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ORIGINAL ARTICLE
Year : 2022  |  Volume : 18  |  Issue : 2  |  Page : 391-398

The survival outcomes of very young and elderly patients with high-risk prostate cancer after radical treatments: A population-matched study


1 Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
2 The First Clinical Medical College of Lanzhou University, Lanzhou, Gansu Province, China

Date of Submission17-Oct-2021
Date of Acceptance06-Jan-2022
Date of Web Publication20-May-2022

Correspondence Address:
Qiang Dong
Department of Urology, Institute of Urology, West China Hospital, Sichuan University, No. 37, Guoxue Lane, Wuhou District, Chengdu, 610041, Sichuan Province
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcrt.jcrt_1862_21

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 > Abstract 


Objective: This study evaluated the survival outcomes of young (<50 years) and elderly patients (>80 years) with high-risk prostate cancer (PCa) postradical local treatments.
Materials and Methods: We identified <50 and >80-year-old patients with high-risk PCa between 2004 and 2015 in the Surveillance, Epidemiology, and End Results database. The patients aged 65 and 66 years were also identified as the control group. The propensity-score matching method was adopted to compare the young and elderly patients with the control group. Kaplan–Meier analysis and Cox regression were conducted to evaluate the PCa-specific survival (PCSS) and overall survival.
Results: A total of 17726 patients were identified, and 3355 were under 50 years old, whereas 4798 of them were >80 years old. The young patient group (<50 years) had similar PCSS with the control group (65–66 years) in both the overall cohort (hazard ratio [HR]: 0.88, 95% confidence interval [CI] [0.73–1.06], P = 0.132) and matched cohort (HR: 0.96, 95% CI [0.74–1.24], P = 0.527). Young patients with both high-risk and very high-risk PCa after radical prostatectomy (RP) treatment had apparent longer mean cancer-specific survival time than those after external-beam radiotherapy (EBRT) and/or brachytherapy (BT) treatment (high-risk group: 153.38 ± 0.82 months vs. 149.72 ± 3.03 months; very high-risk group: 148.3 ± 1.84 months vs. 139.33 ± 3.25 months). For the elderly patients (>80 years), the PCSS outcomes were significantly worse than the control group (65–66 years) in both overall cohort (HR: 2.69, 95% CI [2.31–3.13], P < 0.001) and matched cohort (HR: 1.61, 95% CI [1.34–1.94], P < 0.001). Patients receiving RP treatment had similar PCSS outcomes with those receiving EBRT and/or BT in the high-risk PCa group (139.45 ± 9.98 months vs. 139.41 ± 1.84 months), and better PCSS in very high-risk PCa group (132.73 ± 13.56 months vs. 128.82 ± 3.43 months).
Conclusion: The PCSS outcomes of young PCa patients (<0 years) were identical to those of the control group (65–66 years). RP had similar or better PCSS benefits than EBRT and/or BT in both young (<50 years) and elderly patients (>80 years).

Keywords: Prostate cancer, radical treatments, Surveillance, Epidemiology, and End Results, survival, young and elderly patients


How to cite this article:
Ma K, Song P, Qing Y, Li Y, Shu M, Yang L, Dong Q. The survival outcomes of very young and elderly patients with high-risk prostate cancer after radical treatments: A population-matched study. J Can Res Ther 2022;18:391-8

How to cite this URL:
Ma K, Song P, Qing Y, Li Y, Shu M, Yang L, Dong Q. The survival outcomes of very young and elderly patients with high-risk prostate cancer after radical treatments: A population-matched study. J Can Res Ther [serial online] 2022 [cited 2022 Jul 7];18:391-8. Available from: https://www.cancerjournal.net/text.asp?2022/18/2/391/345534

Kai Ma, Pan Song contributed to the paper equally.





 > Introduction Top


Prostate cancer (PCa) ranks first among the diagnoses of male malignancies, accounting for about 15% of all malignant tumors globally.[1],[2] Although most PCa cases progress slowly, many patients still progress to localized high-risk, locally advanced, and even metastatic stages.[3] The treatments for local/local diseases are essential because radical treatment can be conducted. For localized/locally PCa, the radical treatments include radical prostatectomy (RP), external-beam radiotherapy (EBRT), and brachytherapy (BT).[4] These radical local treatments can significantly improve the survival effects for most PCa patients.

The incidence of PCa is closely correlated with age.[5] It is rare among patients with PCa under the age of 50 years. Early-onset PCa is different from PCa in elderly men in some aspects determined to be a distinct clinicopathological phenotype.[6] It has more aggressive tumor characteristics with a poor prognosis.[6] Thus, men with high grade/stage and early-onset PCa are more likely to die of their cancer, with higher cause-specific mortality than other ages.[6] Nevertheless, young people generally have better physical conditions, fewer underlying diseases, more treatment options, higher treatment tolerance, and faster treatment recovery than elderly patients.[7],[8],[9] Whether the young patients possess a better or worse prognosis than the elderly patients is still inconclusive. For patients >80 years old, their choice options for treatments are limited. The survival outcomes of these patients are affected by many factors, including age, physical conditions, risk degree of the tumor, and detailed treatments. Since these patients are uncommon, their detailed survival time in different risk groups and treatments remain unclear. Therefore, the very young (<50 years) and elderly patients (>80 years) make up two special subgroups in the PCa population. We evaluated the survival outcomes of these two special groups after radical local treatments in this study (RP, EBRT, and/or BT).


 > Materials and Methods Top


Data source

All data in this study were derived from Surveillance, Epidemiology, and End Results (SEER) database. In addition, patients with localized/regional PCa from January 01, 2004, to December 31, 2015, were retrospectively identified.

Inclusion and exclusion criteria

Patients were considered eligible if they met the following criteria: (1) patients were diagnosed with high-risk PCa following the NCCN guideline; (2) the main treatments were radical local treatments, such as RP, EBRT, and/or BT; and (3) the age of patients was under 50, 65–66 years, and over 80 years at the time of diagnosis.

The following criteria were used for data exclusion: (1) multiple tumors; (2) important information, such as age, PSA, GS, TNM stages, and follow-up time was incomplete or missing; and (3) the survival status at the end of the follow-up was unclear.

Variables and main outcomes

We collected patients' basic characteristics from the database. The variables included age at diagnosis, race (white, black, other races), marital status (married, unmarried, divorced, or separated), T stage (T1, T2a-b, T2c-3a, T3b-4), PSA level (<10.0 ng/ml, 10.0–20.0 ng/ml, >20.0 ng/ml), Gleason score (≤7, 8, 9–10), therapy (RP, EBRT, and/or BT), living status (alive or dead), cancer-specific living status (alive, dead for other reasons, dead for PCa), and survival time. In this study, the age group of 65–66 years functioned as the control group. The overall survival (OS) and PCa-specific survival (PCSS) were regarded as the main outcomes.

Statistical analysis

A Chi-square test was adopted to assess the differences among <50 years group, 65–66 group, and >80 years group. Propensity-score matching (PSM) was conducted to balance the covariates and generate new matched cohorts. The OS and PCSS curves were constructed using Kaplan–Meier (K-M) analysis. Five-year and 10-year OS and PCSS were calculated using survival tables. Multivariate Cox analysis was conducted on the variables with P < 0.1. The effects of age on survival and prognoses were evaluated using a hazard ratio (HR) with 95% confidence interval (95% CI). All statistical operations above were conducted using the software SPSS 25 and Graphpad prism 7.0. P < 0.05 was considered statistically significant.


 > Results Top


A total of 17,726 patients diagnosed with high-risk PCa were identified, and 3355 of them were in age <50 years group. In addition, 9573 patients were included in 65–66 group and 4798 in >80 group. The median follow-up time of the overall cohort was 66 (37–100) months. After PSM, there were 2889 patients in the <50 years group versus 65–66 years group and 3072 patients in the >80 years group versus 65–66 years group. The baseline characteristics of included patients in the overall cohort and the matched cohorts are presented in [Table 1] and [Table 2].
Table 1: Baseline characteristics of included patients in overall cohort

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Table 2: Baseline characteristics of patients in propensity-score matched cohorts

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Survival outcomes

Survival curves of the overall cohort and matched cohort

In the overall cohort, no significant difference of PCSS was detected between <50 years and the control group (65–66 years) both in the overall cohort [HR: 0.88 (0.73–1.06), [Figure 1]a1] and matched cohort [HR: 0.96, 95% CI (0.74–1.24), P = 0.527, [Figure 1]b1]. The mean PCSS time of age <50 years and the control group was 148.57 ± 1.0 and 147.68 ± 0.7 months, separately [Table 3]. The PCSS of age >80 years group was obviously worse than the control group both in the overall cohort [HR: 2.69, 95% CI (2.31–3.13), P < 0.001, [Figure 1]a1] and the matched cohort [HR: 1.61 (1.34–1.94), P < 0.001, [Figure 1]c1]. The mean PCSS time for >80 years and 65–66 years was 136.82 ± 1.66 months versus 147.68 ± 0.7 months [Table 3]. The OS curves and mean OS time of different age groups in the overall cohort are presented in [Figure 1]a2 and [Table 3] and the matched cohort are presented in [Figure 1]b2 and [Figure 1]c2.
Figure 1: (a1) The prostate cancer-specific survival curve of the overall cohort. (a2) The overall survival curve of the overall cohort. (b1) The prostate cancer-specific survival curve of <50 years old vs 65-66 years old of the matched cohort. (b2) The overall survival curve of <50 years old vs 65-66 years old of the matched cohort. (c1) The prostate cancer-specific survival curve of >80 years old vs 65-66 years old of the match cohort. (c2) The overall survival curve of >80 years old vs 65-66 years old of the match cohort

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Table 3: The mean survival time of patients in the overall cohort

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Survival outcomes of three age groups with different treatments

The survival outcomes of three age groups with high-risk/very high-risk PCa after the treatments of RP or EBRT and/or BT are presented in [Figure 2] and [Table 3]. In the age <50 years group, the RP had more survival benefits than EBRT ± BT in both high-risk PCa and very high-risk PCa patients. The mean PCSS time for patients with high-risk PCa after RP and EBRT and/or BT were 153.38 ± 0.82 months and 149.72 ± 3.03 months, respectively. The mean PCSS for very high-risk PCa patients after RP and EBRT ± BT was 148.3 ± 1.84 months and 139.33 ± 3.25 months, respectively.
Figure 2: (a1) The prostate cancer-specific survival curve of <50 years after the treatments of RP or EBRT and/or BT.(a2) The overall survival curve of 65-66 years after the treatments of RP or EBRT and/or BT.(b1) The prostate cancer-specific survival curve of 65-66 years after the treatments of RP or EBRT and/or BT.(b2) The overall survival curve of 65-66 years after the treatments of RP or EBRT and/or BT.(c1) The prostate cancer-specific survival curve of >80 years after the treatments of RP or EBRT and/or BT.(c2) The overall survival curve of >80 years after the treatments of RP or EBRT and/or BT

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For elderly patients above 80 years, patients with high-risk PCa treated with RP had similar mean cancer-specific survival time with those treated with EBRT and/or BT (139.45 ± 9.98 months vs. 139.41 ± 1.84 months). However, very high-risk PCa patients after RP treatments had longer PCSS time than those after EBRT and/or BT treatment (132.73 ± 13.56 months vs. 128.82 ± 3.43 months). For the control group, the RP had more survival benefit than EBRT and/or BT in both high-risk PCa patients (152.43 ± 0.68 months vs. 145.74 ± 1.76 months) and very high-risk PCa patients (146.71 ± 1.41 months vs. 136.61 ± 3.02 months). The survival time of patients in different groups is shown in [Table 3].

Multivariate Cox analysis for prostate cancer-specific survival

Multivariate COX analysis results of PCSS are presented in [Table 4]. With 65–66 years group as the reference in the overall cohort, the HR and 95% CI of the <50 years group were 0.92 (0.76–1.12). The difference was not statistically significant, with P = 0.402. Compared with the 65–66 years group, the HR and 95% CI of >80 years group were 1.62 (1.39–1.89). Similar results could be found in the matched cohorts. With the 65–66 years group as the reference, the HR and 95% CI of <50 years and >80 years were 0.96 (0.74–-1.23) and 1.57 (1.30–1.89), respectively.
Table 4: Multivariate Cox analysis of the prostate cancer-specific survival for patients in the overall cohort and matched cohorts

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 > Discussion Top


At present, over 90% of organ-confined PCa cases opted for curative treatments, as is shown by a study of data from Cancer of the Prostate Strategic Urologic Research Endeavor.[10] However, the benefits of radical treatments vary significantly among different patients, so do the prognoses. Age plays a vital role in PCa's onset, treatment, and prognosis. The PCa patients under 50 and above 80 years old can be listed as two special subgroups for the small proportion. They have particular treatment decisions and prognostic characteristics. The detailed survival outcomes of these patients after radical local treatments were not clearly known so far.

With a total of 17,726 cases identified in the analysis, our results demonstrated that the young patients (<50 years) did not present a better or worse cancer-specific survival than the 65–66 years group. No matter in patients with high-risk or very high-risk PCa, young patients with RP treatment had a better prognosis than those patients with EBRT and/or BT treatments. Pompe et al.[11] reported no significant difference in the survival outcomes between young and elderly patients after radical local treatments. Riopel et al.[12] included 85 men under 50 years old who had undergone anatomic RP for clinically localized PCa. Their results indicated that young men aged <50 have a lower rate of positive surgical margins and similar pathologic variables compared with older patients. Khan et al.[13] reported no statistical significance between <50 years old group and 60–69 group in 10- and 15-year biochemical disease-free progression rate after RP. Magheli et al.[14] claimed the similarity of biochemical recurrence rate between patients >65 years and <45 years with an HR of 1.6 (0.8–3.0). Other series of research also revealed that no significance was detected between the young patients' survival outcomes and older men after brachytherapy[15],[16],[17] or radiation therapy.[18],[19],[20] As for the detailed treatment option recommended for young men, a series of studies confirmed the advantages of RP[13],[21],[22],[23],[24],[25] over others. In their text, Smith et al.[21] manifested that patients of 50 years old or younger with RP enjoyed a more favorable disease-free outcome. Khan et al.[13] included 341 men younger than 50 in all. They concluded that anatomical RRP yielded excellent long-term results, and RRP was curative more often in men younger than 50. The theoretical benefits of RP as first-line treatment are tumor volume reduction and optimal local control. Moreover, the evaluation of prostatectomy and nodal specimens, as well as postoperative PSA levels, allows for more accurate staging and risk stratification that will help select men who may benefit from postoperative adjuvant treatments.[26]

Elderly patients were associated with significantly worse survival outcomes than the control group. For elderly patients with high-risk PCa, compared with those treated with EBRT and/or BT, the patients receiving RP had similar PCSS. But in the very high-risk group, PCSS outcomes after RP were apparently better. Kirk et al.[27] proposed in their article that four points constitute the impact of old age on cancer management: short life expectancy, increased risk of significant comorbidity, intolerance to some forms of treatment, and social problems. Old age at diagnosis has been associated with an increased risk of upstaging and upgrading at RP.[28],[29],[30] Pettersson et al.[31] also reported the correlation between old age and a higher risk of PCa death among men treated with RP, but not among men treated with radiotherapy. A SEER study[32] included 149,967 men treated with radiotherapy. It was claimed that older age at diagnosis presented poorer prognosis among men with low-or intermediate-risk disease, but less so among high-risk disease. Loeb et al.[33] also reported that older age had a better prognosis. Besides, older cases may also have a prolonged recovery period from surgery and may be at an increased risk for postoperative complications, including urinary, erectile, and bowel toxicity.[34] In general, RT and/or BT should be considered more instead of RP for elderly patients.

There were a few limitations in our study. First one was the loss of comorbidity data. For prognostic analysis, comorbidity is significant since it affects patients' prognoses, quality of life, and the choice of treatments. Therefore, it is supposed to be included. However, limited by the available raw data from the SEER database, no relational data was reported. As a result, we could not take this index into our analysis. Moreover, this was a retrospective analysis. Some unavoidable confounders and risk biases might exist. Our results might be influenced by these factors. Therefore, more high-quality studies are needed for future verifications.


 > Conclusion Top


For patients with high-risk PCa, age did not significantly influence the cancer-specific survival outcomes in the comparison between young patients (<50 years) and patients aged 65–66. The RP had better PCSS benefits than EBRT and/or BT in young and elderly patients with very high-risk PCa. Despite the above, with the limitations of our study, high-quality studies are needed for future evaluations.

Financial support and sponsorship

This work was supported by a Key Project of National Natural Science Foundation of China, Grant ID: 8177060452 and Project of Science and Technology Department of Sichuan Province, Grant ID:2021YFS0117. The funding bodies had no role in the design of the study and collection, analysis, and interpretation of data and writing the manuscript.

Conflicts of interest

There are no conflicts of interest.



 
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  [Table 1], [Table 2], [Table 3], [Table 4]



 

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