Abstract
Objectives
To investigate the impact of age and life expectancy on treatment decisions and its consequences for outcomes among men with intermediate and high‐risk prostate cancer (PCa).
Materials and methods
We studied men in Prostate Cancer data Base Sweden (PCBaSe) diagnosed between 2008 and 2022 with intermediate‐risk or high‐risk localized or locally advanced PCa and life expectancy between 2.5 and 15 years in the absence of PCa. Estimates of life expectancy were based on age and two comorbidity indices.
Results
A total of 32 196 men were included in the analyses. Of these, 17 419 (54%) had a life expectancy between 10 and 15 years, of whom 11 147 (64%) received primary radical treatment. Age had a stronger influence than life expectancy on the selection of treatment. Around 10% of deaths within 10 years of diagnosis could potentially have been avoided if men with >10 years life expectancy, regardless of age, had received radical treatment, based on assumptions of high treatment efficacy (30% reduction in all‐cause mortality) and high uptake of treatment (90%).
Conclusion
A substantial proportion of healthy older men with intermediate and high‐risk PCa did not undergo radical treatment. According to our model and assumptions, 10% of deaths within 10 years of diagnosis in these men could potentially have been avoided if they had received radical treatment.
Keywords: age, comorbidity, life expectancy, prostate cancer, radical treatment
1. INTRODUCTION
The risk of progression and prostate cancer (PCa) death depends on cancer characteristics, treatment and life expectancy. Risk category and life expectancy are crucial for selection of treatment, and hence the European Association of Urology (EAU) Guidelines, the National Comprehensive Cancer Network (NCCN) guidelines, as well as the Swedish prostate cancer guidelines, recommend that life expectancy be central in clinical decisions on treatment for PCa. 1 , 2 , 3
EAU guidelines recommend radical treatment for men with high‐risk PCa and life expectancy >10 years, 1 whereas NCCN guidelines recommend radical treatment for men with high‐risk and very high‐risk PCa and life expectancy >5 years. 2 The Swedish guidelines recommend radical treatment for men with unfavourable intermediate‐risk and high‐risk PCa who have a life expectancy >10 years, and that radical treatment for men with very high‐risk PCa and life expectancy > 5 years should be discussed at a multidisciplinary conference. 3
The aims of this study were to investigate the impact of age and life expectancy on treatment decisions among men with intermediate and high‐risk localized and locally advanced PCa and its consequences for outcomes.
2. MATERIALS AND METHODS
2.1. Data sources
The National Prostate Cancer Register (NPCR) of Sweden collects data on tumour characteristics, mode of detection and treatment, enabling studies on treatment and adherence to national guidelines. 4 , 5 In Prostate Cancer data Base Sweden (PCBaSe), NPCR has been linked to several health care registers 6 by use of the unique Swedish Personal Identity Number. In this study, we use data from NPCR, the National Patient Register, the National Prescribed Drug Register and the Cause of Death Register. Reporting of new cases of PCa is mandatory by law to the Swedish Cancer Registry, and PCBaSe is estimated to include 99% of all men registered with PCa between 2008 and 2022 in the Swedish Cancer Register. 7
2.2. Study population
We selected men in PCBaSe diagnosed between January 1, 2008, and June 30, 2021, with unfavourable intermediate‐risk, high‐risk and very high‐risk localized or locally advanced PCa who had a life expectancy between 2.5 and 15 years in the absence of PCa. Men with a life expectancy >15 years were not included in the study, as a large majority of these men should unequivocally receive radical treatment. Men with a life expectancy between 2.5 and 5 years at diagnosis were included to improve the statistical fitting of cubic splines. To allow for treatment decisions to have been made, follow‐up commenced at 180 days after the date of diagnosis and continued until death, emigration, or December 31, 2021, whichever event came first. Risk categories were defined according to a modification of the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (NCCN Guidelines) adopted by NPCR that closely resemble the risk stratification in the Swedish National Guidelines for Prostate Cancer:
Unfavourable intermediate‐risk PCa: Gleason score 4 + 3 with PSA < 20 ng/ml or Gleason 6 with PSA > 15–20 ng/ml and stage T1–2.
High‐risk PCa: Gleason 8–10, or 20 ≤ PSA < 50 ng/ml, or stage T3.
Very high‐risk PCa: Any Gleason, stage T4, N1 or 50 ≤ PSA < 100 ng/ml, or 50 ≤ PSA < 500 if M0 according to bone scan.
2.3. Exposure
Life expectancy in the absence of PCa was calculated based on age, a Drug Comorbidity Index (DCI) 8 , 9 and a Multidimensional Diagnosis‐based Comorbidity Index (MDCI) 10 according to a previously used method. 11 The DCI was based on all drug prescriptions registered in the National Prescribed Drug Register within 365 days preceding the date of PCa diagnosis. 8 The MDCI used all ICD‐10 codes related to hospital discharges registered up to 10 years prior to the date of PCa diagnosis in the Inpatient and Outpatient Registers. 10 Both comorbidity indices have previously been shown to outperform the Charlson Comorbidity Index (CCI) in predicting death. 8 , 12 The estimated life expectancy was calculated as the area under the simulated survival curve.
2.4. Outcomes
Radical treatment was defined as radical prostatectomy or radical radiotherapy registered as primary treatment in NPCR. 13 Primary treatment registered in NPCR has previously been found to correspond closely to the actual primary treatment received. 14 Men who did not undergo radical treatment were defined as conservatively treated. The outcome in the survival analysis was death from any cause.
2.5. Statistical analyses
The probability of radical treatment for PCa was determined for combinations of age and life expectancy. The interaction effect between age at diagnosis and life expectancy on the probability to receive radical treatment was modelled using logistic regression as a restricted two‐dimensional cubic spline via the gam‐function in the R‐package mgcv. These analyses were stratified by risk category and presented in ‘heat maps’ showing probability for radical treatment.
To assess potential gain in survival from radical treatment, we analysed five groups of men where guidelines recommend radical treatment: i) unfavourable intermediate‐risk PCa and life expectancy of 10–15 years; ii) high‐risk PCa and life expectancy of 10–15years; iii) very‐high risk PCa and life expectancy of 10–15 years; iv) high‐risk PCa and life expectancy of 5–10 years; and v) very high‐risk PCa and life expectancy of 5–10 years. Each group was further divided into men who received radical treatment and those who received conservative treatment. In each of these groups, relative survival for men with PCa was compared to PCa‐free men with similar age and comorbidities. This was done by firstly calculating predicted survival curves by simulating survival for PCa‐free men with similar age, DCI and MDCI as men with PCa. 15 Next, the predicted survival curve was fitted to the observed survival for men with PCa by applying a proportional hazards model. The relative survival for men in each risk category/life expectancy group was determined from the survival curve deviating the least from observed survival at 8–11 years of follow‐up.
The potential life years gained from radical treatment for conservatively treated men with PCa was estimated by calculating the area under the relative survival curves assuming hypothetical reductions in all‐cause mortality of 10%, 20% and 30% with treatment (Figure S1). Confidence intervals were determined by bootstrapping within each group.
We then estimated the proportion of deaths avoided within 10 years for combinations of hypothetical relative reductions in all‐cause mortality (10%, 20% and 30%) with radical treatment and different uptake of radical treatment (100%, 90%, 75% and 60%), by calculating the difference in proportions of deaths from any cause within 10 years between the relative survival curve and the potential gain survival curves.
3. RESULTS
3.1. Patient characteristics
A total of 32 196 men diagnosed with PCa between 2008 and 2021 were included in the analyses (Figure S2 Flow chart). The median age at diagnosis was 76 years (IQR 73–81) (Table 1). 32% of men in the study cohort had unfavourable intermediate‐risk PCa, 51% high‐risk PCa and 17% very high‐risk PCa. Eight percent of men had a life expectancy between 2.5 and 5 years, 38% had a life expectancy between 5 and 10 years and 54% had a life expectancy between 10 and 15 years and the proportions of men who received radical treatment were 4%, 17% and 64% for men within the life expectancy categories, respectively.
TABLE 1.
Baseline characteristics of men with unfavourable intermediate risk, high‐risk, and very‐high risk prostate cancer in Prostate Cancer data Base Sweden diagnosed 2008–2022 stratified by life expectancy.
| Life expectancy | ||||||||
|---|---|---|---|---|---|---|---|---|
| 2.5–5 years (n = 2442) | 5–10 years (n = 12 335) | 10–15 years (n = 17 419) | Any (n = 32 196) | |||||
| Age, median (Q 1 ‐Q 3 ) | 84 | (80–88) | 81 | (77–83) | 74 | (72–76) | 76 | (73–81) |
| ≤75, n (%) | 224 | (9) | 1616 | (13) | 10 229 | (59) | 12 069 | (37) |
| 76–80 | 372 | (15) | 3246 | (26) | 6856 | (39) | 10 474 | (33) |
| 81–85 | 635 | (26) | 5484 | (44) | 334 | (2) | 6453 | (20) |
| 86+ | 1211 | (50) | 1989 | (16) | 3200 | (10) | ||
| MDCI, n (%) | ||||||||
| median (Q 1 ‐Q 3 ) | 1.2 | (0.7–1.8) | 0.3 | (0.0–0.8) | 0.0 | (−0.1–0.3) | 0.1 | (0.0–0.6) |
| <0 | 63 | (3) | 2771 | (22) | 8425 | (48) | 11 259 | (35) |
| 0–2 | 928 | (38) | 7644 | (62) | 8601 | (49) | 17 173 | (53) |
| 2–4 | 1012 | (41) | 1784 | (14) | 392 | (2) | 3188 | (10) |
| 4+ | 439 | (18) | 136 | (1) | 1 | (0) | 576 | (2) |
| DCI | ||||||||
| median (Q 1 ‐Q 3 ) | 3.5 | (2.2–4.8) | 1.7 | (0.8–2.9) | 0.8 | (0.3–1.7) | 1.3 | (0.5–2.4) |
| −0.8–1, n (%) | 168 | (7) | 3832 | (31) | 9781 | (56) | 13 781 | (43) |
| 1.01–2 | 345 | (14) | 3224 | (26) | 4305 | (25) | 7874 | (24) |
| 2.01–3 | 479 | (20) | 2429 | (20) | 1999 | (11) | 4907 | (15) |
| 3.01–4 | 503 | (21) | 1478 | (12) | 839 | (5) | 2820 | (9) |
| 4+ | 947 | (39) | 1372 | (11) | 495 | (3) | 2814 | (9) |
| T‐stage, n (%) | ||||||||
| T1 | 583 | (24) | 3365 | (27) | 6793 | (39) | 10 741 | (33) |
| T2 | 931 | (38) | 5120 | (42) | 6854 | (39) | 12 905 | (40) |
| T3 | 816 | (33) | 3557 | (29) | 3560 | (20) | 7933 | (25) |
| T4 | 112 | (5) | 293 | (2) | 212 | (1) | 617 | (2) |
| PSA, n (%) | ||||||||
| 0–9.99 | 330 | (14) | 2285 | (19) | 5156 | (30) | 7771 | (24) |
| 10–19.99 | 726 | (30) | 4318 | (35) | 6777 | (39) | 11 821 | (37) |
| 20–49.99 | 891 | (36) | 3876 | (31) | 3838 | (22) | 8605 | (27) |
| 50+ | 495 | (20) | 1856 | (15) | 1648 | (9) | 3999 | (12) |
| Gleason, n (%) | ||||||||
| Gleason 6 | 233 | (10) | 1328 | (11) | 2440 | (14) | 4001 | (12) |
| Gleason 7 (3 + 4) | 453 | (19) | 2560 | (21) | 3738 | (21) | 6751 | (21) |
| Gleason 7 (4 + 3) | 599 | (25) | 3101 | (25) | 4931 | (28) | 8631 | (27) |
| Gleason 8 | 490 | (20) | 2388 | (19) | 3024 | (17) | 5902 | (18) |
| Gleason 9–10 | 667 | (27) | 2958 | (24) | 3286 | (19) | 6911 | (21) |
| Risk category, n (%) | ||||||||
| Unfavourable intermediate‐risk | 446 | (18) | 3158 | (26) | 6714 | (39) | 10 318 | (32) |
| High‐risk | 1404 | (57) | 6879 | (56) | 8215 | (47) | 16 498 | (51) |
| Very high‐risk | 592 | (24) | 2298 | (19) | 2490 | (14) | 5380 | (17) |
|
Mode of detection, n (%) |
||||||||
| Screening | 698 | (29) | 4658 | (38) | 8650 | (50) | 14 006 | (44) |
| LUTS | 1086 | (44) | 5114 | (41) | 5766 | (33) | 11 966 | (37) |
| Symptoms | 603 | (25) | 2198 | (18) | 2428 | (14) | 5229 | (16) |
| Missing | 55 | (2) | 365 | (3) | 575 | (3) | 995 | (3) |
| Curative intention, n (%) | ||||||||
| Yes | 94 | (4) | 2058 | (17) | 11 147 | (64) | 13 299 | (41) |
| No | 35 | (1) | 135 | (1) | 130 | (1) | 300 | (1) |
3.2. Probability of radical treatment
For a given life expectancy, the probability of radical treatment decreased with age. For example, for men with unfavourable intermediate‐risk PCa and a life expectancy of 10 years, the probability of radical treatment was <40% for men aged above 75 years, <30% for men aged above 77 years and <20% for men aged above 80 years (Figure 1).
FIGURE 1.
Probability of radical treatment according to life expectancy and age. Combined heat maps and scatterplots depicting probability of radical treatment according to life expectancy and age. Treatment according to age and life expectancy is indicated by dots. Each dot represents one of 5000 randomly selected men in each risk category; grey dots represent radical treatment, and blue dots conservative treatment. Green curves are gradients of probabilities of radical treatment. Light green indicates a low probability for radical treatment. A vertical direction implies that radical treatment was driven by age whereas a horizontal direction implies that treatment was driven by life expectancy.
3.3. Survival analysis
Figure 2 shows observed, simulated and relative survival for men with PCa and PCa‐free men with similar life expectancy. For men who underwent radical treatment, the relative survival ranged between 0.71 and 1.33, with the highest relative survival seen for men with very high‐risk PCa and a life expectancy of 10–15 years. The relative survival ranged between 0.36 and 0.70 for conservatively treated men and was lowest for men with very high‐risk PCa with a life expectancy of 10–15 years. Good agreement between observed and relative survival was found in most strata. The largest difference was seen in conservatively treated men with high‐risk and very high‐risk PCa for whom observed survival was substantially shorter than the relative survival.
FIGURE 2.
Observed, expected, and relative survival for men with prostate cancer and matched prostate cancer‐free control men. Green lines depict observed survival for men with prostate cancer (PCa). Black lines depict expected survival based on PCa‐free men with the same age, CCI and DCI as the PCa men. Grey lines depict relative survival curves with HR adjustments ranging from 0.5 to 2. Red lines depict the relative survival curve with least deviation from the observed survival curve at 8–11 years of follow‐up.
3.4. Potential years of life gained and proportion of deaths potentially avoidable with curative treatment
According to our model, between 9% and 12% of deaths within 10 years could potentially have been avoided if conservatively treated men had received radical treatment, assuming high efficacy of radical treatment (30% reduction in all‐cause mortality) and high uptake of radical treatment (90%) (Table 2).
TABLE 2.
Potential years of life gained and proportion of deaths avoided at 10 years post‐diagnosis.
| Intermediate‐risk PCa life expectancy 10–15 years | High‐risk PCa life expectancy 10–15 years | Very high‐risk PCa life expectancy 10–15 years | High‐risk PCa life expectancy 5–10 years | Very high‐risk PCa life expectancy 5–10 years | ||
|---|---|---|---|---|---|---|
| Potential years of life gained assuming all‐cause mortality reduction of: | ||||||
| 10% | 0.49 yrs (0.47–0.51) | 0.47 yrs (0.45–0.48) | 0.45 yrs (0.42–0.47) | 0.40 yrs (0.39–0.41) | 0.37 yrs (0.35–0.39) | |
| 20% | 1.05 yrs (1.01–1.10) | 1.01 yrs (0.98–1.04) | 0.96 yrs (0.91–1.01) | 0.87 yrs (0.84–0.90) | 0.82 yrs (0.77–0.86) | |
| 30% | 1.72 yrs (1.65–1.79) | 1.65 yrs (1.59–1.70) | 1.57 yrs (1.49–1.65) | 1.44 yrs (1.39–1.49) | 1.35 yrs (1.28–1.43) | |
| Proportion of deaths avoided within 10 years assuming | ||||||
| Reduction in all‐cause mortality | Uptake of Radical Rx | |||||
| 10% | 100% | 3.6% (3.4% ‐3.7%) | 3.8% (3.8% ‐3.9%) | 3.8% (3.7% ‐3.9%) | 3.2% (3.1% ‐3.3%) | 2.7% (2.4% ‐2.9%) |
| 90% | 3.2% (3.1% ‐3.3%) | 3.4% (3.4% ‐3.5%) | 3.4% (3.3% ‐3.5%) | 2.8% (2.7% ‐2.9%) | 2.4% (2.1% ‐2.6%) | |
| 75% | 2.6% (2.6% ‐2.7%) | 2.8% (2.8% ‐2.9%) | 2.8% (2.8% ‐2.9%) | 2.3% (2.2% ‐2.4%) | 1.9% (1.7% ‐2.1%) | |
| 60% | 2.1% (2.0% ‐2.2%) | 2.3% (2.2% ‐2.3%) | 2.2% (2.2% ‐2.3%) | 1.8% (1.8% ‐1.9%) | 1.5% (1.4% ‐1.7%) | |
| 20% | 100% | 7.4% (7.1% ‐7.6%) | 8.0% (7.9% ‐8.1%) | 8.1% (8.0% ‐8.2%) | 7.0% (6.8% ‐7.2%) | 6.0% (5.5% ‐6.5%) |
| 90% | 6.6% (6.4% ‐6.8%) | 7.2% (7.1% ‐7.2%) | 7.2% (7.1% ‐7.3%) | 6.2% (6.0% ‐6.4%) | 5.3% (4.8% ‐5.7%) | |
| 75% | 5.4% (5.2% ‐5.6%) | 5.9% (5.8% ‐5.9%) | 5.9% (5.8% ‐6.0%) | 5.0% (4.8% ‐5.2%) | 4.2% (3.8% ‐4.6%) | |
| 60% | 4.3% (4.2% ‐4.4%) | 4.6% (4.6% ‐4.7%) | 4.6% (4.5% ‐4.7%) | 3.9% (3.7% ‐4.0%) | 3.3% (3.0% ‐3.6%) | |
| 30% | 100% | 11.5% (11.0% ‐11.9%) | 12.6% (12.4% ‐12.8%) | 13.0% (12.9% ‐13.1%) | 11.6% (11.3% ‐11.9%) | 10.2% (9.4% ‐10.9%) |
| 90% | 10.2% (9.8% ‐10.5%) | 11.2% (11.0% ‐11.3%) | 11.5% (11.4% ‐11.5%) | 10.1% (9.8% ‐10.4%) | 8.8% (8.1% ‐9.5%) | |
| 75% | 8.4% (8.1% ‐8.6%) | 9.1% (9.0% ‐9.2%) | 9.3% (9.2% ‐9.4%) | 8.1% (7.8% ‐8.3%) | 7.0% (6.4% ‐7.5%) | |
| 60% | 6.6% (6.4% ‐6.8%) | 7.2% (7.1% ‐7.2%) | 7.2% (7.1% ‐7.3%) | 6.2% (6.0% ‐6.4%) | 5.3% (4.8% ‐5.7%) | |
Abbreviations: HR: hazard ratio;
Rx: treatment.
4. DISCUSSION
4.1. Key results
In this population‐based nationwide cohort study in Sweden of men with intermediate or high‐risk localized or locally advanced PCa diagnosed in 2008–2022 who were potentially eligible for radical treatment, age had a stronger influence than life expectancy on the selection of treatment, despite guidelines recommendations to take larger consideration to life expectancy. According to our models, 10% of deaths in older men with these cancers could potentially have been avoided if more weight had been placed on life expectancy.
4.2. Strengths and limitations
Strengths of our study include the population‐based design that includes virtually all men in these PCa risk categories in an entire nation and a very high capture rate of radical treatment. 14 Furthermore, assessment of life expectancy was based on two newly created highly granulated comorbidity indices: the Drug Comorbidity Index (DCI) 8 , 9 and the Multidimensional Diagnosis‐based Comorbidity Index (MDCI) 10 ¨ which both outperform the commonly used Charlson Comorbidity Index. 10
Limitations include estimates of life expectancy did not include data on diagnosis from primary care, but for almost all chronic diseases that affect life expectancy, these diseases are treated with drugs and hence captured by the DCI. Furthermore, we did not have measures of lifestyle factors and frailty, such as grip strength, chair standing or balance testing, which are important predictors of life expectancy in older people. 16
4.3. Interpretation
The high relative survival of radically treated men, sometimes above 1, suggests that men who received radical treatment were highly selected, as treatment efficacy is not 100%. A substantial proportion of men with high‐risk and very high‐risk PCa with estimated life expectancy > 10 years according to our measures did not receive radical treatment despite guideline recommendations. 4 , 5 Estimates of life expectancy in old men are notoriously difficult in clinical practice, and these results indicate that clinicians may often underestimate life expectancy.
The observed survival in conservatively treated men with high‐risk/very high‐risk PCa and a life expectancy above 10 years deviated sharply from the relative survival. This could, in part, be explained by undetected metastatic disease in these men. In contrast, most men selected for radical treatment will undergo staging imaging. 17
4.4. Use of radical treatment in older men and ensuing effect on outcome in previous studies
Our model indicates that around 10% of deaths, mostly from PCa, could possibly have been avoided if conservatively treated men who had >10 years life expectancy according to our measures had received radical treatment.
Use of radical treatment among older men in other Nordic countries has been documented to have increased sharply with a concomitant modest decrease in mortality. 18 , 19 Of note, Swedish guidelines emphasize that biological age and not chronological age should inform treatment decisions. Thus, adherence to national guidelines will lead to increased use of radical treatment among healthy old men with an ensuing increase in survival. 20 A 32% risk reduction in all‐cause mortality was found for radical radiotherapy and ADT vs ADT only for locally advanced PCa in The Scandinavian Prostate Cancer Group Study (SPCG) 7 21 and in SPCG‐4 there was a 14% reduction in all‐cause mortality for radical prostatectomy vs watchful waiting in men ≥65 years of age. 22
In other studies of old men with PCa, results have been quite similar. 23 , 24 For instance, a review of studies on radical radiotherapy among older men with PCa indicated increased survival, especially for those with high‐risk PCa and little comorbidity. 23 In a previous study in PCBaSe, there was an increase in the use of radical treatment in men with locally advanced PCa from 15% in 2000–2003 to 43% in 2012–2016, and the ensuing decrease in risk of PCa death was most pronounced in men 65–74 years. 24 The hypothesized relative reductions of 10–30% in all‐cause mortality with radical treatment that we applied in our model are in line with the results in these studies. However, our result of a 9–12 % decrease in all‐cause mortality could be an overestimation as treatment effect seems to decline with older age.
4.5. Adverse effects of radical treatment in older men
Radical treatment is often avoided in older men irrespective of life expectancy due to concerns about adverse effects and perceived lack of survival benefit, and it is also likely that some older healthy men themselves actively select conservative treatment. 25 However, given the recent advancements in prostate cancer treatment, the benefit/risk balance is shifting in favour of radical treatment to treat high‐risk PCa, also in old men. For example, intensity modulated radiotherapy, now commonly used, is associated with fewer gastrointestinal and genitourinary toxicities 26 than the previously used 3D‐conformal radiotherapy. Moreover, the risk of adverse effects from radiotherapy or decrease in quality of life was not a function of age according to some studies. 27 , 28 , 29
We argue that our results are generalizable to countries and regions with similar health care standards as in Sweden.
5. CONCLUSION
Despite guideline recommendations, chronological age had a stronger influence than life expectancy on the selection of radical treatment in old men with intermediate and high‐risk localized or locally advanced PCa in Sweden. A substantial proportion of men with these cancers who were old but had long life expectancy received conservative treatment. According to our model, 10% of deaths in these men could potentially have been avoided if decisions on radical treatment had put more weight on life expectancy than on age.
AUTHOR CONTRIBUTIONS
Conception and design: Sandra Irenaeus, Hans Garmo, Rolf Gedeborg, Pär Stattin, andKerri Beckmann. Acquisition of data: Hans Garmo, Rolf Gedeborg, and Pär Stattin. Analysis and interpretation of data: Sandra Irenaeus, Hans Garmo, Rolf Gedeborg, PärStattin, and Kerri Beckmann. Drafting of the manuscript: Sandra Irenaeus, Pär Stattin, and Kerri Beckmann. Critical revision of the manuscript for important intellectual content: Rolf Gedeborg, Mats Ahlberg, and David Robinson. Statistical analyses: Hans Garmo, Rolf Gedeborg, and Kerri Beckmann. Obtaining funding: Rolf Gedeborg and Pär Stattin. Administrative, technical, or material support: Mats Ahlberg, David Robinson, KerriBeckmann, and Pär Stattin. Supervision: Pär Stattin and Kerri Beckmann.
CONFLICT OF INTEREST STATEMENT
The authors report no conflicts of interest.
DISCLAIMER
Rolf Gedeborg is also employed by the Medical Products Agency (MPA) in Sweden. The MPA is a Swedish Government Agency. The views expressed in this article may not represent the views of the MPA.
Supporting information
Figure S1. Life years gained assuming different reductions in all‐cause mortality with radical treatment. Dark shaded lines depict relative survival of PCa men conservatively treated. Lighter shaded lines depict simulated survival assuming reductions in all‐cause mortality with radical treatment of 10%, 20% and 30% respectively. Life years gained was calculated as the difference in area under the survival curves, respectively.
Figure S2. Study flow chart.
ACKNOWLEDGEMENTS
This project was made possible by the continuous work of the National Prostate Cancer Register of Sweden (NPCR) steering group: Elin Axén, Johan Styrke, Andreas Josefsson, Camilla Thellenberg, Hampus Nugin, Ingrida Verbiené, Stefan Carlsson, Anna Kristiansen, Mats Andén, Kimia Kohestani, Jon Kindblom, Thomas Jiborn, Olof Ståhl, Olof Akre, Eva Johansson, Magnus Törnblom, Fredrik Jäderling, Marie Hjälm‐Eriksson, Lotta Renström Koskela, Erik Thimansson, Johan Stranne, Elin Trägårdh, Viktoria Gaspar, Fredrik Sandin, Petrus Stenson, Lena Pettersson, Mia Brus, Gustaf Hedström, Anna Hedström, Maria Moutran, Nina Hageman, and Maria Nyberg and patient representatives Hans Joelsson and Gert Malmberg.
Irenaeus S, Garmo H, Gedeborg R, Ahlberg M, Robinson D, Stattin P, et al. Potential gains from radical treatment of men with prostate cancer according to life expectancy. BJUI Compass. 2025;6(9):e70076. 10.1002/bco2.70076
Funding information This project was supported by the Swedish Research Council (2022‐00544), and the Swedish Cancer Society [22 2051]. The sponsors had no involvement with the planning, execution or completion of the study.
REFERENCES
- 1. EAU‐EANM‐ESTRO‐ESUR‐ISUP‐SIOG . Guidelines on Prostate Cancer. 2023. [retrieved November 3, 2023]; https://uroweb.org/guidelines/prostate-cancer
- 2. National Comprehensive Cancer Network . Prostate Cancer (Version 4.2023). [retrieved March 7, 2024]; https://jnccn.org/view/journals/jnccn/21/10/article-p1067.xml
- 3. Regionala cancercentrum i Samverkan . Nationellt vårdprogram prostatacancer 2022. https://kunskapsbanken.cancercentrum.se/diagnoser/prostatacancer/vardprogram/
- 4. Bratt O, Carlsson S, Fransson P, Thellenberg Karlsson C, Stranne J, Kindblom J. The Swedish national guidelines on prostate cancer, part 1: Early detection, diagnostics, staging, patient support and primary management of non‐metastatic disease. Scand J Urol. 2022;56(4):265–273. 10.1080/21681805.2022.2094462 [DOI] [PubMed] [Google Scholar]
- 5. Bratt O, Carlsson S, Fransson P, Kindblom J, Stranne J, Karlsson CT, et al. The Swedish national guidelines on prostate cancer, part 2: recurrent, metastatic and castration resistant disease. Scand J Urol. 2022;56(4):278–284. 10.1080/21681805.2022.2093396 [DOI] [PubMed] [Google Scholar]
- 6. Van Hemelrijck M, Wigertz A, Sandin F, Garmo H, Hellström K, Fransson P, et al. Cohort Profile: the National Prostate Cancer Register of Sweden and Prostate Cancer data Base Sweden 2.0. Int J Epidemiol. 2013;42(4):956–967. 10.1093/ije/dys068 [DOI] [PubMed] [Google Scholar]
- 7. RATTEN ‐ Interactive On Line Report from NPCR. [retrieved July 3, 2024]; https://statistik.incanet.se/npcr/
- 8. Gedeborg R, Sund M, Lambe M, Plym A, Fredriksson I, Syrjä J, et al. An aggregated comorbidity measure based on history of filled drug prescriptions: Development and evaluation in two separate cohorts. Epidemiology. 2021;32:607–615. [DOI] [PubMed] [Google Scholar]
- 9. Gedeborg R, Garmo H, Robinson D, Stattin P. Prescription‐based prediction of baseline mortality risk among older men. PLoS ONE. 2020;15(10):e0241439. 10.1371/journal.pone.0241439 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10. Westerberg M, Irenaeus S, Garmo H, Stattin P, Gedeborg R. Development and validation of a multi‐dimensional diagnosis‐based comorbidity index that improves prediction of death in men with prostate cancer: Nationwide, population‐based register study. PLoS ONE. 2024;19(1):e0296804. 10.1371/journal.pone.0296804 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11. Van Hemelrijck M, Ventimiglia E, Robinson D, Gedeborg R, Holmberg L, Stattin P, et al. Population‐based estimates of age and comorbidity specific life expectancy: a first application in Swedish males. BMC Med Inform Decis Mak. 2022;22:35. 10.1186/s12911-022-01766-0 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12. Westerberg M, Garmo H, Robinson D, Stattin P, Gedeborg R. Target trial emulation using new comorbidity indices provided risk estimates comparable to a randomized trial. J Clin Epidemiol. 2024;174:111504. 10.1016/j.jclinepi.2024.111504 [DOI] [PubMed] [Google Scholar]
- 13. Beckmann K, Garmo H, Nilsson P, Franck Lissbrant I, Widmark A, Stattin P. Radical radiotherapy for prostate cancer: patterns of care in Sweden 1998‐2016. Acta Oncol. 2020. May;59(5):549–557. 10.1080/0284186X.2020.1730003 [DOI] [PubMed] [Google Scholar]
- 14. Tomic K, Sandin F, Wigertz A, Robinson D, Lambe M, Stattin P. Evaluation of data quality in the National Prostate Cancer Register of Sweden. Eur J Cancer. 2015;51(1):101–111. 10.1016/j.ejca.2014.10.025 [DOI] [PubMed] [Google Scholar]
- 15. Westerberg M, Ahlberg M, Orrason AW, Gedeborg R. Assessment of variability in life expectancy in older men by use of new comorbidity indices. A nationwide population‐based study. Scand J Urol. 2024;59:207–209. [DOI] [PubMed] [Google Scholar]
- 16. Schoenborn NL, Blackford AL, Joshu CE, Boyd CM, Varadhan R. Life expectancy estimates based on comorbidities and frailty to inform preventive care. J Am Geriatr Soc. 2022;70(1):99–109. 10.1111/jgs.17468 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17. Pettersson A, Robinson D, Garmo H, Holmberg L, Stattin P. Age at diagnosis and prostate cancer treatment and prognosis: A population‐based cohort study. Ann Oncol. 2018;29(1):377–385. [DOI] [PubMed] [Google Scholar]
- 18. Aas K, Dorothea Fosså S, Åge Myklebust T, Møller B, Kvåle R, Vlatkovic L, et al. Increased curative treatment is associated with decreased prostate cancer‐specific and overall mortality in senior adults with high‐risk prostate cancer; results from a national registry‐based cohort study. Cancer Med. 2020;9(18):6646–6657. 10.1002/cam4.3297 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19. Lundberg F, Robinson D, Bratt O, Fallara G, Lambe M, Johansson ALV. Time trends in the use of curative treatment in men 70 years and older with nonmetastatic prostate cancer. Acta Oncol. 2024;63:95–104. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20. Stattin P. How to survey adherence to guidelines by use of clinical cancer registers. Scand J Urol. 2022;56(4):285–286. 10.1080/21681805.2022.2107069 [DOI] [PubMed] [Google Scholar]
- 21. Widmark A, Klepp O, Solberg A, Damber JE, Angelsen A, Fransson P, et al. Endocrine treatment, with or without radiotherapy, in locally advanced prostate cancer (SPCG‐7/SFUO‐3): An open randomised phase III trial. Lancet. 2009;373:301–308. [DOI] [PubMed] [Google Scholar]
- 22. Bill‐Axelson A, Holmberg L, Garmo H, Taari K, Busch C, Nordling S, et al. Radical Prostatectomy or Watchful Waiting in Prostate Cancer — 29‐Year Follow‐up. N Engl J Med. 2018;379(24):2319–2329. 10.1056/NEJMoa1807801 [DOI] [PubMed] [Google Scholar]
- 23. Marotte D, Chand‐Fouche ME, Boulahssass R, Hannoun‐Levi JM. Irradiation of localized prostate cancer in the elderly: A systematic literature review. Clin Transl Radiat Oncol. 2022;35:1–8. 10.1016/j.ctro.2022.04.006 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24. Orrason AW, Westerberg M, Garmo H, Lissbrant IF, Robinson D, Stattin P. Changes in treatment and mortality in men with locally advanced prostate cancer between 2000 and 2016: a nationwide, population‐based study in Sweden. BJU Int. 2020;126(1):142–151. 10.1111/bju.15077 [DOI] [PubMed] [Google Scholar]
- 25. Jha GG, Anand V, Soubra A, Konety BR. Challenges of managing elderly men with prostate cancer. Nat Rev Clin Oncol. 2014;11(6):354–364. 10.1038/nrclinonc.2014.71 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26. Zelefsky MJ, Levin EJ, Hunt M, Yamada Y, Shippy AM, Jackson A, et al. Incidence of late rectal and urinary toxicities after three‐dimensional conformal radiotherapy and intensity‐modulated radiotherapy for localized prostate cancer. Int J Radiat Oncol Biol Phys. 2008;70:1124–1129. [DOI] [PubMed] [Google Scholar]
- 27. Jani AB, Parikh SD, Vijayakumar S, Gratzle J. Analysis of influence of age on acute and chronic radiotherapy toxicity in treatment of prostate cancer. Urology. 2005. Jun;65(6):1157–1162. 10.1016/j.urology.2004.12.041 [DOI] [PubMed] [Google Scholar]
- 28. Fiorica F, Berretta M, Colosimo C, Berretta S, Ristagno M, Palmucci T, et al. Safety and efficacy of radiotherapy treatment in elderly patients with localized prostate cancer: a retrospective analysis. Arch Gerontol Geriatr. 2010;51(3):277–282. 10.1016/j.archger.2009.11.019 [DOI] [PubMed] [Google Scholar]
- 29. Sletten R, Berger Christiansen O, Oldervoll LM, Åstrøm L, Kjesbu Skjellegrind H, Šaltytė Benth J, et al. The association between age and long‐term quality of life after curative treatment for prostate cancer: A cross‐sectional study. Scand J Urol. 2024;59:31–38. 10.2340/sju.v59.18616 [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Figure S1. Life years gained assuming different reductions in all‐cause mortality with radical treatment. Dark shaded lines depict relative survival of PCa men conservatively treated. Lighter shaded lines depict simulated survival assuming reductions in all‐cause mortality with radical treatment of 10%, 20% and 30% respectively. Life years gained was calculated as the difference in area under the survival curves, respectively.
Figure S2. Study flow chart.