Advertisement

Strahlentherapie und Onkologie

, Volume 191, Issue 4, pp 310–320 | Cite as

Adjuvant radiotherapy after salvage lymph node dissection because of nodal relapse of prostate cancer versus salvage lymph node dissection only

  • Hans Christian Rischke
  • Wolfgang Schultze-Seemann
  • Gesche Wieser
  • Malte Krönig
  • Vanessa Drendel
  • Petra Stegmaier
  • Tobias Krauss
  • Karl Henne
  • Natalia Volegova-Neher
  • Daniel Schlager
  • Simon Kirste
  • Anca-Ligia Grosu
  • Cordula Annette JilgEmail author
Original article

Abstract

Background

Nodal pelvic/retroperitoneal recurrent prostate cancer (PCa) after primary therapy can be treated with salvage lymph node dissection (salvage-LND) in order to delay disease progression and offer cure for a subset of patients. Whether adjuvant radiotherapy (ART) in affected regions improves the outcome by elimination of residual tumour burden remains unclear.

Methods

A total of 93 patients with exclusively nodal PCa relapse underwent choline-positron-emission tomography-computed-tomography-directed pelvic/retroperitoneal salvage-LND; 46 patients had surgery only and 47 patients received ART in regions with proven lymph node metastases. In case of subsequent prostate specific antigen (PSA) progression, different imaging modalities were performed to confirm next relapse within or outside the treated region (TR). Mean follow-up was 3.2 years.

Results

Lymphatic tumour burden was balanced between the two groups. Additional ART resulted in delayed relapse within TR (5-year relapse-free rate 70.7 %) versus surgery only (5-year relapse-free rate 26.3 %, p < 0.0001). In both treatment arms, time to next relapse outside the TR was almost equal (median 27 months versus 29.6 months, p = 0.359). With respect to the detection of the first new lesion, regardless if present within or outside the TR, 5 years after the treatment 34.3 % of patients in the group with additional ART were free of relapse, versus 15.4 % in the surgery only group (p = 0.0122). ART had no influence on the extent of PSA reduction at latest follow-up compared to treatment with surgery only.

Conclusion

ART after salvage-LND provides stable local control in TR and results in overall significant improved next-relapse-free survival, compared to patients who received surgery only in case of nodal PCa-relapse.

Keywords

Prostate cancer relapse Salvage lymph node dissection Adjuvant radiotherapy Lymph node metastases Salvage radiotherapy 

Abbreviations

ART

Adjuvant radiotherapy

AHT

Antihormonal therapy

CI

Confidence interval

CT

Computed tomography

CTV

Clinical target volume

IGRT

Image-guided radiotherapy

IMRT

Intensity-modulated radiotherapy

LN

Lymph nodes

LNM

Lymph node metastases

MRI

Magnetic resonance imaging

PET/CT

Positron emission tomography/computed tomography

PCa

Prostate cancer

PSA

Prostate-specific antigen

PTV

Planning target volume

Salvage-LND

Salvage lymph node dissection

SD

Standard deviation

Sup

Supplement

TR

Treated region

Adjuvante Strahlentherapie nach Salvage-Lymphadenektomie beim nodalen Prostatakarzinomrezidiv im Vergleich zur alleinigen Salvage-Lymphadenektomie

Zusammenfassung

Hintergrund

Das nodal positive Prostatakarzinom(PCa)-Rezidiv nach Primärtherapie kann durch eine Salvage-Lymphadenektomie (Salvage-LND) therapiert werden. Der Krankheitsprogress wird aufgehalten und selektionierte Patienten erhalten eine zweite Chance auf eine Kuration. Ob eine adjuvante Strahlentherapie (ART Eradikation von verbleibenden Tumorzellen in der betreffenden Region) die Tumorfreiheitsrate verbessert, ist ungeklärt.

Material und Methoden

Insgesamt 93 Patienten mit einem ausschließlich nodalen PCa-Rezidiv wurden nach Diagnostik mittels Cholin-Positronenemissionstomographie/Computertomographie einer Salvage-LND unterzogen; 46/93 Patienten wurden ausschließlich operiert, 47/93 Patienten erhielten zusätzlich eine ART. Im Fall einer PSA-(prostataspezifisches-Antigen)-Progression wurde durch bildgebende Verfahren das nächste Rezidiv innerhalb oder außerhalb der behandelten Region (TR) diagnostiziert. Der mittlere Beobachtungszeitraum lag bei 3,2 Jahren.

Ergebnisse

Die Anzahl der Lymphknotenmetastasen war in den zwei Gruppen gleichverteilt. Eine zusätzliche ART bewirkte ein verzögertes Auftreten von neuen Metastasen in der TR (metastasenfreies 5-Jahres-Überleben 70,7 %) im Vergleich zur alleinigen Salvage-LND (metastasenfreies 5-Jahres-Überleben 26,3 %; p < 0,0001). Der Zeitpunkt bis zur Diagnose von Metastasen außerhalb der TR war in beiden Behandlungsarmen nicht signifikant unterschiedlich (27 Monate versus 29,6 Monate; p = 0,359). Unabhängig von der Lokalisation der neuen Metastasen lag das metastasenfreie 5-Jahres-Überleben bei Patienten mit einer Kombinationstherapie bei 34,3 %, bei Patienten mit alleiniger Operation hingegen bei 15,4 % (p = 0,0122). Die zusätzliche Strahlentherapie verursachte, verglichen mit einer alleinigen Operation, keinen signifikanten Unterschied bezüglich der PSA-Wert-Reduktion am Ende des Beobachtungszeitraums.

Schlussfolgerung

Eine zusätzliche ART bewirkt eine stabile lokale Tumorkontrolle in der behandelten Region und resultiert in einem signifikant verlängerten metastasenfreien Überleben verglichen mit einer alleinigen Salvage-LND beim nodalen Prostatakarzinomrezidiv.

Schlüsselwörter

Prostatakarzinomrezidiv Salvage-Lymphadenektomie Adjuvante Strahlentherapie Lymphknotenmetastasen Salvage-Radiotherapie 

Notes

Compliance with ethical guidelines

Conflict of interest

H.C. Rischke, W. Schultze-Seemann, G. Wieser, M. Krönig, V. Drendel, P. Stegmaier, T. Krauss, K. Henne, N. Volegova-Neher, D. Schlager, S. Kirste, A.-L. Grosu, and C.A. Jilg state that there are no conflicts of interest.

All studies on humans described in the present manuscript were carried out with the approval of the responsible ethics committee and in accordance with national law and the Helsinki Declaration of 1975 (in its current, revised form). Informed consent was obtained from all patients included in studies.

Supplementary material

66_2014_763_MOESM1_ESM.docx (112 kb)
(DOCX 113 kb)
66_2014_763_MOESM2_ESM.pdf (779 kb)
(PDF 780 kb)

References

  1. 1.
    Benson RC (1993) Total androgen blockade: the United States experience. Eur Urol 24:72–76PubMedGoogle Scholar
  2. 2.
    Bolla M, Van Poppel H, Tombal B et al (2012) Postoperative radiotherapy after radical prostatectomy for high-risk prostate cancer: long-term results of a randomised controlled trial (EORTC trial 22911). Lancet 380:2018–2027CrossRefPubMedGoogle Scholar
  3. 3.
    Bottke D, Bartkowiak D, Schrader M et al (2012) Radiotherapy after radical prostatectomy: immediate or early delayed? Strahlenther Onkol 188:1096–1101CrossRefPubMedGoogle Scholar
  4. 4.
    Briganti A, Joniau S, Gandaglia G et al (2013) Patterns and predictors of early biochemical recurrence after radical prostatectomy and adjuvant radiation therapy in men with pT3N0 prostate cancer: implications for multimodal therapies. Int J Radiat Oncol Biol Phys 87:960–967CrossRefPubMedGoogle Scholar
  5. 5.
    Casamassima F, Masi L, Menichelli C et al (2011) Efficacy of eradicative radiotherapy for limited nodal metastases detected with choline PET scan in prostate cancer patients. Tumori 97:49–55PubMedGoogle Scholar
  6. 6.
    Coleman CN, Beard CJ, Kantoff PW et al (1994) Rate of relapse following treatment for localized prostate cancer: a critical analysis of retrospective reports. Int J Radiat Oncol Biol Phys 28:303–313CrossRefPubMedGoogle Scholar
  7. 7.
    Ctcaev4.0 N (2009) National Cancer Institute common terminology criteria for adverse events v4.0 NCI, NIH, DHHS. NIH publication # 09-7473Google Scholar
  8. 8.
    Da Pozzo LF, Cozzarini C, Briganti A et al (2009) Long-term follow-up of patients with prostate cancer and nodal metastases treated by pelvic lymphadenectomy and radical prostatectomy: the positive impact of adjuvant radiotherapy. Eur Urol 55:1003–1011CrossRefPubMedGoogle Scholar
  9. 9.
    Fiorino C, Alongi F, Perna L et al (2009) Dose-volume relationships for acute bowel toxicity in patients treated with pelvic nodal irradiation for prostate cancer. Int J Radiat Oncol Biol Phys 75:29–35CrossRefPubMedGoogle Scholar
  10. 10.
    Guckenberger M, Lawrenz I, Flentje M (2014) Moderately hypofractionated radiotherapy for localized prostate cancer: long-term outcome using IMRT and volumetric IGRT. Strahlenther Onkol 190:48–53CrossRefPubMedGoogle Scholar
  11. 11.
    Guerrero Urbano T, Khoo V, Staffurth J et al (2010) Intensity-modulated radiotherapy allows escalation of the radiation dose to the pelvic lymph nodes in patients with locally advanced prostate cancer: preliminary results of a phase I dose escalation study. Clin Oncol (R Coll Radiol) 22:236–244CrossRefGoogle Scholar
  12. 12.
    Han M, Partin AW, Zahurak M (2003) Biochemical (prostate specific antigen) recurrence probability following radical prostatectomy for clinically localized prostate cancer. J Urol 169:517–523CrossRefPubMedGoogle Scholar
  13. 13.
    Heidenreich A, Bastian PJ, Bellmunt J et al (2014) EAU guidelines on prostate cancer. Part 1: screening, diagnosis, and local treatment with curative intent-update 2013. Eur Urol 65:124–137CrossRefPubMedGoogle Scholar
  14. 14.
    Heidenreich A, Bastian PJ, Bellmunt J et al (2014) EAU guidelines on prostate cancer. Part II: treatment of advanced, relapsing, and castration-resistant prostate cancer. Eur Urol 65:467–479CrossRefPubMedGoogle Scholar
  15. 15.
    Higano CS (2003) Side effects of androgen deprivation therapy: monitoring and minimizing toxicity. Urology 61:32–38CrossRefPubMedGoogle Scholar
  16. 16.
    Jereczek-Fossa BA, Beltramo G, Fariselli L et al (2012) Robotic image-guided stereotactic radiotherapy, for isolated recurrent primary, lymph node or metastatic prostate cancer. Int J Radiat Oncol Biol Phys 82:889–897CrossRefPubMedGoogle Scholar
  17. 17.
    Jilg CA, Rischke HC, Schultze-Seemann W (2012) Salvage lymph node dissection with adjuvant radiotherapy for choline-PET-CT positive lymph nodes in patients with nodal recurrence of prostate cancer. J Urol 2012 Dec;188(6):2190–2197. doi:10.1016/j. juro.2012.08.041. (Epub 2012 Oct 18)Google Scholar
  18. 18.
    Jilg CA, Leifert A, Schnell D et al (2014) Toxicity and quality of life after choline-PET/CT directed salvage lymph node dissection and adjuvant radiotherapy in nodal recurrent prostate cancer. Radiat Oncol 9:178Google Scholar
  19. 19.
    Jilg CA, Schultze-Seemann W, Drendel V et al (2014) Detection of lymph node metastasis in patients with nodal prostate cancer relapse using F/C-choline positron emission tomography/computerized tomography: influence of size of nodal tumor infiltration and accuracy related to lymph node regions. J Urol 2014 Feb 8. pii: S0022-5347(14)00119-0. doi:10.1016/j.juro.2013.12.054. (Epub ahead of print)Google Scholar
  20. 20.
    Lawton CA, Michalski J, El-Naqa I et al (2009) RTOG GU radiation oncology specialists reach consensus on pelvic lymph node volumes for high-risk prostate cancer. Int J Radiat Oncol Biol Phys 74:383–387CrossRefPubMedCentralPubMedGoogle Scholar
  21. 21.
    Leibowitz-Amit R, Templeton AJ, Omlin A et al (2014) Clinical variables associated with PSA response to abiraterone acetate in patients with metastatic castration-resistant prostate cancer. Ann Oncol 25:657–662CrossRefPubMedGoogle Scholar
  22. 22.
    Lohm G, Lutcke J, Jamil B et al (2014) Salvage radiotherapy in patients with prostate cancer and biochemical relapse after radical prostatectomy: long-term follow-up of a single-center survey. Strahlenther Onkol 190:727–731CrossRefPubMedGoogle Scholar
  23. 23.
    Lu-Yao GL, Yao SL (1997) Population-based study of long-term survival in patients with clinically localised prostate cancer. Lancet 349:906–910CrossRefPubMedGoogle Scholar
  24. 24.
    Martini T, Mayr R, Trenti E et al (2012) The role of C-choline-PET/CT-guided secondary lymphadenectomy in patients with PSA failure after radical prostatectomy: lessons learned from eight cases. Adv Urol 2012:601572Google Scholar
  25. 25.
    Millar J, Boyd R, Sutherland J (2008) An update of the phase III trial comparing whole pelvic to prostate only radiotherapy and neoadjuvant to adjuvant total androgen suppression: updated analysis of RTOG 94-13, with emphasis on unexpected hormone/radiation interactions: in regard to Lawton et al. (Int J Radiat Oncol Biol Phys 2007;69:646–655.). Int J Radiat Oncol Biol Phys 71:316 (author reply 316)Google Scholar
  26. 26.
    Pasquier D, Ballereau C (2008) Adjuvant and salvage radiotherapy after prostatectomy for prostate cancer: a literature review. Int J Radiat Oncol Biol Phys 72:972–979CrossRefPubMedGoogle Scholar
  27. 27.
    Picchio M, Briganti A, Fanti S et al (2011) The role of choline positron emission tomography/computed tomography in the management of patients with prostate-specific antigen progression after radical treatment of prostate cancer. Eur Urol 59:51–60CrossRefPubMedGoogle Scholar
  28. 28.
    Picchio M, Berardi G, Fodor A et al (2014) C-choline PET/CT as a guide to radiation treatment planning of lymph-node relapses in prostate cancer patients. Eur J Nucl Med Mol Imaging 41:1270–1279Google Scholar
  29. 29.
    Rigatti P, Suardi N, Briganti A (2011) Pelvic/retroperitoneal salvage lymph node dissection for patients treated with radical prostatectomy with biochemical recurrence and nodal recurrence detected by [11C]choline positron emission tomography/computed tomography. Eur Urol 60:935–943CrossRefPubMedGoogle Scholar
  30. 30.
    Rinnab L, Mottaghy FM, Blumstein NM (2007) Evaluation of [11C]-choline positron-emission/computed tomography in patients with increasing prostate-specific antigen levels after primary treatment for prostate cancer. BJU Int 100:786–793CrossRefPubMedGoogle Scholar
  31. 31.
    Rischke HC, Knippen S, Kirste S et al (2012) Treatment of recurrent prostate cancer following radical prostatectomy: the radiation-oncologists point of view. Q J Nucl Med Mol Imaging 56:409–420PubMedGoogle Scholar
  32. 32.
    Sanpaolo P, Barbieri V, Genovesi D (2014) Biologically effective dose and definitive radiation treatment for localized prostate cancer: treatment gaps do affect the risk of biochemical failure. Strahlenther Onkol 190:732–738CrossRefPubMedGoogle Scholar
  33. 33.
    Schiller K, Petrucci A, Geinitz H et al (2014) Impact of different setup approaches in image-guided radiotherapy as primary treatment for prostate cancer: a study of 2940 setup deviations in 980 MVCTs. Strahlenther Onkol 190:722–726CrossRefPubMedGoogle Scholar
  34. 34.
    Suardi N, Gandaglia G, Gallina A et al (2014) Long-term outcomes of salvage lymph node dissection for clinically recurrent prostate cancer: results of a single-institution series with a minimum follow-up of 5 years. Eur Urol 2014 Feb 18. pii: S0302-2838(14)00130-4. doi:10.1016/j.eururo.2014.02.011. (Epub ahead of print)Google Scholar
  35. 35.
    Thompson IM, Tangen CM, Paradelo J et al (2009) Adjuvant radiotherapy for pathological T3N0M0 prostate cancer significantly reduces risk of metastases and improves survival: long-term followup of a randomized clinical trial. J Urol 181:956–962CrossRefPubMedCentralPubMedGoogle Scholar
  36. 36.
    Wiegel T, Bartkowiak D, Bottke D et al (2014) Adjuvant radiotherapy versus wait-and-see after radical prostatectomy: 10-year follow-up of the ARO 96-02/AUO AP 09/95 trial. Eur Urol. 2014 Mar 21. pii: S0302-2838(14)00247-4. doi:10.1016/j.eururo.2014.03.011. (Epub ahead of print)Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Hans Christian Rischke
    • 1
    • 2
  • Wolfgang Schultze-Seemann
    • 5
  • Gesche Wieser
    • 2
  • Malte Krönig
    • 5
  • Vanessa Drendel
    • 4
  • Petra Stegmaier
    • 1
  • Tobias Krauss
    • 3
  • Karl Henne
    • 1
  • Natalia Volegova-Neher
    • 1
  • Daniel Schlager
    • 5
  • Simon Kirste
    • 3
  • Anca-Ligia Grosu
    • 1
  • Cordula Annette Jilg
    • 5
    Email author
  1. 1.Department of Radiation OncologyUniversity of FreiburgFreiburgGermany
  2. 2.Department of Nuclear MedicineUniversity of FreiburgFreiburgGermany
  3. 3.Department of RadiologyUniversity of FreiburgFreiburgGermany
  4. 4.Department of PathologyUniversity of FreiburgFreiburgGermany
  5. 5.Department of UrologyUniversity of FreiburgFreiburgGermany

Personalised recommendations