Abstract
Purpose
To evaluate whether tumor zonal origin is associated with clinical, pathological, and prognostic outcomes in patients with prostate cancer (PC) treated with radical prostatectomy (RP).
Patients and Methods
This retrospective cohort study analyzed 488 patients who underwent RP at UNICAMP between 1997 and 2017. Tumor zonal origin was defined by the dominant (index) lesion, identified through standardized whole-mount pathological analysis based on the highest ISUP grade and largest tumor volume. The primary endpoint was a composite of biochemical recurrence and/or metastasis, selected to capture clinically significant disease relapse and ensure statistical robustness in a long-term cohort. Associations were assessed using the Mann–Whitney U-test and the Chi-square test. Multivariate logistic regression was performed to identify independent predictors of progression (p < 0.05).
Results
The index tumor originated in the peripheral zone (PZ) in 79.9% of cases and in the transition zone (TZ) in 6.5%. During follow-up, 38.3% of patients experienced biochemical recurrence or metastasis. Tumor location was not significantly associated with biochemical recurrence or metastasis (p = 0.428). Independent predictors included clinical stage (risk classification), pathological ISUP grade, positive surgical margins, and extra prostatic extension. Notably, biopsy ISUP grade and lymph node status were not independently predictive. The limited representation of TZ tumors may have constrained the statistical power to detect subtle prognostic differences.
Conclusion
Within the limitations of this cohort, tumor zonal origin was not independently associated with biochemical recurrence or metastasis following RP. Established pathological factors remain the primary determinants of disease progression.
Keywords: prostate cancer, radical prostatectomy, zonal origin, transition zone, prognosis, biochemical recurrence
Plain Language Summary
In men treated with radical prostatectomy for prostate cancer, the area of the prostate where the main tumor begins does not appear to influence the risk of cancer recurrence or spread. Instead, well-established pathological features, such as risk classification, tumor grade, surgical margins, and extra prostatic extension, remain the most important predictors of outcome. These findings support the use of comprehensive pathological assessment to guide prognosis and treatment decisions.
Introduction
Prostate cancer (PC) remains one of the most prevalent malignancies among men and a leading cause of cancer-related mortality in Brazil, with approximately 72,000 new cases estimated in 2024 according to national data.1 Radical prostatectomy (RP) continues to represent a primary curative strategy for localized disease.2 Despite advances in diagnosis and treatment, PC exhibits significant biological heterogeneity, complicating prognostic assessment and therapeutic decision-making.
The prostate is anatomically divided into three main zones: peripheral (PZ), transitional (TZ), and central (CZ), each with distinct embryological and histological characteristics.3,4 Historically, most cancers arise in the PZ. Tumors originating in the TZ have been described as presenting distinct pathological and biological features, while CZ carcinomas are rare and less frequently characterized.4–6
Several studies have suggested that TZ tumors may be associated with more favorable pathological characteristics and improved recurrence-free survival compared to PZ tumors.7–9 However, inconsistencies across studies, including variations in pathological mapping, statistical modeling, and endpoint definitions, have limited the ability to draw definitive conclusions. Clarifying the prognostic relevance of tumor zonal origin may contribute to refined risk stratification and more individualized management strategies.
In this context and given the ongoing uncertainty regarding the independent prognostic value of zonal tumor origin, we aimed to evaluate whether tumor zonal origin, defined according to standardized whole-gland pathological mapping, is associated with oncologic outcomes following radical prostatectomy.10
Although several prior studies have explored the prognostic relevance of tumor zonal origin, results remain inconsistent, and many cohorts were limited by short follow-up, heterogeneous pathological assessment, or inclusion of multiple zonal categories. The present study aims to address these gaps by evaluating a large single-center cohort with long-term follow-up and standardized whole-gland pathological mapping, focusing exclusively on peripheral and transitional zone tumors.
Given the low frequency of central zone tumors and their limited representation in our cohort, the present analysis focused specifically on tumors arising in the peripheral and transitional zones.
Materials and Methods
Study Design
Patients
This retrospective cohort study was conducted by analyzing the medical records of patients diagnosed with prostate cancer (PC) and undergoing radical prostatectomy (RP) at the Hospital de Clínicas of the State University of Campinas (UNICAMP) between January 1997 and December 2017, after local Ethics Committee approval CAAE # 79463524.2.0000.5404. Patients who received neoadjuvant or adjuvant androgen-deprivation therapy prior to surgery were not included in the study. The objective was to evaluate the correlation between the tumor-affected prostate regions, clinical, therapeutic, and prognostic factors, biochemical recurrence, and metastasis. All patients underwent radical prostatectomy as primary treatment. None received neoadjuvant androgen deprivation therapy or other systemic treatment prior to surgery.
Data Collection
Clinical data were obtained from electronic and physical medical records and included the tumor-affected prostate region (peripheral and transition zones). The latter was performed using a standardized anatomopathological report form, in which the prostate was systematically divided into quadrants of the upper and lower halves, allowing for detailed mapping of tumor distribution.
Whole-mount prostate specimens were processed using standardized institutional protocols. Tumor localization was determined by systematic histopathological mapping performed by a dedicated genitourinary pathologist (AB), according to predefined zonal criteria.
The entire radical prostatectomy specimen for each patient was divided into 32 paraffin blocks and processed without the results of the initial biopsy in hand, to avoid comparison bias. Extra-prostatic extension was considered when the tumor reached peri-prostatic adipose tissue.11
Histopathological evaluation was performed centrally within the same institution, minimizing variability. Zonal assignment followed predefined anatomical landmarks to reduce subjectivity in classification.
Tumor zonal origin was defined according to the location of the dominant (index) lesion, determined by the highest ISUP grade and largest tumor volume in whole-mount pathological analysis. In cases of multifocal disease, classification was based on this index lesion. All specimens were evaluated using standardized whole-gland mapping protocols to ensure reproducibility and reflect the lesion most likely to influence clinical outcomes.
Additional information included the patients’ clinical and pathological characteristics, the treatment modality adopted, and clinical course and outcomes, such as biochemical recurrence and metastases.
Ethical Considerations
The study was approved by the Hospital das Clínicas, Universidade Estadual de Campinas (UNICAMP) Ethics Committee (CAAE # 79463524.2.0000.5404). All procedures were conducted in accordance with the ethical standards of the institutional and national research committee and with the 1964 Declaration of Helsinki and its later amendments.
Written informed consent was obtained from all living patients at the time of data collection. For deceased patients, consent for data use was obtained from legally authorized family representatives in accordance with institutional ethics committee approval. The proportion of cases requiring proxy consent was minimal and did not result in measurable demographic or clinical imbalance in the analyzed cohort.
Statistical Analysis
Descriptive analyses were performed using frequency tables for categorical variables and measures of central tendency and dispersion (mean, standard deviation, minimum, median, and maximum) for continuous variables. Associations between clinic-pathological variables and disease recurrence or progression were assessed using the Mann–Whitney U-test for continuous data and the Chi-square test for categorical variables. Risk assessment before and after surgery was conducted using the symmetry test and the weighted Kappa coefficient.
Variables with p < 0.20 in the univariate analysis were entered into the multivariate logistic regression model using a stepwise backward selection approach to identify independent predictors. To ensure statistical robustness and account for the low incidence of isolated metastatic events, a composite endpoint of biochemical recurrence and/or metastasis was adopted. Effect estimates were reported as odds ratios (ORs) with 95% confidence intervals (CIs). A significance level of 5% (p < 0.05) was adopted for all statistical tests.
Results
Between January 1997 and December 2017, 512 patients with a diagnosis of prostate cancer (PC) were identified, of which 507 underwent radical prostatectomy (RP). After excluding 19 cases due to record failures, refusal of the Informed Consent Term, or loss of follow-up, the final sample consisted of 488 patients.
Studied Population
The studied population was composed of men with an average age of 62.7, of whom 78.7% self-identified as white and 21.3% as non-white. The average PSA at diagnosis was 9.7 ng/dL. Regarding biopsies, 59.1% of patients were classified as ISUP 1; 26.6% as ISUP 2; 6.7% as ISUP 3; 5.5% as ISUP 4; and 2.1% as ISUP 5. After evaluation of the radical prostatectomy specimens, 29.6% of patients were classified as ISUP 1; 48.9% as ISUP 2; 14.6% as ISUP 3; 2.3% as ISUP 4; and 4.8% as ISUP 5. Regarding staging, 97.3% were staged up to pT2b, and 2.7% were staged between pT2c and pT3b. Considering risk groups, 22.2% were low risk, 61.5% were intermediate risk, and 16.3% were high risk. Lymphadenectomy was performed on 49.8% of the patients. Among these, 94.9% were pN0 and 5.1% pN1. The general characteristics of the studied population are presented in Table 1.
Table 1.
General Characteristics of the Study Population
| Age - mean ± SD (n) | 62.7 ± 6.6 (509) |
| Ethnicity (%) | |
| White | 78.7 |
| Nonwhite | 21.3 |
| PSA - mean ± SD | 9.7 ± 7.2 |
| Biopsy ISUP - n (%) | |
| 1 | 309 (59.1) |
| 2 | 139 (26.6) |
| 3 | 35 (6.7) |
| 4 | 29 (5.5) |
| 5 | 11 (2.1) |
| Prostatectomy ISUP - n (%) | |
| 1 | 155 (25.5) |
| 2 | 257 (48.9) |
| 3 | 77 (14.6) |
| 4 | 12 (2.3) |
| 5 | 25 (4.8) |
| Staging - n (%) | |
| pT1a | 6 (1.1) |
| pT1b | 3 (0.6) |
| pT1c | 269 (51.3) |
| pT2 | 12 (2.3) |
| pT2a | 160 (30.5) |
| pT2b | 60 (11.5) |
| pT2c | 11 (2.1) |
| pT3a | 2 (0.4) |
| pT3b | 1 (0.2) |
| Risk Stratification | |
| Low | 177 (22.2) |
| Intermediary | 324 (61.5) |
| High | 86 (16.3) |
| Lymph nodes staging | |
| pNx | 257 (50.2) |
| pN0 | 242 (47.3) |
| pN1 | 13 (2.5) |
Note: Values are presented as mean ± standard deviation (SD) or number (percentage) as indicated.
Abbreviations: SD, standard deviation; ISUP, International Society of Urological Pathology; PSA, prostate-specific antigen; pT, pathological tumor stage; pNx, lymph nodes not assessed; pN0, no nodal involvement; pN1, nodal metastasis present.
Tumor Location
The index tumor originated in the peripheral zone in 79.9% of patients and in the transition zone in 6.5%. Both groups were compared (Table 2), and there was no significant difference in average patient age, ISUP classification, risk groups, presence of a compromised surgical margin, or extra prostatic extension.
Table 2.
Comparison of Groups with Index Tumor Predominantly Located in the Peripheral Zone and in the Transition Zone
| Index Tumor Mainly on Peripheral Zone |
Index Tumor Mainly on Transition Zone |
P-value | |
|---|---|---|---|
| Age - Mean ± SD (n) | 63.0 ± 6.6 (405) | 62.8 ± 6.7 (33) | 0.9589 |
| Pathological Staging - n (%) | |||
| pT1a/pT1b | 4 (1.0) | 1 (3.0) | 0.5704 |
| pT1c | 219 (54.3) | 18 (54.5) | |
| pT2 | 6 (1.5) | 0 (0.0) | |
| pT2a | 127 (31.5) | 9 (27.3) | |
| pT2b | 38 (9.4) | 5 (15.2) | |
| ≥ pT2c | 9 (2.2) | 0 (0.0) | |
| Prostatectomy ISUP - n (%) | |||
| 1 | 119 (29.5) | 13 (39.4) | 0.4213 |
| 2/3 | 260 (64.4) | 19 (57.6) | |
| 4/5 | 25 (6.2) | 1 (3.0) | |
| Risk Stratification - n (%) | |||
| Low | 94 (23.2) | 10 (30.3) | 0.3490 |
| Intermediary | 254 (62.7) | 21 (63.6) | |
| High | 57 (14.1) | 2 (6.1) | |
| Lymph nodes - n (%) | |||
| pNx | 202 (49.9) | 21 (63.6) | 0.2366 |
| pN0 | 196 (48.4) | 11 (33.3) | |
| pN1 | 7 (1.7) | 1 (3.0) | |
| Surgical margins - n (%) | |||
| Free | 211 (52.4) | 21 (63.6) | 0.2119 |
| Compromised | 192 (47.6) | 12 (36.4) | |
| Extra prostatic extension - n (%) | |||
| Absent | 286 (71.1) | 19 (57.6) | 0.1016 |
| Present | 116 (28.9) | 14 (42.4) |
Note: Values are presented as mean ± standard deviation (SD) or number (percentage) as indicated.
Abbreviations: SD, standard deviation; ISUP, International Society of Urological Pathology; pT, pathological tumor stage; pNx, lymph nodes not assessed; pN0, no nodal involvement; pN1, nodal metastasis present.
Main Findings
During the follow-up period, the incidence of biochemical recurrence and/or metastasis was 38.3%. Tumor location failed as a predictor of biochemical or clinical relapse (metastasis) (p = 0.428).
A comparative analysis was conducted between patients who developed biochemical recurrence and/or metastasis and those who remained free of disease throughout the study period, with odds ratios and 95% CI (Table 3).
Table 3.
Comparing Groups That Evolved with and without Biochemical Recurrence and/or Metastasis
| Biochemical Recurrence and/or Metastasis No |
Biochemical Recurrence and/or Metastasis Yes |
Odds Ratio (95% CI) |
P-value | |
|---|---|---|---|---|
| Age - Mean ± SD (n) | 62.9 ± 6.5 (307) | 62.4 ± 6.8 (202) | 1.004 (0.996; 1.013) | 0.4936 |
| Pathological Staging | ||||
| pT1a | 5 (1.6) | 0 (0.0) | Reference [pT1a, b, c] | 0.1102 |
| pT1b | 2 (0.7) | 1 (0.5) | ||
| pT1c | 167 (54.9) | 97 (49.0) | [pT2a, b] | |
| pT2a | 91 (29.9) | 60 (30.3) | 1.133 (0.735; 1.476) | |
| pT2b | 30 (9.9) | 27 (13.6) | [≥ pT2c] | |
| ≥ pT2c | 3 (1.3) | 7 (4.5) | 1.251 (0.977; 1.602) | |
| Biopsy ISUP - n (%) | ||||
| 1 | 190 (62.1) | 106 (53.8) | Reference | 0.2205 |
| 2 | 75 (24.5) | 59 (29.9) | [ISUP 2 / 3] | |
| 3 | 21 (6.8) | 14 (7.1) | 1.370 (0.931; 2.016) | |
| 4 | 13 (4.2) | 14 (7.1) | [ISUP 4 / 5] | |
| 5 | 7 (2.3) | 4 (2.0) | 1.622 (0.822; 3.200) | |
| Prostatectomy ISUP | ||||
| 1 | 105 (34.4) | 44 (21.9) | Reference | 0.0256 |
| 2 | 143 (46.9) | 103 (51.2) | [ISUP 2 / 3] | |
| 3 | 37 (12.1) | 38 (18.9) | 1.869 (1.234; 2.831) | |
| 4 | 7 (2.3) | 5 (2.5) | [ISUP 4 / 5] | |
| 5 | 13 (4.3) | 11 (5.5) | 1.909 (0.906; 4.024) | |
| Risk Stratification | ||||
| Low | 87 (28.5) | 27 (13.4) | Reference | 0.0001 |
| Intermediary | 177 (58.0) | 133 (65.8) | 1.186 (0.710; 1.981) | |
| High | 41 (13.4) | 42 (20.8) | 3.693 (1.482; 9.202) | |
| Lymph nodes | ||||
| pNx | 151 (49.7) | 97 (51.6) | Reference | 0.4137 |
| pN0 | 147 (48.4) | 84 (44.7) | 0.890 (0.614; 1.288) | |
| pN1 | 6 (2.0) | 7 (3.7) | 1.816 (0.593; 5.565) | |
| Surgical margins | ||||
| Free | 183 (60.0) | 76 (37.6) | 3.183 (1.941; 5.220) | <0.0001 |
| Compromised | 122 (40.0) | 126 (62.4) | ||
| Extra prostatic extension | ||||
| Absent | 216 (70.8) | 118 (58.7) | 1.707 (1.175; 2.481) | 0.0049 |
| Present | 89 (29.2) | 83 (41.3) | ||
| Index Tumor | ||||
| Peripheral zone | 240 (79.7%) | 149 (79.7%) | Reference | 0.6010 |
| Transition zone | 22 (7.3%) | 10 (5.3%) | 0.732 (0.337; 1.589) | |
| Non-predominant | 39 (13.0%) | 28 (15.0%) | 1.156 (0.683; 1.958) |
Factors associated with disease relapse included clinical staging (risk stratification), ISUP classification of the prostatectomy specimen, positive surgical margins, and extra prostatic extension. In contrast, lymph node involvement and the ISUP grade from the diagnostic biopsy were not correlated with higher biochemical recurrence or metastasis rates.
Discussion
Our data confirm that most of the prostate cancer (PC) tumors originate in the peripheral zone (PZ), followed by the central (CZ) and transition zones (TZ). Although some literature suggests a more favorable prognosis for TZ tumors,12 our findings showed no statistically significant differences in biochemical recurrence or metastasis between prostate tumor zone predominance. This corroborates previous investigations indicating that established pathological factors, such as ISUP grade, extra-prostatic extension, and surgical margins, are the primary drivers of risk, rather than zonal origin.10
Conversely, certain studies have identified a potential prognostic role for tumor location, particularly within specific cohorts or when integrating molecular characteristics. These discrepancies may be attributed to variations in cohort composition, pathological assessment methods, and follow-up duration across the literature. The results presented by Ali et al indicated that tumor location may influence prognosis but highlighted the need for more in-depth molecular analyses to better elucidate this association.10 Similarly, Reis et al suggested differentiated surgical approaches based on tumor location, which can be explored in future studies to optimize risk stratification and clinical management.11
On the other hand, a meta-analysis by Jin et al, involving 16 cohorts and 19,365 patients, demonstrated that PC originating in the TZ is associated with a lower risk of biochemical recurrence than PC originating in the PZ (RR = 0.79; 95% CI: 0.69–0.92). These results suggest that tumor origin in the TZ may be an independent prognostic factor for better biochemical outcomes after treatment, notwithstanding the heterogeneous definitions of biochemical recurrence and zonal origin classifications across included studies that rely on sampling pathological reports.12
Also, the discrepancy between our findings and previous meta-analytic data may be partially explained by the relatively small proportion of transitional zone tumors in our cohort (6.5%), due to rigorous mapping and tumor zone definition in whole-mount prostate specimens, which may also have limited statistical power for subgroup comparisons. Importantly, the absence of statistically significant differences between peripheral and transitional zone tumors should not be interpreted as definitive evidence of equivalence. The limited number of transitional zone cases increases the possibility of a type II error, potentially masking modest prognostic differences. Additionally, variations in pathological mapping techniques, inclusion criteria, and follow-up duration across studies may contribute to heterogeneity in reported outcomes.
Similar results were reported by Takamatsu et al, who analyzed 638 patients, of which 293 (46%) had cancer in the TZ and 345 (54%) in the PZ. Tumors in the TZ were significantly associated with higher levels of prostate-specific antigen (PSA) (P = 0.012), lower positivity rates in biopsy fragments (P = 0.020), lower pathological Gleason score (P = 0.017), lower pathological stage (P = 0.002), and lower rates of invasion of the seminal vesicles (P = 0.002). Tumor origin in the PZ (hazard ratio: 1.68, P = 0.033) and extra prostatic extension were identified as independent risk factors for biochemical recurrence. Thus, the authors concluded that PC from the TZ presents more favorable pathological characteristics and better oncological outcomes than tumors from the PZ, especially in cases of pathological stage pT3a.13
Additional studies reinforce this perspective. Lee et al reported that PC from the TZ is associated with more favorable pathological characteristics and greater recurrence-free survival, despite being related to larger tumors and higher PSA levels at the time of diagnosis.14 In contrast, Cohen et al highlighted that carcinoma of the CZ is a rare but highly aggressive form of PC, with a distinct pattern of dissemination compared to the other zones. Preoperative identification is hindered by the absence of biopsies directed to this region. However, when diagnosed early, an aggressive therapeutic approach might improve the prognosis.15
Teloken et al demonstrated that, in high-grade prostate cancer originating in the transition zone, there was an association with higher PSA levels, greater tumor volume, and a higher incidence of positive surgical margins. However, these tumors showed a lower incidence of intraductal carcinoma, extra-prostatic extension, seminal vesicle invasion, lymph node involvement, and biochemical failure after radical prostatectomy. Furthermore, patients with low-grade prostate cancer showed excellent biochemical recurrence-free survival, regardless of tumor origin.16
Billis et al reported that index tumors with predominant location in the posterior region were significantly associated with greater total tumor extent, higher Gleason score in the biopsy and in the radical prostatectomy, positive lymph nodes, and elevated preoperative PSA levels. On the other hand, tumors with predominant location in the basal region showed a significant association with elevated preoperative PSA levels, pathological stage greater than pT2, extra-prostatic extension, and invasion of the seminal vesicles. The predominant location of the index tumor is associated with prognosis in radical prostatectomies; however, in multivariate analysis, it did not show prognostic advantage over other already established factors.17
The multivariate analysis indicated that the factors most strongly associated with disease progression were clinical staging (risk stratification), ISUP grade of the prostatectomy specimen, positive surgical margins, and extra-prostatic extension. These findings are consistent with previous evidence, which recognizes these factors as robust and well-established prognostic determinants.10 On the other hand, the absence of correlation between biochemical recurrence and/or metastasis and the Gleason score or ISUP of the biopsy, as well as lymph node status, reinforces the limitations of the initial biopsy in precisely predicting tumor behavior, highlighting the importance of postoperative analysis for more accurate prognostication.18
This study has some limitations that must be acknowledged. First, its retrospective design may introduce selection bias. Second, although the cohort spans two decades, it is derived from a single center, which may limit the generalizability of the findings to other populations or clinical settings. Third, despite the relatively large sample size, subgroup analyses (eg, tumor location within the prostate) may remain underpowered to detect subtle prognostic differences. Therefore, the absence of statistical significance should not be interpreted as definitive evidence of biological irrelevance. Additionally, given the extended study period, potential temporal variations in surgical techniques or pathological assessment protocols may have influenced certain outcomes, although institutional standardization aimed to minimize such effects. Also, given the relatively small number of transitional zone tumors, subgroup comparisons may be underpowered to detect modest differences. Therefore, findings should be interpreted with the potential for type II error in mind.
On the other hand, the study also has important strengths. It comprises a homogeneous cohort of patients treated with radical prostatectomy and provides a long-term follow-up, allowing a robust assessment of oncological outcomes. Furthermore, the detailed pathological characterization and comparison across tumor zones in the whole gland (not by sample) contribute to the ongoing debate regarding the prognostic role of tumor location in prostate cancer.
Taken together, previous literature presents heterogeneous findings, likely reflecting differences in cohort composition, pathological assessment, and statistical power. Although previous studies from our group have explored tumor location and pathological characteristics, the present analysis differs by focusing specifically on long-term oncologic outcomes in a larger cohort with extended follow-up and standardized whole-gland mapping.
Future investigations may clarify whether tumor zonal origin interacts with emerging molecular and genomic classifiers, such as Decipher®, Prolaris®, or Oncotype DX®, to refine risk stratification models. Rather than acting as an isolated prognostic factor, zonal origin may contribute incremental value when integrated into multifactorial predictive frameworks.
Conclusion
In this retrospective, single-center cohort with long-term follow-up, tumor zonal origin in whole-mount prostate specimens was not independently associated with biochemical recurrence or metastatic progression. These findings suggest that, within the constraints of current clinical practice, tumor location alone does not alter postoperative risk stratification, as established pathological factors remain the primary determinants of disease progression.
However, given the potential limitations in statistical power, these results should be interpreted with caution. Further multicenter studies and investigations integrating molecular profiling are warranted to clarify whether anatomical location contributes to biological heterogeneity, potentially refining individualized management strategies in prostate cancer.
Acknowledgments
To the patients, to those who offered patient care, and to the involved institutions.
Funding Statement
This study was financed in part by: National Council for Scientific and Technological Development, CNPq, Research Productivity, grant number: #310135/2022-2, and INCT-UROGEN #408576/2024-3 (Reis LO).
Data Sharing Statement
The original contributions presented in this study are included in the article. Further inquiries can be directed to the corresponding author.
Informed Consent Statement
The study was approved by the Hospital das Clínicas Unicamp Ethics Committee CAAE # 79463524.2.0000.5404. Informed consent was obtained from all subjects involved in the study when applicable.
Author Contributions
NDA, RAFF were responsible for patient data collection and analysis. MBS and G.B. assisted with analysis and contributed to the final writing of the manuscript. FD and AB were responsible for the samples and participated in manuscript writing and review. L.O.R. conceived and designed the study and coordinated the research. All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.
Disclosure
The authors declare no conflicts of interest in this work.
References
- 1.Jalalizadeh M, Roesch HRM, Korkes F, Dien-Trinh Q, Reis LO. Prostate cancer temporal and regional trends in Brazil. Oncol Res. 2024;32(10):1565–9. doi: 10.32604/or.2024.052179 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Holmberg L, Bill-Axelson A, Helgesen F, et al; Scandinavian Prostatic Cancer Group Study Number 4. A randomized trial comparing radical prostatectomy with watchful waiting in early prostate cancer. N Engl J Med. 2002;347(11):781–789. doi: 10.1056/NEJMoa012794 [DOI] [PubMed] [Google Scholar]
- 3.McNeal JE. Regional morphology and pathology of the prostate. Am J Clin Pathol. 1968;49(3):347–357. doi: 10.1093/ajcp/49.3.347 [DOI] [PubMed] [Google Scholar]
- 4.McNeal JE, Redwine EA, Freiha FS, Stamey TA. Zonal distribution of prostatic adenocarcinoma: correlation with histologic pattern and direction of spread. Am J Surg Pathol. 1988;12(12):897–906. doi: 10.1097/00000478-198812000-00001 [DOI] [PubMed] [Google Scholar]
- 5.Garcia JJ, Hafez MJ, Bostwick DG, et al. Do prostatic transition zone tumors have a distinct morphology? Am J Surg Pathol. 2008;32(11):1709–1714. doi: 10.1097/PAS.0b013e318172ee97 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Greene DR, Wheeler TM, Egawa S, Dunn JK, Scardino PT. A comparison of the morphological features of cancer arising in the transition zone and in the peripheral zone of the prostate. J Urol. 1991;146(4):1069–1076. doi: 10.1016/S0022-5347(17)38003-5 [DOI] [PubMed] [Google Scholar]
- 7.Sato S, Kimura T, Onuma H, Egawa S, Takahashi H. Transition zone prostate cancer is associated with better clinical outcomes than peripheral zone cancer. BJUI Compass. 2021;2(3):169–177. doi: 10.1002/bco2.47 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Sakai I, Harada K, Kurahashi T, et al. Analysis of differences in clinicopathological features between prostate cancers located in the transition and peripheral zones. Int J Urol. 2006;13(4):368–372. doi: 10.1111/j.1442-2042.2006.01307.x [DOI] [PubMed] [Google Scholar]
- 9.Azal Neto W, Andrade GM, Billis A, Reis LO. Biopsy core length in white versus African descendant prostate cancer patients. Scand J Urol. 2020;54(3):188–193. doi: 10.1080/21681805.2020.1754907 [DOI] [PubMed] [Google Scholar]
- 10.Ali A, Du Feu A, Oliveira P, Choudhury A, Bristow RG, Baena E. Prostate zones and cancer: lost in transition? Nat Rev Urol. 2022;19(2):101–115. doi: 10.1038/s41585-021-00524-7 [DOI] [PubMed] [Google Scholar]
- 11.Reis LO, Zani EL, Billis A, Prudente A, Denardi F, Ferreira U. The triple clinicopathologic features to seminal vesicle-sparing radical prostatectomy. J Endourol. 2010;24(9):1535–1539. doi: 10.1089/end.2009.0655 [DOI] [PubMed] [Google Scholar]
- 12.Jin S, Wu L, Liang Z, Yan W. The prognostic value of zonal origin in clinically localized prostate cancer: a systematic review and meta-analysis. Front Oncol. 2023;13:1248222. doi: 10.3389/fonc.2023.1248222 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Takamatsu K, Matsumoto K, Shojo K, et al. The prognostic value of zonal origin and extraprostatic extension of prostate cancer for biochemical recurrence after radical prostatectomy. Urol Oncol. 2019;37(9):575.e19–575.e25. doi: 10.1016/j.urolonc.2019.03.012 [DOI] [PubMed] [Google Scholar]
- 14.Lee JJ, Thomas IC, Nolley R, Ferrari M, Brooks JD, Leppert JT. Biologic differences between peripheral and transition zone prostate cancer. Prostate. 2015;75(2):183–190. doi: 10.1002/pros.22903 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Cohen RJ, Shannon BA, Phillips M, Moorin RE, Wheeler TM, Garrett KL. Central zone carcinoma of the prostate gland: a distinct tumor type with poor prognostic features. J Urol. 2008;179(5):1762–1767. doi: 10.1016/j.juro.2008.01.017 [DOI] [PubMed] [Google Scholar]
- 16.Teloken PE, Li J, Woods CG, Cohen RJ. The impact of prostate cancer zonal origin on pathological parameters at radical prostatectomy and subsequent biochemical failure. J Urol. 2017;198(6):1316–1323. doi: 10.1016/j.juro.2017.05.075 [DOI] [PubMed] [Google Scholar]
- 17.Billis A, Freitas LLL, Costa LBE, et al. Does index tumor predominant location influence prognostic factors in radical prostatectomies? Int Braz J Urol. 2017;43(4):686–697. doi: 10.1590/s1677-5538.ibju.2016.0335 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Gillessen S, Attard G, Beer TM, et al. Management of patients with advanced prostate cancer: report of the Advanced Prostate Cancer Consensus Conference (APCCC). Eur Urol. 2020;77(4):508–547. doi: 10.1016/j.eururo.2020.01.012 [DOI] [PubMed] [Google Scholar]
Associated Data
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Data Availability Statement
The original contributions presented in this study are included in the article. Further inquiries can be directed to the corresponding author.