Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Clinical Research
  • Published:

The predictive value of machine learning and nomograms for lymph node metastasis of prostate cancer: a systematic review and meta-analysis

Abstract

Background

In clinical practice, there are currently a variety of nomograms for predicting lymph node metastasis (LNM) of prostate cancer. At the same time, some scholars have introduced machine learning (ML) into the prediction of LNM of prostate cancer. However, the predictive value of nomograms and ML remains controversial. Based on this situation, this systematic review and meta-analysis was performed to explore the predictive value of various nomograms currently recommended and newly-developed ML models for LNM in prostate cancer patients.

Evidence acquisition

Cochrane, PubMed, Embase, and Web of Science were searched up to November 1, 2022.

Summary of evidence

The risk of bias in the included studies was evaluated using the Prediction model Risk of Bias Assessment Tool (PROBAST). The concordance index (C-index), sensitivity, and specificity were adopted to evaluate the predictive accuracy of the models.

Results

Thirty-one studies (18,803 patients) were included. Seven kinds of nomograms currently recommended, dominated by Briganti nomogram or MSKCC nomogram, were covered in the included studies. For newly-developed ML models, the C-index for LNM prediction in the training set and validation set was 0.846 [95%CI (0.818, 0.873)] and 0.862 [95%CI (0.819–0.905)] respectively. Most ML models in the training set were based on Logistic Regression (LR), which had a sensitivity of 0.78 [95%CI (0.70, 0.85)] and a specificity of 0.85 [95%CI (0.77, 0.90)] in the training set, and a sensitivity of 0.81 [95%CI (0.67, 0.89)] and a specificity of 0.82 [95%CI (0.75, 0.88)] in the validation set. For the recommended nomograms, the C-index in the validation set was 0.745 [95%CI (0.701, 0.790)] for the Briganti nomogram and 0.714 [95%CI (0.662, 0.765)] for the MSKCC nomogram.

Conclusion

The predictive accuracy of ML is superior to existing clinically recommended nomograms, and appropriate updates can be conducted to existing nomograms according to special situations.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Fig. 1
Fig. 2: Forest plots of results of risk of bias assessment and the sensitivity and specificity of meta-analysis for included models.
Fig. 3: Forest plots of C-index of radiomics-based MLs.
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Data availability

Data sharing not applicable to this article as no datasets were generated or analyzed during the current study.

References

  1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. Cancer J Clin. 2021;71:209–49.

    Article  Google Scholar 

  2. Gandaglia G, Leni R, Bray F, Fleshner N, Freedland SJ, Kibel A, et al. Epidemiology and prevention of prostate cancer. Eur Urol Oncol. 2021;4:877–92.

    Article  PubMed  Google Scholar 

  3. Wilczak W, Wittmer C, Clauditz T, Minner S, Steurer S, Büscheck F, et al. Marked prognostic impact of minimal lymphatic tumor spread in prostate cancer. Eur Urol. 2018;74:376–86.

    Article  PubMed  Google Scholar 

  4. von Bodman C, Godoy G, Chade DC, Cronin A, Tafe LJ, Fine SW, et al. Predicting biochemical recurrence-free survival for patients with positive pelvic lymph nodes at radical prostatectomy. J Urol. 2010;184:143–8.

    Article  Google Scholar 

  5. Mottet N, Bellmunt J, Bolla M, Briers E, Cumberbatch MG, De Santis M, et al. EAU-ESTRO-SIOG guidelines on prostate cancer. Part 1: screening, diagnosis, and local treatment with curative intent. Eur Urol. 2017;71:618–29.

    Article  PubMed  Google Scholar 

  6. Park SY, Shin SJ, Jung DC, Cho NH, Choi YD, Rha KH, et al. PI-RADS version 2: Preoperative role in the detection of normal-sized pelvic lymph node metastasis in prostate cancer. Eur J Radiol. 2017;91:22–28.

    Article  PubMed  Google Scholar 

  7. Venclovas Z, Muilwijk T, Matjosaitis AJ, Jievaltas M, Joniau S, Milonas D. Head-to-head comparison of two nomograms predicting probability of lymph node invasion in prostate cancer and the therapeutic impact of higher nomogram threshold. J Clin Med. 2021;10:5.

    Article  Google Scholar 

  8. Bourbonne V, Jaouen V, Nguyen TA, Tissot V, Doucet L, Hatt M, et al. Development of a radiomic-based model predicting lymph node involvement in prostate cancer patients. Cancers. 2021;13:22.

    Article  Google Scholar 

  9. Huang C, Song G, Wang H, Lin Z, Wang H, Ji G, et al. Preoperative PI-RADS Version 2 scores helps improve accuracy of clinical nomograms for predicting pelvic lymph node metastasis at radical prostatectomy. Prostate Cancer Prostatic Dis. 2020;23:116–26.

    Article  PubMed  Google Scholar 

  10. Hou Y, Bao J, Song Y, Bao ML, Jiang KW, Zhang J, et al. Integration of clinicopathologic` identification and deep transferrable image feature representation improves predictions of lymph node metastasis in prostate cancer. EBioMedicine. 2021;68:103395.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Zheng H, Miao Q, Liu Y, Mirak SA, Hosseiny M, Scalzo F, et al. Multiparametric MRI-based radiomics model to predict pelvic lymph node invasion for patients with prostate cancer. Eur Radiol. 2022;32:5688–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Tosco L, Devos G, De Coster G, Roumeguère T, Everaerts W, Quackels T, et al. Development and external validation of a nomogram to predict lymph node invasion after robot assisted radical prostatectomy. Urol Oncol. 2020;38:37.e11–20.

    Article  PubMed  Google Scholar 

  13. Oliveira AL. Biotechnology, big data and artificial intelligence. Biotechnol J. 2019;14:e1800613.

    Article  PubMed  Google Scholar 

  14. Mirza B, Wang W, Wang J, Choi H, Chung NC, Ping P. Machine learning and integrative analysis of biomedical big data. Genes. 2019;10:2.

    Article  Google Scholar 

  15. Bi Q, Goodman KE, Kaminsky J, Lessler J. What is machine learning? A primer for the epidemiologist. Am J Epidemiol. 2019;188:2222–39.

    PubMed  Google Scholar 

  16. Wang Z, Li H, Carpenter C, Guan Y. Challenge-enabled machine learning to drug-response prediction. AAPS J. 2020;22:106.

    Article  PubMed  Google Scholar 

  17. Handelman GS, Kok HK, Chandra RV, Razavi AH, Lee MJ, Asadi H. eDoctor: machine learning and the future of medicine. J Intern Med. 2018;284:603–19.

    Article  CAS  PubMed  Google Scholar 

  18. Fleuren LM, Klausch TLT, Zwager CL, Schoonmade LJ, Guo T, Roggeveen LF, et al. Machine learning for the prediction of sepsis: a systematic review and meta-analysis of diagnostic test accuracy. Intensive Care Med. 2020;46:383–400.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Chen C, Qin Y, Chen H, Zhu D, Gao F, Zhou X. A meta-analysis of the diagnostic performance of machine learning-based MRI in the prediction of axillary lymph node metastasis in breast cancer patients. Insights Imaging. 2021;12:156.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Wolff RF, Moons KGM, Riley RD, Whiting PF, Westwood M, Collins GS, et al. PROBASt: a tool to assess the risk of bias and applicability of prediction model studies. Ann Intern Med. 2019;170:51–58.

    Article  PubMed  Google Scholar 

  21. Debray TP, Damen JA, Riley RD, Snell K, Reitsma JB, Hooft L, et al. A framework for meta-analysis of prediction model studies with binary and time-to-event outcomes. Stat Methods Med Res. 2019;28:2768–86.

    Article  PubMed  Google Scholar 

  22. Zhou X, Zhong Y, Song L, Wang Y, Wang Y, Zhang Q, et al. Nomograms to predict the presence and extent of inguinal lymph node metastasis in penile cancer patients with clinically positive lymph nodes. Transl Androl Urol. 2020;9:621–8.

    Article  PubMed  PubMed Central  Google Scholar 

  23. von Below C, Wassberg C, Grzegorek R, Kullberg J, Gestblom C, Sörensen J, et al. MRI and (11)C acetate PET/CT for prediction of regional lymph node metastasis in newly diagnosed prostate cancer. Radiol Oncol. 2018;52:90–97.

    Article  Google Scholar 

  24. Winter A, Kneib T, Wasylow C, Reinhardt L, Henke RP, Engels S, et al. Updated nomogram incorporating percentage of positive cores to predict probability of lymph node invasion in prostate cancer patients undergoing sentinel lymph node dissection. J Cancer. 2017;8:2692–8.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Zheng Z, Mao S, Gu Z, Wang R, Guo Y, Zhang W, et al. A genomic-clinicopathologic nomogram for the prediction of lymph node invasion in prostate cancer. J Oncol. 2021;2021:5554708.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Winter A, Kneib T, Rohde M, Henke RP, Wawroschek F. First nomogram predicting the probability of lymph node involvement in prostate cancer patients undergoing radioisotope guided sentinel lymph node dissection. Urol Int. 2015;95:422–8.

    Article  CAS  PubMed  Google Scholar 

  27. Brembilla G, Dell'Oglio P, Stabile A, Ambrosi A, Cristel G, Brunetti L, et al. Preoperative multiparametric MRI of the prostate for the prediction of lymph node metastases in prostate cancer patients treated with extended pelvic lymph node dissection. Eur Radiol. 2018;28:1969–76.

    Article  PubMed  Google Scholar 

  28. Briganti A, Capitanio U, Abdollah F, Gallina A, Suardi N, Bianchi M, et al. Assessing the risk of lymph node invasion in patients with intermediate risk prostate cancer treated with extended pelvic lymph node dissection. A novel prediction tool. Prostate. 2012;72:499–506.

    Article  PubMed  Google Scholar 

  29. Briganti A, Gallina A, Suardi N, Chun FK, Walz J, Heuer R, et al. A nomogram is more accurate than a regression tree in predicting lymph node invasion in prostate cancer. BJU Int. 2008;101:556–60.

    Article  PubMed  Google Scholar 

  30. Briganti A, Larcher A, Abdollah F, Capitanio U, Gallina A, Suardi N, et al. Updated nomogram predicting lymph node invasion in patients with prostate cancer undergoing extended pelvic lymph node dissection: the essential importance of percentage of positive cores. Eur Urol. 2012;61:480–7.

    Article  PubMed  Google Scholar 

  31. Di Trapani E, Luzzago S, Peveri G, Catellani M, Ferro M, Cordima G, et al. A novel nomogram predicting lymph node invasion among patients with prostate cancer: The importance of extracapsular extension at multiparametric magnetic resonance imaging. Urol Oncol. 2021;39:431.e415–e422.

    Article  Google Scholar 

  32. Hu B, Deng Y, Chen J, Kuang S, Tang W, He B, et al. Evaluation of MR elastography for prediction of lymph node metastasis in prostate cancer. Abdom Radiol. 2021;46:3387–400.

    Article  Google Scholar 

  33. Koerber SA, Stach G, Kratochwil C, Haefner MF, Rathke H, Herfarth K, et al. Lymph node involvement in treatment-naïve prostate cancer patients: correlation of PSMA PET/CT imaging and roach formula in 280 men in radiotherapeutic management. J Nucl Med. 2020;61:46–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Liu X, Tian J, Wu J, Zhang Y, Wang X, Zhang X, et al. Utility of diffusion weighted imaging-based radiomics nomogram to predict pelvic lymph nodes metastasis in prostate cancer. BMC Med Imaging. 2022;22:190.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Liu X, Wang X, Zhang Y, Sun Z, Zhang X, Wang X. Preoperative prediction of pelvic lymph nodes metastasis in prostate cancer using an ADC-based radiomics model: comparison with clinical nomograms and PI-RADS assessment. Abdom Radiol. 2022;47:3327–37.

    Article  Google Scholar 

  36. Małkiewicz B, Ptaszkowski K, Knecht K, Gurwin A, Wilk K, Kiełb P, et al. External validation of the briganti nomogram to predict lymph node invasion in prostate cancer-setting a new threshold value. Life. 2021;11:6.

    Article  Google Scholar 

  37. Wang L, Hricak H, Kattan MW, Schwartz LH, Eberhardt SC, Chen HN, et al. Combined endorectal and phased-array MRI in the prediction of pelvic lymph node metastasis in prostate cancer. Am J Roentgenol. 2006;186:743–8.

    Article  Google Scholar 

  38. Peilleron N, Seigneurin A, Herault C, Verry C, Bolla M, Rambeaud JJ, et al. External evaluation of the Briganti nomogram to predict lymph node metastases in intermediate-risk prostate cancer patients. World J Urol. 2021;39:1489–97.

    Article  PubMed  Google Scholar 

  39. Onal C, Ozyigit G, Oymak E, Guler OC, Hurmuz P, Tilki B, et al. Clinical parameters and nomograms for predicting lymph node metastasis detected with (68) Ga-PSMA-PET/CT in prostate cancer patients candidate to definitive radiotherapy. Prostate. 2021;81:648–56.

    Article  CAS  PubMed  Google Scholar 

  40. Peeken JC, Shouman MA, Kroenke M, Rauscher I, Maurer T, Gschwend JE, et al. A CT-based radiomics model to detect prostate cancer lymph node metastases in PSMA radioguided surgery patients. Eur J Nucl Med Mol Imaging. 2020;47:2968–77.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Cysouw MCF, Jansen BHE, van de Brug T, Oprea-Lager DE, Pfaehler E, de Vries BM, et al. Machine learning-based analysis of [(18)F]DCFPyL PET radiomics for risk stratification in primary prostate cancer. Eur J Nucl Med Mol imaging. 2021;48:340–9.

    Article  CAS  PubMed  Google Scholar 

  42. Gandaglia G, Martini A, Ploussard G, Fossati N, Stabile A, De Visschere P, et al. External validation of the 2019 Briganti nomogram for the identification of prostate cancer patients who should be considered for an extended pelvic lymph node dissection. Eur Urol. 2020;78:138–42.

    Article  PubMed  Google Scholar 

  43. Wessels F, Schmitt M, Krieghoff-Henning E, Jutzi T, Worst TS, Waldbillig F, et al. Deep learning approach to predict lymph node metastasis directly from primary tumour histology in prostate cancer. BJU Int. 2021;128:352–60.

    Article  CAS  PubMed  Google Scholar 

  44. Wei L, Huang Y, Chen Z, Lei H, Qin X, Cui L, et al. Artificial intelligence combined with big data to predict lymph node involvement in prostate cancer: a population-based study. Front Oncol. 2021;11:763381.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Gandaglia G, Ploussard G, Valerio M, Mattei A, Fiori C, Fossati N, et al. A novel nomogram to identify candidates for extended pelvic lymph node dissection among patients with clinically localized prostate cancer diagnosed with magnetic resonance imaging-targeted and systematic biopsies. Eur Urol. 2019;75:506–14.

    Article  PubMed  Google Scholar 

  46. Eiber M, Beer AJ, Holzapfel K, Tauber R, Ganter C, Weirich G, et al. Preliminary results for characterization of pelvic lymph nodes in patients with prostate cancer by diffusion-weighted MR-imaging. Investig Radiol. 2010;45:15–23.

    Article  Google Scholar 

  47. Noguchi M, Stamey TA, McNeal JE, Yemoto CM. Relationship between systematic biopsies and histological features of 222 radical prostatectomy specimens: lack of prediction of tumor significance for men with nonpalpable prostate cancer. J Urol. 2001;166:104–9. discussion 109-110

    Article  CAS  PubMed  Google Scholar 

  48. Coakley FV, Kurhanewicz J, Lu Y, Jones KD, Swanson MG, Chang SD, et al. Prostate cancer tumor volume: measurement with endorectal MR and MR spectroscopic imaging. Radiology. 2002;223:91–97.

    Article  PubMed  Google Scholar 

  49. Turkbey B, Mani H, Aras O, Rastinehad AR, Shah V, Bernardo M, et al. Correlation of magnetic resonance imaging tumor volume with histopathology. J Urol. 2012;188:1157–63.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Harvey H, Orton MR, Morgan VA, Parker C, Dearnaley D, Fisher C, et al. Volumetry of the dominant intraprostatic tumour lesion: intersequence and interobserver differences on multiparametric MRI. Br J Radiol. 2017;90:20160416.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Zheng X, He B, Hu Y, Ren M, Chen Z, Zhang Z, et al. Diagnostic accuracy of deep learning and radiomics in lung cancer staging: a systematic review and meta-analysis. Front Public Health. 2022;10:938113.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Li L, Zhang J, Zhe X, Tang M, Zhang X, Lei X, et al. A meta-analysis of MRI-based radiomic features for predicting lymph node metastasis in patients with cervical cancer. Eur J Radiol. 2022;151:110243.

    Article  PubMed  Google Scholar 

  53. Bedrikovetski S, Dudi-Venkata NN, Kroon HM, Seow W, Vather R, Carneiro G, et al. Artificial intelligence for pre-operative lymph node staging in colorectal cancer: a systematic review and meta-analysis. BMC Cancer. 2021;21:1058.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Calabrese A, Santucci D, Landi R, Beomonte Zobel B, Faiella E, de Felice C. Radiomics MRI for lymph node status prediction in breast cancer patients: the state of art. J Cancer Res Clin Oncol. 2021;147:1587–97.

    Article  PubMed  Google Scholar 

  55. Pesapane F, Rotili A, Agazzi GM, Botta F, Raimondi S, Penco S, et al. Recent radiomics advancements in breast cancer: lessons and pitfalls for the next. Future Curr Oncol. 2021;28:2351–72.

    Article  PubMed  Google Scholar 

  56. Fiz F, Jayakody Arachchige VS, Gionso M, Pecorella I, Selvam A, Wheeler DR, et al. Radiomics of biliary tumors: a systematic review of current evidence. Diagnostics. 2022;12:4.

    Article  Google Scholar 

  57. Giannitto C, Mercante G, Ammirabile A, Cerri L, De Giorgi T, Lofino L, et al. Radiomics-based machine learning for the diagnosis of lymph node metastases in patients with head and neck cancer: systematic review. Head Neck. 2023;45:482–91.

    Article  PubMed  Google Scholar 

  58. Fiori C, Checcucci E, Stura I, Amparore D, De Cillis S, Piana A, et al. Development of a novel nomogram to identify the candidate to extended pelvic lymph node dissection in patients who underwent mpMRI and target biopsy only. Prostate Cancer Prostatic Dis. 2023;26:388–94.

    Article  PubMed  Google Scholar 

  59. Elsholtz FHJ, Asbach P, Haas M, Becker M, Beets-Tan RGH, Thoeny HC, et al. Introducing the node reporting and data system 1.0 (Node-RADS): a concept for standardized assessment of lymph nodes in cancer. Eur Radiol. 2021;31:6116–24.

    Article  PubMed  PubMed Central  Google Scholar 

  60. Lucciola S, Pisciotti ML, Frisenda M, Magliocca F, Gentilucci A, Del Giudice F, et al. Predictive role of node-rads score in patients with prostate cancer candidates for radical prostatectomy with extended lymph node dissection: comparative analysis with validated nomograms. Prostate Cancer Prostatic Dis. 2023;26:379–87.

    Article  PubMed  Google Scholar 

  61. Lombardo R, De Nunzio C. Nomograms in PCa: where do we stand. Prostate Cancer Prostatic Dis. 2023; https://doi.org/10.1038/s41391-023-00642-w.

Download references

Author information

Authors and Affiliations

Authors

Contributions

Conceptualization: ZX; Methodology: HW; Formal analysis and investigation: JS; Writing original draft preparation: HW; Writing review and editing: HW; Supervision: JW, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Ji Wu.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, H., Xia, Z., Xu, Y. et al. The predictive value of machine learning and nomograms for lymph node metastasis of prostate cancer: a systematic review and meta-analysis. Prostate Cancer Prostatic Dis 26, 602–613 (2023). https://doi.org/10.1038/s41391-023-00704-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41391-023-00704-z

This article is cited by

Search

Quick links