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Expression of Ku70 predicts results of radiotherapy in prostate cancer

Ku70-Expression prognostiziert Ergebnisse der Strahlentherapie beim Prostatakarzinom

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Abstract

Background and purpose

Therapeutic strategy for prostate cancer is decided according to T stage, Gleason score, and prostate-specific antigen (PSA) level. These clinical factors are not accurate enough to predict individual risk of local failure of prostate cancer after radiotherapy. Parameters involved with radiosensitivity are required to improve the predictive capability for local relapse.

Patients and methods

We analyzed 58 patients with localized adenocarcinoma of the prostate between August 2007 and October 2010 treated with 76 Gy of intensity-modulated radiotherapy (IMRT) as a discovery cohort and 42 patients between March 2001 and May 2007 treated with three-dimensional conformal radiotherapy (3D-CRT) as a validation cohort. Immunohistochemical examination for proteins involved in nonhomologous end-joining was performed using biopsy specimens.

Results

Ku70 expression was not correlated with various clinical parameters, such as the Gleason score and D’amico risk classification, indicating that Ku70 expression was an independent prognostic factor. The predictive value for PSA relapse was markedly improved after the combination of Gleason score and Ku70 expression, as compared with Gleason score alone. In patients treated with radiotherapy and androgen deprivation therapy (ADT), no relapses were observed in patients with Gleason score ≤7 or low Ku70 expression. In contrast, patients with Gleason score ≥8 and high Ku70 expression had high PSA relapse rates. In the validation cohort, similar results were obtained.

Conclusion

Treatment with 76 Gy and ADT can be effective for patients with Gleason score ≤7 or low Ku70 expression, but is not enough for patients with Gleason score ≥8 and high Ku70 expression and, thus, require other treatment approaches.

Zusammenfassung

Hintergrund und Ziel

Die Behandlung beim Prostatakarzinom ist abhängig von T‑Stadium, Gleason-Score und prostataspezifischem Antigen (PSA). Diese klinischen Faktoren sind jedoch zu ungenau, um das individuelle Lokalrezidivrisiko beim Prostatakarzinom nach Strahlentherapie zu prognostizieren. Für eine bessere Vorhersagbarkeit eines Lokalrezidivs sind weitere Parameter zur Strahlenempfindlichkeit erforderlich.

Patienten und Methoden

Wir untersuchten zwischen August 2007 und Oktober 2010 als Entwicklungskohorte 58 mit intensitätsmodulierter Strahlentherapie (IMRT, 76 Gy) behandelte Patienten mit einem lokalisierten Prostataadenokarzinom sowie zwischen März 2001 und Mai 2007 als Validierungskohorte 42 mit dreidimensionaler konformaler Strahlentherapie (3D-CRT) behandelte Patienten. Eine immunhistochemische Untersuchung der am nichthomologen Endjoining beteiligten Proteine wurde unter Verwendung von Biopsaten durchgeführt.

Ergebnisse

Die Ku70-Expression wurde nicht mit verschiedenen klinischen Parametern korreliert, wie z. B. Gleason-Score und Risikostratifizierung nach D’Amico, und scheint daher einen unabhängigen Prognosefaktor darzustellen. Der Vorhersagewert war für PSA-Rezidive nach Kombination von Gleason-Score und Ku70-Expression im Vergleich zum Gleason-Score allein deutlich besser. Bei Strahlentherapie und Androgendeprivationstherapie (ADT) zeigten Patienten mit Gleason-Score ≤7 oder niedriger Ku70-Expression keine Rezidive. Dagegen war bei einem Gleason-Score ≥8 und hoher Ku70-Expression die PSA-Rezidivrate hoch. Ähnliche Ergebnisse lieferte die Validierungskohorte.

Schlussfolgerung

Die Behandlung mit 76 Gy und ADT kann bei Patienten mit Gleason-Score ≤7 oder niedriger Ku70-Expression wirksam sein, ist aber bei einem Gleason-Score ≥8 und hoher Ku70-Expression nicht ausreichend, so dass in diesen Fällen andere Behandlungsansätze erforderlich sind.

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Acknowledgements

This investigation was partly supported by a Grant-in Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

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Authors and Affiliations

  1. Department of Radiology, Sapporo Medical University School of medicine, 060-8543, Chuo-ku, Sapporo, Hokkaido, Japan

    Tomokazu Hasegawa MD, Masanori Someya MD, PhD, Masakazu Hori MD, PhD, Kensei Nakata MD, Mio Kitagawa MD, Takaaki Tsuchiya MD & Koh-ichi Sakata MD, PhD

  2. Tokyo Institute of Technology, Research Laboratory for Nuclear Reactors, Meguro-ku, Tokyo, Japan

    Yoshihisa Matsumoto MD, PhD

  3. The Institute of Medical Science Hospital, The University of Tokyo, 4-6-1 Shirokanedai, 108-8639, Minatoku, Tokyo, Japan

    Masanori Nojima MD, PhD

  4. Department of Urology, Sapporo Medical University School of medicine, 065-8543, Chuo-ku, Sapporo, Hokkaido, Japan

    Naoya Masumori MD, PhD

  5. Department of Surgical Pathology, Sapporo Medical University School of medicine, 060-8543, Chuo-ku, Sapporo, Hokkaido, Japan

    Tadashi Hasegawa MD, PhD

Authors
  1. Tomokazu Hasegawa MD
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  2. Masanori Someya MD, PhD
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  3. Masakazu Hori MD, PhD
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  4. Yoshihisa Matsumoto MD, PhD
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  5. Kensei Nakata MD
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  6. Masanori Nojima MD, PhD
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  7. Mio Kitagawa MD
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  8. Takaaki Tsuchiya MD
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  9. Naoya Masumori MD, PhD
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  10. Tadashi Hasegawa MD, PhD
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  11. Koh-ichi Sakata MD, PhD
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Corresponding author

Correspondence to Koh-ichi Sakata MD, PhD.

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Conflict of interest

T. Hasegawa, M. Someya, M. Hori, Y. Matsumoto, K. Nakata, M. Nojima, M. Kitagawa, T. Tsuchiya, N. Masumori, T. Hasegawa, and K. Sakata declare that they have no competing interest.

Ethical standards

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.

Additional information

This study was approved by the Institutional Review Board of the Sapporo Medical University.

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Hasegawa, T., Someya, M., Hori, M. et al. Expression of Ku70 predicts results of radiotherapy in prostate cancer. Strahlenther Onkol 193, 29–37 (2017). https://doi.org/10.1007/s00066-016-1023-7

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  • DOI: https://doi.org/10.1007/s00066-016-1023-7

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