Rare cancers

Key points

• Every year 22%, i.e. one fifth of the new cancer patients receive a rare cancer diagnosis. The proportion is the same in Finland as in the rest of Europe.
• Almost all cancers in children and young adults are rare.
• Offering cancer care for a rare cancer patient often requires a multidisciplinary team.
• In rare cancers, the survival rates are significantly lower than in other cancers. In Finland, the relative 5-year survival rate in rare cancers is 54%, while in common cancer patients it is 71%.

According to the European Union’s definition, diseases and syndromes are considered rare when they affect no more than five individuals per 10 000 people.

Prevalence criterion has shortcomings as a measure of cancer being rare, however, as different tumor types are associated with very different life expectancy. Cancers with low incidence but good survival would, by definition of prevalence, be common cancers. Similarly, a cancer which is common by incident amount but have a poor prognosis, would be rare.

Prevalence is a good indicator for describing the occurrence of many rare chronic diseases, but the clinical onset  of most cancers is often more subacute. Based on the course of the disease and life expectancy, incidence rate may be a better indicator defining rare cancer than prevalence.

The Finnish Cancer Registry is involved in the joint European RARECARE research project that studies the treatment of rare cancer patients, and how treatment centralization impacts the treatment pathway and prognosis of the patient. RARECARE has created a list of rare cancer types based on morphology codes from the World Health Organization (WHO). RARECARE has proposed a  definition that cancer is called rare when it affects fewer than six people in 100 000 each year and the list is made using that threshold. [1]

_{Figure 1. Distribution of common and rare cancers in Finland in 2007−2013 and proportions of different cancer types among rare cancers.}

The incidence rate

According to the RARECARE definition, an estimated 585 000 new rare cancers are annually detected in Europe. This means that every year 22%, i.e. one fifth of the new European cancer patients receive a rare cancer diagnosis. Approximately one in three of the rare cancers is of a particularly rare type, which means that the disease affects less than one person in 100 000 every year. [1]

In Finland, the incidence of rare cancers is about 70 new cancers per 100 000 people. Approximately 6 700 Finns get a diagnosis of a rare cancer each year. The proportion of all rare cancers in Finland is exactly the same as in Europe generally (Figure 1).

The proportion of  rare cancers from all cancer types, however, varies substantially by site of origin. Up to 75 percent of all lymphoid and hematopoietic tissue cancers are rare, but of new breast cancers only a few percent.

_{Figure 2. Relative one-, five- and ten-year survival ratios (%) for patients diagnosed with rare and common cancers in Finland in 2007–2013.}

Relative survival rate

Survival differences between common and rare cancers are rather small one year after the diagnosis (Figure 2). After this, survival for rare cancers declines markedly. In rare cancers found in Finland in 2007-2013, the relative five-year survival rate was 54%, while it was 71% in common cancers.

Survival rates in rare and common cancers decrease with age, in both genders.  Of children and young adults with a rare cancer, more than 80% are alive after five years of the cancer diagnosis, but only 35% of patients aged 75 and older (Figure 3).

The older the patient is at the time of detecting the cancer, the more the survival rates vary between rare and common cancers. Almost all cancers in children and young adult are rare. These cancers are often embryonal or haematological types  for which effective treatments are available. Most rare cancers in elderly patients are rare subtypes of epithelial cancers, for which no equally effective treatments exist.

Rare cancers have, on average, worse survival than common cancers. The differences in survival rates could be attributed to delays in accurate diagnosis, leading to rare cancers spreading more widely before diagnosis. Also, lack of effective and evidence-based treatments impact the survival rates of rare cancer types.

_{Figure 3. Relative five-year survival ratios (%) for patients diagnosed with rare and common cancers in Finland in 2007–2013 by age group.}

Challenge for the patient and health care

Rarity creates many challenges. Diagnostics may be incomplete and delayed because doctors in basic health care do not have enough information on rare cancers. The expertise of any pathologists required for the correct diagnosis will be limited. A significant proportion of patients visit several doctors before receiving the correct diagnosis. Many patients also receive one or more incorrect diagnosis first.

The timely diagnosis of a rare disease often requires a multidisciplinary team, but a multidisciplinary approach is currently not being optimally executed in the health care system. [2]

RARECARE investigated if any defects occur in notifying rare cancers to cancer registers and if rare cancers are registered in accordance with the international disease classifications. The study reviewed the original notification data of about 18 000 rare cancers, which were mainly pathology reports. Most of the registered unspecified diagnoses (NOS) remained imprecise after re-examination. The results suggest that the registration has practically no shortcomings, but the poorly specified morphology is mainly due to genuine difficulty in reaching a precise diagnosis of a rare cancer [1].

The lack of good and well-established treatments and clinical practice is also common for rare cancers. The development of treatment practices and health services should be based on knowledge, and thus research focusing specifically on rare cancers is needed.

However, it is difficult to collect sufficient patient data on rare cancers for clinical and epidemiological research, because patient numbers are small and the diagnostics are inadequate. It is often impossible to obtain a sufficient number of patients for randomized, controlled trials.  In addition, there is lack of interest in designing clinical trials and developing new therapies by the pharmaceutical industry. Companies are often not interested in developing treatments for small patient groups, when the economic benefit received from new medicines is uncertain.

Due to their small incidence, rare cancers also require centralization, so that those suffering from the disease receive high-quality treatment and rehabilitation. In addition, international collaboration and sample collection is required in order to maintain the relevance of the studies of rare cancers and to ensure conclusions can be drawn from the research results.

Receiving a cancer diagnosis is always a shock and will inevitably affect everyday life. In many cases, the knowledge of the disease helps to control strong emotions related to the diagnosis, and patients are actively looking for information and peer support from others with experience of the same disease. However, for those with a rare cancer, it is more difficult to find information on their illness, or information does not exist. These patients are also less likely to meet other people with the same type of cancer. Rare cancer patients may feel themselves isolated and, thus, are more prone to psychological and social problems. Furthermore, rare cancer patients may need to travel to a specialist hospital for treatment which can be far away from home. This means the patient may need to be separated from their family members and friends who are a major source of psychological support.

Literature

_{[1] Gatta G, van der Zwan JM, Casali PG et al. Rare cancers are not so rare: The rare cancer burden in Europe. Eur J Cancer 2011; 47: 2493–511.}

_{[2] Harvinaisten sairauksien kansallinen ohjelma 2014–2017. Steering group’s report. Reports and memorandums 2/2014. Helsinki: STM 2014.}