Multiple primary tumors following stage II and III rectal cancer in patients receiving radiotherapy, 1998–2010

  • Julie Smith-Gagen
  • George A. GoodwinIII
  • Jonathan Tay
Original Article – Cancer Research



This report investigated the impact of radiation therapy among stage II/III rectal cancer patients who were resected for cure and then developed second primary cancer.


The analysis included patients diagnosed with rectal cancer from 1992 to 2010 and who were registered in the National Cancer Institute’s Surveillance, Epidemiology and End Results database. Standardized incidence ratios assessed the location of second primary cancers by the receipt and sequence of radiation therapy. A Cox proportional hazards model examined the predictors for patients who developed second primary cancers.


The hazard ratio for developing any type of second primary was 12 % higher in patients receiving preoperative radiotherapy, Hazard Ratio and 95 % confidence interval, HR 95 % CI 1.12 (1.0, 1.2), and 33 % lower for patients receiving postoperative radiotherapy, HR 95 % CI 0.75 (0.7, 0.8), relative to patients who did not receive radiation therapy. The location of the second cancer varied by both the receipt and sequence of radiation therapy. Secondary rectal cancers were reduced 170 % after postoperative radiation and 103 % after preoperative radiation, compared to the non-receipt of radiation therapy. The impact of radiation therapy on secondary colon cancers was not as marked. Rectal cancer patients undergoing radiation therapy are at a higher risk of thyroid cancers and leukemia, but males have a lower risk of prostate cancer.


While preoperative radiation therapy is advantageous for reducing rectal cancer recurrence, this study identifies advantages of postoperative radiation for reducing second primary cancers. This research will help improve recommendations for postdiagnosis surveillance in patients with rectal cancer.


Rectal cancer Second primary cancer Radiation therapy National Cancer Institute SEER 


  1. Aarnio M, Sankila R, Pukkala E, Salovaara R, Aaltonen LA, de la Chapelle A, Peltomäki P, Mecklin JP, Järvinen HJ (1999) Cancer risk in mutation carriers of DNA-mismatch-repair genes. Int J Cancer 81(2):214–218PubMedCrossRefGoogle Scholar
  2. Abern MR, Dude AM, Tsivian M, Coogan CL (2013) The characteristics of bladder cancer after radiotherapy for prostate cancer. Urol Oncol 31(8):1628–1634PubMedCrossRefGoogle Scholar
  3. American Cancer Society (2013) Cancer facts & figures 2013. American Cancer Society, AtlantaGoogle Scholar
  4. Baxter NN, Tepper JE, Durham SB, Rothenberger DA, Virnig BA (2005) Increased risk of rectal cancer after prostate radiation: a population-based study. Gastroenterology 128(4):819–824PubMedCrossRefGoogle Scholar
  5. Benson AB III, Bekaii-Saab T, Chan E et al (2012) Rectal cancer. J Natl Compr Cancer Netw 10:1528–1564Google Scholar
  6. Bergfeldt K, Silfverswärd C, Einhorn S, Hall P (2000) Overestimated risk of second primary malignancies in ovarian cancer patients. Eur J Cancer 36(1):100–105PubMedCrossRefGoogle Scholar
  7. Birgisson H, Påhlman L, Gunnarsson U, Glimelius B (2005) Occurrence of second cancers in patients treated with radiotherapy for rectal cancer. J Clin Oncol 23(25):6126–6131PubMedCrossRefGoogle Scholar
  8. Bosset JF (2006) Distal rectal cancer: sphincter-sparing is also a challenge for the radiation oncologist. Radiother Oncol 80(1):1–3PubMedCrossRefGoogle Scholar
  9. Bujko K, Nowacki MP, Nasierowska-Guttmejer A et al (2004) Sphincter preservation following pre-operative radiotherapy for rectal cancer: report of a randomized trial comparing short-term radiotherapy vs conventionally fractionated radiochemotherapy. Radiother Oncol 72:15–24Google Scholar
  10. Cress RD, Zaslavsky AM, West DW, Wolf RE, Felter MC, Ayanian JZ (2003) Completeness of information on adjuvant therapies for colorectal cancer in population-based cancer registries. Med Care 41:1006–1012PubMedCrossRefGoogle Scholar
  11. Dong C, Hemminki K (2001) Second primary neoplasms among 53 159 haematolymphoproliferative malignancy patients in Sweden, 1958–1996: a search for common mechanisms. Br J Cancer 85(7):997–1005PubMedCentralPubMedCrossRefGoogle Scholar
  12. Edge SB, Byrd DR, Compton CC et al (eds) (2009) American joint committee on cancer staging manual, 7th edn. Springer, New YorkGoogle Scholar
  13. Fast stats: an interactive tool for access to SEER cancer statistics. Surveillance Research Program, National Cancer Institute. Accessed 6 Dec 2013
  14. Fitzgerald TL, Zervos E, Wong JH (2013) Patterns of pelvic radiotherapy in patients with Stage II/III rectal cancer. J Cancer Epidemiol 2013:408–460CrossRefGoogle Scholar
  15. Hemminki K, Li X, Dong C (2001) Second primary cancers after sporadic and familial colorectal cancer. Cancer Epidemiol Biomark Prev 10:793–798Google Scholar
  16. Hiotis SP, Weber SM, Cohen AM et al (2002) Assessing the predictive value of clinical complete response to neoadjuvant therapy for rectal cancer: an analysis of 488 patients. J Am Coll Surg 194:131–136PubMedCrossRefGoogle Scholar
  17. Howlader N, Noone AM, Krapcho M, Garshell J, Neyman N, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z, Cho H, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds) (2013) SEER cancer statistics review, 1975–2010, National Cancer Institute. Bethesda, MD. Accessed 2 Dec 2013
  18. Johnson C, Peace S, Adamo P, Fritz A, Percy-Laurry A, Edwards BK (2007) The 2007 multiple primary and histology coding rules. National Cancer Institute, BethesdaGoogle Scholar
  19. Koontz MZ, Horning SJ, Balise R, Greenberg PL, Rosenberg SA, Hoppe RT, Advani RH (2013) Risk of therapy-related secondary leukemia in Hodgkin lymphoma: the Stanford University experience over three generations of clinical trials. J Clin Oncol 31(5):592–598PubMedCentralPubMedCrossRefGoogle Scholar
  20. Krieger N, Chen JT, Waterman PD, Soobader MJ, Subramanian SV, Carson R (2002) Geocoding and monitoring of US socioeconomic inequalities in mortality and cancer incidence: does the choice of area-based measure and geographic level matter?: the Public Health Disparities Geocoding Project. Am J Epidemiol 156:471–482PubMedCrossRefGoogle Scholar
  21. Lachin JM (2000) Biostatistical methods: the assessment of relative risks. Wiley, New YorkCrossRefGoogle Scholar
  22. Lichtenstein P, Holm NV, Verkasalo PK, Iliadou A, Kaprio J, Koskenvuo M, Pukkala E, Skytthe A, Hemminki K (2000) Environmental and heritable factors in the causation of cancer—analyses of cohorts of twins from Sweden, Denmark, and Finland. N Engl J Med 343(2):78–85PubMedCrossRefGoogle Scholar
  23. Maul JS, Warner NR, Kuwada SK, Burt RW, Cannon-Albright LA (2006) Extracolonic cancers associated with hereditary nonpolyposis colorectal cancer in the Utah Population Database. Am J Gastroenterol 101(7):1591–1596PubMedCrossRefGoogle Scholar
  24. Meyer JE, Narang T, Schnoll-Sussman FH, Pochapin MB, Christos PJ, Sherr DL (2010) Increasing incidence of rectal cancer in patients aged younger than 40 years: an analysis of the surveillance, epidemiology, and end results database. Cancer 116(18):4354–4359PubMedCentralPubMedCrossRefGoogle Scholar
  25. National Cancer Institute: PDQ® Colon Cancer Treatment (2013a) Bethesda, MD: National Cancer Institute. Accessed 6 Dec 2013
  26. National Cancer Institute: PDQ® Rectal Cancer Treatment (2013b) Bethesda, MD: National Cancer Institute. Accessed 6 Dec 2013
  27. National Comprehensive Cancer Network Practice Guidelines in Oncology 2010 (2011) Accessed 6 Dec 2013
  28. Phipps AI, Chan AT, Ogino S (2013) Anatomic subsite of primary colorectal cancer and subsequent risk and distribution of second cancers. Cancer 119:3140–3147PubMedCrossRefGoogle Scholar
  29. Raj KP, Taylor TH, Wray C, Stamos MJ, Zell JA (2011) Risk of second primary colorectal cancer among colorectal cancer cases: a population-based analysis. J Carcinog 17(10):6Google Scholar
  30. Ron E (2003) Cancer risks from medical radiation. Health Phys 85(1):47–59PubMedCrossRefGoogle Scholar
  31. Sauer R, Becker H, Hohenberger W et al (2004) Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 351:1731–1740PubMedCrossRefGoogle Scholar
  32. Sauer R, Liersch T, Merkel S et al (2012) Preoperative versus postoperative chemoradiotherapy for locally advanced rectal cancer: results of the German CAO/ARO/AIO-94 randomized phase III trial after a median follow-up of 11 years. J Clin Oncol 30:1926–1933PubMedCrossRefGoogle Scholar
  33. Sawka AM, Thabane L, Parlea L, Ibrahim-Zada I, Tsang RW, Brierley JD, Straus S, Ezzat S, Goldstein DP (2009) Second primary malignancy risk after radioactive iodine treatment for thyroid cancer: a systematic review and meta-analysis. Thyroid 19(5):451–457PubMedCrossRefGoogle Scholar
  34. Schonfeld SJ, Lee C, Berrington de González A (2011) Medical exposure to radiation and thyroid cancer. Clin Oncol (R Coll Radiol) 23(4):244–250CrossRefGoogle Scholar
  35. Surveillance, Epidemiology, and End Results (SEER) Program. SEER*Stat Database: Incidence—SEER 9 Regs Research Data, November 2012 submission, Vintage 2009 Populations (1992–2010) <Katrina/Rita Population Adjustment> Linked to County Attributes—Total US, 1969-2010 Counties. Bethesda, MD: National Cancer Institute, Surveillance Research Program, Cancer Statistics Branch; released April 2012, based on the November 2012 submission. Accessed 7 Dec 2013
  36. Swedish Rectal Cancer Trial (1997) Improved survival with preoperative radiotherapy in resectable rectal cancer. N Engl J Med 336:980–987CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Julie Smith-Gagen
    • 1
  • George A. GoodwinIII
    • 1
  • Jonathan Tay
    • 2
    • 3
  1. 1.School of Community Health SciencesUniversity of NevadaRenoUSA
  2. 2.Saint Mary’s Center for CancerRenoUSA
  3. 3.Reno CyberKnifeRenoUSA

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