Introduction
Prostate cancer (PCa) is the most frequently diagnosed male cancer and second leading cancer-related cause of death in males, where overall and cancer-specific survival rates are >90% even at 15 years of localized disease (1). Not many epidemiological studies on PCa in Turkey are reported; however, the Urooncology Association in Turkey conducted and reported “Prostate Cancer Incidence in Turkey” back in 2009 (2).This study aimed to present the data of patients with PCa, whose information was stored in the Urologic Cancer Database-Prostate, Urooncology Association in Turkey (UroCaD-P), as well as compare the current results with the previous report (2) and demonstrate the paradigm changes in PCa diagnosis and treatment.
Materials and Methods
The data source for the present study was the nationwide database of UroCaD-P. Data collection revealed 5,040 patients with PCa in UroCaD-P. The study data were collected by REDCap data collection software that was developed by Vanderbilt University and licensed by Urooncology Association in Turkey (3,4). All the data are kept in a secure server, and all personal information of patients was anonymized. Since this study is designed as a database report ethics committee approval was not obtained.
Study Parameters
-Demographic properties (age, place of birth, place of residence, etc.)
-Clinical Features (complaints, concomitant diseases, family history of PCa, etc.)
-Digital rectal examination (DRE) findings
• Prostate-specific antigen (PSA) levels at the time of diagnosis
• Pre-diagnostic magnetic resonance imaging (MRI)
-Biopsy modality
-Histopathologic findings on biopsy
-First-line treatment choices
-Preferred surgical modalities
-Histopathologic findings on surgery
-Pathological stage
-Follow-up data
Statistical Analysis
Statistical analyses were performed with python. The libraries used for analysis include Pandas (5,6), Numpy (7), and Scipy (7). JupyterLab (8) was used as the coding interface. The scaler variables were investigated using visual (Histograms, QQ Plots) and analytical methods (Kolmogorov-Smirnov, Shapiro-Wilk, and D’Agostino’s k2 tests) to determine the normality of distribution. Descriptive statistics are given as mean and standard deviation if the scalar variable is distributed normally and as median and interquartile range if not. Case numbers and percent were given for statistical analysis of categorical variables. This is a sectional study, thus no hypothesis tests and p-values.
Results
The study consisted of 5,040 patients with PCa who were diagnosed between 1995 and 2021 from 19 different data-providing centers across Turkey. The patient’s birthplace and place of the residence revealed that patients were from 80 different cities of Turkey. The mean patient age was 63.6±7.5 years. Most patients were between the ages of 60 and 69 years (Figure 1).
Of the patients, 51.8% had complaints at the time of diagnosis. The most common complaint was lower urinary tract symptoms (Figure 2). Most patients (75.1%) had no pathological finding on their initial DRE. The mean PSA value of patients was 16.2±27.5. Most patients (41.7%) had a PSA value between 4 and 10 (Figure 3).
Our results revealed that MRI before PCa diagnosis has become an increasingly preferred examination over the years (Figure 4). The most common lesion group in patients with PCa was Prostate Imaging-Reporting and Data System (PI-RADS) 4. MRI and MR-guided biopsies increased over the years; however, the ultrasound-guided transrectal biopsy was still the most commonly (90.9%) used technique for PCa diagnosis. The cancer detection ratio was slightly higher in MR-guided biopsies. Of the patients, 57.4% have a (PI-RADS) 5 lesion, thus PCa is diagnosed.
The metastatic disease ratio at the time of diagnosis was 8.9%. The use of Gallium (Ga)-68 prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography scintigraphy was determined in 198 patients, of whom 25.3% had metastasis.
The most commonly chosen treatment was radical prostatectomy (RP). Minimally invasive surgical techniques, such as robotic or laparoscopic RP, have been increasing over the past years; however, open RP was still the most common RP modality (62.6%). The most seen pathological stage was T2, which was observed at the rate of 45.8% in patients after RP.
The follow-up revealed a progression of disease in 8.9% of patients. Biochemical progression was more commonly observed (62.9%) compared to radiological or clinical progression.
Discussion
Turkey had very little reliable data on the epidemiological aspects of PCa. In 2009, Eser et al. (9) published their epidemiological data and demonstrated PCa as the fifth most common cancer in İzmir, and revealed an increased PCa incidence over the years. In the same year, the “Prostate Cancer Incidence in Turkey” project is conducted with the Urooncology Association in Turkey and revealed that 39% of patients were between 60 and 69 years of age (2). Likewise, the most common age group in PCa diagnosis was 60-69 years (49.8%) in this study. Previous studies showed that PCa is rarely observed before the age of 65 years and is more commonly seen between the ages 65 and 70 years, which was in concordance with our study (10,11). Our study revealed that 51. 8% of patients were symptomatic at the time of diagnosis. The presence of symptoms was determined in 88.6% in 2009 data. The presence of complaints was quite different between the two studies; however, DRE positivity was similar (24.9% vs. 25.4%).
In 2009, most patients had a PSA level of <10 ng/dL, which was consistent with our results. The current report revealed that the mean PSA level at the time of diagnosis was similar to 2009 data and two other past studies conducted in Greece and Spain (11,12). Previous data suggests that patients have more advanced PCa with the increasing PSA levels (13,14). Current data also showed that patients with clinically significant PCa were in the higher percentage in the higher PSA level groups. More patients have PSA values of <4 ng/dL in this study compared to previous studies. Some clinics revealed that the threshold for normal PSA value is regarded as 2.5 ng/dL in Turkey and this may be the cause of the increased percentage of patients with lower PSA levels.
Multiparametric prostate MRI has been a promising modality for diagnosing clinically significant PCa (15,16) and is now regarded as one of the first-line imaging modalities before prostate biopsy in the European Association of Urology guidelines with strong recommendations (17). Consistently, data of the current report shows that the use of both MRI and MR-guided biopsies for PCa diagnosis is increasing in recent years.
The treatment methods examination after the diagnosis revealed that 73.9% of patients had undergone RP. This rate was 51.8% in 2009. Robotic and laparoscopic approaches, which are among the surgical modalities, have increased over the years. Similarly, a study in the US demonstrated increased minimally invasive surgical techniques over the years (18).The metastatic disease rate in our study was lower compared to the 2009 study, which may be due to an increased awareness of PCa in the population, increased availability of healthcare services, and increased usage of PSA testing by general practitioners. In recent years, Ga-68 PSMA PET is also used for screening patients with PCa for metastasis. A recent study revealed that the sensitivity and specificity of PSMA PET for lymph node metastasis wave 53.3% and 85.7%, respectively (19). Our study revealed a limited number of patients who had PSMA PET screening before initial treatment and metastasis ratio as 25.3%. A recent study observed the advanced disease in 35.3% of high-risk patients with PCa (20). Our study included not only high-risk patients but also low and intermediate-risk ones, thus our result seems to be in concordance with this recent study.
The progression rate was 8.9% for all the patient groups in our study. Most studies on progression focus on specific patient groups or risk factors (obesity etc.). This study is a population base report, thus further risk factor analysis for progression was not performed; however, our study demonstrates that in most patients, PCa progression is seen as a biochemical progression.
Study Limitations
Our study is not without limitations. It is a population-based study, thus having more participating centers and patients would increase its strength; however, authors feel confident that results of this report could be generalized nationwide since all participating centers were referral centers in their region and all over Turkey.
Conclusion
Therefore, technological advancements for PCa diagnosis (MRI and MR-guided biopsies) are becoming a routine part of daily practice compared to the results of the “Prostate Cancer Incidence in Turkey” project conducted in 2009. The study comparative results revealed that the rate of symptomatic and metastatic disease decreases at the time of diagnosis, and laparoscopic and robotic surgery methods are used at increasing rates for localized disease.
Acknowledgements
Publication: The results of the study were not published in full or in part in form of abstracts.
Contribution: There is not any contributors who may not be listed as authors.
Conflict of Interest: No conflict of interest was declared by the authors.
Financial Disclosure: We would like to thank AstraZeneca for their unconditional support for this project.
Ethics
Ethics Committee Approval: Since this study is designed as a database report ethics committee approval was not obtained.
Informed Consent: All the data are kept in a secure server, and all personal information of patients was anonymized.
Peer-review: Externally peer-reviewed.
Authorship Contributions
Supervision: S.E., G.A., S.S., S.A., L.T., Concept: İ.T., S.E., G.A., S.S., S.A., L.T., Design: İ.T., S.E., G.A., S.S., S.A., L.T., Data Collection or Processing: B.Ş., Analysis or Interpretation: B.Ş., Literature Search: B.Ş., Writing: B.Ş., S.Ç., İ.T.