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18F-FDG PET/CT as a prognostic factor in penile cancer

  • André Salazar
  • Eduardo Paulino Júnior
  • Paulo Guilherme O. Salles
  • Raul Silva-Filho
  • Edna A. Reis
  • Marcelo MamedeEmail author
Original Article

Abstract

Purpose

Penile cancer (PC) is a rare neoplasm with an aggressive behavior and variable prognosis. Lymph node (LN) involvement and pathological features of the primary lesion have been proven to be the most important survival factors. Positron emission tomography/computed tomography with fluorodeoxyglucose labelled with fluorine-18 (18F-FDG PET/CT) provides information on tumor staging and works as a prognostic factor, with promising results in other carcinomas. The aim of the present study is to evaluate PET/CT as a prognostic factor in PC.

Methods

Fifty-five patients (mean age 56.6 y) diagnosed with penile squamous cell carcinoma were prospectively evaluated from 2012 to 2014. All subjects underwent 18F-FDG PET/CT before treatment and were regularly followed after surgery.

Results

Out of the 53 patients selected, 17 (32.1%) had localized disease (cT1–2) and 24 (45.3%) had palpable nodes (cN+). Partial penile amputation was performed in 38 patients (71.7%) and inguinal lymphadenectomy (LND) in 30 (56.6%). From the LND group, 16 (53.3%) presented with positive neoplastic cells (pN+). Patients with more aggressive disease had a significantly (p = 0.019) higher 18F-FDG tumor uptake (pSUVmax), while inguinal LN uptake (nSUVmax) was able to recognize metastatic LN (p = 0.039). Some pathological prognostic features, when presented, have shown significant changes in pSUVmax values. Receiver operating characteristic (ROC) curves were performed and specific cutoff values of pSUVmax were evaluated to determine sensitivity and specificity. Regarding regional LNs, PET/CT presented a 76.2% accuracy in cN+ patients. After a 39-month follow up, pSUVmax of 16.6 (p = 0.0001) and nSUVmax of 6.5 (p = 0.019) were established as the ideal values to predict cancer-specific survival. The multivariate analysis confirmed nSUVmax as a predictor for LN metastasis (p = 0.043) and pSUVmax as a mean to estimate survival rate (p = 0.05).

Conclusion

This study showed promising results on the use of 18F-FDG PET/CT as a prognostic tool for PC, using specific cutoff values of pSUVmax and nSUVmax.

Keywords

18F-FDG PET/CT Penile cancer Prognostic value Survival 

Notes

Acknowledgments

The authors thank Rodrigo Corradi, M.D., and Sofia Lage for the text revision.

Compliance with ethical standards

The authors declare no conflict of interest. All procedures performed in this study 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.

References

  1. 1.
  2. 2.
    Instituto Nacional do Câncer. 2018. http://www2.inca.gov.br/wps/wcm/connect/tiposdecancer/ site/home/penis. Accessed in 08/01/18.
  3. 3.
    Clark PE. National Comprehensive Cancer Network. Penile cancer: clinical practice guidelines in oncology. J Natl Compr Cancer Netw. 2013;11:594–615.CrossRefGoogle Scholar
  4. 4.
    Hakenberg OW. EAU guidelines on penile cancer: 2014 update. Eur Urol. 2017;67:142–50.CrossRefGoogle Scholar
  5. 5.
    Hughes B. Noninvasive and minimally invasive staging of regional lymph nodes in penile cancer. World J Urol. 2009;27:197–203.CrossRefGoogle Scholar
  6. 6.
    Zhu Y. Development and evaluation of a nomogram to predict inguinal lymph node metastasis in patients with penile cancer and clinically negative lymph nodes. J Urol. 2010;184:539–345.CrossRefGoogle Scholar
  7. 7.
    Wespes E. The management of regional lymph nodes in patients with penile carcinoma and reliability of sentinel node biopsy. Eur Urol. 2007;52:15–6.CrossRefGoogle Scholar
  8. 8.
    Gupta S. Emerging systemic therapies for the Management of Penile Cancer. Urol Clin N Am. 2016;10:1–11.Google Scholar
  9. 9.
    Rohren EM. Clinical applications of PET in oncology. Radiology. 2004;231:305–32.CrossRefGoogle Scholar
  10. 10.
    Ter-Pogossian MM. A positron-emission transaxial tomograph for nuclear imaging (PETT). Radiology. 1975;114:89–98.CrossRefGoogle Scholar
  11. 11.
    Toyokawa G. Elevated metabolic activity on 18F-FDG PET/CT is associated with the expression of EZH2 in non-small cell lung ca. Anticancer Res. 2017;37:1393–402.CrossRefGoogle Scholar
  12. 12.
    Shimizu M. Prognostic value of 2-[(18) F]fluoro-2-deoxy-d-glucose positron emission tomography for patients with oral squamous cell carcinoma treated with retrograde superselective intra-arterial chemotherapy and daily concurrent radiotherapy. Oral Surg Oral Med Oral Pathol Oral Radiol. 2016;121(3):239–47.CrossRefGoogle Scholar
  13. 13.
    Mamede M. FDG-PET/CT tumor segmentation-derived indices of metabolic activity to assess response to neoadjuvant therapy and progression-free survival in esophageal cancer: correlation with histopathology results. Am J Clin Oncol. 2007;30:377–88.CrossRefGoogle Scholar
  14. 14.
    Ravizzini G. Positron emission tomography detection of metastatic penile squamous cell carcinoma. J Urol. 2001;165:1633–4.CrossRefGoogle Scholar
  15. 15.
    Schlenker B. Detection of inguinal lymph node involvement in penile squamous cell carcinoma by 18F-fluorodeoxyglucose PET/CT: a prospective single-center study. Urol Oncol. 2012;30:55–9.CrossRefGoogle Scholar
  16. 16.
    Henkenberens C. 68Ga-PSMA ligand PET/CT-based radiotherapy for lymph node relapse of prostate Cancer after primary therapy delays initiation of systemic therapy. Anticancer Res. 2017;37:1273–80.CrossRefGoogle Scholar
  17. 17.
    Mena E. Value of Intratumoral metabolic heterogeneity and quantitative 18F-FDG PET/CT parameters to predict prognosis in patients with HPV-positive primary oropharyngeal squamous cell carcinoma. Clin Nucl Med. 2017;42(5):e227–34.CrossRefGoogle Scholar
  18. 18.
    Morgan DJ. Lean body mass as a predictor of drug dosage: implications for drug therapy. Clin Pharmacokinet. 1994;26:292–307.CrossRefGoogle Scholar
  19. 19.
    Sugawara Y. Reevaluation of the standardized uptake value for FDG: variations with body weight and methods for correction. Radiology. 1999;213:521–5.CrossRefGoogle Scholar
  20. 20.
    Moch H. Tumours of the penis. In: WHO classification of tumours of the urinary system and male genital organs. Lyon: IARC; 2016. p. 259–85.Google Scholar
  21. 21.
    Sobin LH. TNM classification of malignant Tumours. UICC International Union against Cancer. 7th ed. Hoboken: Wiley-Blackwell; 2009. p. 336.Google Scholar
  22. 22.
    Scher B, et al. 18F-FDG PET/CT for staging of penile cancer. J Nucl Med. 2005;46:1460–5.Google Scholar
  23. 23.
    Spiess PE. Current concepts in penile cancer. J Natl Compr Cancer Netw. 2013;11:617–24.CrossRefGoogle Scholar
  24. 24.
    Li J. Organ-sparing surgery for penile cancer: complications and outcomes. Urology. 2011;78:1121–4.CrossRefGoogle Scholar
  25. 25.
    Bozzini G. Role of penile doppler US in the preoperative assessment of penile squamous cell carcinoma patients: results from a large prospective multicenter European study. Urology. 2016;90:131–5.CrossRefGoogle Scholar
  26. 26.
    Ornellas AA. Prognostic factors in invasive squamous cell carcinoma of the penis: analysis of 196 patients treated at the Brazilian National Cancer Institute. J Urol. 2008;180:1354–9.CrossRefGoogle Scholar
  27. 27.
    Chaux A. The prognostic index: a useful pathologic guide for prediction of nodal metastases and survival in penile squamous cell carcinoma. Am J Surg Pathol. 2009;33(7):1049–57.CrossRefGoogle Scholar
  28. 28.
    Velazquez EF. Histologic grade and perineural invasion are more important than tumor thickness as predictor of nodal metastasis in penile squamous cell carcinoma invading 5 to 10 mm. Am J Surg Pathol. 2008;32(7):974–9.CrossRefGoogle Scholar
  29. 29.
    Cubilla AL. The role of pathologic prognostic factors in squamous cell carcinoma of the penis. World J Urol. 2009;27:166–9.CrossRefGoogle Scholar
  30. 30.
    Souillac I. Prospective evaluation of 18F-FDG PET/CT to assess inguinal lymph node status in invasive squamous cell carcinoma of the penis. J Urol. 2012;187:493–7.CrossRefGoogle Scholar
  31. 31.
    Jakobsen JK. DaPeCa-3: promising results of sentinel node biopsy combined with 18F-fluorodeoxyglucose positron emission tomography/computed tomography in clinically lymph node-negative patients with penile cancer - a national study from Denmark. BJU Int. 2015;28:1–10.Google Scholar
  32. 32.
    Van Westreenen HL. Systematic review of the staging performance of FDG PET in esophageal cancer. J Clin Oncol. 2004;18:3805–12.CrossRefGoogle Scholar
  33. 33.
    Sadeghi R. Accuracy of 18F-FDG PET/CT for diagnosing inguinal lymph node involvement in penile squamous cell carcinoma: systematic review and meta-analysis of the literature. Clin Nucl Med. 2012;37:436–41.CrossRefGoogle Scholar
  34. 34.
    Buonerba C. Prognostic and predictive factors in patients with advanced penile cancer receiving salvage (2nd or later line) systemic treatment: a retrospective, multi-center study. Front Pharm. 2016;7:487.CrossRefGoogle Scholar
  35. 35.
    Hwang SH. Prognostic value of pretreatment metabolic tumor volume and total lesion glycolysis using 18F-FDG PET/CT in patients with metastatic renal cell carcinoma treated with anti–vascular endothelial growth factor–targeted agents. Clin Nucl Med. 2017;42(5):e235–41.CrossRefGoogle Scholar
  36. 36.
    Chu KP. Prognostic value of metabolic tumor volume and velocity in predicting head-and-neck cancer outcomes. Int J Radiat Oncol Biol Phys. 2012;83(5):1521–7.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Urology SectionMario Penna InstituteBelo HorizonteBrazil
  2. 2.Pathology and Forensic Department, School of MedicineFederal University of Minas GeraisBelo HorizonteBrazil
  3. 3.Pathology SectionMario Penna InstituteBelo HorizonteBrazil
  4. 4.Anatomy and Imaging Department, School of MedicineFederal University of Minas GeraisBelo HorizonteBrazil
  5. 5.Statistics Department, Exact Science InstituteFederal University of Minas GeraisBelo HorizonteBrazil

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