Managing pelvic lymph nodes and related toxicity - Radiation perspective - Thomas Wiegel
Points of Discussion <ul><li>RT of suspected disease (cNx) </li></ul><ul><li>RT of positive node PCA (pN+) </li></ul><ul><...
RT of suspected disease (cNx)
Risk of LN(+) for cN0 PCA - „High Risk“ (>15%) - Roach III, Int. J. Radiat. Oncol. Biol. Phys. 28, 1993 <ul><li>LN(+)=(2/3...
RTOG 9413 Roach III M et al., J Clin Oncol 10, 2003 <ul><ul><li>04/1995 and 6/1996, 1.323 patients localized PCA with PSA ...
RTOG 9413 Roach III M et al., J Clin Oncol 10, 2003
RTOG 9413 Roach III M  et al.,  J Clin Oncol 10, 2003
RTOG 9413 Roach III M et al., J Clin Oncol 10, 2003
RTOG 9413 - Update Lawton CA et al., Int J Radiat Oncol Biol Phys 69, 2007
RTOG 9413 – Update - med. FU 6.6 years Lawton CA et al., Int J Radiat Oncol Biol Phys 69, 2007
RTOG 9413 - Update Lawton CA et al., Int J Radiat Oncol Biol Phys 69, 2007
RTOG 9413 - Update Lawton CA et al., Int J Radiat Oncol Biol Phys 69, 2007
RTOG 9413 - Update Lawton CA et al., Int J Radiat Oncol Biol Phys 69, 2007 bNED protocol definition Phoenix definition
RTOG 9413 - Update Lawton CA et al., Int J Radiat Oncol Biol Phys 69, 2007
GETUG-01 Pommier P et al., J Clin Oncol 25, 2007 <ul><ul><li>12/1998 and 6/2004, 444 patients, T1b-T3, cN0  M0 </li></ul><...
GETUG-01: Progression-free survival Pommier P et al., J Clin Oncol 25, 2007 High-risk group Low-risk group 5-year PFS and ...
Roach et al., Br. J. Cancer 2005 All major elderly Phase-III-studies with RT  pel. LN
RT of positive node PCA (pN+)
MD-Anderson-trial (retrospective) Zagars et al., Urology 58, 2001 <ul><li>255 men, LN (+), no RP, staging LADN </li></ul><...
MD-Anderson-trial (retrospective) Zagars et al., Urology 58, 2001 Clear advantage for RT + AA OS PFS
Lawton et al., J. Clin. Oncol. 23, 2005 AA + RT versus RT (RTOG 85-31) Retrospective subgroup-analysis
Lawton et al., J. Clin. Oncol. 23, 2005 AA + RT versus RT alone (RTOG-trial 85-31) OS
Lawton et al., J. Clin. Oncol. 23, 2005 No data from a prospective trial are available. „ So until such data are available...
Da. Pozzo et al., Eur. Urol. 55, 2009 Adjuvant RT for LN (+) – pts. after RP Retrospective series N=250 Patients
Da. Pozzo et al., Eur. Urol. 55, 2009 Adjuvant RT for LN (+) – pts. after RP
Briganti et al., Eur. Urol. 2011, in press Adjuvant RT for LN (+) – pts. after RP <ul><li>Retrospective matched pair analy...
Briganti et al., Eur. Urol. 2011, in press OS in the overall matched population 84% vs. 65% 19% better OS
Briganti et al., Eur. Urol. 2011, in press OS for pts. with <= two LN 19% better OS
<ul><li>When to treat, </li></ul><ul><li>how to treat pelvic lymph nodes? </li></ul><ul><li>Target volume </li></ul><ul><l...
Lawton et al., Int. J. Radiat. Oncol. Biol. Phys.74, 2009 <ul><li>14 RTOG GU-Radiation-Oncologists </li></ul><ul><li>Conto...
Lawton et al., Int. J. Radiat. Oncol. Biol. Phys.74, 2009 <ul><li>Results: </li></ul><ul><li>Minimum,maximum. mean iliac v...
Lawton et al., Int. J. Radiat. Oncol. Biol. Phys.74, 2009 Conclusion: Consus urgently needed
Periprostatic LN www-rtog.org RTOG consensus for delineation of the target volume
Iliac lymph nodes www-rtog.org/ Lawton CA, Int. J. Radiat. Oncol. Biol. Phys. 74, 2009
Presacral nodes RT Pelvic Lymphatics (CTV) www-rtog.org
IMRT of the pelvic lymphatics - Comparison 3D-planning vs. IMRT - 3-D-RT IMRT
Dose wash <ul><li>3-D-Planning </li></ul><ul><li>IMRT </li></ul>5 Fields 6 Fields
„ Fast“ IMRT – Rapid Arc/Volumetric Arc Technique/Tomo Yoo et al., Int J Radiat Oncol Biol Phys 76 (2010)  Bladder- and re...
Ashman et al., Int. J. Radiat. Oncol. Biol. Phys.63, 2005 Wang-Chesebro et al., Int. J. Radiat. Oncol. Biol. Phys. 66, 200...
Side effects
RTOG 9413 Roach III M et al., J Clin Oncol 10, 2003 •  Neoadj. TAB 2 mo. before/during RT pel. LN + Boost •  Neoadj. TAB 2...
GETUG-01: Acute and late Toxicity Pommier P  et al.,  J Clin Oncol 25, 2007
Chung et al., Int. J. Radiat. Oncol. Biol. Phys. 71, 2009 Comparison IMRT vs. IMRT/IGRT RT pelvic lymphatics Significant r...
Upcoming ARO-study for pN+ after RP (ART-2)
 
ART-2-Study bNED after 5 years for pN+ Bern study – none HT 1 LN+: 24.7% bNED >= 2 LN+: 11.8%   4.9% Schuhmacher et al., E...
ART-2-Study Augsburg (unpublished) - pN+ bNED after 3 years – none HT micro metastases (0.2 – 2mm)(20/56): 64% metastases ...
Flow-Chart ART-2 study No hormonal treatment! RP  (</= 2 LK-mets) Central pathologic review PSA Undetectable range  (<0.1 ...
ART-2-study Endpoint and statistics <ul><li>bNED after 4 years: 40% and 55% </li></ul><ul><li>Power 80%, alpha-error 5% </...
ART-2-study Radiotherapy <ul><li>RT pel. LN: IMRT/IGRT </li></ul><ul><li>SD 1.8 Gy </li></ul><ul><li>TD 50.4 Gy </li></ul>...
ART-2-study   Stratification Gleason-score <7 vs.  >=7 Margin R1  vs. R0 Stage: pT2 vs. >pT2 PSA before R.: <0.03  vs. >0....
Conclusions <ul><li>cNx: to belive or not to belive </li></ul><ul><li>pN+: Studies needed </li></ul><ul><li>Technique: low...
Urologists and Radiation Oncologists are friends!
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ECCLU 2011 - T. Wiegel - Prostate cancer: Managing of pelvic nodes - Radiation perspective

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ECCLU 2011 - T. Wiegel - Prostate cancer: Managing of pelvic nodes - Radiation perspective

  1. 1. Managing pelvic lymph nodes and related toxicity - Radiation perspective - Thomas Wiegel
  2. 2. Points of Discussion <ul><li>RT of suspected disease (cNx) </li></ul><ul><li>RT of positive node PCA (pN+) </li></ul><ul><li>When to treat, how to treat pelvic nodes? </li></ul><ul><li>Side effects </li></ul><ul><li>Upcomig ARO-study for pN+ patients after RP </li></ul>
  3. 3. RT of suspected disease (cNx)
  4. 4. Risk of LN(+) for cN0 PCA - „High Risk“ (>15%) - Roach III, Int. J. Radiat. Oncol. Biol. Phys. 28, 1993 <ul><li>LN(+)=(2/3) PSA+[(GS-6)  10] </li></ul><ul><li>PSA: 30 Gleason score:8 = est. risk 40% </li></ul><ul><li>• Risk overestimated, only 212 Pat. investigated </li></ul><ul><li>Standard RTOG (formerly) </li></ul>
  5. 5. RTOG 9413 Roach III M et al., J Clin Oncol 10, 2003 <ul><ul><li>04/1995 and 6/1996, 1.323 patients localized PCA with PSA  100 ng/mL and estimated risk of LN(+) >15%* </li></ul></ul><ul><ul><li>Whole-pelvic (WP) RT + neoadjuvant and concurrent HT (NCHT) </li></ul></ul><ul><ul><li>Prostate-only (PO) RT + NCHT </li></ul></ul><ul><ul><li>WP + adjuvant hormonal therapy (AHT) </li></ul></ul><ul><ul><li>PO + AHT </li></ul></ul><ul><ul><li>Med. follow-up: 60 months </li></ul></ul><ul><ul><li>Primary endpoint: PFS after 5 years </li></ul></ul><ul><ul><li>* LN(+)=(2/3) PSA+[(GS-6)  10] </li></ul></ul>
  6. 6. RTOG 9413 Roach III M et al., J Clin Oncol 10, 2003
  7. 7. RTOG 9413 Roach III M et al., J Clin Oncol 10, 2003
  8. 8. RTOG 9413 Roach III M et al., J Clin Oncol 10, 2003
  9. 9. RTOG 9413 - Update Lawton CA et al., Int J Radiat Oncol Biol Phys 69, 2007
  10. 10. RTOG 9413 – Update - med. FU 6.6 years Lawton CA et al., Int J Radiat Oncol Biol Phys 69, 2007
  11. 11. RTOG 9413 - Update Lawton CA et al., Int J Radiat Oncol Biol Phys 69, 2007
  12. 12. RTOG 9413 - Update Lawton CA et al., Int J Radiat Oncol Biol Phys 69, 2007
  13. 13. RTOG 9413 - Update Lawton CA et al., Int J Radiat Oncol Biol Phys 69, 2007 bNED protocol definition Phoenix definition
  14. 14. RTOG 9413 - Update Lawton CA et al., Int J Radiat Oncol Biol Phys 69, 2007
  15. 15. GETUG-01 Pommier P et al., J Clin Oncol 25, 2007 <ul><ul><li>12/1998 and 6/2004, 444 patients, T1b-T3, cN0 M0 </li></ul></ul><ul><ul><li>Low risk LN+: T1-2, Gleason <7, PSA < 3x upper local limit </li></ul></ul><ul><ul><li>High risk: T3, Gleason >6 and/or PSA > 3x upper local limit </li></ul></ul><ul><ul><li>pelvic and prostate RT or prostate RT only </li></ul></ul><ul><ul><li>stratified according LN involvement </li></ul></ul><ul><ul><li>Short-term 6-month neoadjuvant and concomitant HT allowed only high-risk group </li></ul></ul><ul><ul><li>Pelvic dose 46 Gy, Total dose prostate: 66 – 70 Gy </li></ul></ul><ul><ul><li>Med. follow-up: 42 months </li></ul></ul>
  16. 16. GETUG-01: Progression-free survival Pommier P et al., J Clin Oncol 25, 2007 High-risk group Low-risk group 5-year PFS and overall survival similar in the two treatment arms
  17. 17. Roach et al., Br. J. Cancer 2005 All major elderly Phase-III-studies with RT pel. LN
  18. 18. RT of positive node PCA (pN+)
  19. 19. MD-Anderson-trial (retrospective) Zagars et al., Urology 58, 2001 <ul><li>255 men, LN (+), no RP, staging LADN </li></ul><ul><li>N=183, androgen ablation alone </li></ul><ul><li>N=72, plus RT (discretion of the urologist) ) </li></ul>
  20. 20. MD-Anderson-trial (retrospective) Zagars et al., Urology 58, 2001 Clear advantage for RT + AA OS PFS
  21. 21. Lawton et al., J. Clin. Oncol. 23, 2005 AA + RT versus RT (RTOG 85-31) Retrospective subgroup-analysis
  22. 22. Lawton et al., J. Clin. Oncol. 23, 2005 AA + RT versus RT alone (RTOG-trial 85-31) OS
  23. 23. Lawton et al., J. Clin. Oncol. 23, 2005 No data from a prospective trial are available. „ So until such data are available, RT and immediate hormonal manipulation clearly remain an effective means to control pN+ PCA in a significant cohort of men with such aggresive disease...“
  24. 24. Da. Pozzo et al., Eur. Urol. 55, 2009 Adjuvant RT for LN (+) – pts. after RP Retrospective series N=250 Patients
  25. 25. Da. Pozzo et al., Eur. Urol. 55, 2009 Adjuvant RT for LN (+) – pts. after RP
  26. 26. Briganti et al., Eur. Urol. 2011, in press Adjuvant RT for LN (+) – pts. after RP <ul><li>Retrospective matched pair analysis </li></ul><ul><li>Milan and Rochester </li></ul><ul><li>N=703 pts. 1986-2002 </li></ul><ul><li>All RP, stage pT2-4 pN1 </li></ul><ul><li>Group I: 117/171 pts. ART+HT </li></ul><ul><li>Group II: 247/532 pts. HT </li></ul><ul><li>Median FU: 95 months </li></ul><ul><li>Lack of standardised HT and RT </li></ul>
  27. 27. Briganti et al., Eur. Urol. 2011, in press OS in the overall matched population 84% vs. 65% 19% better OS
  28. 28. Briganti et al., Eur. Urol. 2011, in press OS for pts. with <= two LN 19% better OS
  29. 29. <ul><li>When to treat, </li></ul><ul><li>how to treat pelvic lymph nodes? </li></ul><ul><li>Target volume </li></ul><ul><li>Technique </li></ul>
  30. 30. Lawton et al., Int. J. Radiat. Oncol. Biol. Phys.74, 2009 <ul><li>14 RTOG GU-Radiation-Oncologists </li></ul><ul><li>Contoured the iliac and presacral lymph nodes </li></ul><ul><li>2 men available for treatment planning </li></ul>
  31. 31. Lawton et al., Int. J. Radiat. Oncol. Biol. Phys.74, 2009 <ul><li>Results: </li></ul><ul><li>Minimum,maximum. mean iliac volumes: 82, 877 and 338 ml </li></ul><ul><li>Overall agreement „moderate“ (kappa=0.53 and kappa 0.48) </li></ul><ul><li>0.61-0.8 „substantial“ agreement </li></ul><ul><li>No volume of 100% agreement for either two presacral volumes </li></ul>
  32. 32. Lawton et al., Int. J. Radiat. Oncol. Biol. Phys.74, 2009 Conclusion: Consus urgently needed
  33. 33. Periprostatic LN www-rtog.org RTOG consensus for delineation of the target volume
  34. 34. Iliac lymph nodes www-rtog.org/ Lawton CA, Int. J. Radiat. Oncol. Biol. Phys. 74, 2009
  35. 35. Presacral nodes RT Pelvic Lymphatics (CTV) www-rtog.org
  36. 36. IMRT of the pelvic lymphatics - Comparison 3D-planning vs. IMRT - 3-D-RT IMRT
  37. 37. Dose wash <ul><li>3-D-Planning </li></ul><ul><li>IMRT </li></ul>5 Fields 6 Fields
  38. 38. „ Fast“ IMRT – Rapid Arc/Volumetric Arc Technique/Tomo Yoo et al., Int J Radiat Oncol Biol Phys 76 (2010) Bladder- and rectum sparing
  39. 39. Ashman et al., Int. J. Radiat. Oncol. Biol. Phys.63, 2005 Wang-Chesebro et al., Int. J. Radiat. Oncol. Biol. Phys. 66, 2006 Ganswind et al, Int J. Radiat. Oncol. Biol. Phys. 67, 2007 IMRT of the pelvic lymphatics Reduction of dose and volume to small bowel Mean dose: 33 Gy vs. 26 Gy
  40. 40. Side effects
  41. 41. RTOG 9413 Roach III M et al., J Clin Oncol 10, 2003 • Neoadj. TAB 2 mo. before/during RT pel. LN + Boost • Neoadj. TAB 2 Mo. before/during RT of prostate • RT pel. LN + prostate + 4 mo. adjuvant HT • RT prostate + 4 mo. adjuvant HT
  42. 42. GETUG-01: Acute and late Toxicity Pommier P et al., J Clin Oncol 25, 2007
  43. 43. Chung et al., Int. J. Radiat. Oncol. Biol. Phys. 71, 2009 Comparison IMRT vs. IMRT/IGRT RT pelvic lymphatics Significant reduced acute Side effects II (p=0.004) Small prospective series – 10 vs. 15 Pts.
  44. 44. Upcoming ARO-study for pN+ after RP (ART-2)
  45. 46. ART-2-Study bNED after 5 years for pN+ Bern study – none HT 1 LN+: 24.7% bNED >= 2 LN+: 11.8% 4.9% Schuhmacher et al., Eur. Uro. 54, 2008
  46. 47. ART-2-Study Augsburg (unpublished) - pN+ bNED after 3 years – none HT micro metastases (0.2 – 2mm)(20/56): 64% metastases (55/74): 35% 1micro metastasis: undetectable range: 86% 1 metastasis: undetectable range: 56% >1 metastasis: 47% Weckermann et al., Augsburg
  47. 48. Flow-Chart ART-2 study No hormonal treatment! RP (</= 2 LK-mets) Central pathologic review PSA Undetectable range (<0.1 ng/ml) R Wait and See RT pelvic lymphatics (50.4 Gy) SM +: 64.8 Gy SM: + or -
  48. 49. ART-2-study Endpoint and statistics <ul><li>bNED after 4 years: 40% and 55% </li></ul><ul><li>Power 80%, alpha-error 5% </li></ul><ul><li>Drop-out 10% </li></ul><ul><li>Per arm 103 patients </li></ul><ul><li>Total: 206 patients </li></ul><ul><li>20 centers 2-3 pts/year </li></ul><ul><li>central path. review before R </li></ul>
  49. 50. ART-2-study Radiotherapy <ul><li>RT pel. LN: IMRT/IGRT </li></ul><ul><li>SD 1.8 Gy </li></ul><ul><li>TD 50.4 Gy </li></ul><ul><li>Prostate bed: 50.4 Gy </li></ul><ul><li>R1: 64.8 Gy </li></ul><ul><li>Target volume: RTOG </li></ul>
  50. 51. ART-2-study Stratification Gleason-score <7 vs. >=7 Margin R1 vs. R0 Stage: pT2 vs. >pT2 PSA before R.: <0.03 vs. >0.03<0.1 Metastases: Micromets. vs. 1 Mets. vs. 2 Mets
  51. 52. Conclusions <ul><li>cNx: to belive or not to belive </li></ul><ul><li>pN+: Studies needed </li></ul><ul><li>Technique: low side effects with IMRT/IGRT </li></ul>
  52. 53. Urologists and Radiation Oncologists are friends!

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