Systematic review and meta-analysis of the volume-outcome relationship in pancreatic surgery.

BACKGROUND: Many studies have shown lower mortality and higher survival rates after pancreatic surgery with high-volume providers, suggesting that centralization of pancreatic surgery can improve outcomes. The methodological quality of these studies is open to question. This study involves a systematic review of the volume-outcome relationship for pancreatic surgery with a meta-analysis of studies considered to be of good quality. METHODS: A systematic search of electronic databases up to February 2010 was performed to identify all primary studies examining the effects of hospital or surgeon volume on postoperative mortality and survival after pancreatic surgery. All articles were critically appraised with regard to methodological quality and risk of bias. After strict inclusion, meta-analysis assuming a random-effects model was done to estimate the effect of higher surgeon or hospital volume on patient outcome. RESULTS: Fourteen studies were included in the meta-analysis. The results showed a significant association between hospital volume and postoperative mortality (odds ratio 0.32, 95 per cent confidence interval 0.16 to 0.64), and between hospital volume and survival (hazard ratio 0.79, 0.70 to 0.89).The effect of surgeon volume on postoperative mortality was not significant (odds ratio 0.46, 0.17 to 1.26). Significant heterogeneity was seen in the analysis of hospital volume and mortality. Sensitivity analysis showed no correlation with the extent of risk adjustment or study country; after removing one outlier study, the result was homogeneous. The data did not suggest publication bias. CONCLUSION: There was a consistent association between high hospital volume and lower postoperative mortality rates with improved long-term survival.

A systematic review and meta-analysis of the volume-outcome relationship in the surgical treatment of breast cancer. Are breast cancer patients better of with a high volume provider?

AIMS: To conduct a systematic review of the literature on the volume-outcome relationship for the surgical treatment of breast cancer with consideration of the methodological quality of the available evidence and to perform a meta-analysis on the studies of considered good quality. METHODS: A systematic search was done to identify all articles examining the effects of hospital or surgeon volume on clinical outcome of the surgical treatment of breast cancer. Reviews, opinion articles and surveys were excluded. All articles were critically appraised on methodological quality and risk of bias. After strict inclusion, meta-analysis assuming a random effects model was done to estimate the effect of higher hospital or surgeon volume on patient outcome. RESULTS: We found 12 studies of good methodological quality which could be included for meta-analysis. The results showed a significant association between high volume providers and an improved survival. The association is the most robust for surgeon volume (HR 0.80 (0.71-0.90) and RR 0.85 (0.80-0.90). In addition there is an effect of hospital volume on the in-hospital mortality, although the mortality was very low (0.1-0.2%). Results of meta-analysis were heterogeneous. Sensitivity analysis showed a larger effect size for studies also adjusting for comorbidity for both studies on hospital and surgeon volume. The data were not suggestive for publication bias. CONCLUSIONS: The results show that survival after breast cancer surgery is significantly associated with high volume providers.

Volume and outcome in colorectal cancer surgery.

AIMS: There is a growing consensus to concentrate high-risk surgical procedures to high volume surgeons in high volume hospitals. However, there is fierce debate about centralizing more common malignancies such as colorectal cancer. The objective of this review is to conduct a meta-analysis using the best evidence available on the volume-outcome relationship for colorectal cancer treatment. METHODS: A systematic search was performed to identify all relevant articles studying the relation between hospital and/or surgeon volume and clinical outcomes for colorectal cancer. Using strict inclusion criteria, 23 articles were selected concerning colon cancer, rectal cancer or both diseases together as 'colorectal cancer'. Pooled estimated effect sizes were calculated using the casemix adjusted outcomes of the highest volume group opposed to the lowest volume group. RESULTS: High volume hospitals have a significantly lower postoperative mortality in half of the pooled results. Non significant results show a trend in favour of high volume hospitals. All results showed a significantly better long term survival in high volume hospitals. High volume surgeons have a lower postoperative mortality, although evidence is sparse. All analyses showed a significantly better long term survival in favour of high volume surgeons. CONCLUSIONS: The results show a clear and consistent relation between high volume providers and improved long term survival. This applies to both high volume hospitals and high volume surgeons. Most results show a relation between high volume providers and a reduced postoperative mortality, but evidence is less convincing. In the ideal world, extensive population based audit registrations with casemix adjusted feedback should make rigid minimal volume standards obsolete. Until then, using volume criteria for hospitals and surgeons treating colorectal cancer can improve mortality and especially long term survival.

Declining incidence of peptic ulcer but not of its complications: a nation-wide study in The Netherlands.

BACKGROUND: Despite reports of decreasing hospitalizations and mortality due to peptic ulcer, it is unclear whether the incidence has truly declined over time. AIM: To investigate time trends in the incidence of and in hospital admission rates for peptic ulcer in the Netherlands. METHODS: The nationwide registry of pathology reports (PALGA) and the national registry of hospital admissions (Landelijke Medische Registratie) were used. Standardized morbidity ratios were calculated to assess the magnitude of the changes. RESULTS: The age-adjusted incidence of gastric ulcer halved for both men (standardized morbidity ratio 0.48; CI 0.46-0.49) and women (standardized morbidity ratio 0.49; CI 0.47-0.51). Although the number of gastric biopsies obtained at endoscopy increased, the proportion with a diagnosis of peptic ulcer decreased by more than 50% (standardized morbidity ratio 0.47; CI 0.46-0.49). The admission rate for peptic ulcer more than halved between 1980 and 2003. In contrast, admission rates for complicated ulcers barely changed and slightly increased among women. CONCLUSIONS: The incidence of histopathologically confirmed gastric ulcer halved between 1992 and 2003 in the Netherlands. As the number of gastric biopsies increased in this period, a true decrease is likely. Hospital admissions for peptic ulcer declined dramatically between 1980 and 2003, but remained unchanged or slightly increased for complicated ulcers.

Optimal follow-up strategies after aorto-iliac prosthetic reconstruction: a decision analysis and cost-effectiveness analysis.

OBJECTIVE: The primary aim of ultrasound follow-up after aorto-iliac prosthetic reconstruction is to correct false aneurysms before rupture occurs. We investigated whether follow-up improves the life expectancy of patients and sought to identify the most cost-effective follow-up strategy. DESIGN OF THE STUDY: A Monte Carlo Markov decision model was constructed. The occurrence of false aneurysms was modelled as a time-dependent process for each anastomotic site, based on published series. Using this model, the impact of various follow-up strategies was investigated for three types of prostheses, aorto-distal tube, aorto-bi-iliac, and aorto-bi-femoral prostheses. Main outcome measures were discounted quality adjusted life years (dQALYs), discounted costs, and (discounted) cost-effectiveness (CE) ratios. RESULTS: Follow-up of patients with aorto-distal tube and aorto-bifemoral prostheses did not result in an improvement life expectancy and was not cost-effective, QALYs 7.53 and 7.62 years, respectively. The results for aorto-distal tube and aorto-bifemoral prostheses were not sensitive to any variation in the model parameters. In the base case analysis, the life expectancy of patients with aorto-bi-iliac prostheses was 7.50 QALYs (95% confidence interval 7.46-7.54) whether or not they underwent routine follow-up. However, patients aged 54 years or younger gained 0.11 QALYs with annual follow-up (p<0.05). The most cost-effective strategy was annual follow-up that starts 10 years after the initial operation, and continues up to 30 years after surgery (4600 Euro; CE ratio 21,000 Euro per QALY). When perioperative mortality of elective reconstruction of false aneurysms is 2% or lower (e.g. when endovascular treatment is used), a small improvement is observed (7.56 vs. 7.50 QALYs; p<0.05; CE ratio 35,000 Euro per QALY). CONCLUSIONS: Annual follow-up of aorto-bi-iliac prostheses should be restricted to patients aged 54 or younger and not start before 10 years after surgery. The same strategy can only be considered for older patients if mortality for secondary intervention is lower than 2%. Since patients with aorto-distal tube and aorto-bi-femoral prostheses do not benefit from follow-up for the detection of false aneurysms, this practice should be discouraged in these patient groups.

[The epidemiology of tumors of the testes in the Netherlands: accurate rendering by the Registry of Histopathology and Cytopathology (PALGA)]. / Epidemiologie van testistumoren in Nederland: accurate weergave in de PALGA-registratie.

OBJECTIVE: To investigate recent trends in the incidence of testicular cancer and to describe epidemiological characteristics of various subtypes of testicular cancer. DESIGN: Descriptive. METHOD: Using the nationwide registry of pathology reports (PALGA), the incidence of all newly-diagnosed cases of testicular cancer between the years 1991 and 2002 was analyzed according to age and subtype. To test the accuracy of the PALGA figures, a comparison was made with incidence figures (1991-1998) produced by the Netherlands Cancer Registry. RESULTS: 5856 cases of testicular cancer were diagnosed. The age-adjusted incidence increased from 4.8 to 6.6 per 100,000. The incidence of non-seminoma increased to a larger extent than that of seminoma. The incidence of malignant lymphoma of testicular origin did not increase, but it remained the most frequent testicular tumour beyond the age of 65. Non-seminoma was the most common tumour below the age of 30, while seminoma was the most commonly found tumour between the ages of 30 and 65. When PALGA began recording statistics, the incidence figures showed a difference of up to 10% with the figures produced by the cancer registry, but this has decreased to 1-2% in more recent years. CONCLUSION: The incidence of testicular cancer increased from the 1990s up to 2002. The incidence figures of histopathologically confirmed cases of cancer in the PALGA registry were timely and accurate.

Saphenous vein versus PTFE for above-knee femoropopliteal bypass. A review of the literature.

The autogenous saphenous vein is considered the best bypass graft material for arterial bypasses below the inguinal ligament. However, a synthetic graft or prosthesis is considered an acceptable alternative, especially when the distal anastomosis is situated above the knee. Some studies even suggest that patency rates for vein and synthetic grafts are comparable, whereas others indicate that a vein graft is superior to a prosthetic graft, even above the knee. To test the hypothesis that both vein grafts and synthetic prostheses are equally beneficial in the above-knee position, we performed a systematic review of available studies comparing the patency of saphenous vein and polytetrafluoroethylene (PTFE) as bypass material. English and German medical literature from 1966 to 2002 was searched using Medline, and 25 articles meeting our inclusion and exclusion criteria were selected. The patency of venous bypasses was superior to that of PTFE bypasses at all time intervals studied. After 2 years, the primary patency rate of venous bypasses was 81% as compared to 67% for PTFE bypasses, and after 5 years it was 69 and 49%, respectively. After 5 years, the secondary patency of PTFE bypasses reached 60%. When only randomized trials were considered, venous bypasses were again superior to PTFE bypasses at all intervals studied. After 2 years, the primary patency rate of venous and PTFE bypasses was 80 and 69%, respectively, and after 5 years it was 74 and 39%, respectively. Since both randomized and retrospective studies comparing venous with PTFE bypasses showed that vein grafts were 'better' than PTFE prostheses, the null hypothesis that there is no difference between the two types of graft material was rejected (p=0.008). We conclude from this systematic review that if a saphenous vein is available, a venous bypass should be chosen at all times, even if patients have an anticipated short life expectancy (<2 years). If the saphenous vein is absent or not suitable for bypass grafting, PTFE is a good alternative as bypass material.

The utility of health states after stroke: a systematic review of the literature.

BACKGROUND: To perform decision analyses that include stroke as one of the possible health states, the utilities of stroke states must be determined. We reviewed the literature to obtain estimates of the utility of stroke and explored the impact of the study population and the elicitation method. SUMMARY OF REVIEW: We searched various databases for articles reporting empirical assessment of utilities. Mean utilities of major stroke (Rankin Scale 4 to 5) and minor stroke (Rankin Scale 2 to 3) were calculated, stratified by study population and elicitation method. Additionally, the modified Rankin Scale was mapped onto the EuroQol classification system. Utilities were obtained from 23 articles. Patients at risk for stroke assigned utilities of 0.26 and 0.55 to major and minor stroke, respectively. Stroke survivors assigned higher utilities to both major (0.41) and minor stroke (0.72). The EuroQol completed by stroke survivors revealed a utility of 0.32 and 0.71 for major and minor stroke, respectively. Utilities elicited by the Standard Gamble were generally higher, while those obtained by the Visual Analogue Scale were lower than the Time Trade Off values. Remaining variation between utilities may be caused by differences in definitions of the health states. The mapped EuroQol indicated a utility of 0.64 for minor stroke and a value just below zero for major stroke. CONCLUSIONS: For minor stroke, a utility between 0.50 and 0.70 seems to be reasonable for both decision analyses and cost-effectiveness studies. The utility of major stroke may range between 0 and 0.30 and may possibly be negative.

The independent prognostic value of comorbidity among men aged < 75 years with localized prostate cancer: a population-based study.

OBJECTIVE: To investigate which prognostic factors apply in patients with localized prostate cancer diagnosed after the introduction of prostate-specific antigen (PSA) testing, as comorbidity has significant prognostic value for patients who were diagnosed with localized prostate cancer in the 1970s. Patients and methods Using the Eindhoven Cancer Registry, we assessed a population-based cohort of patients aged < 75 years with localized (T1-T3M0) prostate cancer diagnosed between 1993 and 1995 in a defined area with 2 million inhabitants in the southern Netherlands (n = 894). After a mean follow-up of 2.9 years, overall survival was modelled by Cox regression analyses. RESULTS: Comorbidity was the most important prognostic factor, especially for those aged < 70 years; at 60 years old, patients with one concomitant disease were twice as likely to die than those with no comorbidity (95% confidence interval, CI, 1.0-4.3), whereas the hazard ratio (HR) was 7.2 (3.1-16.6) for two or more diseases. This was not caused by a reduced use of curative treatment for these patients. At the age of 74 years, comorbidity was no longer a significant prognostic factor. Poor differentiation of the tumour was also an important prognostic factor at all ages; this became increasingly apparent 2 years after diagnosis (HR 3.4, CI 1.5-7.7). Conclusion Comorbidity had a decisive influence on the prognosis for patients with localized prostate cancer. Because this effect was stronger in younger patients the assessment of comorbidity seems most important when evaluating the risk of early death.

Long-term survival of prostate cancer in southeastern Netherlands.

With the increase in detection at an early stage, only a few and conflicting results have been reported on the long-term outcome for prostate cancer beyond 10 years. The vast majority of prostate cancer patients diagnosed between 1955 and 1984 in southeastern Netherlands, with a population of almost one million inhabitants, did not receive any curative treatment. We calculated the prognosis for 10-year survivors of prostate cancer diagnosed in the era preceding prostate-specific antigen (PSA) testing to determine how long these patients exhibited excess mortality. All patients under age 70 diagnosed with prostate cancer and registered in the population-based Eindhoven Cancer Registry between 1955 and 1984 were included in the study. Relative survival was calculated for those who survived for at least 10 years (n = 174). Initially, these patients still exhibited an almost 25% excess mortality risk, but this decreased with time and no excess mortality was found after 15 years.

Serious co-morbidity among unselected cancer patients newly diagnosed in the southeastern part of The Netherlands in 1993-1996.

The purpose of this study was to determine the prevalence of serious concomitant conditions at diagnosis among unselected patients with cancer, increasingly older in industrialized countries. About 34,000 newly diagnosed cancer patients were recorded in the Eindhoven Cancer Registry between 1993 and 1996; subsequently data on serious co-morbidity, classified according to the Charlson scheme (J Chron Dis 1987; 40: 373-383), were collected from the clinical records by registry personnel. Co-morbid conditions were present in 12% of adult patients below 45 years of age, 28% of those 45-59 years, 53% of those 60-74 years, and 63% of patients over 75 years of age, the prevalence being highest for patients with lung (58%), kidney (54%), stomach (53%), bladder (53%), and prostate cancer (51%). Males exhibited a 10% higher prevalence than females with similar tumors. Among patients over 60 years the most frequent conditions were heart and vascular diseases (ranging across the various tumors from 10% to 30%), hypertension (11-25%), another cancer (10-20%), COPD (chronic obstructive pulmonary disease) (3-25%), and diabetes mellitus (5-25%). Inclusion of frequent co-morbid conditions in prognostic research as well as the development of specific guidelines for patient care seems warranted.

Comorbidity in patients with prostate cancer and its relevance to treatment choice.

OBJECTIVE: To evaluate the prevalence of comorbidity among patients with prostate cancer in relation to tumour and patient characteristics and to assess if comorbidity was a determining factor in the treatment choice for patients with localized prostate cancer. PATIENTS AND METHODS: Serious comorbidity was recorded in the Eindhoven Cancer Registry (according to a published list of such diseases) for all patients (2941) with prostate cancer newly diagnosed between 1993 and 1996 in the southern part of The Netherlands. Logistic regression was then used to assess which factors determined the treatment choice. RESULTS: The prevalence of at least one serious comorbid condition was 38% for patients aged 60-69 years, 48% when aged 70-74 years and 53% for those aged >/=75 years, the cardiovascular and chronic obstructive lung diseases being most frequent. Patients aged 60-69 years were more likely to be treated with radical prostatectomy for moderately differentiated tumour confined to the prostate, or when younger and diagnosed in a hospital with a high case-load. The presence of comorbidity had little influence of this choice. CONCLUSION: Comorbidity was common in patients with prostate cancer, but the decision of urologists in the southern Netherlands to use radical prostatectomy was determined largely by the patient's age and the urologist's experience.

Trend and variation in treatment of localized prostate cancer in the southern part of The Netherlands, 1988-1996. Regional Study Group for Urological Oncology IKZ, Eindhoven.

OBJECTIVE: To investigate whether the large increase in the incidence of early prostate cancer has led to subsequent increased application of curative treatment and whether similar patterns of treatment were observed in the various hospitals in the area of this investigation. METHODS: Using the Eindhoven Cancer Registry, all patients newly diagnosed with prostate cancer between 1988 and 1996 in the southern part of The Netherlands were included in the study. Initial treatment was analyzed for 4,073 patients, of whom the proportion with clinically localized prostate cancer (T1-T3, M0-Mx) increased from 52% in 1988-1990 to 74% in 1994-1996. RESULTS: The proportion of patients with localized prostate cancer treated with radical prostatectomy increased from 11 to 34% among patients under age 70. Especially in 1994-1996, a group of smaller hospitals (n = 11) with a rather low proportion of patients treated by radical prostatectomy (5-52%) could be distinguished from a group of larger hospitals (n = 5) with a large proportion of patients treated by radical prostatectomy (35-67%). Radiotherapy was a more frequent option in hospitals with low radical prostatectomy rates. The proportion of patients aged 70-74 years undergoing radiotherapy increased from 31 to 41%. Over 80% of the patients aged 75 years or older were treated conservatively during the whole study period. CONCLUSION: Increased detection of localized prostate cancer resulted in increased application of curative treatment for patients under 70 years of age, but a substantial variation was observed between hospitals in the application of radical prostatectomy and radiotherapy.

Striking increase in incidence of prostate cancer in men aged < 60 years without improvement in prognosis.

Increased awareness and improved diagnostic techniques have led to earlier diagnosis of prostate cancer and increased detection of subclinical cases, resulting in improved prognosis. We postulated that the considerable increase in incidence under age 60 is not attributable only to increased detection. To test this hypothesis, we studied incidence, mortality and relative survival among middle-aged patients diagnosed in south-east Netherlands and East Anglia (UK) between 1971 and 1994. Prostate-specific antigen (PSA) testing did not occur before 1990. Between 1971 and 1989, the age-standardized incidence at ages 40-59 increased from 8.8 to 12.5 per 10(5) in The Netherlands and from 7.0 to 11.6 per 10(5) in East Anglia. Five-year relative survival did not improve in East Anglia and even declined in southeast Netherlands from 65% [95% confidence interval (CI) 47-83) in 1975-79 to 48% (CI 34-62) in 1985-89. Mortality due to prostate cancer among men aged 45-64 years increased by 50% in south-east Netherlands and by 61% in East Anglia between 1971 and 1989, but decreased slightly in the 1990s. Because other factors adversely influencing the prognosis are unlikely, our results indicate an increase in the incidence of fatal prostate cancer among younger men in the era preceding PSA testing.

Increased risk of fatal prostate cancer may explain the rise in mortality in The Netherlands.

BACKGROUND: Several lines of evidence suggest that, as a result of improved diagnostic techniques, the increase in incidence of prostate cancer is due largely to increased detection of subclinical cases. Between 1971 and 1989, a considerable increase in incidence was found in Southeastern Netherlands among men aged under 60 years without an improvement in prognosis. We hypothesized that in addition to the increase due to increased detection, a genuine increase in incidence has occurred in the last two decades and that this should be reflected in national mortality rates. METHODS: Age-specific and age-adjusted mortality rates were calculated to determine whether mortality due to prostate cancer continued to increase after 1990. Using log-linear Poisson modelling according to Clayton and Schifflers, we estimated the contribution of period and cohort effects to prostate cancer mortality between 1955 and 1994. RESULTS: The age-adjusted mortality increased from 22 in 1955-1959 to 33 per 10(5) in 1990-1994 (European standardized rate). For men under 65, the rates stabilized after 1989. The age-cohort model fitted the data better than the age-period model. Therefore, the increase in mortality can be explained largely by the increasing risk for successive birth cohorts for men born until 1930. However, more frequent reporting of prostate cancer as the underlying cause of death (partly attributable to a decline in competing causes of death) may have occurred as well. CONCLUSIONS: Our findings suggest an increased risk of fatal prostate cancer in The Netherlands between 1955 and 1994.

Trends in survival of prostate cancer in southeastern Netherlands, 1971-1989.

The increase in the incidence of prostate cancer observed over the past 2 decades is suggested to be largely due to increased detection of insignificant tumors. To explore this assumption, we investigated trends in survival of prostate cancer patients in southeastern Netherlands, an area with almost 1 million inhabitants, where the age-adjusted incidence of prostate cancer increased by 53% between 1971 and 1989, i.e., before the introduction of prostate-specific antigen testing. Survival was calculated for all patients registered in the Eindhoven Cancer Registry between 1971 and 1989 (n = 2,562). In spite of earlier diagnosis, survival barely changed during this time period. Five-year relative survival improved slightly from 53% [95% confidence interval (CI) 47%, 59%] in 1975-1979 to 56% (CI 51%, 61%) in 1985-1989. Stratified analyses suggested an improvement since 1980 for patients below 75 years with localized tumors but, despite possible stage migration, decreased survival for those with metastasized and/or poorly differentiated tumors. Patients below 75 years whose tumors were diagnosed unexpectedly during transurethral resection of the prostate (TURP) exhibited a relative survival of 85% 5 years and 68% 10 years after diagnosis. Less extensive application of TURP in The Netherlands might explain why our findings do not agree with those in Sweden and the United States. Inference from country-specific trends in survival appears not to be necessarily generalizable to other countries with a similar increase in the incidence of prostate cancer. We conclude from our results that earlier diagnosis of prostate cancer between 1971 and 1989 may be accompanied by an increased incidence of an aggressive variant.

Trends in incidence and mortality rates for prostate cancer before and after prostate-specific antigen introduction. A registry-based study in southeastern Netherlands, 1971-1995.

The incidence of prostate cancer has increased considerably over the past two decades, partly due to the increased detection of subclinical cases. In southeastern Netherlands, a region of almost 1 million inhabitants with good access to specialised medical care, prostate-specific antigen (PSA) assays were not introduced until 1990, allowing us to investigate the nature of the increases in incidence. Age-adjusted (European Standardised Rate) and age-specific rates were calculated using incidence data from the population-based Eindhoven Cancer Registry and mortality data from Statistics Netherlands. The age-adjusted incidence, which increased from 36 per 100,000 in 1971 to 55 per 100,000 in 1989, included all grades as well as metastasised prostate cancer. The age-adjusted mortality mainly fluctuated in this period, but increased among men aged 55-64 years from 12 per 100,000 in 1980 to 25 per 100,000 in 1989. After 1990, the age-adjusted incidence further increased to 80 per 100,000 in 1995, the increase representing mainly low-grade localised prostate cancer, presumably due to increasing opportunistic PSA testing, especially after 1993. A real increase in incidence may have occurred before 1993. However, pending results of randomised trials, judicious application of PSA testing seems justifiable to avoid unnecessary intervention without reducing mortality.

Modest decline in late mortality following Hodgkin's disease in the southeastern Netherlands since 1972.

Since prolonged remission can be induced in the majority of patients with Hodgkin's disease (HD), treatment-related mortality and morbidity have emerged. We investigated whether awareness of toxicity diminished treatment-related mortality for unselected patients treated between 1972 and 1993 in general hospitals in the southeastern Netherlands. We also estimated the prevalence of treatment-related morbidity among patients treated in the 1980s. Data were collected on all 345 HD patients registered in the Eindhoven Cancer Registry between 1972 and 1993. Medical records and histology were reviewed; follow-up ended in 1994. Administration of MOPP chemotherapy decreased, and there was a shift from total nodal irradiation to less extended low-dose radiotherapy. For cured patients the 10-year relative survival improved from 84% in the 1970s to 90% in the 1980s, which is reflected by a decline in excess mortality from 16% to 10%. The 10-year relative mortality risk due to secondary malignancies decreased from 4.3 (95% CI, 1.2-7.4) to 3.0 (CI 0.2-5.8), which is also reflected by a decline in the 10-year cumulative incidence for all cancers from 10% to 5%. However, the relative risk of late cardiovascular death, which is closely related to previous irradiation, barely changed, as shown by a decrease from 2.4 (CI 0.4-4.5) to 2.2 (CI.0-4.7). HD survivors profited less from the sharp decline in cardiovascular mortality observed for the general population. Among patients, the prevalence of serious treatment-related morbidity 5 years or more after initial diagnosis was 34%. In conclusion, modest decline in excess mortality among cured HD patients was observed in the 1980s, as reflected by a decrease in mortality due to second malignancies. However, late mortality, especially due to radiation-related cardiovascular disease, is still substantial. About one third of HD survivors suffer radiation-induced sequelae. Clinical trials to find ways to minimize iatrogenic complications are important.