opportunity to detect small lymph node metastases (LNM) (>5 mm) in prostate cancer (PCa) with exact topographic allocation. PSA development after resection of single LN recurrence detected via [11C]choline PET/CT without adjuvant therapy is not yet analyzed. We wanted to evaluate the potential of [11C]choline PET/CT in the diagnosis of single LN recurrence after radical prostatectomy (RPE) and whether secondary resection can result in PSA remission. Methods: We investigated 6 patients with biochemical recurrence (PSA: median 2.04, range 0.67–4.51 ng/ml) after RPE. A single suspicious LN was detected on PET/CT without suspicion of local relapse or distant metastasis. The suspicious and nearby LN were open dissected (09/2004–02/2008). Histological and PET/CT findings were compared and the postoperative PSA development was examined. Results: All metastasis-suspicious LN could be confirmed histologically. The additionally removed 10 LN were all correctly negative for cancer. Three patients showed a complete permanent PSA remission (<0.01 (n = 2), <0.03 ng/ml (n = 1)) without adjuvant therapy (follow-up: median 24, range 21–35 months). Conclusions: In this small selected collective [11C]choline PET/CT achieved reliable results. After resection of single LNM in all patients the oncologic criteria of a remission were fulfilled. Three of 6 patients had a complete PSA remission without adjuvant therapy. Whether cure or a positive influence on the course of disease can be achieved in individual patients has to be shown in further studies.

Sentinel lymph node dissection in more than 1200 prostate cancer cases: Rate and prediction of lymph node involvement depending on preoperative tumor characteristics

To stratify the rate and prediction of lymph node involvement in prostate cancer patients undergoing sentinel‐lymphadenectomy depending on preoperative tumor characteristics, and to compare the outcome with the European Association of Urology Guideline indication for lymphadenectomy.

Sentinel Node Procedure in Prostate Cancer: A Systematic Review to Assess Diagnostic Accuracy

CONTEXT Extended pelvic lymph node dissection (ePLND) is the gold standard for detecting lymph node (LN) metastases in prostate cancer (PCa). The benefit of sentinel node biopsy (SNB), which is the first draining LN as assessed by imaging of locally injected tracers, remains controversial. OBJECTIVE To assess the diagnostic accuracy of SNB in PCa. EVIDENCE ACQUISITION A systematic literature search of Medline, Embase, and the Cochrane Library (1999-2016) was undertaken using PRISMA guidelines. All studies of SNB in men with PCa using PLND as reference standard were included. The primary outcomes were the nondiagnostic rate (NDR), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and false positive (FP) and false negative (FN) rates. Relevant sensitivity analyses based on SN definitions, ePLND as reference standard, and disease risk were undertaken, including a risk of bias (RoB) assessment. EVIDENCE SYNTHESIS Of 373 articles identified, 21 studies recruiting a total of 2509 patients were eligible for inclusion. Median cumulative percentage (interquartile range) results were 4.1% (1.5-10.7%) for NDR, 95.2% (81.8-100%) for sensitivity, 100% (95.0-100%) for specificity, 100% (87.0-100%) for PPV, 98.0% (94.3-100%) for NPV, 0% (0-5.0%) for the FP rate, and 4.8% (0-18.2%) for the FN rate. The findings did not change significantly on sensitivity analyses. Most studies (17/22) had low RoB for index test and reference standard domains. CONCLUSIONS SNB appears to have diagnostic accuracy comparable to ePLND, with high sensitivity, specificity, PPV and NPV, and a low FN rate. With a low FP rate (rate of detecting positive nodes outside the ePLND template), SNB may not have any additional diagnostic value over and above ePLND, although SNB appears to increase nodal yield by increasing the number of affected nodes when combined with ePLND. Thus, in high-risk disease it may be prudent to combine ePLND with SNB. PATIENT SUMMARY This literature review showed a high diagnostic accuracy for sentinel node biopsy in detecting positive lymph nodes in prostate cancer, but further studies are needed to explore the effect of sentinel node biopsy on complications and oncologic outcome.

Komplikationsrate der pelvinen Lymphadenektomie beim klinisch lokalisierten Prostatakarzinom: Unterschiedliche Techniken im Vergleich und Abhängigkeit von der Anzahl entfernter Lymphknoten

PURPOSE The EAU guidelines recommend extended pelvic lymphadenectomy (ePLND) or sentinel-guided PLND (SLNE) for lymph node (LN) stag-ing in prostate cancer. However, the additional expenditure and increased morbidity of ePLND has led to a limitation of the PLND area and so to a reduced detection of metastases in many clinics. The SLNE offers the advantage of selective removal of sentinel LN. Therefore, we have compared the complications of SLNE and other different PLND techniques. MATERIALS AND METHODS Patients with prostate cancer who had received an open PLND (PLND: n = 90, PLND + radical retropubic prostatectomy: n = 409) were assessed. The complications of three PLND techniques were compared: group 1 (n = 216): SLNE, group 2 (n = 117): SLNE + modified (m) PLND (fossa obturatoria- und Iliaca-externa-region), group 3 (n = 163): SLNE + ePLND (fossa obturatoria- + Iliaca-externa- + Iliaca-interna-region). The complications were evaluated with special reference to the PLND-induced morbidity (e. g., lymphoceles). RESULTS In SLNE the total complications were low-er than in the two more extended PLND variants. The lymphatic complications (11.2 %) were significant (χ (2) = 8.616, p = 0.013) lower than in SLNE + mPLND (21.2 %) and SLNE + ePLND (22.0 %). With an increasing number of dissected LN the complication rate increased significantly. If ≥ 15 LN have been removed total and lymphatic complications increased significantly (χ (2) = 11.578, p = 0.021; χ (2) = 12.271, p = 0.015). CONCLUSIONS In PLND the lymphatic complications increase significantly with the number of dissected LN. The SLNE has, in spite of the dissection of LN in difficultly accessible regions (presacral, iliaca-interna-region), a low complication rate. As a method with a small number of LN to be removed, the SLNE offers a good compromise between high sensitivity and low morbidity and is therefore preferable to the more extended PLND variants.

Comparison of prostate cancer survival in Germany and the USA: can differences be attributed to differences in stage distributions?

To better understand the influence of prostate‐specific antigen (PSA) screening and other health system determinants on prognosis of prostate cancer, up‐to‐date relative survival (RS), stage distributions, and trends in survival and incidence in Germany were evaluated and compared with the United States of America (USA).

Complete PSA Remission without Adjuvant Therapy after Secondary Lymph Node Surgery in Selected Patients with Biochemical Relapse after Radical Prostatectomy and Pelvic Lymph Node Dissection

Introduction. To evaluate whether secondary resection of lymph node (LN) metastases (LNMs) can result in PSA remission, we analysed the PSA outcome after resection of LNM detected on PET/CT in patients with biochemical failure. Materials and Methods. 11 patients with PSA relapse (mean 3.02 ng/mL, range 0.5–9.55 ng/mL) after radical prostatectomy without adjuvant therapy were included. Suspicious LN (1–3) detected on choline PET/CT and nearby LN were openly dissected (09/04–02/11). The PSA development was examined. Histological and PET/CT findings were compared. Results. 9 of 10 patients with histologically confirmed LNM showed a PSA response. 4 of 9 patients with single LNM had a complete permanent PSA remission (mean followup 31.8, range 1–48 months). Of metastasis-suspicious LNs (14) 12 could be histologically confirmed. The additionally removed 25 LNs were all correctly negative. Conclusions. The complete PSA remissions after secondary resection of single LNM argue for a feasible therapeutic benefit without adjuvant therapy. For this purpose the choline PET/CT is in spite of its limitations currently the most reliable routinely available diagnostic tool.

Sentinel node biopsy for prostate cancer: Report from a consensus panel meeting

To explore the evidence and knowledge gaps in sentinel node biopsy (SNB) in prostate cancer through a consensus panel of experts.

Erste Ergebnisse der PET / CT-gesteuerten sekundären Lymphknotenchirurgie bei Patienten mit PSA-Anstieg nach radikaler Prostatektomie

PURPOSE CT and MRT are not applicable for the early detection of lymph node (LN) recurrence in prostate cancer. The PET / CT ((11)C-, (18)F-choline) technique can detect lesions >or= 5 mm and allows their topographic localisation. We have analysed positive (11)C-choline PET / CT LN findings in the case of a PSA increase after radical prostatectomy (RPE) histologicaly and documented the developing of PSA. MATERIALS AND METHODS 8 patients with PSA relapse after RPE and lymphadenedtomy (LA) were diagnosed as having LNM by means of (11)C-choline PET / CT. Using PET / CT, metastasis suspicious and nearby LN were openly dissected. Histological and PET / CT results were compared and the postoperative PSA-development was examined. RESULTS Of the metastasis suspicious LN (11) 9 were histologically reconfirmed. All additionally removed LN (12) were correct negative. LNM were mostly (7 of 9) located in the iliaca interna area and pararectal. 6 of 7 patients with histological metastasis detection showed a PSA response. 3 of 6 patients with single metastasis had complete PSA remission (< 0.01 ng / ml, maximum follow-up: 28 months) without adjuvant therapy. CONCLUSIONS (11)C-choline PET / CT could detect LNM with high specificity in our collective. These often lie beyond standard LA area, where they were primarily only resected by use of extended or sentinel LA. Because 3 patients with single LNM reached a complete PSA remission (< 0.01 ng / ml) without adjuvant therapy, the selected collective seems to benefit from secondary LN surgery. Whether or not individual patients can be cured by this surgery has to be demonstrated in a longitudinal study. However, an optimal imaging and experience in LN surgery have to be assured.

First Nomogram Predicting the Probability of Lymph Node Involvement in Prostate Cancer Patients Undergoing Radioisotope Guided Sentinel Lymph Node Dissection.

Introduction: Existing nomograms predicting lymph node involvement (LNI) in prostate cancer (PCa) are based on conventional lymphadenectomy. The aim of the study was to develop the first nomogram for predicting LNI in PCa patients undergoing sentinel guided pelvic lymph node dissection (sPLND). Materials and Methods: Analysis was performed on 1,296 patients with PCa who underwent radioisotope guided sPLND and retropubic radical prostatectomy (2005-2010). Median prostate specific antigen (PSA): 7.4 ng/ml (IQR 5.3-11.5 ng/ml). Clinical T-categories: T1: 54.8%, T2: 42.4%, T3: 2.8%. Biopsy Gleason sums: ≤6: 55.1%, 7: 39.5%, ≥8: 5.4%. Multivariate logistic regression models tested the association between all of the above predictors and LNI. Regression-based coefficients were used to develop a nomogram for predicting LNI. Accuracy was quantified using the area under the curve (AUC). Results: The median number of LNs removed was 10 (IQR 7-13). Overall, 17.8% of patients (n = 231) had LNI. The nomogram had a high predictive accuracy (AUC of 82%). All the variables were statistically significant multivariate predictors of LNI (p = 0.001). Univariate predictive accuracy for PSA, Gleason sum and clinical stage was 69, 75 and 69%, respectively. Conclusions: The sentinel nomogram can predict LNI at a sPLND very accurately and, for the first time, aid clinicians and patients in making important decisions on the indication of a sPLND. The high rate of LN+ patients underscores the sensitivity of sPLND.

Updated Nomogram Incorporating Percentage of Positive Cores to Predict Probability of Lymph Node Invasion in Prostate Cancer Patients Undergoing Sentinel Lymph Node Dissection.

Objectives: To update the first sentinel nomogram predicting the presence of lymph node invasion (LNI) in prostate cancer patients undergoing sentinel lymph node dissection (sPLND), taking into account the percentage of positive cores. Patients and Methods: Analysis included 1,870 prostate cancer patients who underwent radioisotope-guided sPLND and retropubic radical prostatectomy. Prostate-specific antigen (PSA), clinical T category, primary and secondary biopsy Gleason grade, and percentage of positive cores were included in univariate and multivariate logistic regression models predicting LNI, and constituted the basis for the regression coefficient-based nomogram. Bootstrapping was applied to generate 95% confidence intervals for predicted probabilities. The area under the receiver operator characteristic curve (AUC) was obtained to quantify accuracy. Results: Median PSA was 7.68 ng/ml (interquartile range (IQR) 5.5-12.3). The number of lymph nodes removed was 10 (IQR 7-13). Overall, 352 patients (18.8%) had LNI. All preoperative prostate cancer characteristics differed significantly between LNI-positive and LNI-negative patients (P<0.001). In univariate accuracy analyses, the proportion of positive cores was the foremost predictor of LNI (AUC, 77%) followed by PSA (71.1%), clinical T category (69.9%), and primary and secondary Gleason grade (66.6% and 61.3%, respectively). For multivariate logistic regression models, all parameters were independent predictors of LNI (P<0.001). The nomogram exhibited a high predictive accuracy (AUC, 83.5%). Conclusion: The first update of the only available sentinel nomogram predicting LNI in prostate cancer patients demonstrates even better predictive accuracy and improved calibration. As an additional factor, the percentage of positive cores represents the leading predictor of LNI. This updated sentinel model should be externally validated and compared with results of extended PLND-based nomograms.