The prognostic and predictive role of pain before systemic chemotherapy in recurrent ovarian cancer: an individual participant data meta-analysis of the North-Eastern German Society of Gynecological Oncology (NOGGO) of 1226 patients

  • H. WoopenEmail author
  • R. Richter
  • G. Inci
  • S. Alavi
  • R. Chekerov
  • J. Sehouli
Original Article



Aim of this study was to analyze the impact of pain on quality of life and survival in recurrent OC patients.


Raw data including the QLQ-C30 questionnaire from three phase II/III trials (“Topotecan phase III,” “Hector,” and “TRIAS”) conducted by the North-Eastern German Society of Gynecological Oncology (NOGGO) were synthesized and analyzed using logistic and Cox regression analyses.


Data on pain was available for 952 patients out of 1226. Moderate to severe pain, which was defined as pain ≥ 50 in the QLQ-C30 symptom scale, was experienced by more than one-third of patients (36.6%). A total of 31% were taking non-opioid pain medication and 16% opioids. Median age at randomization was 61 years (range 25–84). Most patients (84.7%) were diagnosed in FIGO III/IV. Pain was independent from age, FIGO stage, grading, amount of recurrences, and chemotherapy-free interval. ECOG was significantly worse in patients with pain (p < 0.001). Fatigue, nausea/vomiting, sleeping disorders, and abdominal symptoms such as loss of appetite, diarrhea, and constipation were more frequently found in patients with pain (all p < 0.001). Quality of life was significantly diminished (p < 0.001). Pain was also an independent marker for overall survival (OS). Median OS was 18.2 months in patients with pain compared with 22.0 months in patients without pain (p = 0.013, HR 1.25, 95% confidence interval 1.05–1.48). OS was shorter in patients with pain and without pain medication compared with those on sufficient pain medication, whereas OS was mostly decreased in patients having pain despite pain medication (18.5, 19.6, and 15.0 months respectively; p = 0.026). Progression-free survival and prior treatment discontinuation were not associated with pain.


Best supportive care including sufficient pain medication should be delivered as early as possible because effective pain management is crucial for both quality of life and overall survival in patients with recurrent ovarian cancer.


Pain Supportive care Recurrent ovarian cancer Prognosis 


Compliance with ethical standards

Conflict of interest

There are no potential conflicts of interest regarding this article. Dr. Hannah Woopen, MSc was participant in the Charité Clinical Scientist Program funded by the Charité Universitätsmedizin Berlin and the Berlin Institute of Health.


  1. 1.
    Cherny NI (2000) The management of cancer pain. CA Cancer J Clin 50:70–116CrossRefPubMedGoogle Scholar
  2. 2.
    Wang N, Dong Y, Zhao L, Zhao H, Li W, Cui J (2018) Factors associated with optimal pain management in advanced cancer patients. Curr Probl Cancer 43:77–85Google Scholar
  3. 3.
    van den Beuken-van Everdingen MHJ, Hochstenbach LMJ, Joosten EAJ, Tjan-Heijnen VCG, Janssen DJA (2016) Update on prevalence of pain in patients with cancer: systematic review and meta-analysis. J Pain Symptom Manage 51:1070–1090CrossRefPubMedGoogle Scholar
  4. 4.
    Deimling GT, Bowman KF, Wagner LJ (2007) The effects of cancer-related pain and fatigue on functioning of older adult, long-term cancer survivors. Cancer Nurs 30:421–433CrossRefPubMedGoogle Scholar
  5. 5.
    Golčić M, Dobrila-Dintinjana R, Golčić G, Pavlović-Ružić I, Gović-Golčić L (2018) Do physicians underestimate pain in terminal cancer patients? A prospective study in a hospice setting. Clin J Pain 34:1159–1163Google Scholar
  6. 6.
    Gilbertson-White S, Campbell G, Ward S, Sherwood P, Donovan H (2017) Coping with pain severity, distress, and consequences in women with ovarian cancer. Cancer Nurs 40:117–123CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Breivik H, Cherny N, Collett B, de Conno F, Filbet M, Foubert AJ et al (2009) Cancer-related pain: a pan-European survey of prevalence, treatment, and patient attitudes. Ann Oncol 20:1420–1433CrossRefPubMedGoogle Scholar
  8. 8.
    Puetzler J, Feldmann RE, Brascher A-K, Gerhardt A, Benrath J (2014) Improvements in health-related quality of life by comprehensive cancer pain therapy: a pilot study with breast cancer outpatients under palliative chemotherapy. Oncol Res Treat 37:456–462CrossRefPubMedGoogle Scholar
  9. 9.
    Quinten C, Martinelli F, Coens C, Sprangers MAG, Ringash J, Gotay C et al (2014) A global analysis of multitrial data investigating quality of life and symptoms as prognostic factors for survival in different tumor sites. Cancer 120:302–311CrossRefPubMedGoogle Scholar
  10. 10.
    Sehouli J, Stengel D, Oskay-Oezcelik G, Zeimet AG, Sommer H, Klare P et al (2008) Nonplatinum topotecan combinations versus topotecan alone for recurrent ovarian cancer: results of a phase III study of the North-Eastern German Society of Gynecological Oncology Ovarian Cancer Study Group. J Clin Oncol 26:3176–3182CrossRefPubMedGoogle Scholar
  11. 11.
    Sehouli J, Chekerov R, Reinthaller A, Richter R, Gonzalez-Martin A, Harter P et al (2016) Topotecan plus carboplatin versus standard therapy with paclitaxel plus carboplatin (PC) or gemcitabine plus carboplatin (GC) or pegylated liposomal doxorubicin plus carboplatin (PLDC): a randomized phase III trial of the NOGGO-AGO-Study Group-AGO Austria and GEICO-ENGOT-GCIG intergroup study (HECTOR). Ann Oncol 27:2236–2241CrossRefPubMedGoogle Scholar
  12. 12.
    Chekerov R, Hilpert F, Mahner S, El-Balat A, Harter P, De Gregorio N, Fridrich C, Markmann S, Potenberg J, Lorenz R, Oskay-Oezcelik G, Schmidt M, Krabisch P, Lueck HJ, Richter R, Braicu EI, du Bois A, Sehouli J (2018) Sorafenib plus topotecan versus placebo plus topotecan for platinum-resistant ovarian cancer (TRIAS): a multicentre, randomised, double-blind, placebo-controlled, Phase 2 trial. Lancet Oncol 19:1247–1258Google Scholar
  13. 13.
    Joly F, Hilpert F, Okamoto A, Stuart G, Ochiai K, Friedlander M et al (2017) Fifth Ovarian Cancer Consensus Conference of the Gynecologic Cancer InterGroup: recommendations on incorporating patient-reported outcomes in clinical trials in epithelial ovarian cancer. Eur J Cancer 78:133–138CrossRefPubMedGoogle Scholar
  14. 14.
    King MT, Stockler MR, O’Connell RL, Buizen L, Joly F, Lanceley A et al (2018) Measuring what matters MOST: validation of the Measure of Ovarian Symptoms and Treatment, a patient-reported outcome measure of symptom burden and impact of chemotherapy in recurrent ovarian cancer. Qual Life Res 27:59–74CrossRefPubMedGoogle Scholar
  15. 15.
    Ediebah DE, Quinten C, Coens C, Ringash J, Dancey J, Zikos E et al (2018) Quality of life as a prognostic indicator of survival: a pooled analysis of individual patient data from Canadian Cancer Trials Group clinical trials. Cancer 124:3409–3416Google Scholar
  16. 16.
    Shi L, Liu Y, He H, Wang C, Li H, Wang N (2016) Characteristics and prognostic factors for pain management in 152 patients with lung cancer. Patient Prefer Adherence 10:571–577PubMedCentralPubMedGoogle Scholar
  17. 17.
    Bjordal K (2004) Impact of quality of life measurement in daily clinical practice. Ann Oncol 15(Suppl 4):iv279–iv282PubMedGoogle Scholar
  18. 18.
    Chen T-H, Li L, Kochen MM (2005) A systematic review: how to choose appropriate health-related quality of life (HRQOL) measures in routine general practice? J Zhejiang Univ Sci 6:936–940CrossRefGoogle Scholar
  19. 19.
    Mustafa M, Carson-Stevens A, Gillespie D, Edwards AGK (2013) Psychological interventions for women with metastatic breast cancer. Cochrane Database Syst Rev CD004253Google Scholar
  20. 20.
    Du Bois A, Rochon J, Lamparter C, Pfisterer J, PFisterer AGOOOVAR (2005) Pattern of care and impact of participation in clinical studies on the outcome in ovarian cancer. Int J Gynecol Cancer 15:183–191CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • H. Woopen
    • 1
    Email author
  • R. Richter
    • 1
  • G. Inci
    • 1
  • S. Alavi
    • 1
  • R. Chekerov
    • 1
  • J. Sehouli
    • 1
  1. 1.European Competence Center for Ovarian Cancer (EKZE), Department of Gynecology with Center for Oncological SurgeryCharité – University Medicine of Berlin, Campus Virchow KlinikumBerlinGermany

Personalised recommendations