Incidence and survival of rare urogenital cancers in Europe

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Abstract

Background

The RARECARE project aims at increasing knowledge of rare cancers in Europe. This manuscript describes the epidemiology (incidence, prevalence, survival) of rare urogenital cancers, taking into account the morphological characterisation of these tumours.

Methods

We used data gathered by RARECARE on cancer patients diagnosed from 1995 to 2002 and archived in 64 European population-based cancer registries, followed up to December 31st, 2003 or later.

Results

The annual number of males that develop penile cancer in the EU is estimated at 3100, which is equivalent to an age standardised rate (ASR) of 12 per million males. The 5-year relative survival rate is 69%, while squamous cell carcinoma is the predominant morphological entity. Each year around 650 persons in the EU develop cancer of the urethra and 7200 develop cancer of the renal pelvis or ureter (RPU). The ASR for cancer of the urethra and RPU is 1.1 (males 1.6; females 0.6) and 12 (males 16; females 7) per million inhabitants, respectively. The 5-year relative survival rate for cancer of the urethra and RPU is 54% and 51%, respectively. Transitional cell carcinoma is the predominant morphological entity of cancer of the urethra and RPU.

Conclusions

In view of the low number of cases and the fact that one third to one half of the patients die of their disease, centralisation of treatment of these rare tumours to a select number of specialist centres should be promoted.

Introduction

In this review we have identified three main groups of rare urogenital cancers: cancer of the penis, cancer of the urethra and cancer of the upper urinary tract (renal pelvis and ureter).

Cancer of the penis is the rarest cancer of the male genital tract, especially in Islamic countries and Israel.1 Compared to Europe and North America, the incidence is higher in Asia, Africa and South America. The highest rate world-wide was reported for Brasilia (Brazil) during 1998–2001 and amounted to an age standardised rate (ASR) of 40 per million males.

Risk factors for the development of penile cancer are multifactorial. The presence of phimosis has been shown to be strongly associated with the risk of developing penile cancer in a number of studies.2, 3 Circumcision is known to protect against penile cancer.4 Neonatal circumcision may be an explanation for the very low penis cancer incidence in Israel and Islamic countries, where the vast majority of the male population is circumcised in the neonatal period. In contrast, those circumcised after infancy have a higher risk, similar to those not circumcised.5 The mechanism for the protection conveyed by early circumcision is multi-factorial. From a pure anatomical perspective circumcision may prevent roughly one third of penile cancers as about one third of penile cancer is cancer of the foreskin. The remaining cancers mostly originate in the glans penis.

Parkin and Bray estimated that 40% of penile cancers are attributable to infection with human papilloma virus (HPV).6 HPV-16 and HPV-18 are the most common types involved.7 Uncircumcised males generally have a higher HPV prevalence,8 which is probably caused by a reduced clearance of the HPV infection in comparison to circumcised men.9 Circumcision may therefore protect against HPV associated disease by enhancing the resolution of infection. Other risk factors include HIV infection, cigarette smoking, history of trauma and chronic balanitis.

Cancer of the urethra occurs in both sexes and its aetiology is multifactorial. HPV infection may also be a risk factor for cancer of the urethra, but HPV prevalence in the male urethra is much lower than in the penis.10 Wiener reported the presence of oncogenic genotypes HPV-16 and HPV-18 in 59% of female patients with urethral carcinoma.11 There seems also to be a correlation with recurrent urinary tract infections, clean intermittent catheterisation and cancer of the urethra.12 In addition, a history of sexually transmitted diseases and urethral strictures appear to increase the risk of urethral cancer.

The main risk factors for cancer of the renal pelvis and ureter are smoking, long-term use of analgesics and laxatives, as well as several occupational exposures.13, 14 Comparative population-based studies regarding the age standardised incidence of cancer of the renal pelvis, ureter and urethra are not known to us. Moreover, these subsites are not included in Globocan or Cancer Incidence in Five Continents.1, 15

This manuscript describes the epidemiology (incidence, prevalence, survival) of rare urogenital cancers in Europe, taking into account the morphological characterisation of the tumours. With this extra information we were able to define cancer entities with clinical relevance. The present study benefits from a large population-based series of data, collected in the framework of the EC funded project ‘Surveillance of rare cancer in Europe’ (RARECARE).16 For the first time, prevalence will be provided for these cancers. For rare diseases prevalence is a crucial indicator, since the EU Directive on orphan drugs bases the definition of rare diseases on prevalence.17

Section snippets

Patients and methods

For this study we selected data regarding rare urogenital cancers from the RARECARE database.18 Rare urogenital cancers that are described in this article include epithelial cancers of the penis (ICD-O-3 topography code C60), the urethra (C68.0), as well as the renal pelvis (C65) and the ureter (C66). The renal pelvis and the ureter (RPU) were analysed together.

The following morphology groups were distinguished for penis: squamous cell carcinoma (ICD-O-3 morphology codes 8020–8022, 8050–8084,

Incidence

Table 1 shows the crude incidence rate of rare urogenital cancers in Europe during 1995–2002, ASRs by sex, age-specific rates and an estimate of the annual number of new cases (including areas not covered by the registries) diagnosed in the EU27. Squamous cell carcinoma is the most common morphological type of penis cancer (4611 or 92% out of a total of 5016 cases). Adenocarcinoma of the penis is very rare with only 40 cases registered (<1% of all cases). About 3100 penile cancers are estimated

Discussion

The annual number of males that develop penile cancer in the EU is estimated at 3100, which is equivalent to an ASR of 6 per million males + females or 12 per million males. The 5-year relative survival rate is 69%, while squamous cell carcinoma is the predominant morphological entity. Each year around 650 persons in the EU develop cancer of the urethra and 7200 develop cancer of the renal pelvis or ureter. The ASR for cancer of the urethra is 1.6 and 0.6 per million males and females,

Funding

This research was supported by the European Commission through the Executive Agency for Health and Consumers (Grant No. 2006113), and The Programma Italia-USA Malattie Rare (Grant No. 526D/42).

Conflict of interest statement

None declared.

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