Skip to main content
SpringerLink
Log in

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

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

  • Original article
  • Published:
Strahlentherapie und Onkologie Aims and scope Submit manuscript

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.

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

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

References

  1. Benson RC (1993) Total androgen blockade: the United States experience. Eur Urol 24:72–76

    PubMed  Google Scholar 

  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 380:2018–2027

    Article  PubMed  Google Scholar 

  3. Bottke D, Bartkowiak D, Schrader M et al (2012) Radiotherapy after radical prostatectomy: immediate or early delayed? Strahlenther Onkol 188:1096–1101

    Article  CAS  PubMed  Google Scholar 

  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 87:960–967

    Article  PubMed  Google Scholar 

  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 97:49–55

    CAS  PubMed  Google Scholar 

  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 28:303–313

    Article  CAS  PubMed  Google Scholar 

  7. Ctcaev4.0 N (2009) National Cancer Institute common terminology criteria for adverse events v4.0 NCI, NIH, DHHS. NIH publication # 09-7473

  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 55:1003–1011

    Article  PubMed  Google Scholar 

  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 75:29–35

    Article  PubMed  Google Scholar 

  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 190:48–53

    Article  CAS  PubMed  Google Scholar 

  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) 22:236–244

    Article  CAS  Google Scholar 

  12. Han M, Partin AW, Zahurak M (2003) Biochemical (prostate specific antigen) recurrence probability following radical prostatectomy for clinically localized prostate cancer. J Urol 169:517–523

    Article  PubMed  Google Scholar 

  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 65:124–137

    Article  PubMed  Google Scholar 

  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 65:467–479

    Article  CAS  PubMed  Google Scholar 

  15. Higano CS (2003) Side effects of androgen deprivation therapy: monitoring and minimizing toxicity. Urology 61:32–38

    Article  PubMed  Google Scholar 

  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 82:889–897

    Article  PubMed  Google Scholar 

  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)

  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 9:178

  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)

  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 74:383–387

    Article  PubMed Central  PubMed  Google Scholar 

  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 25:657–662

    Article  CAS  PubMed  Google Scholar 

  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 190:727–731

    Article  PubMed  Google Scholar 

  23. Lu-Yao GL, Yao SL (1997) Population-based study of long-term survival in patients with clinically localised prostate cancer. Lancet 349:906–910

    Article  CAS  PubMed  Google Scholar 

  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 2012:601572

  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)

  26. Pasquier D, Ballereau C (2008) Adjuvant and salvage radiotherapy after prostatectomy for prostate cancer: a literature review. Int J Radiat Oncol Biol Phys 72:972–979

    Article  PubMed  Google Scholar 

  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 59:51–60

    Article  PubMed  Google Scholar 

  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 41:1270–1279

  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 60:935–943

    Article  PubMed  Google Scholar 

  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 100:786–793

    Article  CAS  PubMed  Google Scholar 

  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 56:409–420

    CAS  PubMed  Google Scholar 

  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 190:732–738

    Article  CAS  PubMed  Google Scholar 

  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 190:722–726

    Article  PubMed  Google Scholar 

  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)

  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 181:956–962

    Article  PubMed Central  PubMed  Google Scholar 

  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)

Download references

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.

Author information

Authors and Affiliations

  1. Department of Radiation Oncology, University of Freiburg, Freiburg, Germany

    Hans Christian Rischke,  Petra Stegmaier,  Karl Henne,  Natalia Volegova-Neher &  Anca-Ligia Grosu

  2. Department of Nuclear Medicine, University of Freiburg, Freiburg, Germany

    Hans Christian Rischke &  Gesche Wieser

  3. Department of Radiology, University of Freiburg, Freiburg, Germany

    Tobias Krauss &  Simon Kirste

  4. Department of Pathology, University of Freiburg, Freiburg, Germany

    Vanessa Drendel

  5. Department of Urology, University of Freiburg, Hugstetterstr. 55, 79106, Freiburg, Germany

    Wolfgang Schultze-Seemann,  Malte Krönig,  Daniel Schlager & Cordula Annette Jilg

Authors
  1. Hans Christian Rischke
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wolfgang Schultze-Seemann
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gesche Wieser
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Malte Krönig
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Vanessa Drendel
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Petra Stegmaier
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Tobias Krauss
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Karl Henne
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Natalia Volegova-Neher
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Daniel Schlager
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Simon Kirste
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Anca-Ligia Grosu
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Cordula Annette Jilg
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Cordula Annette Jilg.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Rischke, H., Schultze-Seemann, W., Wieser, G. et al. Adjuvant radiotherapy after salvage lymph node dissection because of nodal relapse of prostate cancer versus salvage lymph node dissection only. Strahlenther Onkol 191, 310–320 (2015). https://doi.org/10.1007/s00066-014-0763-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00066-014-0763-5

Keywords

Schlüsselwörter

Search

Navigation