Exploring Prostate Cancer Incidence Trends and Age Change in Cancer Registration Areas of Jiangsu Province, China, 2009 to 2019

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The authors aimed to describe recent trends in PCa incidence rates and age-specific characteristics from 2009 to 2019 in Jiangsu Province, providing a comprehensive view of age-related changes. The methodology is robust and the figures and tables are clear. Despite the interest in a large-scale population study, a clinical implication is missing. What do the changes in the age at diagnosis stand for? Were there changes in the stage of the presentation? Were there changes in screening programs? Maybe during the years, the increase in the diagnosis of PCa is just related to a more careful assessment of the disease. Those aspects should be taken into account before stating conclusions. Moreover, were data available on the baseline characteristics of the population studied? They should be provided. Were data available on survival? Were data available on the incidental PCa that may represent 1/3 of those new diagnoses (PMID= 38506561)? It would be of interest, to increase the overall quality of the manuscript that as it stands now is not suitable for publication in the current journal. 

Author Response

Comment 1: Despite the interest in a large-scale population study, a clinical implication is missing.

Response 1: We believe that our epidemiological analysis of cancer incidence and prevalence can provide valuable insights for clinical practice.

In our research, we observed that the incidence of prostate cancer is growing most rapidly among the 0-59 age group, which suggests that Jiangsu might also be experiencing an "early-onset cancer epidemic." Studies have shown that early-onset (age ≤55 years) prostate cancer recently has been determined to be a distinct clinicopathological phenotype that is often more aggressive and associated with poorer prognosis. Therefore, greater attention should be paid to the diagnosis of prostate cancer in younger men in future clinical practice.

 

Comment 2: What do the changes in the age at diagnosis stand for?

Response 2: We aim to answer this question by examining two dimensions: the potential reasons behind the shifts in age and the consequences of these changes for informing future strategic decisions.

Several factors may contribute to this trend. First, rapid economic development has altered residents' diets and lifestyles, leading to earlier exposure to carcinogenic risk factors. Studies suggest that early exposure to such risk factors increases the likelihood of developing prostate cancer. Second, advancements in serum prostate-specific antigen (PSA) testing technology have facilitated earlier detection of prostate cancer.

Understanding the changes in the age of onset of prostate cancer is of great significance for the allocation of medical resources and the identification of key populations for intervention. Some studies (see below [Ref 1]) have pointed out that age is closely related to the prognosis of prostate cancer, and the results of this study showed that the older the age, the worse the prognosis of the patients, with the best prognosis in patients under 60 years old.

[Ref 1] Abudoubari S, Bu K, Mei Y, Maimaitiyiming A, An H and Tao N (2023) Prostate cancer epidemiology and prognostic factors in the United States. Front. Oncol. 13:1142976.doi: 10.3389/fonc.2023.1142976

 

Comment 3: Were these changes in the stage of the presentation

Response 3: We agree that this is an important perspective that deserves in-depth study.

However, we can hardly answer this question in this study, because the prostate incidence data in Jiangsu province lacks the information of the stage of the presentation. And, we have described this limitation of our study in the last paragraph of the Discussion Section.

We speculate that the absence of data is caused by two factors. Firstly, a biopsy is required for the staging of prostate cancer, but the patient's willingness to undergo the procedure is not strong. Secondly, the diagnostic capabilities of many hospitals are limited, making it difficult to accurately stage and classify tumors.

We hope that with the improvement of data collection efforts, we will be able to answer this question in the future.

 

Comment 4: Were there changes in screening programs?

Response 4: Actually, at present there is no population-based government-funded prostate cancer screening program in Jiangsu, with only certain hospitals or organizations conducting small-scale self-funded prostate cancer screenings. We notice that there are two versions of guidelines of Prostate Cancer Screening in China, as detailed in the following. And, we expect a leap from guideline to actual screening program in the future.

The Chinese Anti-Cancer Association compiled and published the first "Chinese Expert Consensus on Prostate Cancer Screening" in 2017. Prior to this, physicians conducted serum prostate-specific antigen (PSA) testing for patients based on clinical experience.

The "Guidelines for Prostate Cancer Screening and Early Detection and Treatment in China (2022, Beijing)" released in 2022 raised the starting age for screening from 50 years old as recommended in the 2017 guidelines to 60 years old. The screening age for residents with a family history of prostate cancer remains unchanged. The new guidelines also define men aged 40 and above carrying the breast cancer susceptibility gene 2 (BRCA2) mutation as a high-risk group. However, at present, there are no population-based government-funded prostate cancer screening programs in place in Jiangsu, with only certain hospitals or organizations conducting small-scale self-funded prostate cancer screenings.

 

Comment 5: Maybe during the years, the increase in the diagnosis of PCa is just related to a more careful assessment of the disease.

Response 5: We agree that a more careful assessment of the disease has close relation to the increase in the diagnosis of PCa. A recent study (see below Ref 1) reveals that medical imaging and other examination methods will also affect the incidence rate, prevalence, survival rate and other prognosis of prostate cancer. We have added this in the second paragraph in the Discussion Section.

Besides improved assessment of disease, we would like to highlight another two crucial factors for the increase in the diagnosis of PCa. Firstly, studies (see below Ref 2, 3, 4) have shown that increased body weight, physical inactivity and Diabetes mellitus (DM) and westernized diet may increase the risk of PC. Secondly, the emergence of early-onset prostate cancer should be considered.

[Ref 1] Abudoubari S, Bu K, Mei Y, Maimaitiyiming A, An H and Tao N (2023) Prostate cancer epidemiology and prognostic factors in the United States.Front. Oncol. 13:1142976.doi: 10.3389/fonc.2023.1142976

[Ref 2] Venkateswaran V, Klotz LH. Diet and Prostate Cancer: Mechanisms of Action and Implications for Chemoprevention. Nat Rev Urol (2010) 7(8):442–53.

[Ref 3] Aronson WJ, Barnard RJ, Freedland SJ, Henning S, Elashoff D, Jardack PM,et al. Growth Inhibitory Effect of Low Fat Diet on Prostate Cancer Cells:Results of a Prospective, Randomized Dietary Intervention Trial in Men With Prostate Cancer. J Urol (2010) 183(1):345–50.）

[Ref 4] Obesity is positively correlated with the incidence and mortality of high-grade advanced PC (Parekh N, Lin Y, Dipaola RS, Marcella S, Lu-Yao G. Obesity and Prostate Cancer Detection: Insights From Three National Surveys. Am J Med (2010) 123(9):829–35.).

 

Comment 6: Those aspects should be taken into account before stating conclusions.

Response 6: Thanks for your constructive suggestions. We have included description and discussion about these aspects before our conclusions.

 

Comment 7: Moreover, were data available on the baseline characteristics of the population studied? They should be provided.

Response 7: Thanks for your reminding. We have added a table in our revised manuscript for this. Please refer to the Table 1 and Table 2 in our revised manuscript.

 

Comment 8: Were data available on survival?

Response 8: Our current data does not contain survival data.

The Jiangsu Cancer Registry collects epidemiological data on cancer, including information on birth date, gender, household registration address, primary tumor site, date of onset, age, and other details pertinent to cancer epidemiology. However, there are gaps in the data regarding cancer clinical characteristics, such as tumor morphologic features and stage at diagnosis, initial treatment course, and life-state follow-up.

Currently, we are advancing the collection of clinical data related to prognostic analysis. In future research, we hope to conduct a more in-depth analysis based on tumor clinical characteristic. This is one of the limitations of this study, which has be presented in the last paragraph of the Discussion Section.

 

Comment 9: Were data available on the incidental PCa that may represent 1/3 of those new diagnoses (PMID=38506561)?

Response 9: Based on the current cancer incidence surveillance data we have collected, we cannot identify the incidental prostate cancer. In future research, we will enhance the collection and organization of this portion of data.

Reviewer 2 Report

Comments and Suggestions for Authors

Thank you for the opportunity to review the manuscript ID: curroncol-3191243. This study aimed to describe recent trends in prostate cancer incidence rates and age-specific characteristics from 2009 to 2019 in Jiangsu Province.

 

Comments:

 

In the Introduction section, relevant information was presented in detail, which indicated the importance of this issue in the observed population.

 

In general, the authors use the latest, relevant references in a high-quality and correct manner in writing this paper. 

 

Page 2: Before the last paragraph, add one new paragraph describing the practice of prostate cancer screening in this population (year of implementation, mandatory or opportunistic, for which age, population or regional, whether paid or free, type of screening test , % screening coverage, etc.).

 

Before subsection `2.1. Data source and quality control`, add a new subsection `Study design`, with an appropriate description.

 

Page 2/3: Specify which value for the maximum number of joinpoints you have determined. Also, specify which value for the minimum number of joinpoints you have determined.

 

Page 4: Explain the basis of the claim `Rural areas exhibited a more rapid increase in PCa incidence rates among individuals aged 50 and above compared to urban areas (Figure 2)`.

 

Page 5: Check if the description, I quote `Comparing 2019 to 2009, the proportion of PCa cases standardized by age increased for the 55-64 age group but decreased for those over 75 (Figure 3). In urban areas, the standardized incidence proportions for ages 50-54, 70-74, and 80 and above decreased, while they increased for the 55-69 and 75-79 age groups. Conversely, in rural areas, the peak age group shifted from 75-79 years to 70-74 years, with a significant increase in the 55-64 age group and a decrease in those aged 75 and above.`, corresponds to Figure 3. Check data for urban areas /rural areas, and correct this.

 

The discussion section, with a paragraph on the strength and limitations of this study, correctly compared the presented results with the results of other similar studies. Possible explanations of the presented results are also provided.

 

Page 9: Explain the sentence `Informed Consent Statement: Informed consent was obtained from all subjects involved in the study`. Specify who were `all subjects involved in the study`. 

 

 

Author Response

Comment 1: Page 2: Before the last paragraph, add one new paragraph describing the practice of prostate cancer screening in this population (year of implementation, mandatory or opportunistic, for which age, population or regional, whether paid or free, type of screening test, screening coverage, etc.).

Response 1: Thanks for your suggestion. We agree with you that for the completeness of this study, it is preferable to add a new paragraph describing the practice of prostate cancer screening.

But, actually, at present there is no population-based government-funded prostate cancer screening program in Jiangsu, with only certain hospitals or organizations conducting small-scale self-funded prostate cancer screenings. We notice that there are two versions of guidelines of Prostate Cancer Screening in China, as detailed in the following. And, we expect a leap from guideline to actual screening program in the future.

The Chinese Anti-Cancer Association compiled and published the first "Chinese Expert Consensus on Prostate Cancer Screening" in 2017. Prior to this, physicians conducted serum prostate-specific antigen (PSA) testing for patients based on clinical experience.

The "Guidelines for Prostate Cancer Screening and Early Detection and Treatment in China (2022, Beijing)" released in 2022 raised the starting age for screening from 50 years old as recommended in the 2017 guidelines to 60 years old. The screening age for residents with a family history of prostate cancer remains unchanged. The new guidelines also define men aged 40 and above carrying the breast cancer susceptibility gene 2 (BRCA2) mutation as a high-risk group. However, at present, there are no population-based government-funded prostate cancer screening programs in place in Jiangsu, with only certain hospitals or organizations conducting small-scale self-funded prostate cancer screenings.

 

 

Comment 2: Before subsection `2.1. Data source and quality control`, add a new subsection `Study design`, with an appropriate description.

Response 2: Thanks for your reminding. We have added a subsection of “Study Design” in our revised manuscript, which is also presented in the following.

“This is a descriptive epidemiological study based on population-level cancer registry data from Jiangsu Province, designed to analyze trends and age-related changes in prostate cancer incidence between 2009 and 2019. Data were obtained from the Jiangsu Provincial Center for Disease Control and Prevention (CDC), which oversees the collection, quality evaluation, and publication of cancer registration data from local population-based cancer registries. Cancer diagnoses are reported to local registries from multiple sources, including hospitals, community health centers, the Urban Resident Basic Medical Insurance program, and the New Rural Cooperative Medical Scheme. Data items included in the analysis were demographics (date of birth or age, area of residents), and tumor characteristics (date of diagnosis, histology). The analysis used the most recent data from 16 population-based cancer registries, covering approximately 17.3 million people, or about 22.15% of Jiangsu’s total population.

The data analysis followed a three-step process: first, we calculated crude and age-specific incidence rates, the average age at onset, and age-specific composition ratios. Standardization was performed using Segi’s world population. Second, we constructed birth cohorts (1929–2019) to assess prostate cancer incidence by birth year. Third, we examined temporal trends in incidence rates from 2009 to 2019 by fitting joinpoint models, and used a linear regression model to explore the relationship between the average age at onset and calendar year. All analyses were stratified by geographic areas and age groups.”

Comment 3: Page 2/3: Specify which value for the maximum number of joinpoints you have determined. Also, specify which value for the minimum number of joinpoints you have determined.

Response 3: To prevent erroneous trend change results, when analyzing with Joinpoint software, all models are set to a maximum of 2 joinpoints (i.e., the trend is divided into at most 3 segments). We have added the description about this in Section 2.3.1 of our revised manuscript.

 

 

Comment 4: Page 4: Explain the basis of the claim ` Rural areas exhibited a more rapid increase in PCa incidence rates among individuals aged 50 and above compared to urban areas (Figure 2).

Response 4: We make a table for clear explanation in the following uploaded figure. Based on the birth cohort, the trend of prostate cancer incidence rates among residents born in different years within the same age group was calculated, and the Annual Average Percentage Change (AAPC) along with its 95% Confidence Interval (CI) was determined. The results revealed that rural areas showed a more rapid increase in prostate cancer incidence rates among individuals aged 50 and above compared to urban areas.

 

Comment 5: Page 5: Check if the description, I quote `Comparing 2019 to 2009, the proportion of PCa cases standardized by age increased for the 55-64 age group but decreased for those over 75 (Figure 3). In urban areas, the standardized incidence proportions for ages 50-54, 70-74, and 80 and above decreased, while they increased for the 55-69 and 75-79 age groups. Conversely, in rural areas, the peak age group shifted from 75-79 years to 70-74 years, with a significant increase in the 55-64 age group and a decrease in those aged 75 and above.`, corresponds to Figure 3. Check data for urban areas /rural areas, and correct this.

Response 5: Thanks for your kind reminding. We made a careless typo: the “urban areas” and “rural areas” in the caption of Figure 3 should be exchanged. We have corrected this in our revised manuscript.

 

Comment 6: Page 9: Explain the sentence `Informed Consent Statement: Informed consent was obtained from all subjects involved in the study`. Specify who were `all subjects involved in the study`. 

Response 6: As for “Informed Consent Statement”, we should choose “Not applicable” rather than “Informed consent was obtained from all subjects involved in the study”.

Thanks for your reminding, and we have corrected this.

Reviewer 3 Report

Comments and Suggestions for Authors

Thank you for the opportunity to review this manuscript. While this manuscript is well written, it has some room for improvement in the results section. Please add a table on population characteristics or demographics of the study population. The representation of Figure 2 can be improved by creating a line graph showing trends, because the way it is presented in its current format appears to be a little unclear. A dotted line graph representation will be clearer and easier to read than the floating line presented in the paper. 

Author Response

Comment 1: Please add a table on population characteristics or demographics of the study population.

Response 1: Thanks for your reminding. We have added two tables (Table 1 and 2) in our revised manuscript. We also uploaded these two tables here in the format of image.

Comment 2: The representation of Figure 2 can be improved by creating a line graph showing trends, because the way it is presented in its current format appears to be a little unclear. A dotted line graph representation will be clearer and easier to read than the floating line presented in the paper.

Response 2: Thanks for your suggestion. In our revised manuscript, we have added dotted line graph into our Figure, which makes the trends more clear and readable.

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

All comment raised have been addressed properly

Reviewer 2 Report

Comments and Suggestions for Authors

Thank you for the opportunity to re-review the manuscript ID: curroncol-3191243. The authors have correctly, honestly and in a quality manner responded to all my questions and made the necessary changes to the manuscript. The revised manuscript is clear, readable and informative and will provide valuable findings for this issue. Thank you to the authors for their responses to my comments.

 

One suggestion to the authors: Part of the text that follows is contained in responses to my comments. Check if that text has been included in the revised version of this paper.

 

Given that prostate cancer screening is inevitably mentioned several times in the text, perhaps the authors should include that part of the response to my comment in the revised version of this paper.

 

I quote:

 

The Chinese Anti-Cancer Association compiled and published the first "Chinese Expert Consensus on Prostate Cancer Screening" in 2017. Prior to this, physicians conducted serum prostate-specific antigen (PSA) testing for patients based on clinical experience.

 

The "Guidelines for Prostate Cancer Screening and Early Detection and Treatment in China (2022, Beijing)" released in 2022 raised the starting age for screening from 50 years old as recommended in the 2017 guidelines to 60 years old. The screening age for residents with a family history of prostate cancer remains unchanged. The new guidelines also define men aged 40 and above carrying the breast cancer susceptibility gene 2 (BRCA2) mutation as a high-risk group. However, at present, there are no population-based government-funded prostate cancer screening programs in place in Jiangsu, with only certain hospitals or organizations conducting small-scale self-funded prostate cancer screenings.