Indian Journal of Cancer
Home  ICS  Feedback Subscribe Top cited articles Login 
Users Online :441
Small font sizeDefault font sizeIncrease font size
Navigate here
Resource links
 »  Similar in PUBMED
 »  Search Pubmed for
 »  Search in Google Scholar for
 »Related articles
 »  Article in PDF (499 KB)
 »  Citation Manager
 »  Access Statistics
 »  Reader Comments
 »  Email Alert *
 »  Add to My List *
* Registration required (free)  

  In this article
 »  Abstract
 » Introduction
 »  Materials and Me...
 » Results
 » Discussion
 » Conclusions
 »  References
 »  Article Figures
 »  Article Tables

 Article Access Statistics
    PDF Downloaded326    
    Comments [Add]    
    Cited by others 7    

Recommend this journal


  Table of Contents  
Year : 2016  |  Volume : 53  |  Issue : 4  |  Page : 595-599

Second primary malignancy: A retrospective analysis report from a tertiary cancer center of North India

Department of Radiation Oncology, VMMC and Safdarjung Hospital, New Delhi, India

Date of Web Publication21-Apr-2017

Correspondence Address:
D Sharma
Department of Radiation Oncology, VMMC and Safdarjung Hospital, New Delhi
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijc.IJC_542_16

Rights and Permissions

 » Abstract 

AIM OF STUDY: We analyzed the data of second primary malignancy (SPM) from one of the tertiary cancer centers of North India, and the basic aim was to retrieve incidence, prognosis, and outcomes. MATERIALS AND METHODS: A retrospective study was conducted in the Department of Radiation Oncology in a tertiary cancer center between January 1, 2011, and December 31, 2015. A total of 6000 cases of cancer were analyzed, out of which cases who presented with histological proven synchronous SPM were included in this study. RESULTS: The present study showed three cases (8.1%) of SPM who are attributed to field carcinogenesis. There were five cases in which metachronous malignancy develops in the previous radiation therapy field. There is 26% of synchronous malignancy as compared to 74% of metachronous malignancy. In the present study, most diagnosed synchronous malignancies were carcinoma breast, while in metachronous malignancies, carcinoma breast and gynecological cancers were most common. CONCLUSIONS: SPMs are not very rare. Hence, pretreatment and follow-up evaluation should be meticulous to rule out SPMs.

Keywords: Field carcinogenesis, metachronous, second primary malignancy, synchronous

How to cite this article:
Sharma D, Singh G, Kakkar N, Raj S. Second primary malignancy: A retrospective analysis report from a tertiary cancer center of North India. Indian J Cancer 2016;53:595-9

How to cite this URL:
Sharma D, Singh G, Kakkar N, Raj S. Second primary malignancy: A retrospective analysis report from a tertiary cancer center of North India. Indian J Cancer [serial online] 2016 [cited 2022 Dec 3];53:595-9. Available from:

 » Introduction Top

The incidence of double malignancy is not uncommon.[1],[2],[3] Bugher in 1934 analyzed cases of double primary malignancies and derived an equation for the probability of death during a specified period with a new second malignancy.[4]

The second primary malignancy (SPM) is defined as a second de novo malignant neoplasm with known cancer. An SPM can be synchronous or metachronous. Warren and Gates first gave the criteria used for the diagnosis of SPM.

Warren and Gates criteria for diagnosis of multiple primary malignancies are as follows.[5]

  1. Each of the tumors must be malignant, each confirmed by histology
  2. Each must be geographically separate and distinct. The lesions should be separated by normal mucosa
  3. Probability of one being the metastasis of the other must be excluded.

An SPM can be synchronous or metachronous. When the SPM is diagnosed within 6 months of the primary tumor, it is known as synchronous malignancy and the term metachronous is used when the SPM is diagnosed more than 6 months after the diagnosis of the primary tumor.[6] In literature, data regarding the occurrence and the outcome of SPM from the Indian subcontinent are limited. Hence, we present the data of SPM from one of the tertiary cancer centers from North India with a review of relevant literature.

 » Materials and Methods Top

We conducted a retrospective observational study in the Department of Radiation Oncology in a tertiary cancer center between January 1, 2011, and December 31, 2015. A total of 6000 cases of cancer were analyzed, out of which cases who presented with histological proven synchronous and metachronous primary as per the Warren and Gates criteria were included in the study. Time interval which was taken to differentiate between synchronous and metachronous malignancies was 6 months.[7],[8],[9] Details such as age of diagnosis of each tumor, sex, any family history, site of origin, histopathological and radiological imaging, whether the tumor was synchronous or metachronous, clinical staging, treatment received by patient, and status at last follow-up were recorded.

 » Results Top

During a period of 5 years between January 1, 2011, and December 31, 2015, total of 6000 patients were registered, out of which 38 patients presented either with metachronous malignancy or with synchronous malignancy. In the present study, one patient presented with synchronous malignancy (carcinoma breast and urinary bladder cancer) and developed carcinoma cervix IIB after 7 years at as metachronous malignancy.

The most common site of primary malignancy is carcinoma breast (11 cases), followed by head and neck squamous cell carcinoma (HNSCC) (10 cases) [Figure 1] and [Figure 2].
Figure 1: Site distribution of primary malignancy

Click here to view
Figure 2: Site distribution of second malignancy

Click here to view

Synchronous malignancy

A total of ten cases were diagnosed with synchronous malignancy. Out of these ten cases of synchronous malignancy, five were male and five were female. Median age of diagnosis was 58 years (range, 28–85 years) [Table 1].
Table 1: Summary of synchronous malignancy

Click here to view

Metachronous malignancy

A total of 29 cases were diagnosed with metachronous malignancy. Male-female ratio is 0.75. The median age for the primary tumor was 52 years (range, 25–76 years) and that for the metachronous malignancy was 59 years (range, 27–80 years). The median time interval between the primary and secondary malignancy was 5.5 years (range, 1–16 years) [Table 2].
Table 2: Summary of metachronous malignancy

Click here to view

 » Discussion Top

The incidence of SPM is not uncommon; it is common for the last 100 years.[6] The etiopathology of SPM can either be various genetic events or common environmental risk factor.[3] SPMs have been associated with DNA microsatellite instability, for example, Lynch I and Lynch II syndromes.[10] Carcinoma of breast, esophagus, and soft tissue has been associate with mutation in tumor suppressor genes such as p16, p53, PTEN, and Rb gene.[11]

It has been found that the cumulative lifetime risk of SPM in HNSCC is 36%.[9] This has been attributed to field carcinogenesis in response to exposure to risk factors such as tobacco, smoking, and alcohol consumption.[9],[12] In our study, there are three cases (8.1%) in which SPM is attributed to field carcinogenesis. Another cause of SPM is ionizing radiation.[13] Various studies have shown that the risk of lung cancer, sarcoma increases with a radiation dose above 5 Gy. Such type of cancer usually occurs in the prior radiation field and usually after a latent period of ten or more years.[14],[15],[16] In the present study, there are five cases in which metachronous malignancy develops in the previous radiation therapy field [Table 3].
Table 3: List of second primary malignancy in the irradiated field

Click here to view

SPM can occur at any age. Various studies done so far revealed that it is more common in old age.[17],[18],[19],[20],[21] In the present study, the median age at the time of second tumor diagnosis is 59 years and 70% of patients with SPM were more than 50 years of age. In the reviewed literature, male/female ratio varies between 0.9 and 3.5, with male predominance.[20],[22],[23] In the present study, the male: female ratio is 0.85.

The ratio of synchronous to metachronous malignancies differs in different studies. In a study by Aydiner et al., synchronous malignancy was 34% as compared to metachronous malignancy which was 66%.[19] Flannery et al. reported 20% of synchronous and 80% of metachronous tumors in their SPM series.[24] In the present study, there are 26% of synchronous malignancy as compared to 74% of metachronous malignancy. Usually, synchronous SPMs are seen in genitourinary and gastrointestinal systems.[25],[26] In the present study, most diagnosed synchronous malignancies were carcinoma breast; in metachronous malignancies, carcinoma breast and gynecological cancers were most common.

As per the SEER data results (1973–2003), the most common primary cancers in patients with SPM are breast carcinoma, prostate carcinoma, respiratory system and lung cancers, colorectal cancer, and urinary system cancers.[27] In the present study, the most common primary tumors were carcinoma breast, HNSCC, gynecological cancers, gastrointestinal tract (GIT) malignancy In males, most common primary malignancies were HNSCC, GIT malignancy, and genitourinary malignancy and that in female were carcinoma breast and gynecological cancers. In other studies, most common tumors were carcinoma larynx, lung cancer, and breast cancer.[20],[22],[28]

The possibility of SPM must always be considered while pretreatment evaluation. For early detection of SPM, screening procedures are useful, and this in turn will improve the outcome of the patients with SPM. However, the optimal screening modalities and strategies to reduce mortality from SPM remain to be defined for most tumor sites.[29]

 » Conclusions Top

SPM is not uncommon. It manifests either as synchronous or metachronous malignancy. The early diagnosis of SPM should not be missed during follow-up. And also, during follow-up, cancer patients should be informed the role of preventive medicine and encourage use of screening methods.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

 » References Top

Vaslamatzis M, Alevizopoulos N, Petraki C. Second primary neoplasms (SPN) in cancer patients. Proc ASCO 2003;22:3581.  Back to cited text no. 1
Morgenfeld EL, Tognelli GF, Deza E, Santillan D, Ares S. Synchronous and metachronous second (ST) and third (TT) primary tumors in a large patient population. Proc ASCO 2003;22:3152.  Back to cited text no. 2
Irimie A, Achimas-Cadariu P, Burz C, Puscas E. Multiple primary malignancies–epidemiological analysis at a single tertiary institution. J Gastrointestin Liver Dis 2010;19:69-73.  Back to cited text no. 3
Bugher JC. The probability of the chance of accurence of multiple malignant neoplasms. Am J Cancer 1934;21:2309-824.  Back to cited text no. 4
Warren S, Gates O. Multiple primary malignant tumors: A survey of the literature and statistical study. Am J Cancer 1932;16:1358-414.  Back to cited text no. 5
Vaamonde P, Martín C, del Río M, LaBella T. Second primary malignancies in patients with cancer of the head and neck. Otolaryngol Head Neck Surg 2003;129:65-70.  Back to cited text no. 6
Suzuki T, Takahashi H, Yao K, Inagi K, Nakayama M, Makoshi T, et al. Multiple primary malignancies in the head and neck: A clinical review of 121 patients. Acta Otolaryngol Suppl 2002;547:88-92.  Back to cited text no. 7
Morris LG, Sikora AG, Patel SG, Hayes RB, Ganly I. Second primary cancers after an index head and neck cancer: Subsite-specific trends in the era of human papillomavirus-associated oropharyngeal cancer. J Clin Oncol 2011;29:739-46.  Back to cited text no. 8
Cheng HY, Chu CH, Chang WH, Hsu TC, Lin SC, Liu CC, et al. Clinical analysis of multiple primary malignancies in the digestive system: A hospital-based study. World J Gastroenterol 2005;11:4215-9.  Back to cited text no. 9
Horii A, Han HJ, Shimada M, Yanagisawa A, Kato Y, Ohta H, et al. Frequent replication errors at microsatellite loci in tumors of patients with multiple primary cancers. Cancer Res 1994;54:3373-5.  Back to cited text no. 10
Kimura K, Shinmura K, Hasegawa T, Beppu Y, Yokoyama R, Yokota J. Germline p53 mutation in a patient with multiple primary cancers. Jpn J Clin Oncol 2001;31:349-51.  Back to cited text no. 11
Morris LG, Sikora AG, Hayes RB, Patel SG, Ganly I. Anatomic sites at elevated risk of second primary cancer after an index head and neck cancer. Cancer Causes Control 2011;22:671-9.  Back to cited text no. 12
Jablon C. Epidemiologic perspectives in radiation carcinogenesis. In: Boice JD Jr., editors. Radiation Carcinogenesis: Epidemiology and Biological Significance. New York: Raven Press, International Agency; 1994. p. 1-8.  Back to cited text no. 13
Gilbert ES, Stovall M, Gospodarowicz M, Van Leeuwen FE, Andersson M, Glimelius B, et al. Lung cancer after treatment for Hodgkin's disease: Focus on radiation effects. Radiat Res 2003;159:161-73.  Back to cited text no. 14
Rubino C, Shamsaldin A, Lê MG, Labbé M, Guinebretière JM, Chavaudra J, et al. Radiation dose and risk of soft tissue and bone sarcoma after breast cancer treatment. Breast Cancer Res Treat 2005;89:277-88.  Back to cited text no. 15
Travis LB, Gospodarowicz M, Curtis RE, Clarke EA, Andersson M, Glimelius B, et al. Lung cancer following chemotherapy and radiotherapy for Hodgkin's disease. J Natl Cancer Inst 2002;94:182-92.  Back to cited text no. 16
Hajdu SI, Hajdu EO. Multiple primary malignant tumors. J Am Geriatr Soc 1968;16:16-26.  Back to cited text no. 17
Berge T, Cederqvist L, Schönebeck J. Multiple primary malignant tumours. An autopsy study of a circumscribed population. Acta Pathol Microbiol Scand 1969;76:171-83.  Back to cited text no. 18
Aydiner A, Karadeniz A, Uygun K, Tas S, Tas F, Disci R, et al. Multiple primary neoplasms at a single institution: Differences between synchronous and metachronous neoplasms. Am J Clin Oncol 2000;23:364-70.  Back to cited text no. 19
Lee TK, Barringer M, Myers RT, Sterchi JM. Multiple primary carcinomas of the colon and associated extracolonic primary malignant tumors. Ann Surg 1982;195:501-7.  Back to cited text no. 20
Vyas JJ, Deshpande RK, Sharma S, Desai PB. Multiple primary cancers in Indian population: Metachronous and synchronous lesions. J Surg Oncol 1983;23:239-49.  Back to cited text no. 21
Lee TK, Myers RT, Scharyj M, Marshall RB. Multiple primary malignant tumors (MPMT): Study of 68 autopsy cases (1963-1980). J Am Geriatr Soc 1982;30:744-53.  Back to cited text no. 22
Gursel B, Meydan D, Özbek N, Ozdemir O, Odabas E. Multiple primary malignant neoplasms from the black sea region of Turkey. J Int Med Res 2011;39:667-74.  Back to cited text no. 23
Flannery JT, Boice JD Jr., Devesa SS, Kleinerman RA, Curtis RE, Fraumeni JF Jr. Cancer registration in Connecticut and the study of multiple primary cancers, 1935-1982. Natl Cancer Inst Monogr 1985;68:13-24.  Back to cited text no. 24
Balat O, Kudelka AP, Ro JY, Edwards CL, Balbay D, Dinney C, et al. Two synchronous primary tumors of the ovary and kidney: A case report. Eur J Gynaecol Oncol 1996;17:257-9.  Back to cited text no. 25
Ozturk MA, Dane F, Kaygusuz I, Asmaz O, Uzay A, Bayik M, et al. Synchronous renal cell carcinoma and multiple myeloma: Report of two cases and review of the literature. J BUON 2009;14:511-4.  Back to cited text no. 26
Hayat MJ, Howlader N, Reichman ME, Edwards BK. Cancer statistics, trends, and multiple primary cancer analyses from the Surveillance, Epidemiology, and End Results (SEER) program. Oncologist 2007;12:20-37.  Back to cited text no. 27
Engin K. Cancers in multiple primary sites. Int Surg 1994;79:33-7.  Back to cited text no. 28
Vogel VG. Identifying and screening patients at risk of second cancers. Cancer Epidemiol Biomarkers Prev 2006;15:2027-32.  Back to cited text no. 29


  [Figure 1], [Figure 2]

  [Table 1], [Table 2], [Table 3]

This article has been cited by
1 Synchronous renal cell carcinoma and urothelial carcinoma in a female: A rare case
Srilata Chitti, Arvind Ahuja, Sumit Gahlawat, RaviHari Phulware
Journal of Medical Evidence. 2022; 3(2): 155
[Pubmed] | [DOI]
2 The First Literature Case Report: Synchronous Squamous Cell Carcinoma of Esophagus and Adenocarcinoma of Gallbladder
Gautam Sarma, Jyotiman Nath, Shiraj Ahmed, Partha Sarathi Roy, Gaurav Das
Journal of Gastrointestinal Cancer. 2021; 52(3): 1159
[Pubmed] | [DOI]
3 Definitive radiotherapy in patients of synchronous esophageal and head and neck cancer-treatment outcome and toxicity
Gautam Sarma, Jyotiman Nath, Partha P Medhi, Faridha J Momin, Apurba K Kalita, Mouchumee Bhattacharyya
Cancer Treatment and Research Communications. 2020; 25: 100248
[Pubmed] | [DOI]
4 Triple Metachronous Malignancies with Thyroid Involvement: A Brief Overview of Five Case Reports over 20 Years of Institutional Experience
Marius-Ioan Badan, Doina Piciu
Diagnostics. 2020; 10(3): 168
[Pubmed] | [DOI]
5 Second primary malignancies in patients with radiotherapy-treated laryngeal carcinoma - A commentary
Deepti Sharma,Neha Sharma,Vineeta Goel
Indian Journal of Cancer. 2019; 56(1): 35
[Pubmed] | [DOI]
6 The Conundrum of Dual Primary Malignancies: Four Years’ Experience of a Single Tertiary Care Institute in India
Niharika Bisht, Sankalp Singh, Arti Sarin, Samir Gupta, Harinder Pal Singh, Amul Kapoor, Deepak Mulajker, Richa Joshi, Abhishek Purkayastha, Prabha Shankar Mishra, Divya Shelly
Indian Journal of Medical and Paediatric Oncology. 2019; 40(04): 521
[Pubmed] | [DOI]
7 Multiple Primary Malignancies of Cancer of Ovary and Cervix in A Young Woman: A Rare Case Report
Sangeeta Pankaj,Anjili Kumari,Syed Nazneen,Jaya Kumari,Vijayanand Choudhary,Anita Kmari
Indian Journal of Gynecologic Oncology. 2018; 16(2)
[Pubmed] | [DOI]


Print this article  Email this article


  Site Map | What's new | Copyright and Disclaimer | Privacy Notice
  Online since 1st April '07
  © 2007 - Indian Journal of Cancer | Published by Wolters Kluwer - Medknow