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Title: Sentinel Lymph Node Dissection to Select Clinically Node-negative Prostate Cancer Patients for Pelvic Radiation Therapy: Effect on Biochemical Recurrence and Systemic Progression

Abstract

Purpose: To assess the efficacy of robotic-assisted laparoscopic sentinel lymph node (SLN) dissection (SLND) to select those patients with prostate cancer (PCa) who would benefit from additional pelvic external beam radiation therapy and long-term androgen deprivation therapy (ADT). Methods and Materials: Radioisotope-guided SLND was performed in 224 clinically node-negative patients scheduled to undergo external beam radiation therapy. Patients with histologically positive SLNs (pN1) were also offered radiation therapy to the pelvic lymph nodes, combined with 3 years of ADT. Biochemical recurrence (BCR), overall survival, and metastasis-free (including pelvic and nonregional lymph nodes) survival (MFS) rates were retrospectively calculated. The Briganti and Kattan nomogram predictions were compared with the observed pN status and BCR. Results: The median prostate-specific antigen (PSA) value was 15.4 ng/mL (interquartile range [IQR] 8-29). A total number of 834 SLNs (median 3 per patient; IQR 2-5) were removed. Nodal metastases were diagnosed in 42% of the patients, with 150 SLNs affected (median 1; IQR 1-2). The 5-year BCR-free and MFS rates for pN0 patients were 67.9% and 87.8%, respectively. The corresponding values for pN1 patients were 43% and 66.6%. The PSA level and number of removed SLNs were independent predictors of BCR and MFS, and pN status was anmore » additional independent predictor of BCR. The 5-year overall survival rate was 97.6% and correlated only with pN status. The predictive accuracy of the Briganti nomogram was 0.665. Patients in the higher quartiles of Kattan nomogram prediction of BCR had better than expected outcomes. The complication rate from SLND was 8.9%. Conclusions: For radioisotope-guided SLND, the high staging accuracy is accompanied by low morbidity. The better than expected outcomes observed in the lower quartiles of BCR prediction suggest a role for SLN biopsy as a potential selection tool for the addition of pelvic radiation therapy and ADT intensification in pN1 patients.« less

Authors:
 [1];  [1];  [2];  [3];  [4]; ; ;  [1];  [1];  [5]; ;  [1]
  1. Department of Urology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands)
  2. Department of Radiation Oncology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands)
  3. Department of Pathology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands)
  4. Department of Nuclear Medicine, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands)
  5. (Netherlands)
Publication Date:
OSTI Identifier:
22645773
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 97; Journal Issue: 2; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; DISEASE INCIDENCE; EXTERNAL BEAM RADIATION THERAPY; FORECASTING; LYMPH NODES; NEOPLASMS; NOMOGRAMS; PATIENTS; PROSTATE

Citation Formats

Grivas, Nikolaos, E-mail: n.grivas@nki.nl, Wit, Esther, Pos, Floris, Jong, Jeroen de, Vegt, Erik, Bex, Axel, Hendricksen, Kees, Horenblas, Simon, KleinJan, Gijs, Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Leiden, Rhijn, Bas van, and Poel, Henk van der. Sentinel Lymph Node Dissection to Select Clinically Node-negative Prostate Cancer Patients for Pelvic Radiation Therapy: Effect on Biochemical Recurrence and Systemic Progression. United States: N. p., 2017. Web. doi:10.1016/J.IJROBP.2016.10.016.
Grivas, Nikolaos, E-mail: n.grivas@nki.nl, Wit, Esther, Pos, Floris, Jong, Jeroen de, Vegt, Erik, Bex, Axel, Hendricksen, Kees, Horenblas, Simon, KleinJan, Gijs, Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Leiden, Rhijn, Bas van, & Poel, Henk van der. Sentinel Lymph Node Dissection to Select Clinically Node-negative Prostate Cancer Patients for Pelvic Radiation Therapy: Effect on Biochemical Recurrence and Systemic Progression. United States. doi:10.1016/J.IJROBP.2016.10.016.
Grivas, Nikolaos, E-mail: n.grivas@nki.nl, Wit, Esther, Pos, Floris, Jong, Jeroen de, Vegt, Erik, Bex, Axel, Hendricksen, Kees, Horenblas, Simon, KleinJan, Gijs, Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Leiden, Rhijn, Bas van, and Poel, Henk van der. Wed . "Sentinel Lymph Node Dissection to Select Clinically Node-negative Prostate Cancer Patients for Pelvic Radiation Therapy: Effect on Biochemical Recurrence and Systemic Progression". United States. doi:10.1016/J.IJROBP.2016.10.016.
@article{osti_22645773,
title = {Sentinel Lymph Node Dissection to Select Clinically Node-negative Prostate Cancer Patients for Pelvic Radiation Therapy: Effect on Biochemical Recurrence and Systemic Progression},
author = {Grivas, Nikolaos, E-mail: n.grivas@nki.nl and Wit, Esther and Pos, Floris and Jong, Jeroen de and Vegt, Erik and Bex, Axel and Hendricksen, Kees and Horenblas, Simon and KleinJan, Gijs and Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Leiden and Rhijn, Bas van and Poel, Henk van der},
abstractNote = {Purpose: To assess the efficacy of robotic-assisted laparoscopic sentinel lymph node (SLN) dissection (SLND) to select those patients with prostate cancer (PCa) who would benefit from additional pelvic external beam radiation therapy and long-term androgen deprivation therapy (ADT). Methods and Materials: Radioisotope-guided SLND was performed in 224 clinically node-negative patients scheduled to undergo external beam radiation therapy. Patients with histologically positive SLNs (pN1) were also offered radiation therapy to the pelvic lymph nodes, combined with 3 years of ADT. Biochemical recurrence (BCR), overall survival, and metastasis-free (including pelvic and nonregional lymph nodes) survival (MFS) rates were retrospectively calculated. The Briganti and Kattan nomogram predictions were compared with the observed pN status and BCR. Results: The median prostate-specific antigen (PSA) value was 15.4 ng/mL (interquartile range [IQR] 8-29). A total number of 834 SLNs (median 3 per patient; IQR 2-5) were removed. Nodal metastases were diagnosed in 42% of the patients, with 150 SLNs affected (median 1; IQR 1-2). The 5-year BCR-free and MFS rates for pN0 patients were 67.9% and 87.8%, respectively. The corresponding values for pN1 patients were 43% and 66.6%. The PSA level and number of removed SLNs were independent predictors of BCR and MFS, and pN status was an additional independent predictor of BCR. The 5-year overall survival rate was 97.6% and correlated only with pN status. The predictive accuracy of the Briganti nomogram was 0.665. Patients in the higher quartiles of Kattan nomogram prediction of BCR had better than expected outcomes. The complication rate from SLND was 8.9%. Conclusions: For radioisotope-guided SLND, the high staging accuracy is accompanied by low morbidity. The better than expected outcomes observed in the lower quartiles of BCR prediction suggest a role for SLN biopsy as a potential selection tool for the addition of pelvic radiation therapy and ADT intensification in pN1 patients.},
doi = {10.1016/J.IJROBP.2016.10.016},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 2,
volume = 97,
place = {United States},
year = {Wed Feb 01 00:00:00 EST 2017},
month = {Wed Feb 01 00:00:00 EST 2017}
}
  • Purpose: We sought to determine the rate of postmastectomy radiation therapy (PMRT) among women treated with axillary lymph node dissection (ALND) after positive sentinel lymph node (SLN) biopsy results and to establish the effect of negative ALND results and PMRT on locoregional recurrence (LRR) and overall survival (OS). Methods and Materials: All patients were treated with mastectomy and ALND after positive SLN biopsy results. All patients had clinical N0 or NX disease at the time of mastectomy and received no neoadjuvant therapy. The presence of lymphovascular space invasion, presence of multifocality, number of positive SLNs and non-SLNs, clinical and pathologicmore » stage, extranodal extension, age, and use of PMRT were evaluated for significance regarding the rates of OS and LRR. Results: A total of 345 patients were analyzed. ALND after positive SLN biopsy results was negative in 235 patients (68.1%), and a total of 112 patients (32.5%) received radiation therapy. On multivariate analysis, only pathologic stage III predicted for lower OS (hazard ratio, 3.32; P<.001). The rate of 10-year freedom from LRR was 87.9% and 95.3% in patients with positive ALND results and patients with negative ALND results, respectively. In patients with negative ALND results with ≥3 positive SLNs, the rate of freedom from LRR was 74.7% compared with 96.7% in those with <3 positive SLNs (P=.009). In patients with negative ALND results, ≥3 positive SLNs predicted for an increase in LRR on multivariate analysis (hazard ratio, 10.10; P=.034). Conclusions: A low proportion of cT1-2, N0 patients with positive SLNs who undergo mastectomy receive PMRT after ALND. Even in this low-risk cohort, patients with ≥3 positive SLNs and negative ALND results are at increased risk of LRR and may benefit from PMRT.« less
  • Purpose: Irradiation of adjuvant lymph nodes in high-risk prostate cancer was shown to be associated with improved rates of biochemical nonevidence of disease in the Radiation Therapy Oncology Group trial (RTOG 94-13). To account for the highly individual lymphatic drainage pattern we tested an intensity-modulated radiation therapy (IMRT) approach based on the determination of pelvic sentinel lymph nodes (SN). Methods and Materials: Patients with a risk of more than 15% lymph node involvement were included. For treatment planning, SN localizations were included into the pelvic clinical target volume. Dose prescriptions were 50.4 Gy to the adjuvant area and 70.0 Gymore » to the prostate. All treatment plans were generated using equivalent uniform dose (EUD)-based optimization algorithms and Monte Carlo dose calculations and compared with 3D conventional plans. Results: A total of 25 patients were treated and 142 SN were detectable (mean: n = 5.7; range, 0-13). Most SN were found in the external iliac (35%), the internal iliac (18.3%), and the iliac commune (11.3%) regions. Using a standard CT-based planning target volume, relevant SN would have been missed in 19 of 25 patients, mostly in the presacral/perirectal area (22 SN in 12 patients). The comparison of conventional 3D plans with the respective IMRT plans revealed a clear superiority of the IMRT plans. No gastrointestinal or genitourinary acute toxicity Grade 3 or 4 (RTOG criteria) occurred. Conclusions: Distributions of SN are highly variable. Data for SN derived from single photon emission computed tomography are easily integrated into an IMRT-based treatment strategy. By using SN data the probability of a geographic miss is reduced. The use of IMRT allows sparing of normal tissue irradiation.« less
  • Purpose: To investigate the pattern of lymph node spread in prostate cancer patients with a biochemical recurrence after radical prostatectomy, eligible for salvage radiotherapy; and to determine whether the clinical target volume (CTV) for elective pelvic irradiation in the primary setting can be applied in the salvage setting for patients with (a high risk of) lymph node metastases. Methods and Materials: The charts of 47 prostate cancer patients with PSA recurrence after prostatectomy who had positive lymph nodes on magnetic resonance lymphography (MRL) were reviewed. Positive lymph nodes were assigned to a lymph node region according to the guidelines ofmore » the Radiation Therapy Oncology Group (RTOG) for delineation of the CTV for pelvic irradiation (RTOG-CTV). We defined four lymph node regions for positive nodes outside this RTOG-CTV: the para-aortal, proximal common iliac, pararectal, and paravesical regions. They were referred to as aberrant lymph node regions. For each patient, clinical and pathologic features were recorded, and their association with aberrant lymph drainage was investigated. The distribution of positive lymph nodes was analyzed separately for patients with a prostate-specific antigen (PSA) <1.0 ng/mL. Results: MRL detected positive aberrant lymph nodes in 37 patients (79%). In 20 patients (43%) a positive lymph node was found in the pararectal region. Higher PSA at the time of MRL was associated with the presence of positive lymph nodes in the para-aortic region (2.49 vs. 0.82 ng/mL; p = 0.007) and in the proximal common iliac region (1.95 vs. 0.59 ng/mL; p = 0.009). There were 18 patients with a PSA <1.0 ng/mL. Ten of these patients (61%) had at least one aberrant positive lymph node. Conclusion: Seventy-nine percent of the PSA-recurrent patients had at least one aberrant positive lymph node. Application of the standard RTOG-CTV for pelvic irradiation in the salvage setting therefore seems to be inappropriate.« less
  • Purpose: To assess the efficacy of individual sentinel node (SN)-guided pelvic intensity modulated radiation therapy (IMRT) by determining nodal clearance rate [(n expected nodal involvement − n observed regional recurrences)/n expected nodal involvement] in comparison with surgically staged patients. Methods and Materials: Data on 475 high-risk prostate cancer patients were examined. Sixty-one consecutive patients received pelvic SN-based IMRT (5 × 1.8 Gy/wk to 50.4 Gy [pelvic nodes + individual SN] and an integrated boost with 5 × 2.0 Gy/wk to 70.0 Gy to prostate + [base of] seminal vesicles) and neo-/adjuvant long-term androgen deprivation therapy; 414 patients after SN–pelvic lymph node dissection were used to calculate the expected nodal involvement rate for the radiation therapymore » sample. Biochemical control and overall survival were estimated for the SN-IMRT patients using the Kaplan-Meier method. The expected frequency of nodal involvement in the radiation therapy group was estimated by imputing frequencies of node-positive patients in the surgical sample to the pattern of Gleason, prostate-specific antigen, and T category in the radiation therapy sample. Results: After a median follow-up of 61 months, 5-year OS after SN-guided IMRT reached 84.4%. Biochemical control according to the Phoenix definition was 73.8%. The nodal clearance rate of SN-IMRT reached 94%. Retrospective follow-up evaluation is the main limitation. Conclusions: Radiation treatment of pelvic nodes individualized by inclusion of SNs is an effective regional treatment modality in high-risk prostate cancer patients. The pattern of relapse indicates that the SN-based target volume concept correctly covers individual pelvic nodes. Thus, this SN-based approach justifies further evaluation, including current dose-escalation strategies to the prostate in a larger prospective series.« less
  • Purpose: The aim of this study was to quantify gains in lymph node coverage and critical structure dose reduction for whole-pelvis (WP) and extended-field (EF) radiotherapy in prostate cancer using intensity-modulated radiotherapy (IMRT) compared with three-dimensional conformal radiotherapy (3DCRT) for the first treatment phase of 45 Gy in the concurrent treatment of lymph nodes and prostate. Methods and Materials: From January to August 2005, 35 patients with localized prostate cancer were treated with pelvic IMRT; 7 had nodes defined up to L5-S1 (Group 1), and 28 had nodes defined above L5-S1 (Group 2). Each patient had 2 plans retrospectively generated:more » 1 WP 3DCRT plan using bony landmarks, and 1 EF 3DCRT plan to cover the vascular defined volumes. Dose-volume histograms for the lymph nodes, rectum, bladder, small bowel, and penile bulb were compared by group. Results: For Group 1, WP 3DCRT missed 25% of pelvic nodes with the prescribed dose 45 Gy and missed 18% with the 95% prescribed dose 42.75 Gy, whereas WP IMRT achieved V{sub 45Gy} = 98% and V{sub 42.75Gy} = 100%. Compared with WP 3DCRT, IMRT reduced bladder V{sub 45Gy} by 78%, rectum V{sub 45Gy} by 48%, and small bowel V{sub 45Gy} by 232 cm{sup 3}. EF 3DCRT achieved 95% coverage of nodes for all patients at high cost to critical structures. For Group 2, IMRT decreased bladder V{sub 45Gy} by 90%, rectum V{sub 45Gy} by 54% and small bowel V{sub 45Gy} by 455 cm{sup 3} compared with EF 3DCRT. Conclusion: In this study WP 3DCRT missed a significant percentage of pelvic nodes. Although EF 3DCRT achieved 95% pelvic nodal coverage, it increased critical structure doses. IMRT improved pelvic nodal coverage while decreasing dose to bladder, rectum, small bowel, and penile bulb. For patients with extended node involvement, IMRT especially decreases small bowel dose.« less