Cancer Epidemiology 39 (2015) 842–847

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Trends in incidence and survival for anal cancer in New South Wales, Australia, 1972–2009 Matthew J. Soeberga,* , Kris Rogersa , David C. Currowb , Jane M. Younga,c a b c

Cancer Epidemiology and Services Research (CESR), Sydney School of Public Health, Sydney Medical School, University of Sydney, NSW, Australia Cancer Institute NSW, Australia Surgical Outcomes Research Centre (SOuRCe), Sydney Local Health District and University of Sydney, NSW, Australia

A R T I C L E I N F O

A B S T R A C T

Article history: Received 25 May 2015 Received in revised form 1 October 2015 Accepted 7 October 2015 Available online 24 October 2015

Introduction: Little is known about the incidence and survival of anal cancer in New South Wales (NSW), Australia, as anal cancer cases are often grouped together with other colorectal cancers in descriptive epidemiological analyses. Methods: We studied patterns and trends in the incidence and survival of people diagnosed with anal cancer in NSW, Australia, 1972–2009 (n = 2724). We also predicted anal cancer incidence in NSW during 2010–2032. Given the human papilloma virus-associated aetiology for most anal cancers, we quantified these changes over time in incidence and survival by histological subtype: anal squamous cell carcinoma (ASCC); and anal adenocarcinoma (AAC). Results: There was a linear increase in incident anal cancer cases in NSW with an average annual percentage change (AAPC) of 1.6 (95% CI 1.1–2.0) such that, in combination with age-period-cohort modelling, we predict there will be 198 cases of anal cancer in the 2032 calendar year (95% CI 169–236). Almost all of these anal cancer cases are projected to be ASCC (94%). Survival improved over time regardless of histological subtype. However, five-year relative survival was substantially higher for people with ASCC (70% (95% CI 66–74%)) compared to AAC (51% (95% CI 43–59%)), a 37% difference. Survival was also greater for women (69% (95% CI 64–73%)) with ASCC compared to men (55% (95% CI 50– 60%)). It was not possible to estimate survival by stage at diagnosis particularly given that 8% of all cases were recorded as having distant stage and 22% had missing stage data. Interpretation: Aetiological explanations, namely exposure to oncogenic types of human papillomavirus, along with demographic changes most likely explain the actual and projected increase in ASCC case numbers. Survival differences by gender and histological subtype point to areas where further research is warranted to improve treatment and outcomes for all anal cancer patients. ã 2015 Elsevier Ltd. All rights reserved.

Keywords: Anal cancer Australia Squamous cell carcinoma Adenocarcinoma Incidence Relative survival

1. Introduction The incidence of anal cancer, a rare digestive tract malignant tumour located primarily in the anal canal, is strongly associated with exposure to oncogenic types of human papillomavirus [1]. Reported increases in incidence worldwide have led to greater clarity on the role that HPV plays in anal cancer aetiology including population subgroups at increased risk of disease [2–4], specifically that the aetiology of anal cancer is closer to that of other genital cancers compared to gastrointestinal malignancies. The most common histological subtype of anal cancer is anal squamous

* Corresponding author at: Cancer Epidemiology and Services Research (CESR), Level 6, The Lifehouse (C39Z), RPA Hospital, The University of Sydney, NSW 2006 Australia. Fax: +61 2 9515 3222. E-mail address: [email protected] (M.J. Soeberg). http://dx.doi.org/10.1016/j.canep.2015.10.008 1877-7821/ ã 2015 Elsevier Ltd. All rights reserved.

cell carcinoma (ASCC), estimated to comprise greater than 70% of all anal cancer cases [5]. ASCC is known to have substantially increased in a number of countries over the last fifty years [6–10]. Few studies have simultaneously published incidence data on ASCC and anal adenocarcinoma (AAC). An Australian study of anal cancer for people diagnosed during the 1987–2005 period show increases over time in both ASCC and AAC age-standardised incidence rates per 100,000 person-years [6]. However, the investigators of this study did not estimate the magnitude of any future increase in incidence over time or investigate survival differences by histological subtype. Compared to cancers of the colon and rectum [11,12], little is understood about the survival outcomes of anal cancer in New South Wales and in other jurisdictions. This is primarily due to the fact that anal cancer is a rare outcome making trend measurement and multivariate analyses computationally difficult with sparse

M.J. Soeberg et al. / Cancer Epidemiology 39 (2015) 842–847

data. For example, the investigators of a study of relative survival for anorectal cancers in England and Wales combined data for cancers of the rectum and anus allowing for larger datasets to be analysed in a more complex manner [13]. There is the potential to mask important differences in survival outcomes when, in this example, data for two anatomical sites were aggregated. Given improvements in anal cancer treatment over the last 20 years [5], it is timely to measure incidence and survival for anal cancer in NSW including by histological subtype. The aim of this study was to update incidence trends using more up-to-date cancer registration data, to predict the number of anal cancer cases in New South Wales (NSW) up to 2032, and to compare 5-year relative survival by histological subtype. We hypothesise that incidence for ASCC and AAC have increased over time. Similarly, 5-year survival has improved but that differences exist by sex and histological subtype. 2. Materials and methods 2.1. Data sources De-identified unit records for all unique cases of anal cancer diagnosed in NSW residents between 1972 and 2009 and notified to the NSW Cancer Registry were included. Operational details of the Registry have been published elsewhere [14]. Briefly, notifications to the Registry of invasive cancers are mandated under the NSW Public Health Act 2010. The study cohort was defined using International Classification of Diseases for Oncology (ICD-O-3), 3rd edition, topography and morphology codes. All records for the ICD-O-3 topography code C21, regardless of morphology code, were extracted. Records for ICDO-3 topography code C20 where the ICD-O-3 morphology codes were 8050–8085 or 8120–8131 were also included, consistent with prior knowledge [15], where the majority were squamous cell carcinomas (Supplementary Table 1). Cases of anal cancer were categorised into three histological subtypes: ASCC; AAC; and other anal tumours. Morphology codes used to define each category were adapted from published Australian data [6] (Table 1). Incidence count and survival data were analysed using all anal cancer data combined and for each histological subtype. Due to sparse data, information about people with other anal tumours (7% of all cases) was excluded from time trend incidence analyses. Data presented here are for all anal cancer data combined and for ASCC and AAC. 2.2. Statistical analyses Incidence was calculated as both a count and rate measure, with the age-standardised incidence rate at 100,000 person-years standardised to the Australia population as at 30 June 2001. Incidence was calculated for each combination of calendar year and histological subtype. Changes over time in incidence during 1972–2009 were evaluated by fitting piece-wise linear regression segments [16]. Permutation tests, a method for selecting the optimal number of data segments, were performed. For sensitivity analyses, we fitted the regressions for males and females separately; there was little difference in the magnitude of the

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slope for case numbers and a faster increase over time for males when assessing rates. However, due to sparse data, we only present data here for males and females combined. Using the Nordpred method [17], estimation of future incidence for 2010–2032 was calculated by combining age, period and cohort effects with estimated actual and projected resident population structures in NSW by 5-year age groups and sex [18,19]. Relative survival analysis was restricted to adults aged 15– 99 years and diagnosed with anal cancer between 1972 and 2006. Complete follow-up data were available up to 31 December 2007. We estimated relative survival for people diagnosed up to the end of 2001 using the cohort approach. All remaining cases were estimated using the period approach [20,21], commonly used for more recently diagnosed cases where full five-year follow-up data are not available. Relative survival was calculated for each combination of collapsed age groups (15–54 years, 55–64 years, 65–74 years, and 75 years and older), sex, calendar period (perdecade groupings), and histological subtype. Data were too sparse to estimate relative survival by recorded stage at diagnosis. The Ederer II method [22] was used to calculate expected survival using life tables constructed from raw population mortality data for each combination of calendar year, sex, and single year of age. Incidence data were analysed using SAS version 9.3 [23], with trend analysis performed in JoinPoint software [24], and projections undertaken in Nordpred software [25]. Relative survival was calculated using the strs program [26] in Stata Statistical Software: 12.0, StataCorp., Lp, College Station, Texas. 3. Results 3.1. Characteristics of persons with ASCC and AAC Overall, there were 2724 newly diagnosed with anal cancer recorded in the NSW Cancer Registry between 1972 and 2009 (Table 2). The majority of these people (72%) were diagnosed with ASCC. There was an even distribution of the number of cases by age group for all anal cancers combined and for ASCC. People with AAC tended to be older at diagnosis, with 40% of these being diagnosed in people aged 75 years and older. More women than men were diagnosed with all anal cancers combined and ASCC, with more men diagnosed with AAC. For all anal cancer cases combined, there was an apparent increase in the number of cases in the most recent decades with a notable peak in the number AAC in the 1990s (see Section 3.2). Almost all cases of anal cancer were confirmed on the NSW Cancer Registry through histopathology information. Approximately 40% of all anal cancer cases, regardless of histological subtype, had local extent of disease within the first four months of diagnosis, with around 8% of cases having distant disease. Extent of diagnosis was missing for about 20% of all cases. For people who were recorded as having died, 41% of ASCC cases had died of their anal cancer compared to 29% for people with AAC. 3.2. Actual and projected incidence of ASCC and AAC For all histological subtypes combined, there was a linear increase in the incidence of anal cancer (Fig. 1a). In 2009, the age-

Table 1 ICD-O-3 morphology codes using to define anal squamous cell carcinoma (ASCC), anal adenocarcinoma (AAC), and other anal tumours. Histological subtype

ICD-O-3 Morphology codes used to define

Anal squamous cell carcinoma (ASCC) Anal adenocarcinoma (AAC) Other anal tumour

8050–8051; 8052; 8070–8073; 8076; 8083; 8120; 8123–8124; and 8130 8140; 8143–8144; 8120–8211; 8215; 8260–8261; 8263; 8430; 8480–8481; 8490; and 8542 8000; 8010; 8012–8013; 8020–8021; 8033; 8041; 8090; 8094; 8231; 8240; 8246; 8560; 8720–8721; 8743; 8890; 8900; 8936; 9140; 9540; and 9680

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Table 2 Number and percent distribution of people with anal squamous cell carcinoma and anal adenocarcinoma in New South Wales, Australia, 1972–2009, by age group, sex, calendar period, basis of diagnosis, stage within four months of diagnosis, and recorded cause of death. All malignant anal tumours

Squamous cell carcinoma

Adenocarcinoma

Number

Percent distribution

Number

Percent distribution

Number

Percent distribution

Age group 15–54 years 55–64 years 65–74 years 75+ years All age groups

695 616 678 735 2724

(25) (23) (25) (27) (100)

563 478 489 426 1956

(29) (24) (25) (22) (100)

90 110 147 235 582

(16) (19) (25) (40) (100)

Sex Male Female

1219 1505

(45) (55)

812 1144

(42) (58)

316 266

(54) (46)

Calendar period 1972–1981 1982–1991 1992–2001 2002–2009

387 540 928 869

(14) (20) (34) (32)

287 361 627 681

(15) (18) (32) (35)

78 131 247 126

(13) (23) (42) (22)

Best basis of diagnosis Histopathology Clinical Other

2586 108 30

(95) (4) (1)

1863 73 0

(95) (4) (1)

571 9