Oncologic impact of concomitant prostate cancer characteristics at the time of radical cystoprostatectomy for bladder cancer: a population-based analysis

Abstract

Objective

The aim of this study was to evaluate the prognostic impact of concomitant prostate cancer (PCa) of the cancer-specific mortality (CSM) in the aging patient’s papulation with bladder cancer (BCa) treated with radical cystoprostatectomy (RCP).

Materials and Methods

Within the SEER database (2004–2015), 1468 patients were treated with RCP for BCa harboring histopathological PCa findings. To account for other cause mortality (OCM), multivariable competing risk regression (CRR) tested for potential BCa-CSM differences according to PCa characteristics risk factors predicting CSM

Results

CRR analysis revealed that only following BCa characteristics, as high pathological tumor stages(Ta/Tis/T1 [REF.] vs. T2; HR 2.03, 95% CI: 1.16-3.57, p = 0.014 vs. T3; HR 4.32, 95% CI: 2.45-7.61, p < 0.001 vs. T4; HR 5.06, 95% CI: 2.77–9.22, p < 0.001), as well unfavorable BCa grade IV (Grade I–II [REF.] vs. Grade IV; HR 0.58, 95% CI: 0.35-0.98, p < 0.041) achieved independent predictor status of CSM. With regard to PCa characteristics, none of the covariates yielded independent predictor status of CSM.

Conclusions

Our study, based on the largest population cohort, demonstrates that even in organ-confined BCa patients, concomitant PCa as second malignancy does not represent a risk factor for survival.

Keywords:

• Prostate cancer
• bladder cancer
• SEER

Introduction

Radical cystoprostatectomy (RCP) represents the gold standard therapy for patients diagnosed with muscle-invasive or treatment-refractory non-muscle-invasive bladder cancer (BCa) [1]. Histopathological work-up often reveals concomitant prostate cancer (PCa) in male patients [2]. However, despite frequent co-prevalence of both malignancies, only a limited number of series examined if certain features of concomitant PCa affect survival outcomes in patients undergoing RCP [1,3–9]. This is of particular importance, given that the majority of male BCa patients are of advanced age with a peak BCa incidence at 70 years [10]. Specifically, both malignancies, BCa and PCa, share advanced age as a common risk factor of respective unfavorable tumor characteristics [10,11]. This observation is suggestive for worsening of the oncological outcomes in patients in whom both malignancies are presented compared to those diagnosed with BCa exclusively [1,6–9,12–15]. Moreover, multiple studies suggested that the demographic phenomenon of co-prevalent PCa and BCa could be explained through similarities in their respective carcinogenic pathways [12–14]

Most series on this topic are limited by sample size, historical cohorts, and overall great heterogeneity of study findings [1,3–9,15–17]. For example, many Surveillance, Epidemiology, and End Results (SEER) studies aimed to examine causal associations between irradiated PCa patients with subsequent occurrence of radiogenic BCa or rectal cancer [18,19], and thus, focused on metachronous malignancies following PCa treatment. Other studies evaluated the survival prediction of BCa according to treatment modality [20–22]. To date, no SEER series has examined the potential oncological effects of concomitant PCa at the time of RCP. Moreover, given that higher age is generally associated with greater comorbidity burden and with limited life expectancy, it is crucial to employ multivariable competing risk techniques for survival analyses in such BCa patients, which were rarely applied in previous series.

Specifically, the only existing population-based study to date showed no effect of concomitant PCa on 10- and 15-year cumulative overall mortality in a Danish RCP cohort [4]. Similarly, a French multicenter study with RCP patients from 25 institutions did not demonstrate any influence of PCa on overall survival [5]. Conversely, some series suggest that concomitant PCa represents a risk factor of overall survival [1,6–9]. For example, Buse et al. [6] reported PCa at the time of RCP to be associated with higher overall mortality after multivariable adjustment. Taken together, it remains unclear if certain unfavorable PCa characteristics adversely affect BCa specific survival in non-metastatic patients undergoing RCP.

Therefore, we employed nationally representative SEER data to (1) evaluate the impact of concomitant PCa on survival outcomes after RCP for BCa and (2) to identify potential unfavorable PCa characteristics to adversely affect cancer-specific mortality.

Patients and methods

Patient selection

Patient records, used in our epidemiological study, were retrieved within the SEER database, which includes patient demographics, cancer incidence, and survival data from 18 cancer registries, accounting for 26% of the U.S. population. Ethical approvals were obtained from participating institutions through their respective institutional review boards. The SEER database provides unidentified individual-level information and is totally available to the public via a formal application. The permission to gain access to the patient information is received.

Patients with a diagnosis of BCa (International Classification of Diseases for Oncology 67.0-67.9; histological codes: 8120, non-papillary urothelial carcinoma; 8130, papillary urothelial carcinoma; 8122, sarcomatoid urothelial carcinoma; 8070, squamous cell carcinoma; 8041, small cell neuroendocrine carcinoma) who underwent cystectomy (surgery site codes: 60, 61, 62, 63, 64, 70, 71, 72 and 80) between 2004 and 2015 were included [1]. The second inclusion criterion was a concomitant diagnosis of adenocarcinoma of the prostate (International Classification of Diseases for Oncology 61.9; histological code: 8140) and a surgical claim of prostatectomy (surgery site codes 50, 70, and 80; with or without radiation therapy) within the same year as aforementioned BCa (n = 1807) or at least a surgical claim of RCP (BCa surgery code 71; n = 142). These selection criteria were used as a proxy for BCa patients with evidence of concomitant PCa at RCP. Only BCa patients without metastatic disease (M0) and lymph node-positive disease (N0), according to the 6^th edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual were included. Tumor grades I (well differentiated), II (moderately differentiated), III (poorly differentiated), and IV (undifferentiated) were used according to the most recent update of the SEER database [20,23]. Patients who had undergone radiotherapy prior to surgery were excluded (n = 4). Moreover, BCa patients with missing pathological BCa tumor stage or pTX (n = 120), as well as, pT0 or missing pT3 (termed “NOS”) PCa tumor stage (n = 14) were excluded. The Gleason Score (GS) is derived from a composite variable based on prostatectomy or biopsy data: If applicable, the prostatectomy GS was used (n = 1085; GS 6 vs. 7 vs. ≥ 8), otherwise the biopsy GS was used (n = 731). Moreover, only the patients who were diagnosed with BCa and PCa as their first of two or more malignancies and second of two or more malignancies, respectively, to further reduce the possibility of another first malignancy other than BCa or PCa as a confounder were included. Finally, these selection criteria resulted in a final cohort of 1468 patients. Prostate-specific antigen (PSA) values were available for selected patients diagnosed 2010–2013 only (n = 416).

Statistical analyses

Descriptive statistics included frequencies and proportions for categorical and medians and interquartile ranges (IQRs) for continuously coded variables. The chi-squared test was used to compare the distribution of categorical variables and t test for continuously coded variables. To account for other cause mortality (OCM), multivariable competing risk regression (CRR) tested for potential bladder cancer-specific mortality (CSM) differences according to PCa characteristics. With regard to general characteristics, covariates consisted of age at BCa diagnosis (continuously coded), year at BCa diagnosis (continuously coded), race, marital status, and socioeconomic status. With regard to BCa characteristics, CRR were also adjusted for year of diagnosis, histological subtype, cancer grade, and pathological tumor stage. With regard to PCa characteristics, CRR were also adjusted for PSA, composite GS, pathological tumor stage, pathological nodal stage, and positive surgical margin status.

Similarly, CRR were repeated in a subgroup of patients who had complete PSA information (n = 416). Here, CRR were adjusted for age (continuously coded), pathological BCa stage, PSA (continuously coded), composite, and pathological tumor stage.

All tests were two-sided, with a statistical significance set at p < 0.05. Analyses were performed with the statistical package for R (the R Foundation for Statistical Computing, version.

Results

Overall, the median age of the patients was 70 years (IQR 62–76; Table 1). Of all 1468 patients, 91% were of Caucasian, 4.4% of African American, and 4.4% of other descent. Regarding the marital status, 69% of the patients were married, 26% were not, and 5.5% had an unknown marital status. The proportion of patients with a low socioeconomic status was 52%.

Table 1. Descriptive characteristics of 1468 BCa patients with cPCa findings at cystoprostatectomy from the Surveillance Epidemiology and End Results database.

Baseline characteristics	Full cohort (n = 1468)		PSA subcohort (n = 416)
Age, years (median, IQR)	70	(62–76)	69	(62–75)
PSA, ng/mL (median, IQR)	2.1	(0.9–4.7)	2.1	(0.9–4.7)
Race (n, %)
Caucasian	1340	91%	375	90%
African American	64	4.4%	22	5.3%
Other	64	4.4%	19	4.6%
Marital status (n, %)
Married	1014	69%	296	71%
Not married	374	26%	102	25%
Unknown	80	5.5%	18	4.3%
Socioeconomic status (n, %)
High	707	48%	218	52%
Low	761	52%	198	48%
Histological type of BCa (n, %):
Papillary urothelial carcinoma	563	38%	188	45%
Non-papillary urothelial carcinoma	842	57%	215	52%
Others^a	63	4.3%	13	3.1%
Tumor grade of BCa (n, %):
Grade I	8	0.5%	3	0.7%
Grade II	51	3.5%	12	2.9%
Grade III	384	26%	118	28%
Grade IV	949	65%	265	64%
Unknown	76	5.2%	18	4.3%
Pathological tumor stage of BCa (n, %):
Ta/Tis/T1	151	10%	48	12%
T2	744	51%	213	51%
T3	428	29%	103	25%
T4	145	9.9%	52	13%
PSA level, ng/ml, n (%):
≤10	387	93%	387	93%
>10–20	17	4.1%	17	4.1%
>20	12	2.9%	12	2.9%
Composite Gleason score (n, %):
6	1041	71%	261	63%
7	375	26%	130	31%
≥8	52	3.5%	25	6.0%
Pathological tumor stage of PCa (n, %):
T2	1365	93%	366	88%
T3a	68	4.6%	32	7.7%
≥T3b	35	2.4%	18	4.3%
Pathological tumor nodal of PCa (n, %):
N0	1366	93%	387	93%
N1	18	1.2%	10	2.4%
NX	84	5.7%	19	4.6%
Surgical margin of PCa (n, %):
Negative	1398	95%	385	93%
Positive	70	4.8%	31	7.5%

IQR: interquartile range; PCa: prostate cancer; BCa: bladder cancer.

Percentages may not total 100 because of rounding.

^aSarcomatoid urothelial or squamous cell or small cell neuroendocrine carcinoma.

PSA subcohort (n = 416) represents patients, who had complete PSA information.

Alt Text: A table presenting descriptive characteristics of 1468 bladder cancer patients with concomitant prostate cancer findings at cystoprostatectomy from the Surveillance Epidemiology and End Results database. A PSA Subcohort represents 416 patients, who had complete PSA information. Baseline characteristics such as age, PSA, race, socioeconomic status, histological type of bladder cancer, tumor grade of bladder cancer, composite Gleason score, pathological tumor stage of prostate cancer, pathological tumor nodal of prostate cancer, surgical margin of prostate cancer were included.

Bladder cancer

Of the histological subtypes of BCa reported within the specimen, 38% had papillary urothelial carcinoma and 57% had non-papillary urothelial carcinoma. Only 1.5%, 1.4%, and 1.5% presented with sarcomatoid urothelial, squamous cell, and small cell neuroendocrine carcinoma (data not shown). High BCa grades of 3 and 4 were present in 26% and 65% of the patients, respectively. Pathological tumor stages of Ta/Tis/T1, T2, T3, and T4 were observed in 10%, 51%, 29%, and 9.9%, respectively.

Prostate cancer

Within those patients with available PSA levels, the median PSA was 2.1 (IQR 0.9-4.7) ng/ml. Proportions of GS 6, 7, and ≥8 were 71%, 26%, and 3.5%, respectively. According to the pathological T stage, 93% of the tumors were organ-confined (T2), and only 4.6% and 2.4% were considered as T3a and ≥ T3b. An unfavorable pathological nodal stage of N1 was reported in 1.2% of the patients. The surgical margin status was positive in 4.8% of the patients. Taken together, the majority of patients, 64%, had low-risk pathological PCa characteristics of pT2 GS6 with the negative nodal stage (N0). In contrast, only 13% of the patients had unfavorable characteristics: pT3, and/or lymph node invasion, and/or positive surgical margin (R1).

Multivariable competing risk regression

Multivariable CRR tested risk factors of bladder CSM adjusted for BCa, as well as PCa characteristics (Table 2). Specifically, age at BCa diagnosis (HR 1.02, 95% CI: 1.01-1.03; p < 0.001) was an independent risk factors of CSM.

Table 2. Multivariable competing risks regression of 1468 BCa patients with incidental PCa findings at cystoprostatectomy from the Surveillance Epidemiology and End Results database.

Predictors	Cancer-specific mortality		Other-cause mortality
	HR (95%, CI)	p-value	HR (95%, CI)	p-value
Age at BCa diagnosis, years	1.02 (1.01–1.03)	<0.001	1.05 (1.04–1.07)	<0.001
Year of BCa diagnosis, years	1.03 (0.99–1.06)	0.12	0.91 (0.88–0.95)	<0.001
Socioeconomic status
High [REF.]	1 (1–1)		1 (1–1)
Low	0.91 (0.73–1.12)	0.4	1.05 (0.82–1.35)	0.7
Race
Caucasian [REF.]	1 (1–1)		1 (1–1)
African American	1.27 (0.78–2.06)	0.3	1.44 (0.83–2.51)	0.2
Other	0.77 (0.43–1.38)	0.4	0.76 (0.38–1.52)	0.4
Marital status
Married [REF.]	1 (1–1)		1 (1–1)
Not married	1.25 (0.98–1.58)	0.07	1.17 (0.88–1.55)	0.3
Unknown	1.34 (0.89–2.03)	0.2	1.6 (0.94–2.72)	0.086
Histological subtype of BCa
Papillary urothelial [REF.]	1 (1–1)		1 (1–1)
Non-papillary urothelial	1 (0.8–1.24)	0.98	0.94 (0.72–1.23)	0.7
Others^a	1.08 (0.61–1.89)	0.8	1.14 (0.56–2.33)	0.7
Tumor grade of BCa
Grade I–II [REF.]	1 (1–1)		1 (1–1)
Grade III	0.72 (0.43–1.22)	0.2	1.17 (0.58–2.35)	0.7
Grade IV	0.58 (0.35–0.98)	0.041	1.25 (0.62–2.51)	0.5
Unknown	0.36 (0.16–0.8)	0.013	0.99 (0.4–2.47)	0.98
Pathological tumor stage of BCa
Ta/Tis/T1 [REF.]	1 (1–1)		1 (1–1)
T2	2.03 (1.16–3.57)	0.014	1.15 (0.68–1.93)	0.6
T3	4.32 (2.45–7.61)	<0.001	1.18 (0.68–2.06)	0.6
T4	5.06 (2.77–9.22)	<0.001	1.73 (0.92–3.25)	0.089
PSA level, ng/ml
≤10 [REF.]	1 (1–1)		1 (1–1)
>10–20	0.52 (0.14–1.94)	0.3	1.33 (0.57–3.14)	0.5
>20	0.36 (0.05–2.52)	0.3	0.74 (0.11–4.91)	0.8
Unknown	1.06 (0.84–1.35)	0.6	1.11 (0.83–1.5)	0.5
Composite Gleason score
6 [REF.]	1 (1–1)		1 (1–1)
7	0.77 (0.6–1.01)	0.056	0.99 (0.72–1.36)	0.96
≥8	0.82 (0.42–1.6)	0.6	0.95 (0.5–1.77)	0.9
Pathological tumor stage of PCa
pT2 [REF.]	1 (1–1)		1 (1–1)
≥pT3	1.42 (0.9–2.23)	0.13	1.06 (0.65–1.71)	0.8
Surgical margin of PCa
Negative [REF.]	1 (1–1)		1 (1–1)
Positive	0.85 (0.48–1.5)	0.6	1.29 (0.77–2.16)	0.3
Pathological nodal stage of PCa
pN0 [REF.]	1 (1–1)		1 (1–1)
pN1	1.12 (0.41–3.03)	0.8	0.95 (0.27–3.28)	0.9
pNX	0.95 (0.63–1.41)	0.8	1.49 (0.97–2.28)	0.067

CI: confidence interval; HR: hazard ratio; Ref.: reference; Pca: prostate cancer; Bca: bladder cancer.

^aSarcomatoid urothelial or squamous cell or small cell neuroendocrine carcinoma.

Alt Text: Multivariable competing risks regression of 1468 bladder cancer patients with incidental prostate cancer findings at cystoprostatectomy from the Surveillance Epidemiology and End Results database. The analysis accounts other-cause mortality as well as bladder cancer-specific mortality. Predictors included: Age at bladder cancer diagnosis, year of bladder cancer diagnosis, socioeconomic status, race, marital status, histological subtype of bladder cancer, tumor grade of bladder cancer, pathological tumor stage of bladder cancer, PSA level, composite Gleason score, pathological tumor stage of prostate cancer, surgical margin of prostate cancer, pathological nodal stage of prostate cancer.

With regard to BCa characteristics only high pathological tumor stages (Ta/Tis/T1 [REF.] vs. T2; HR 2.03, 95% CI: 1.16–3.57, p = 0.014 vs. T3; HR 4.32, 95% CI: 2.45–7.61, p < 0.001 vs. T4; HR 5.06, 95% CI: 2.77–9.22, p < 0.001) achieved independent predictor status of CSM. Moreover, unfavorable BCa grade IV revealed to be independent predictor factor of CSM (well to moderately differentiated, grade I–II [REF.] vs. undifferentiated; anaplastic, grade IV; HR 0.58, 95% CI: 0.35–0.98, p < 0.041).

With regard to PCa characteristics, none of the covariates yielded independent predictor status of CSM, albeit higher GS and pathological tumor stage did not meet conventional levels of statistical significance as risk factors.

Finally, CRR tested the risk factors of CSM in a subgroup of patients who had complete PSA information (n = 416) (Supplementary Table 1). Subgroup analysis was consistent with our main findings within the full cohort. Specifically, within the PSA subgroup, elevated PSA did not hold true as an independent risk factor (HR 0.98, 95% CI: 0.93–1.03, p = 0.4).

Discussion

We retrospectively evaluated patients undergoing RCP for BCa who presented with concomitant PCa at the time of surgery. Tumor characteristics of both tumor entities were assessed and multivariable competing risk regression was employed to identify potential unfavorable PCa characteristics to affect BCa-specific mortality. Our study revealed several important findings.

First, a substantial proportion of RCP patients had advanced, non-organ confined tumor stage (39%) and most aggressive BCa tumor grade IV (65%). Such rates are consistent with the previous series and are often identified in those who undergo aggressive treatment such as RCP [22]. Moreover, unfavorable prognostic effects of adverse pathological stages in the BCa patient were assessed in the previous studies [20,22,24]. In the SEER-based analysis by Palumbo et al., 5-yr cancer-specific survival in the BCa patients with advanced disease was 63% for T3 and 53% for T4 disease [22]. Interestingly, localized PCa disease, diagnosed as a primarily malignancy, similar in its characteristics to cPCa, is associated with high 5-year survival rates of 99% [25]. This can possibly explain a mitigating effect of concomitant PCa findings on BCa specific mortality in the patients with advanced BCa.

Second, in contrast to rather unfavorable BCa characteristics, the vast majority of RCP patients had favorable PCa characteristics despite advanced median age of 70 years, such as 71% GS 6 and 93% pT2 stage compared to only 3.5% with ≥ GS8 or 7.0% with ≥ pT3 disease. Specifically, 64% had the lowest risk concomitant PCa with combined pathological characteristics of pT2, GS6, and N0. Such distinct low-risk proportions were also consistent in our subgroup analyses of those with complete PSA values. Moreover, here, proportion of the lowest PSA group with ≤10ng/ml dominated with 93%. These findings are consistent with the existing literature, where only 5.8–14% of concomitant PCa in BCa patients undergoing RCP was locally advanced [3,5,6,26].

Third, whereas previous series supports the hypothesis that concomitant PCa increases the risk of BCa specific mortality in RCP patients [6,8,26], others observed no significant impact [4,5,17]. A variety of the PCa features was tested in order to identify potential risk factors of BCa specific mortality in the patients treated with RCP. Hereby, we utilized established adverse clinical and pathological PCa characteristics such as PSA levels, pT stage, GS, lymph node status, as well as surgical margin status [1,3,4,8]. Compared to previous studies, our model included the most comprehensive PCa risk factors in order to address a possible impact on CSM in BCa patients. The results of CRR performed in our full cohort, as well as in the subgroups, showed that none of the PCa variables yielded independent predictor status for BCa specific mortality in patients treated with RCP. To date, multiple studies suggested that the demographic phenomenon of co-prevalent PCa and BCa are explained through similarities in their respective carcinogenic pathways [12–14]. Molecular alterations, as tumor suppressor gene p53 mutations [14] or overexpression of fibroblast growth factor receptor 3 [12] and prostate stem cell antigen (PSCA) in BCa specimen [12,13] are deemed as potential risk factors for both cancer entities. In consequence, it cannot be ruled out that inclusion of novel non-morphological PCa factors, such as biochemical and genetic markers, might identify those individuals with truly added risk through PCa, which are not identifiable with conventional PCa characteristics.

Fourth, unlike many previous studies, we accounted for other cause mortality (OCM) by employing CRR [1,3–9]. Due to the advanced age in our cohort, by which 71% of the patients were over 65 and 30% were over 75-year-old (data not shown), a corresponding but unknown proportion of advanced comorbidity burden must be assumed [20].

Fifth, despite a non-negligible amount of missing PCa data, such as PSA-values, within the existing SEER-dataset, which is inherent to previous and current data revisions [27], the CRR model of the full cohort of 1468 patients remained consistent with the subgroup of 416 patients with complete PSA data. Moreover, implementation of stringent selection criteria, where BCa and/or cPCa where assigned primary and secondary malignancy, respectively, ruling out additional confounding malignancies to the best of our knowledge. Taken together, our very comprehensive and strict selection criteria to define our cohort and additional subgroup analyses confirmed the robustness of our results.

Despite their strengths, our study has some limitations. First, as a major limitation of our study, we assume de-centralized review of the histopathological findings, as well as the absence of a standardized sampling technique of RCP specimen, which leads to higher heterogeneity of pathological results. As addressed by Lopez-Beltran et al., variability in slice thicknesses, as well as the fact of whether or not the prostate was totally or partially embedded, could explain high variability within RCP PCa findings [2]. Moreover, in the case of missing pathological RCP GS data, correspondent biopsy GS data was used. The implementation of biopsy GS results, also adds traditional systematic biopsy limitations, like moderately low cancer-detection rates and possible upgrading of biopsy finding GS the prostatectomy [28]. However, the pathological prostate biopsy work-up is usually better standardized than RCP work-up, which may decrease the variability of pathological results [29]. Second, the vast majority of patients (91%) were Caucasian, which might be explained by demographic and geographic as well as age-related and racial differences [30]. This imbalance must be taken into account when analyzing the PCa characteristics as risk factors in our cohort, since previous series demonstrated that African-American men are at greater risk of PCa mortality [31]. In turn, our current findings do not necessarily translate to other race groups despite utilizing multivariable analyses. Third, PSA-values were available only in the minority of the patients and usually represent an independent risk factor in PCa patients. However, our subgroup analyses of those with complete PSA information were consistent with the main cohort. Fourth, lack of information on patient’s comorbidities and performance status represents potential confounding factors, which are unavailable in SEER. However, we accounted for the patient’s age and acknowledged the observation that age represents a proxy and a determinant of possible comorbidities [20,32]. Moreover, other variables, as e.g. radiographic findings, may also be considered as predictors of CSM, which were not recorded in the SEER dataset. Fifth, extremely comprehensive selection criteria were implemented to rule out additional malignancies as possible cofounders and to present the most contemporary SEER-based cohort. Finally, the SEER-database represents only North American patients, which limits generalizability of our findings, as well as all other limitations related to the population-based, retrospective nature of the database. Nonetheless, our study represents the largest recorded population-based cohort of the BCa patients with concomitant PCa findings treated with RCP [4,5].

Conclusion

In conclusion, unfavorable concomitant PCa characteristics do not seem to represent risk factors of BCa-specific mortality. Moreover, our study is the first population-based study on PCa findings in BCa patients treated with RCP conducted in North American patients.

Ethical approval

Patient records, used in our epidemiological study, were retrieved from the SEER database, which includes patient demographics, cancer incidence, and survival data from 18 cancer registries, accounting for 26% of the U.S. population. Ethical approvals were obtained from participating institutions through their respective institutional review boards. The SEER database provides unidentified individual-level information and is totally available to the public via a formal application. The permission to gain access to the patient information is received.

Author contributions

MK: Project development and manuscript writing/editing; MWV: Project development and manuscript writing/editing. PIK: Manuscript writing/editing; AS: Manuscript writing/editing; NL: Manuscript writing/editing; TJ: Manuscript writing/editing; RMP: Manuscript writing/editing; MM: Manuscript writing/editing; MF: Manuscript writing/editing; JHW: Manuscript writing/editing; MG: Manuscript writing/editing; SL-B: Project development, data analysis, and manuscript writing/editing.

Disclosure statement

No potential conflict of interest was reported by the authors.

Data availability statement

The data used in our epidemiological study were retrieved from openly available in the SEER database (https://seer.cancer.gov/).

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

Open Access funding enabled and organized by Projekt DEAL. We acknowledge support from the University of Muenster. No further specific grants from any funding agency in the public, commercial, or not-for-profit sectors were received.