Trends in survival of patients diagnosed with cancers of the brain and nervous system, thyroid, eye, bone, and soft tissues in the Nordic countries 1964–2003 followed up until the end of 2006

Abstract

Background. Diagnoses of cancer of the brain, thyroid, eye, bone, and soft tissues are categorised by heterogeneity in disease frequency, survival, aetiology and prospects for curative therapy. In this paper, temporal trends in patient survival in the Nordic countries are considered. Material and methods. Age-standardised incidence and mortality rates, 5-year relative survival, and excess mortality rates for varying follow-up periods are presented, as are age-specific 5-year relative survival by country, sex and 5-year diagnostic period. Results. Brain cancer incidence rates have been rising but mortality has been relatively stable, with 5-year survival uniformly increasing from the early-1970s, particularly in younger patients. Five-year survival from brain cancer among men varies between 45% and 50% for men and 60% to 70% in women, with excess deaths decreasing with time in each of the Nordic populations. Age-standardised incidence rates of thyroid cancer have been mainly increasing during the 1960s and 1970s, although trends thereafter diverge, with 5-year relative survival increasing 20–30 percentage points over the last 40 years to around 80–90%. Thyroid cancer survival is consistently lower in Denmark, particularly in patients diagnosed aged over 60, while there is less geographic variation in excess deaths three months beyond initial diagnosis. Relative survival from eye cancer increased with time from approximately 60% in 1964–1968 to 80% 1999–2003, while for bone sarcoma, incidence rates remained stable, mortality rates declined, and 5-year survival increased slightly to around 55–65%. Soft tissue sarcoma incidence and survival have been slowly increasing since the 1960s, with little variation in survival (around 65%) for the most recent period. Conclusions. There have been some notable changes in survival that can be linked to epidemiological and clinical factors in different countries over time. Time-varying proportions of the major histological subtypes might however have affected the survival estimates for a number of the cancer forms reviewed here.

The neoplasms considered in this article (cancers of the eye, thyroid, bone, soft tissues and tumours of brain and nervous system) comprise five forms variable in terms of disease frequency, survival, aetiology and prospects for curative therapy. As a group they represent about 5% of all cancers in the Nordic countries, with about 60% of these consisting of brain and central nervous system (CNS) tumours, and a further 15% are thyroid cancers.

Brain and CNS tumours represent a relatively uncommon group of neoplasms in terms of incidence, although they do constitute a somewhat more frequent form of cancer death, representing about 3.5% of the total cancer mortality burden [1]. This group is also heterogeneous in that it includes morphologically malignant tumours as well as benign variants, the latter with a behaviour leading to death of the patient. Secular trends in the incidence of, and mortality from these tumours indicate that rates may be increasing in a number of western countries, particularly among the elderly [2], although a bias related to the introduction of new diagnostic imaging techniques cannot be ruled out. Five-year survival in Europe has been modestly increasing in children [3], and in younger adult patients, while 1-year survival has increased irrespective of age [4]. Despite this, survival remains low and the European age-standardised 5-year relative survival was below 20% for persons diagnosed between 1995 and 1999 [5].

Thyroid cancer is also a relatively uncommon form of cancer in the Nordic populations in terms of incidence, where it represents less than 1% of all cancer, and an even less frequent cause of cancer death. The disease comprises a number of distinct histological types with widely-differing clinical and epidemiological features, and is notable for the two- to three-fold higher incidence in women relative to men [6]. Secular trends in incidence (but not mortality) have been increasing in many parts of Europe, including several Nordic countries [7], an observation that reflects in part the introduction of more sophisticated procedures for the detection of thyroid cancer including ultrasonography and fine needle aspiration biopsy, the latter of which has been in use in the Nordic countries since the 1950s [8], and became standard practice in the mid-1970s.

Cancer of the eye is a rare cancer, constituting about 0.3% of all cancers and there were about 300 recorded cases each year in the five countries [1]. More than 80% of all cases are melanomas, and an additional 10% are retinoblastomas [9], with the latter diagnoses commonly restricted to patients aged below 15. There have been few studies of survival, although a recent Danish report of eye melanomas in Denmark 1943–1997 described relative survival as stable over time [10]. Retinoblastomas tend to be associated with high survival, with a survival of 90% or more estimated for a number of European populations [11].

Bone sarcomas are also quite uncommon, comprising around one in 500 of all cancers diagnosed in the Nordic countries each year. They also represent a heterogeneous group of neoplasms for which the most common malignant primary tumours, osteosarcoma, Ewing's sarcoma and chondrosarcoma, vary both epidemiologically and prognostically [12]. Stiller et al. have shown that survival following osteosarcoma and Ewing's sarcoma has increased in patients aged under 20 in recent years [13]. In a previous EUROCARE study of bone sarcoma patients diagnosed 1978–1989, Denmark had slightly lower survival rates than the other participating Nordic countries [14]. A number of hypotheses for differences in the Nordic countries were provided, including heterogeneity in the age distribution at diagnosis, the proportion that were histologically verified, the levels of diagnostic activity, and the degree of specialised care [14].

Despite the relative rarity of soft tissue sarcomas – they comprise approximately one in 150 cancer diagnoses each year in the Nordic countries – they are an important group of childhood cancers. They also constitute a diverse set of histological subtypes, for which the rhabdomyosarcoma and fibrosarcoma are the most common. Histology is an important prognostic factor for this group of patients with fibrosarcoma associated with a higher survival than rhabdomyosarcoma. Improvements in survival for soft tissue sarcoma and for these specific histological groups have been reported in Europe, particularly among children and adolescent patients [15,16].

The aim of the present study is to describe and contrast the country-, sex- and age-specific trends in relative survival and excess mortality of patients diagnosed with each of these cancer types during the diagnostic period 1964–2003 in the five Nordic populations. A further objective is to elucidate these observations by considering concomitant trends in incidence and mortality, alongside relevant clinical and epidemiologic research.

Material and methods

The materials and methods are described in detail in an accompanying article in this issue [17]. In brief, the NORDCAN database contains comparable data on cancer incidence and mortality in the Nordic countries, as delivered by the national cancer registries, with follow-up information on death or emigration for each cancer patient available up to and including 2006. This paper covers the specific cancer sites of the eye (ICD-10 C69), brain and central nervous system (ICD-10 C70-72, D32-33 and D42-43), thyroid (ICD-10 C73), bone (ICD-10 C40-41) and soft tissues (ICD-10 C49 and C46.1). The vast majority of patients diagnosed with these cancers were those of the central nervous system. For the other specified sites, the numbers of cases included for each diagnostic period tend to run in the hundreds, and particular caution should be applied to the very small number of cases generally, and in particular those associated with the statistics generated for Iceland.

We calculated sex-specific 5-year relative survival for each of the diagnostic groups in each country for eight 5-year periods from 1964–1968 to 1999–2003. For the last 5-year period, so-called hybrid methods were used. Country-specific population mortality rates were used for calculating the expected survival. Age-standardisation used the weights of the International Cancer Survival Standard (ICSS) cancer patient populations [18]. We present age-standardised (World) incidence and mortality rates, 5-year relative survival, and excess mortality rates for the follow-up periods of within one month, one to three months and two to five years following diagnosis, as well as age-specific 5-year relative survival by country, sex and 5-year period.

Results

Eye cancer

Incidence and mortality. The incidence rate was stable around 1 per 100 000 in each of the Nordic countries for both men and women, with a tendency of higher incidence in Denmark and lower incidence in Sweden (Figure 1). Mortality following these tumours has been slightly decreasing from 0.4 to 0.2 per 100 000 in the last period in each country. The decrease was more pronounced in Sweden than in the other countries.

Figure 1. Trends in age-standardised (World) incidence and mortality rates per 100 000 and age-standardised (ICSS) 5-year relative survival for eye cancer by sex and country. Nordic cancer survival study 1964–2003.

Survival. The relative survival has tended to increase with time, rising from about 60% in the period 1964–1968 to 83% in men and 78% in women for diagnoses 1999–2003, although they are somewhat lower in Denmark (Table I). There is a suggestion of a decline in excess deaths from eye cancer over time in each country, with a larger excess of deaths within the first three months following diagnosis (Figure 2), although as the underlying numbers are very small, the inherent random variation is such that any interpretation is tentative at best. Survival appears to have risen over time irrespective of age at diagnosis, although again, there is substantive random variation in these estimates (Table II).

Table I. Trends in survival for eye cancer by sex and country. Number of tumours (N) included and the 5-year age-standardised (ICSS) relative survival in percent with 95% confidence intervals (RS (CI)). Nordic cancer survival study 1964–2003.

	Denmark		Finland		Iceland		Norway		Sweden
	N	RS (CI)	N	RS (CI)	N	RS (CI)	N	RS (CI)	N	RS (CI)
Men
1964–1968	168	60 (49–73)	92	64 (45–92)	5	*	100	63 (52–75)	241	59 (51–70)
1969–1973	170	66 (53–82)	98	64 (45–92)	7	*	111	63 (52–75)	242	63 (53–74)
1974–1978	156	65 (53–79)	111	70 (60–83)	8	*	101	60 (46–78)	257	65 (54–78)
1979–1983	158	57 (47–69)	110	70 (60–83)	6	*	135	74 (61–91)	235	69 (61–79)
1984–1988	152	64 (53–77)	99	48 (39–61)	5	*	116	70 (58–84)	225	60 (52–69)
1989–1993	161	63 (52–76)	151	76 (65–88)	5	*	131	77 (65–91)	254	70 (62–80)
1994–1998	192	59 (51–69)	144	86 (72–102)	4	*	138	76 (65–89)	270	81 (73–90)
1999–2003	203	69 (61–78)	154	83 (74–93)	5	*	155	76 (68–85)	292	77 (71–84)
Women
1964–1968	142	57 (49–65)	111	64 (54–76)	4	*	90	68 (57–81)	225	69 (58–82)
1969–1973	154	57 (49–65)	106	60 (50–71)	1	*	83	68 (57–81)	226	69 (60–79)
1974–1978	136	58 (49–67)	139	60 (50–71)	5	*	104	68 (57–81)	208	69 (60–79)
1979–1983	132	65 (54–77)	114	68 (57–82)	4	*	108	60 (49–73)	192	68 (59–77)
1984–1988	141	62 (52–72)	122	65 (56–77)	2	*	101	72 (61–85)	236	68 (61–76)
1989–1993	154	61 (52–72)	155	68 (60–78)	4	*	138	69 (60–80)	242	72 (64–80)
1994–1998	174	68 (60–77)	146	82 (72–93)	4	*	148	78 (69–88)	264	71 (64–79)
1999–2003	179	70 (63–77)	132	78 (71–86)	5	*	148	77 (70–84)	261	74 (69–80)

Numbers in italics indicate that two or more cells had to be combined to get sufficient number of patients to calculate survival

*Too few patients to calculate survival, see ref. [17].

Table II. Trends in 5-year age-specific relative survival in percent after eye cancer by sex and country. Nordic cancer survival study 1964–2003.

	Men						Women
Age	0–49	50–59	60 – 69	70–79	80–89	90+	0–49	50–59	60–69	70–79	80–89	90+
Denmark
1964–1968	85	60	65	57	36	*	78	72	53	57	28	*
1969–1973	77	58	59	57	96	*	78	72	53	57	28	*
1974–1978	83	84	61	41	83	*	86	67	68	60	0	*
1979–1983	86	54	67	58	20	*	88	64	86	43	52	*
1984–1988	85	71	63	60	49	*	94	74	64	53	34	*
1989–1993	87	62	58	55	67	*	86	81	55	60	33	*
1994–1998	83	76	71	54	12	*	96	85	58	72	35	*
1999–2003	89	70	73	62	60	*	94	83	69	66	44	*
Finland
1964–1968	85	66	54	59	76	*	80	91	55	83	0	*
1969–1973	85	66	54	59	76	*	92	68	65	52	30	*
1974–1978	85	88	84	63	28	*	92	68	65	52	30	*
1979–1983	85	88	84	63	28	*	93	63	62	84	32	*
1984–1988	91	77	54	33	0	*	101	63	85	59	17	*
1989–1993	88	71	88	72	58	*	77	64	80	83	17	*
1994–1998	90	88	74	80	113	*	88	82	78	76	96	*
1999–2003	85	78	71	80	113	*	89	77	79	75	78	*
Norway
1964–1968	82	71	67	65	26	*	82	76	70	60	62	*
1969–1973	82	71	67	65	26	*	82	76	70	60	62	*
1974–1978	101	63	59	48	46	*	80	82	86	49	48	*
1979–1983	93	85	63	69	80	*	90	73	66	45	37	*
1984–1988	85	60	74	78	48	*	94	77	60	80	56	*
1989–1993	81	88	77	69	74	*	90	83	64	65	53	*
1994–1998	95	85	62	73	82	*	92	91	73	83	55	*
1999–2003	95	76	87	69	56	*	86	85	80	76	54	*
Sweden
1964–1968	80	56	68	59	31	*	85	81	58	55	88	*
1969–1973	78	81	61	48	59	*	85	77	61	56	85	*
1974–1978	79	61	67	46	89	*	85	84	68	51	76	*
1979–1983	89	69	71	68	54	*	91	88	64	54	58	*
1984–1988	89	58	60	67	26	*	84	67	78	64	45	*
1989–1993	88	69	60	68	80	*	89	68	71	74	58	53
1994–1998	85	82	68	72	117	*	91	73	71	65	64	*
1999–2003	83	78	65	80	87	81	91	71	68	76	70	*

Numbers in italics indicate that two or more cells had to be combined to get sufficient number of patients to calculate survival

*Too few patients to calculate survival. Iceland not shown for the same reason, see ref. [17].

Figure 2. Trends in age-standardised (ICSS) excess death rates per 100 person years for eye cancer by sex, country, and time since diagnosis in Nordic cancer survival study 1964–2003. No Icelandic curves. Too few partients to calculate survival for Iceland.

Brain and CNS cancer

Incidence and mortality. Incidence rates have been increasing in the Nordic countries in the last few decades, rates ranging from 10 to 12 per 100 000 in men and between 11 and 13 in women circa 2000. The upwards trends are perhaps more apparent in the 1970s and 1980s, but in some countries – most evident in Sweden – recent declines have been observed (Figure 3). In contrast, incidence rates in Norway have been increasing rapidly in the last decade. Mortality rates are however relatively stable with time, at least from the early-1970s with a level around four to six deaths per 100 000.

Figure 3. Trends in age-standardised (World) incidence and mortality rates per 100 000 and age-standardised (ICSS) 5-year relative survival for cancers of the brain & central nervous system by sex and country. Nordic cancer survival study 1964–2003.

Survival. The 5-year survival of patients diagnosed with brain and CNS tumours has been uniformly increasing over time in all Nordic countries since the early-1970s. The magnitude of change in the trends with time is similar between the sexes, although 5-year survival proportions are evidently higher among female patients. Five-year survival among men in the Nordic patient populations varies between 40% and 50% compared with an approximate range of 60 to 70% in women (Table III). The absolute increases in 5-year survival are of the order 20 to 30 percentage points in men and women respectively over the diagnostic period 1964 to 2003.

Table III. Trends in survival for cancer of the brain & nervous system by sex and country. Number of tumours (N) included and the 5-year age-standardised (ICSS) relative survival in percent with 95% confidence intervals (RS (CI)). Nordic cancer survival study 1964–2003.

	Denmark		Finland		Iceland		Norway		Sweden
	N	RS (CI)	N	RS (CI)	N	RS (CI)	N	RS (CI)	N	RS (CI)
Men
1964–1968	1 010	20 (18–23)	605	*	29	*	761	21 (18–25)	2 015	25 (23–27)
1969–1973	1 113	22 (20–25)	639	*	34	*	762	21 (18–25)	2 160	27 (25–29)
1974–1978	1 280	26 (23–28)	726	33 (27–41)	45	*	859	27 (24–30)	1 912	27 (25–29)
1979–1983	1 412	32 (29–35)	1 051	46 (42–51)	43	*	975	32 (28–35)	2 155	35 (33–37)
1984–1988	1 546	35 (33–38)	1 214	46 (43–50)	58	35 (28–45)	1 140	36 (33–39)	2 538	38 (37–40)
1989–1993	1 747	38 (36–41)	1 368	43 (40–46)	83	35 (28–45)	1 164	38 (36–41)	2 707	44 (43–46)
1994–1998	2 026	44 (41–46)	1 458	47 (45–50)	79	40 (34–48)	1 217	42 (39–45)	2 740	48 (46–50)
1999–2003	2 085	46 (44–48)	1 612	52 (50–54)	74	40 (34–48)	1 588	45 (43–47)	2 613	48 (47–50)
Women
1964–1968	935	32 (29–36)	606	35 (31–39)	24	*	596	25 (21–29)	2 204	35 (33–37)
1969–1973	1 070	31 (28–34)	681	42 (38–47)	29	*	598	27 (23–31)	2 382	39 (37–41)
1974–1978	1 298	35 (33–38)	934	44 (41–48)	34	46 (35–61)	780	35 (32–38)	2 045	42 (40–45)
1979–1983	1 426	44 (41–47)	1 398	58 (54–61)	64	46 (35–61)	955	43 (39–46)	2 276	51 (49–53)
1984–1988	1 600	46 (44–49)	1 650	61 (58–64)	58	56 (47–67)	1 099	51 (48–54)	2 821	55 (53–57)
1989–1993	1 862	55 (53–57)	1 708	58 (56–61)	80	56 (47–67)	1 233	59 (56–61)	2 834	57 (56–59)
1994–1998	2 237	59 (57–61)	1 960	62 (60–65)	87	65 (55–76)	1 467	59 (57–62)	3 171	65 (63–67)
1999–2003	2 482	61 (59–63)	2 351	67 (65–69)	92	60 (52–69)	2 027	67 (65–69)	3 071	68 (66–69)

Numbers in italics indicate that two or more cells had to be combined to get sufficient number of patients to calculate survival

*Too few patients to calculate survival, see ref. [17].

Excess deaths per 100 person years have decreased over time in each of the Nordic populations (Figure 4). Since the early-1980s the excess mortality in the first month after diagnosis has been rather stable. Excess deaths tend to be close one to three months after diagnosis, although Denmark historically has a greater number of excess deaths. There are no apparent country-specific differences in the excess deaths beyond three months after diagnosis (data partially shown). While the increasing survival over time is seen across all ages, the absolute increases tend to be greater and more consistent among patients age groups 0–49 and 50–59 (Table IV).

Figure 4. Trends in age-standardised (ICSS) excess death rates per 100 person years for cancers of the brain & central nervous system by sex, country, and time since diagnosis in Nordic cancer survival study 1964–2003.

Table IV. Trends in 5-year age-specific relative survival in percent after cancer of the brain & nervous system by sex and country. Nordic cancer survival study 1964–2003.

	Men						Women
Age	0–49	50–59	60–69	70–79	80–89	90+	0–49	50–59	60–69	70–79	80–89	90 +
Denmark
1964–1968	35	18	12	11	0	*	45	33	26	19	16	*
1969–1973	39	19	13	10	0	*	47	37	20	15	5	*
1974–1978	46	20	13	13	0	*	49	37	31	19	9	*
1979–1983	49	29	23	12	21	*	60	43	41	29	8	0
1984–1988	55	38	21	15	10	*	65	44	38	30	20	*
1989–1993	60	36	25	21	16	*	72	54	48	38	28	0
1994–1998	63	46	34	22	18	0	74	69	51	41	23	0
1999–2003	68	43	35	24	21	0	77	67	57	40	25	25
Finland
1964–1968	34	22	13	7	*	*	49	42	34	10	0	*
1969–1973	46	25	17	27	*	*	56	42	44	26	0	*
1974–1978	44	31	18	25	47	*	60	40	44	27	16	*
1979–1983	65	44	33	28	37	*	72	62	53	37	31	*
1984–1988	68	48	32	32	8	*	72	69	55	49	25	*
1989–1993	65	49	33	14	8	*	77	66	52	33	15	*
1994–1998	71	51	30	21	30	*	79	75	56	38	20	0
1999–2003	72	58	39	27	27	*	80	78	66	46	22	*
Iceland
1964–1968	41	26	16	14	*	*	46	62	18	*	*	*
1969–1973	41	26	16	14	*	*	46	62	18	*	*	*
1974–1978	47	19	49	25	*	*	55	44	49	10	79	*
1979–1983	47	19	49	25	*	*	55	44	49	10	79	*
1984–1988	54	32	19	24	21	*	59	62	54	35	78	*
1989–1993	54	32	19	24	21	*	59	62	54	35	78	*
1994–1998	60	47	21	22	20	*	73	77	61	56	24	*
1999–2003	60	47	21	22	20	*	74	73	44	47	27	*
Norway
1964–1968	30	16	16	13	19	*	35	27	20	16	0	*
1969–1973	30	16	16	13	19	*	38	28	25	12	0	*
1974–1978	46	21	17	16	0	*	51	41	29	12	0	*
1979–1983	49	33	22	11	15	*	60	45	31	24	26	*
1984–1988	58	36	23	18	0	*	71	56	45	25	9	*
1989–1993	62	39	25	18	8	0	77	62	49	42	19	0
1994–1998	63	42	28	20	19	*	74	69	49	44	28	0
1999–2003	65	45	29	32	28	0	79	72	61	54	39	27
Sweden
1964–1968	43	26	16	7	0	0	49	40	32	17	2	0
1969–1973	47	25	17	7	3	0	53	43	35	19	11	0
1974–1978	47	22	21	9	5	0	57	48	37	25	11	0
1979–1983	55	30	27	17	5	*	69	53	40	37	15	*
1984–1988	61	34	26	22	13	*	72	60	47	36	19	52
1989–1993	65	42	35	29	12	*	73	61	49	45	23	0
1994–1998	67	46	33	32	35	*	80	70	55	52	40	52
1999–2003	67	46	35	33	34	*	80	71	60	56	44	13

Numbers in italics indicate that two or more cells had to be combined to get sufficient number of patients to calculate survival

*Too few patients to calculate survival, see ref. [17].

Thyroid cancer

Incidence and mortality. Age-standardised incidence rates of thyroid cancer have been slightly increasing in the Nordic populations in both sexes during the 1960s and 1970s, possibly with the exception of Denmark. Trends thereafter tend to diverge (Figure 5). In Finland and Denmark, incidence rates increased during the 1980s but appear to have stabilised more recently. In contrast, rates in Norway and Sweden have been in long-term decline over the last 25 years. It is evident that the country-specific trends in incidence are quite similar in men and women albeit with a consistent two to three-fold higher rate observed among women relative to men and much larger absolute difference between the countries for women. Icelandic men and women have incidence rates currently around three times higher than elsewhere. The rates are substantially higher in women during the late-1960s through to the mid-1970s. Trends in mortality have, in contrast, been largely decreasing in both men and women (more decipherable on a semi-log scale of Figure 5), with the declines tending to be consistent across countries since the early-1980s. The mortality rates have decreased from around 0.9 and 0.5 per 100 000 for men and women respectively in the early-1960s to about 0.3 for both sexes presently.

Figure 5. Trends in age-standardised (World) incidence and mortality rates per 100 000 and age-standardised (ICSS) 5-year relative survival for thyroid cancer by sex and country. Nordic cancer survival study 1964–2003.

Survival. Age-standardised 5-year relative survival following thyroid cancer has increased 20–30 percentage points over the last 40 years in all Nordic countries and in both sexes to around 80–90%, although survival estimates are consistently lower in Denmark irrespective of the study period (Figure 5). The absolute changes in the survival proportions with time are reasonably similar between countries, particularly during the last 15 years. With the exception of Denmark, recent survival proportions are quite close between countries in absolute terms, with women displaying a clear survival advantage of around 5–10 percentage points over men, an observation that is not restricted to the latest period of diagnosis (Table V).

Table V. Trends in survival for thyroid cancer by sex and country. Number of tumours (N) included and the 5-year age-standardised (ICSS) relative survival in percent with 95% confidence intervals (RS (CI)). Nordic cancer survival study 1964–2003.

	Denmark		Finland		Iceland		Norway		Sweden
	N	RS (CI)	N	RS (CI)	N	RS (CI)	N	RS (CI)	N	RS (CI)
Men
1964–1968	122	50 (41–62)	111	53 (48–59)	13	*	138	51 (44–60)	345	56 (51–62)
1969–1973	143	45 (38–53)	150	53 (48–59)	24	*	167	69 (63–76)	419	58 (53–62)
1974–1978	149	47 (40–56)	220	65 (59–72)	23	92 (80–105)	176	72 (65–79)	422	65 (61–70)
1979–1983	154	51 (44–59)	186	74 (67–83)	30	92 (80–105)	221	81 (76–87)	431	70 (66–75)
1984–1988	157	54 (47–62)	257	72 (66–79)	27	87 (78–98)	201	77 (70–84)	439	72 (68–77)
1989–1993	132	68 (59–79)	264	77 (71–84)	24	87 (78–98)	219	75 (69–83)	396	78 (73–83)
1994–1998	184	72 (64–80)	362	79 (74–84)	30	85 (74–96)	216	77 (71–85)	416	79 (74–83)
1999–2003	209	68 (63–74)	396	81 (77–85)	34	85 (74–96)	243	82 (76–87)	371	81 (77–85)
Women
1964–1968	292	52 (47–58)	372	59 (54–64)	42	81 (66–98)	339	71 (67–76)	890	65 (62–68)
1969–1973	266	51 (46–57)	501	68 (64–72)	80	88 (80–96)	452	73 (69–77)	1 019	72 (69–74)
1974–1978	325	53 (48–58)	694	74 (70–78)	79	81 (72–92)	567	80 (77–84)	1 107	75 (72–77)
1979–1983	388	64 (59–69)	865	78 (75–81)	51	78 (67–92)	688	82 (79–86)	1 200	80 (78–82)
1984–1988	366	70 (65–75)	954	80 (77–83)	61	90 (83–98)	662	84 (81–88)	1 116	82 (79–84)
1989–1993	383	76 (71–81)	1 129	82 (80–85)	63	90 (83–98)	669	88 (84–91)	1 076	84 (81–86)
1994–1998	448	75 (71–80)	1 347	88 (86–90)	82	93 (87–99)	581	87 (84–91)	1 046	84 (82–87)
1999–2003	532	77 (73–80)	1 275	90 (88–91)	75	93 (87–99)	636	86 (83–89)	1 027	86 (84–88)

Numbers in italics indicate that two or more cells had to be combined to get sufficient number of patients to calculate survival

*Too few patients to calculate survival, see ref. [17].

Lower thyroid cancer survival ratios in Denmark are seen irrespective of age and period of diagnosis, although the major differences appear to relate more to the poorer prognosis of patients aged 60 and over (Table VI). The observed overall pattern in all countries is that survival decreases with high age. Danish patients also have a higher excess mortality among patients within the first three months of diagnosis (Figure 6). Within the first three months the Danish excess mortality has been reduced to about 50 per 100 person years circa 2000. There appears to be little variation in the Nordic countries when one considers excess deaths occurring three months after initial diagnosis (data partially shown).

Table VI. Trends in 5-year age-specific relative survival in percent after thyroid cancer by sex and country. Nordic cancer survival study 1964–2003.

	Men						Women
Age	0–49	50–59	60–69	70–79	80–89	90+	0–49	50–59	60–69	70–79	80–89	90 +
Denmark
1964–1968	73	41	36	23	66	*	84	50	37	25	9	*
1969–1973	85	35	13	12	39	*	85	47	34	23	6	*
1974–1978	78	44	26	16	31	*	88	48	33	23	14	*
1979–1983	82	46	43	19	0	*	92	54	56	37	35	*
1984–1988	85	43	49	28	0	*	98	84	52	37	17	0
1989–1993	94	62	42	37	103	*	95	81	80	43	23	*
1994–1998	85	69	72	61	32	*	97	89	59	55	21	*
1999–2003	92	78	57	29	48	*	97	90	67	50	26	0
Finland
1964–1968	87	57	43	9	0	*	86	64	51	25	11	*
1969–1973	87	57	43	9	0	*	95	80	59	28	19	*
1974–1978	91	70	66	27	0	*	97	82	59	46	43	*
1979–1983	99	84	49	60	33	*	99	88	74	47	28	*
1984–1988	96	79	67	36	34	*	98	95	72	51	33	0
1989–1993	95	83	68	63	28	*	99	95	79	59	27	77
1994–1998	96	85	87	47	22	*	100	99	88	70	41	0
1999–2003	96	86	85	47	52	*	100	100	90	75	42	2
Iceland
1964–1968	91	94	69	51	*	*	101	65	77	56	89	*
1969–1973	91	94	69	51	*	*	101	103	85	83	*	*
1974–1978	91	105	91	60	133	*	98	78	67	89	29	*
1979–1983	91	105	91	60	133	*	101	102	72	31	24	*
1984–1988	101	93	78	101	*	*	99	87	90	95	41	*
1989–1993	101	93	78	101	*	*	99	87	90	95	41	*
1994–1998	83	103	67	94	79	*	101	94	96	93	46	*
1999–2003	83	103	67	94	79	*	101	94	96	93	46	*
Norway
1964–1968	82	40	45	26	0	*	100	85	54	26	43	*
1969–1973	94	77	60	48	0	*	94	87	66	41	21	*
1974–1978	91	78	75	43	14	*	97	95	74	59	22	0
1979–1983	99	83	83	62	26	*	99	94	76	58	41	0
1984–1988	94	89	69	49	42	*	100	96	74	65	51	*
1989–1993	93	73	79	44	53	*	98	95	82	78	52	*
1994–1998	91	78	72	62	59	*	99	97	82	73	51	54
1999–2003	95	85	69	69	70	*	98	91	85	66	56	149
Sweden
1964–1968	84	61	38	25	26	*	95	77	48	28	12	*
1969–1973	88	64	41	24	13	*	97	81	64	37	20	0
1974–1978	94	70	54	32	17	*	98	85	71	38	27	30
1979–1983	91	81	62	44	20	*	99	88	74	57	35	45
1984–1988	95	80	68	48	5	*	99	93	75	60	34	47
1989–1993	93	82	67	61	62	*	99	91	74	71	42	45
1994–1998	96	78	70	67	42	*	99	96	78	66	42	22
1999–2003	95	83	76	68	48	*	99	96	85	66	36	19

Numbers in italics indicate that two or more cells had to be combined to get sufficient number of patients to calculate survival

*Too few patients to calculate survival, see ref. [17].

Figure 6. Trends in age-standardised (ICSS) excess death rates per 100 person years for thyroid cancer by sex, country, and time since diagnosis in Nordic cancer survival study 1964–2003.

Bone sarcoma

Incidence and mortality. The age-standardised incidence rates of bone sarcoma have been rather stable over time in each of the Nordic countries in both sexes (Figure 7), although in Finland, rates have been slowly but steadily declining since the beginning of the observation period, while in Norway, incidence appears to be gradually rising, particularly among women since the 1970s. The overall incidence rate in the Nordic countries is below 1 per 100 000 in men and slightly lower in women, at around 0.7. Long-term declines in mortality rates are seen in all countries, with little variation in absolute terms in bone sarcoma mortality circa 2000 between populations, or according to sex. The relative magnitude of these decreasing trends appears to be greater than that seen for incidence. Mortality from bone sarcoma is now at a similar level in the Nordic countries at about 0.4 per 100 000 in men and 0.3 in women.

Figure 7. Trends in age-standardised (World) incidence and mortality rates per 100 000 and age-standardised (ICSS) 5-year relative survival for bone sarcoma by sex and country. Nordic cancer survival study 1964–2003.

Survival. While trends in 5-year relative survival display some variability, they are generally upwards in each Nordic population (Figure 7). Survival proportions were of the order 55–65% for patients diagnosed between 1999 and 2003 in the Nordic countries, although survival is a few percentage points higher in women. Survival from bone sarcoma in Sweden is higher than the other countries in both sexes, an observation that is evident in survival comparisons dating back to around 1980 (Table VII). The steep progression of survival proportions seen in Norwegian women until around 1990 has since shifted downwards but there is uncertainty in these figures due to sparse data. The excess death figures are also difficult to interpret in light of the inherent random variation associated with such a rare cancer, although it does not appear that there is much variation with regards to prognosis across the Nordic populations, irrespective of diagnostic period (Figure 8). The survival trends by age indicate increasing survival in all Nordic countries irrespective of age at diagnosis in both sexes, with the absolute increases in survival most notable in the youngest patients, aged under 50 (Table VIII).

Table VII. Trends in survival for bone sarcoma by sex and country. Number of tumours (N) included and the 5-year age-standardised (ICSS) relative survival in percent with 95% confidence intervals (RS (CI)). Nordic cancer survival study 1964–2003.

	Denmark		Finland		Iceland		Norway		Sweden
	N	RS (CI)	N	RS (CI)	N	RS (CI)	N	RS (CI)	N	RS (CI)
Men
1964–1968	124	38 (32–47)	173	21 (15–29)	4	*	89	39 (30–52)	218	40 (32–49)
1969–1973	167	38 (32–47)	161	35 (28–43)	11	*	69	39 (30–52)	221	52 (44–62)
1974–1978	131	55 (44–69)	145	39 (31–50)	9	*	125	41 (31–54)	228	43 (35–52)
1979–1983	122	39 (29–52)	142	45 (36–56)	9	*	105	56 (43–73)	247	59 (51–68)
1984–1988	131	47 (37–60)	123	53 (42–67)	7	*	109	48 (36–64)	228	56 (49–65)
1989–1993	120	47 (37–59)	98	53 (41–67)	10	*	114	39 (29–51)	218	62 (54–72)
1994–1998	148	51 (43–61)	136	56 (46–67)	10	*	114	54 (43–69)	201	63 (55–73)
1999–2003	128	55 (47–66)	116	62 (54–71)	7	*	129	54 (45–65)	202	64 (58–71)
Women
1964–1968	104	20 (12–32)	135	42 (33–54)	4	*	56	27 (17–42)	149	43 (34–54)
1969–1973	126	43 (33–56)	106	32 (24–42)	3	*	54	27 (17–42)	177	45 (37–56)
1974–1978	81	32 (21–50)	115	50 (41–62)	1	*	58	43 (29–63)	199	49 (41–58)
1979–1983	76	57 (44–74)	97	49 (39–63)	6	*	65	48 (35–66)	174	61 (53–70)
1984–1988	111	40 (32–50)	90	55 (45–68)	7	*	73	63 (48–81)	145	68 (59–78)
1989–1993	90	46 (36–60)	103	63 (52–77)	4	*	84	66 (54–80)	168	69 (61–78)
1994–1998	107	64 (53–77)	91	66 (55–80)	9	*	89	61 (51–74)	145	68 (60–78)
1999–2003	112	57 (48–67)	100	66 (57–76)	2	*	122	58 (49–68)	143	68 (61–76)

Numbers in italics indicate that two or more cells had to be combined to get sufficient number of patients to calculate survival

*Too few patients to calculate survival, see ref. [17].

Table VIII. Trends in 5-year age-specific relative survival in percent after bone sarcoma by sex and country. Nordic cancer survival study 1964–2003.

	Men						Women
Age	0–29	30–39	40–49	50–69	70–89	90+	0–29	30–39	40–49	50–69	70–89	90+
Denmark
1964–1968	34	42	64	36	24	*	31	22	22	21	11	*
1969–1973	34	42	64	36	24	*	39	54	54	47	23	*
1974–1978	39	50	68	69	29	*	47	43	46	26	24	*
1979–1983	35	39	58	45	14	*	42	61	61	64	43	*
1984–1988	43	67	71	44	26	*	60	81	81	14	28	*
1989–1993	59	61	85	37	26	*	55	77	77	37	22	*
1994–1998	62	82	71	55	11	*	64	74	74	67	44	*
1999–2003	62	68	72	56	33	*	66	59	59	65	38	*
Finland
1964–1968	47	23	59	13	0	*	43	59	59	35	33	*
1969–1973	40	73	71	27	0	*	43	63	63	26	0	*
1974–1978	39	71	67	40	0	*	57	69	69	56	15	*
1979–1983	48	62	69	45	18	*	50	71	71	42	34	*
1984–1988	61	73	64	60	17	*	61	82	82	52	26	*
1989–1993	57	80	79	43	35	*	68	77	77	62	47	*
1994–1998	58	67	66	61	30	*	66	65	65	76	50	*
1999–2003	70	71	64	68	43	*	76	76	76	73	37	*
Iceland
1964–1968	45	45	45	*	*	*	*	*	*	*	*	*
1969–1973	45	45	45	*	*	*	*	*	*	*	*	*
1974–1978	50	50	50	*	*	*	*	*	*	*	*	*
1979–1983	50	50	50	*	*	*	*	*	*	*	*	*
1984–1988	83	83	83	*	*	*	*	*	*	*	*	*
1989–1993	83	83	83	*	*	*	*	*	*	*	*	*
1994–1998	79	79	79	*	*	*	*	*	*	*	*	*
1999–2003	79	79	79	*	*	*	*	*	*	*	*	*
Norway
1964–1968	30	50	28	45	34	*	35	34	34	24	20	*
1969–1973	30	50	28	45	34	*	35	34	34	24	20	*
1974–1978	30	37	71	37	31	*	44	67	67	40	16	*
1979–1983	40	73	51	62	42	*	54	62	62	49	27	*
1984–1988	58	78	51	53	20	*	65	67	67	68	46	*
1989–1993	64	76	51	30	16	*	69	87	87	53	61	*
1994–1998	74	45	66	49	57	*	71	90	90	60	24	*
1999–2003	75	37	63	55	50	*	80	68	68	57	41	*
Sweden
1964–1968	30	58	49	43	20	*	39	60	55	45	24	*
1969–1973	42	74	72	48	37	*	44	50	61	45	33	*
1974–1978	47	67	51	36	36	*	55	74	72	48	19	*
1979–1983	54	57	91	60	37	*	61	73	74	57	50	*
1984–1988	51	65	73	64	27	*	69	89	84	72	38	*
1989–1993	67	59	85	64	44	*	64	100	76	66	52	*
1994–1998	64	78	69	62	53	*	76	80	87	77	30	0
1999–2003	61	77	76	66	46	*	76	69	81	77	41	*

Numbers in italics indicate that two or more cells had to be combined to get sufficient number of patients to calculate survival.

*Too few patients to calculate survival, see ref. [17].

Figure 8. Trends in age-standardised (ICSS) excess death rates per 100 person years for bone sarcoma by sex, country, and time since diagnosis in Nordic cancer survival study 1964–2003. No Icelandic curves. Too few partients to calculate survival for Iceland.

Soft tissue sarcoma

Incidence and mortality. In general, soft tissue sarcoma incidence has been slowly increasing among men and women in each of the Nordic populations since the 1960s, although there appear to be sex-specific inconsistencies in the trends in the last decade (Figure 9). Incidence is around 2–2.5 per 100 000 among males in all Nordic countries and slightly below two in females circa 2000, with rates highest in Finland. Trends in mortality are difficult to decipher given the random variation in the time trends but they tend to be either relatively stable or weakly declining in recent years.

Figure 9. Trends in age-standardised (World) incidence and mortality rates per 100 000 and age-standardised (ICSS) 5-year relative survival for soft tissue sarcoma by sex and country. Nordic cancer survival study 1964–2003.

Survival. Gradual increases in 5-year relative survival are suggested in both men and women throughout the period of study, possibly with the exception of Sweden, where trends have been rather stable during the last 30 years (Figure 9). Survival is consistently higher in Norway than elsewhere in both sexes during the most recent 15 years. There is however little difference in overall survival in the most recent period of diagnosis 1999–2003, which varies around 65% (Table IX). While prognosis of patients within the first three months of diagnosis has improved with time, there is no consistent observation of a higher excess mortality in any one or more Nordic countries (Figure 10). The variation in excess deaths between the Nordic populations has been largely removed two to five years after initial diagnosis. Survival proportions have increased across all ages, although estimates are highest in the group of patients aged 0–49 at diagnosis (Table X).

Figure 10. Trends in age-standardised (ICSS) excess death rates per 100 person years for soft tissue sarcoma by sex, country, and time since diagnosis in Nordic cancer survival study 1964–2003. No Icelandic curves. Too few partients to calculate survival in Iceland.

Table IX. Trends in survival for soft tissue sarcoma by sex and country. Number of tumours (N) included and the 5-year age-standardised (ICSS) relative survival in percent with 95% confidence intervals (RS (CI)). Nordic cancer survival study 1964–2003.

	Denmark		Finland		Iceland		Norway		Sweden
	N	RS (CI)	N	RS (CI)	N	RS (CI)	N	RS (CI)	N	RS (CI)
Men
1964–1968	205	59 (51–67)	211	44 (38–51)	9	*	144	36 (28–46)	374	44 (39–50)
1969–1973	143	54 (45–65)	245	44 (38–51)	11	*	231	44 (37–51)	458	56 (51–61)
1974–1978	247	47 (40–54)	264	53 (46–61)	9	*	259	45 (39–52)	443	64 (59–70)
1979–1983	284	51 (44–58)	320	48 (42–55)	14	*	301	57 (51–64)	466	61 (56–66)
1984–1988	281	50 (44–58)	319	57 (51–64)	9	*	250	59 (52–67)	605	61 (56–66)
1989–1993	320	58 (52–65)	353	62 (56–68)	15	*	286	71 (65–78)	684	60 (56–64)
1994–1998	368	60 (54–66)	367	60 (55–65)	19	*	330	67 (61–73)	703	61 (57–65)
1999–2003	392	61 (57–66)	448	65 (61–70)	18	*	321	66 (62–71)	799	62 (59–66)
Women
1964–1968	179	55 (48–64)	222	47 (41–54)	8	*	128	47 (38–57)	310	49 (43–55)
1969–1973	168	58 (50–66)	286	46 (40–53)	9	*	176	48 (40–57)	395	55 (49–60)
1974–1978	211	49 (43–57)	289	52 (46–59)	8	*	249	57 (51–63)	405	63 (58–68)
1979–1983	221	57 (49–65)	292	60 (54–66)	11	*	276	58 (52–65)	484	60 (55–65)
1984–1988	239	55 (48–62)	356	58 (53–64)	14	*	250	65 (58–71)	564	60 (56–65)
1989–1993	300	57 (51–64)	397	64 (58–69)	12	*	273	66 (60–73)	608	53 (49–58)
1994–1998	295	64 (58–71)	409	66 (62–71)	10	*	241	70 (64–77)	636	61 (57–65)
1999–2003	350	64 (59–68)	416	67 (63–71)	9	*	280	71 (66–76)	640	63 (59–66)

Numbers in italics indicate that two or more cells had to be combined to get sufficient number of patients to calculate survival.

*Too few patients to calculate survival, see ref. [17].

Table X. Trends in 5-year age-specific relative survival in percent after soft tissue sarcoma by sex and country. Nordic cancer survival study 1964–2003.

	Men						Women
Age	0–49	50–59	60–69	70–79	80–89	90+	0–49	50–59	60–69	70–79	80–89	90+
Denmark
1964–1968	67	63	46	57	48	*	69	68	45	23	58	*
1969–1973	63	56	42	50	50	*	70	48	62	38	55	*
1974–1978	61	30	48	40	30	*	64	47	56	29	9	*
1979–1983	60	60	43	35	39	*	69	64	48	33	51	*
1984–1988	60	39	45	54	43	128	77	44	42	47	34	*
1989–1993	62	53	63	46	59	*	72	62	45	44	36	0
1994–1998	74	65	50	46	32	0	79	50	67	44	66	56
1999–2003	70	63	57	54	42	7	79	62	56	46	55	17
Finland
1964–1968	54	51	34	30	32	*	64	47	40	39	0	*
1969–1973	54	51	34	30	32	*	68	44	29	33	19	*
1974–1978	62	60	52	31	47	*	61	55	42	46	38	*
1979–1983	67	49	36	21	41	*	72	69	47	49	35	*
1984–1988	74	56	48	50	20	*	77	68	41	40	24	*
1989–1993	66	62	56	65	50	*	79	56	59	50	52	67
1994–1998	78	62	58	38	15	*	85	74	51	51	38	*
1999–2003	78	61	65	47	55	27	80	75	50	61	46	0
Iceland
1964–1968	36	36	36	81	*	*	65	65	65	*	*	*
1969–1973	36	36	36	81	*	*	65	65	65	*	*	*
1974–1978	56	56	56	55	*	*	71	71	71	*	*	*
1979–1983	56	56	56	55	*	*	71	71	71	*	*	*
1984–1988	51	51	51	37	*	*	56	56	56	*	*	*
1989–1993	51	51	51	37	*	*	56	56	56	*	*	*
1994–1998	61	61	61	*	*	*	70	70	70	*	*	*
1999–2003	81	81	81	*	*	*	70	70	70	*	*	*
Norway
1964–1968	28	28	31	70	39	*	59	52	32	27	60	*
1969–1973	53	47	41	28	32	*	52	56	53	33	21	*
1974–1978	62	47	41	32	0	97	82	54	48	28	27	*
1979–1983	72	52	54	36	54	*	72	64	53	40	32	0
1984–1988	75	55	49	35	69	*	86	59	53	47	39	0
1989–1993	76	87	58	65	55	*	75	77	57	58	36	0
1994–1998	80	75	60	55	26	0	76	72	75	63	37	0
1999–2003	74	75	64	50	44	8	79	74	66	60	56	0
Sweden
1964–1968	56	31	48	37	19	*	58	48	56	37	16	*
1969–1973	62	65	49	48	38	*	67	60	41	45	42	*
1974–1978	70	72	60	59	36	*	77	66	55	49	35	*
1979–1983	66	53	58	65	53	94	70	63	60	40	47	0
1984–1988	70	58	55	53	59	0	76	48	60	43	47	71
1989 – 1993	71	64	56	45	37	0	68	51	41	48	38	27
1994 – 1998	74	64	54	47	39	98	82	58	49	45	36	22
1999–2003	71	66	59	51	44	44	80	64	53	43	42	13

Numbers in italics indicate that two or more cells had to be combined to get sufficient number of patients to calculate survival.

*Too few patients to calculate survival

Discussion

This study has attempted to summarise the Nordic patient survival experience following diagnoses of a diverse set of specified, but relatively uncommon cancer sites. The text that follows provides, for each of the neoplasms considered, a synopsis of the key findings and some commentary on their interpretation in relation to the relevant epidemiological and clinical literature.

Brain and CNS cancer constitute a heterogeneous group of histologic types, and there is, at present, a paucity of explanatory factors for the upsurge in brain and CNS incidence in recent decades in the Nordic countries. The lack of decline in mortality with time would suggest that part of the increase in overall brain and CNS survival is artefact related to increasing diagnostic intensity with calendar time. Part of the increase in incidence may be explained by increasing use of, and improvements in, diagnostic techniques, as well as therapeutic or high-dose radiation, the only firmly-established risk determinant [19]. There are several candidate explanations for the decreasing incidence trend in Sweden since the early-1980s, including a reduced autopsy intensity among the elderly, underreporting [20], or an age-specific differential in the use of new imaging techniques. In the latter instance, a tendency to screen younger age groups with symptoms may have led to a subsequent decline in overall incidence.

Survival is generally poorer in adults than in children, and prognosis tend to worsen with age; other survival determinants include performance status and tumour histology [21–23]. The extent of resection appears to be the most consistent prognostic factor in patients with high-grade glioma [24].

The brain and CNS survival proportions in the Nordic countries at five years are higher than in other patient series [4,22], but it is unclear whether progress in imaging and treatment (surgery, chemotherapy and radiotherapy) will have improved childhood and adult CNS tumour survival [3]. The female advantage regarding 5-year survival seen in this study is in line with other European countries as shown based on EUROCARE-4 data [25]. There may however have been some modest survival improvements among patients diagnosed with certain histological subtypes, including medulloblastoma and low-grade and unbiopsied gliomas [4,22].

Interpretation of the geographical and temporal variations of brain and CNS tumours is however beset by potential artefactual concerns. The group represents a vast array of different histological subtypes with varying prognosis. Incidence is heavily influenced by local registration practices concerning the inclusion of benign tumours, unspecified tumours and those of unspecified behaviour, although benign brain tumours are included in the incidence in each of the Nordic registries. The introduction of new technologies including CT scanning and MRI will have improved detection rates over the last 30 years and will certainly explain part of the observed increases in incidence (and probably survival) in the Nordic countries. A degree of underreporting to registries of cancers of the brain and CNS is also possible, but this may be largely restricted to unbiopsied tumours [26].

Mortality rates of thyroid cancer have been decreasing in all Nordic countries during the last 25 years while the 5-year relative survival has been steadily increasing over the same period, leading to an overall survival for patients diagnosed 1999–2003 at 80–90%, an estimate that may be considered quite favourable. Denmark appears to have poorer survival than elsewhere, although the underlying reasons for this disparity and the overall survival improvements are difficult to gauge. A number of factors may be in operation, and the absence of key additional information on, for example, histology and staging limits the depth of the survival analysis and subsequently the scope of our interpretation.

Thyroid cancer incidence tended to increase during the 1960s and 1970s in each population, but rates subsequently stabilised or declined. That rates in Icelandic females exhibited very rapid but transitory increases in the early-1970s lend support to the presence of diagnostic artefact in the numerator, since a very high percentage were diagnosed at incidental autopsy and thus excluded from the survival calculations. Alternatively, the consistently higher rates in both sexes relative to other Nordic regions might additionally imply that levels of background risk are higher in Iceland than elsewhere. Results from Nordic epidemiological studies that have sought to identify the specific determinants have been inconsistent and in short supply.

Accompanying the trends in thyroid cancer incidence rates, population-based patient survival has risen throughout Europe and in the Nordic countries in recent decades [27,28]. Temporal and geographical differences in overall thyroid cancer survival remain difficult to interpret however without further stratification by histological subtype and extent of disease. Heterogeneity in diagnostic intensity, as well as changing histological composition will likely influence the magnitude of these survival estimates, and accordingly, the utility of comparisons between countries and over time. A differential in the distribution of histological subgroups has been shown to be a key prognostic factor for thyroid cancer [27–29]. Prognosis ranges from excellent for the most common form, papillary cancer, to rather poor for poorly-differentiated and anaplastic carcinomas. Colonna and colleagues have speculated that the superior survival observed recently in Norway results from a higher proportion of papillary cancers among its cases (an observation made in 1983 on the basis of a Finland comparison [30]), and in general, that better survival in Europe is seen where the proportion of papillary cancers is highest [28]. This phenomenon may explain the higher survival in women, relative to men [25,31] but other explanations – such as a role for sex hormones – have been postulated [32].

Another possible reason for the observed survival differences may relate to a differential in the use of new diagnostic techniques in the Nordic countries that have improved the ability to diagnose thyroid cancer. Improved fine-needle aspiration techniques and interpretation, along with thyroid ultrasonography has likely increased the proportion of microcarcinomas which may have subsequently led to improvements in survival where practice is more intensive [28].

Both of these factors may partially explain the thyroid cancer survival differentials and in particular, the lower survival from thyroid cancer in Denmark. Treatment for differentiated tumours has not changed appreciably in the last decades [6], although TNM staging including lymph node and distant metastases and complete removal of the tumour in operated patients are significant prognostic factors in Sweden [29]. Differences in stage of presentation and the quality of surgery across the Nordic countries may thus be an important marker of survival differentials. Finally, it has been shown that smokers appear to have an inferior survival following a thyroid cancer diagnosis than non-smokers [29]; given the differentially high prevalence of current smokers in Denmark [33], this factor may be of additional relevance to overall prognosis following a thyroid cancer diagnosis.

For cancers of the eye, mortality rates have fallen moderately while survival has increased. The improved survival in the younger age group was probably the result of improving prognosis among the retinoblastoma group, although a Danish study has reported increases in survival of patients diagnosed with eye melanomas at younger ages [10]. In that study the diagnostics did not appear to change over the period and the changes in treatment did not appear to affect the survival, echoing a Swedish study showing an improved survival of eye cancer patients with calendar time but for unexplained reasons [34].

In simple terms, incidence and mortality rates of bone sarcoma have tended to decline over time in the Nordic countries, irrespective of sex and population, with the downturn in rates seemingly more rapid for mortality. The reduction in case fatality and increases in survival may relate to clinical improvements, but artefactual explanations might also contribute. In Finland, for example, the proportion of unknown histology has uniformly declined with time, and it has been reported that this group probably included a large number of bone metastases of other tumours in early periods [35]. Storm has linked the Nordic differences to the degree of availability of specialist centres for the referral and treatment of patients, citing lower recurrence rates as a possible reason for the higher survival proportions in Sweden [14]. Improving treatment, particularly in children and young adults may be a partial explanation, and is supported by the greatest survival increases observed in the youngest age group in this study. Stiller et al. have shown that bone sarcoma survival has increased in both children and adolescents in Europe, citing local treatment in combination with systemic chemotherapy for treating osteosarcoma and Ewing's sarcoma as a possible explanation [13]. Female gender has been shown to be a strong predictor of favourable outcome in patients with classical osteosarcoma [36].

As with other cancers reviewed in this article (cancers of the brain, thyroid, and soft tissues), the effect of an improving ability to diagnose bone sarcomas over time, and the potential artificial improvements in survival cannot be excluded. A changing distribution of histological types between countries over time may also have had an impact on survival, where, for example, the relative proportion of chondrosarcomas, tumours associated with rather good prognosis, differed. Finally, a high excess mortality 0–3 months after diagnosis was less apparent in Denmark for bone sarcoma in men, although survival was somewhat lower than elsewhere. This might imply a sex-specific differential in factors other than stage at presentation and initial treatment are of importance in explaining the survival differences for certain bone lesion subtypes, but further in-depth analyses examining stage and histology are warranted.

From a European perspective, 5-year relative survival among patients diagnosed with bone sarcoma from the Nordic countries is in line with that of patients from UK and parts of Western Europe (Belgium, Austria, France). Sant and colleagues also showed that 5-year survival, conditional on surviving one year, among Danish patients was higher than in the other Nordic countries [5].

There have been few population-based studies investigating the survival of patients with soft tissue sarcoma. The survival increases seen across Nordic countries in both sexes may suggest improving treatment as a possible factor. Tumour size, histology, primary site, grade and the presence of metastasis have been reported as key prognostic factors in treating the disease [37]. In a recent paper on childhood cancer survival, the 5-year survival of children increased to 74% in the Nordic countries (excluding Sweden) for the period 1993–1997, while corresponding survival for fibrosarcoma was 89% and for rhabdomyosarcoma, 67% [38]. Improvements in the latter subtype have been ascribed to advancements in therapeutic options including better surgery and chemotherapy. The degree of specialisation of care may also be important [14].

Soft tissue sarcoma incidence and survival trends are however difficult to interpret given the low rates, and there are further difficulties in definition and the poor reproducibility of histological subtypes [39]. As with other cancers reviewed here, changing proportions of the major histological subtypes in the different countries over time might affect the overall survival estimates, as could a growing interest and ability to diagnose these tumours in consecutive calendar periods.

Acknowledgement The Nordic Cancer Union (NCU) has financially supported the development of the NORDCAN database and program, as well as the survival analyses in this project.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.