eISSN: 2084-9869
ISSN: 1233-9687
Polish Journal of Pathology
Current issue Archive Manuscripts accepted About the journal Supplements Editorial board Abstracting and indexing Subscription Contact Instructions for authors Ethical standards and procedures
SCImago Journal & Country Rank
1/2016
vol. 67
 
Share:
Share:
more
 
 
Original paper

Influence of gross specimen sampling on the incidence of incidental prostatic carcinoma in cystoprostatectomy specimens of patients with bladder carcinoma

Jernej Mlakar
,
Metka Volavšek

Pol J Pathol 2016; 67 (1): 8-12
Online publish date: 2016/05/10
Article file
- Influence.pdf  [0.27 MB]
Get citation
ENW
EndNote
BIB
JabRef, Mendeley
RIS
Papers, Reference Manager, RefWorks, Zotero
AMA
APA
Chicago
Harvard
MLA
Vancouver
 
 

Introduction

Prostatic carcinoma is the most common non-cutaneous malignant neoplasm in Slovenian male patients. Its incidence has been increasing in recent years, being approximately 130/100,000 in Slovenia, while it is 160/100,000 in the United States. As a result of prostate specific antigen (PSA) determination and earlier detection, the overall 5-year survival of prostatic carcinoma patients has significantly increased [1, 2, 3]. The median age at diagnosis in the United States is currently 67 years and has been dropping since the introduction of PSA determination in the early 1990s [4, 5]. Primary risk factors for disease occurrence are age, race and family history, with age having the strongest impact [6]. Radical prostatectomy is the preferred option for patients with localised disease and long life expectancy. Other options are external beam radiotherapy and brachyradiotherapy. In locally advanced disease, adjuvant androgen deprivation therapy is recommended. In metastatic disease, luteinising hormone releasing hormone agonists are the primary treatment, with chemotherapy in castration-resistant cases [7, 8]. The exact choice of treatment modality (or non-treatment) is dependent upon multiple factors, including Gleason score, stage at diagnosis, PSA, physical performance and patient’s choice [5, 7, 8, 9].
Bladder carcinoma is the second most common malignancy of the urinary tract, with an incidence in Slovenia of approximately 20/100,000; it is 4 times more frequent in males than females. Median age at diagnosis is 69 years for males and 71 years for females [1, 10, 11]. Risk factors involved in bladder carcinoma, in contrast to prostatic carcinoma, are predominantly environmental, especially smoking, arsenic, aromatic amines and infection with Schistosoma [11]. About 80% of patients are diagnosed with the disease limited to the mucosa. These can be managed by transurethral resection, followed by intravesical chemotherapy or bacillus Calmette-Guérin (BCG) instillation. Radical cystoprostatectomy is the gold standard for treatment of patients with disease limited to the mucosa and failure of primary therapy and of patients with muscle-invasive bladder carcinoma, with exceptions that will not be discussed further here [12, 13].
Due to both cancers predominantly occurring in older men and prostatic carcinoma having a high incidence, there is a significant risk of an incidental concurrent prostatic carcinoma in a cystoprostatectomy specimen of a patient with bladder carcinoma. Herein, we assess the frequency of incidental prostate carcinoma in such patients and the influence of the two methods of specimen processing on the incidence and clinical significance of incidentally discovered prostatic carcinoma.

Material and methods

In a retrospective study, documentation of 313 consecutive cystoprostatectomy specimens of patients treated for bladder carcinoma between March 1996 and April 2015 was reviewed. All cases were scored according to the 2005 revised Gleason scoring system and the 2015 reccomendations on new grading system [14, 15]. Cases diagnosed prior to 2005 were reviewed and re-scored according to this system. Information was gathered on the presence of concurrent prostatic carcinoma, its Gleason score, stage, number of prostatic samples, as well as the histological type of bladder carcinoma and stage. The volume of prostatic carcinoma was not determined. We divided patients into two groups:
• cystoprostatectomy cases diagnosed before 2007, when four to eight samples were taken from each prostate;
• cases diagnosed after 2007, when complete prostate sampling, with approximately 3 mm thick slices, was started.
The 2 test was used for comparison of the prostate cancer incidence in the two groups. The Student t-test for independent samples was used for determination of the association of patient age with the presence of incidental prostatic carcinoma, and possible age discordance between the pre-2007 and post-2007 groups. The Mann-Whitney test was used for comparison of the number of prostate samples in both groups. We used SPSS, version 17.0 (IBM, Armonk, NY, United States) for statistical analysis. A level of p < 0.05 was considered statistically significant.

Results

There were 164 cystoprostatectomy samples between March 1996 and December 2006 and 149 samples between January 2007 and April 2015. The average number of samples taken in partially and completely sampled prostates was 6.5 (range 2-17) and 17.4 (range 11-36), respectively. This difference was statistically significant (p < 0.0001). The median age at cystoprostatectomy in our study was 64.2 years (range 36–79 years). The characteristics of urinary bladder carcinomas are presented in Table I. Patients with prostatic carcinoma in our study were younger than patients without it (p = 0.043), but the age difference was small (median 62.6 vs. 64.6 years). The median age of pre-2007 patients was 66.5 years while the median age of the post-2007 group was 62.9. This difference, although small, was statistically significant (p = 0.004). In a group comparison, cases processed after the 2007 policy change had a significantly higher rate of incidental prostatic carcinoma than the pre-2007 group (45 vs. 11 and 30.2% vs. 6.7%, p < 0.0001). There were three cases (27.3%) of pT3a stage or higher and/or Gleason score 7 or higher in the pre-2007 group, while 18 (40%) cases were identified in the post-2007 group (p = 0.003). Of the two pre-2007 cases one had a Gleason score of 7 or more and another had a Gleason score of 8, while also invading the seminal vesicles. Thirteen of the post-2007 cases had a Gleason score of 7 or more, one was stage pT3a and three both had a Gleason score of 7 or more and were pT3a or higher. In an additional post-2007 case the carcinoma had invaded the surgical margin. The characteristics of partially and completely sampled prostates are presented in Table II and Figs. 1 and 2. Examples of moderately differentiated and poorly differentiated prostatic carcinoma are shown in Fig. 3.

Discussion

Incidental prostate cancer has been described in more than 40% of autopsy cases of men older than 60 years and 60% of men older than 80 years [16]. A report of higher incidence of prostate cancer in patients with bladder cancer has been published, in which the authors tried to avoid the bias of urologic examinations and diagnostic procedures [17].
Prostate cancer is a common disease and a non-negligible proportion of samples managed for any condition will harbour incidental prostatic carcinomas. While small (volume less than 0.5 cm3), low-risk carcinomas, defined as stage T2N0M0 or less, Gleason score of 6 or less and no invasion of the surgical margin, are less of a concern and may have little or no influence on post-cystoprostatectomy outcome, clinically significant prostate cancer is associated with a higher incidence of disease relapse and can establish a requirement for more stringent patient monitoring, possible adjuvant radiotherapy or androgen deprivation therapy [18, 19].
There are two possible methods of prostate assessment in radical cystoprostatectomy specimens. One consists of processing the entire prostate, while the other involves only representative sampling, with a variable number of samples and slice thickness among institutions. In the past few years, several reports have been published that indicate a higher diagnostic accuracy of completely processed prostates in cystoprostatectomy specimens of patients with bladder carcinoma [20, 21, 22, 23].
Different approaches to prostate sampling in terms of completeness and slice thickness in cystoprostatectomy specimens are adopted at different institutions and also by pathologists at the same institution. To date, the reported rates of incidental prostate cancer in cystoprostatectomised patients have been in the range of 14-45% in studies with partial sampling and 3-72% in those with complete sampling [23, 24, 25, 26]. Recent evidence shows that complete prostate processing results in a substantially higher rate of finding the carcinoma. In a study by Fritsche et al., it was shown that 19% of partially processed prostates harbour cancer, while the rate was twice as high (40%) after complete processing [20]. In another study, by Wetterauer et al., the rates were 23% and 72% for partially and completely sampled prostates, respectively [23]. In our study, the incidence of prostate cancer in completely processed prostates was approximately 4.5 times higher (6.7% vs. 30.2%) than the incidence in partially sampled prostates.
Significant prostate cancer in radical prostatectomy or cystoprostatectomy specimens is most often considered to have one or more of the following characteristics: Gleason score 7 or more, stage pT3a or more, presence of prostatic tumour in resection margins, tumour volume of 0.5 cm3 or more and lymph node involvement [7, 20, 27, 28]. Four percent to 57% of prostate specimens included in studies with partial processing harboured clinically significant cancer [23, 24]. In our study, 21 out of 56 (37.5%) incidental prostate cancers had a Gleason score of 7 or more and/or a stage of pT3a or more and/or invasion of the surgical margin. Twenty-seven percent of the partially sampled cases fulfilled one of those two criteria, while 40% did so in cases with complete embedding. In keeping with these results, it has been shown by two previous studies that the rate of clinically significant incidental prostate cancer is much higher in completely as opposed to partially processed prostates (18% vs. 9% and 44% vs. 4%, respectively) [20, 23]. Patients with incidental prostatic carcinoma were slightly younger in our study, as compared to those without it. This is probably due to the combination of a slightly rising incidence of bladder cancer in younger patients (less than 60 years old) in Slovenia and the 2007 policy change to complete prostate embedding [1]. The post-2007 group had a larger population of relatively young patients and, in addition, more thoroughly sampled prostates.
Two of the three largest studies to date, which included more than 1100 and almost 4300 cases of incidental prostatic carcinoma in radical cystoprostatectomy samples, did not identify any impact of incidental carcinoma on survival [29, 30]. However, the largest study did identify a 1.9% relapse rate of prostatic carcinoma, and another large study, including more than 1400 patients, identified a higher risk of mortality in patients with concurrent incidental prostatic carcinoma [30, 31]. Prostate cancer, while in most instances an indolent disease when discovered early, can pose a risk of mortality when not discovered but, at the same time, being a significant disease as defined by the criteria discussed above. In these instances, appropriate measures (more frequent follow-up, radiotherapy or androgen deprivation therapy) that could have resulted in a higher rate of recurrence and metastatic disease would not have been undertaken.
To conclude, in our opinion, these data show that complete sampling should be mandatory. In cases when this is not possible due to financial constraints, it should be as thorough as possible.

The authors declare no conflict of interest.

References

1. Primic-Žakelj M, Bračko M, Hočevar M, et al. Cancer in Slovenia 2009. Primic-Žakelj M, Bračko M, Hočevar M, et al. (eds.). Institute of Oncology Ljubljana, Cancer Registry of Republic of Slovenia, Ljubljana, Slovenia 2013; 35-81.
2. Roobol MJ. The prostate-specific antigen test. Expert Opin Med Diagn 2013; 7: 423-426.
3. Siegel R, Ward E, Brawley O, et al. Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin 2011; 61: 212-236.
4. Howlader N, Noone AM, Krapcho M, et al. SEER cancer statistics review, 1975-2012. National Cancer Institute, Bethesda, USA 2010; http://seer.cancer.gov/csr/1975_2012/. Accessed September 15th 2015.
5. Simmons MN, Berglund RK, Jones JS. A practical guide to prostate cancer diagnosis and management. Cleve Clin J Med 2011; 78: 321-331.
6. Magheli A, Rais-Bahrami S, Humphreys EB, et al. Impact of patient age on biochemical recurrence rates following radical prostatectomy. J Urol 2007; 178: 1933-1938.
7. Heidenreich A, Bellmunt J, Bolla M, et al. EAU guidelines on prostate cancer. Part 1: screening, diagnosis, and treatment of clinically localised disease. Eur Urol 2011; 59: 61-71.
8. Heidenreich A, Bastian PJ, Bellmunt J, et al. EAU guidelines on prostate cancer. Part 2: Treatment of advanced, relapsing, and castration-resistant prostate cancer. Eur Urol 2014; 65: 467-479.
9. Freedland SJ. Screening, risk assessment, and the approach to therapy in patients with prostate cancer. Cancer 2011; 117: 1123-1135.
10. Ploeg M, Aben KK, Kiemeney LA. The present and future burden of urinary bladder cancer in the world. World J Urol 2009; 27: 289-293.
11. Letašiová S, Medve’ová A, Šovčíková A, et al. Bladder cancer, a review of the environmental risk factors. Environ Health 2012; 11 Suppl 1: S11.
12. Burger M, Oosterlinck W, Konety B, et al. ICUD-EAU International Consultation on Bladder Cancer 2012. Non-muscle-invasive urothelial carcinoma of the bladder. Eur Urol 2013; 63: 36-44.
13. Gakis G, Efstathiou J, Lerner SP, et al. ICUD-EAU International Consultation on Bladder Cancer 2012: Radical cystectomy and bladder preservation for muscle-invasive urothelial carcinoma of the bladder. Eur Urol 2013; 63: 45-57.
14. Epstein JI, Allsbrook WC Jr, Amin MB, et al. The 2005 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma. Am J Surg Pathol 2005; 29: 1228-1242.
15. Epstein JI, Egevald L, Amin MB, et al. The 2014 International Society of Urological Pathology (ISUP) consensus conference on Gleason grading of prostatic carcinoma: Definition of grading patterns and proposal for a new grading system. Am J surg Pathol 2016; 40: 244-252.
16. Zlotta AR, Egawa S, Pushkar D, et al. Prevalence of prostate cancer on autopsy: cross-sectional study on unscreened Caucasian and Asian men. J Natl Cancer Inst 2013; 105: 1050-1058.
17. Kurokawa K, Ito K, Yamamoto T, et al. Comparative study on the prevalence of clinically detectable prostate cancer in patients with and without bladder cancer. Urology 2004; 63: 268-272.
18. Ploussard G, Epstein JI, Montironi R, et al. The contemporary concept of significant versus insignificant prostate cancer. Eur Urol 2010; 60: 291-303.
19. Grimm P, Billiet I, Bostwick D, et al. Comparative analysis of prostate-specific antigen free survival outcomes for patients with low, intermediate and high risk prostate cancer treatment by radical therapy. Results from the Prostate Cancer Results Study Group. BJU Int 2012; 109 Suppl 1: 22-29.
20. Fritsche HM, Aziz A, Eder F, et al. Potentially clinically relevant prostate cancer is found more frequently after complete than after partial histopathological processing of radical cystoprostatectomy specimens. Virchows Arch 2012; 461: 655-661.
21. Pettus JA, Al-Ahmadie H, Barocas DA, et al. Risk assessment of prostatic pathology in patients undergoing radical cystoprostatectomy. Eur Urol 2008; 53: 370-375.
22. Mazzucchelli R, Barbisan F, Scarpelli M, et al. Is incidentally detected prostate cancer in patients undergoing radical cystoprostatectomy clinically significant? Am J Clin Pathol 2009; 131: 279-283.
23. Wetterauer C, Weibel M, Gsponer JR, et al. Incidental prostate cancer prevalence at radical cystoprostatectomy–importance of the histopathological work-up. Virchows Arch 2014; 465: 629-636.
24. Hosseini SY, Danesh AK, Parvin M, et al. Incidental prostatic adenocarcinoma in patients with PSA less than 4 ng/mL undergoing radical cystoprostatectomy for bladder cancer in Iranian men. Int Braz J Urol 2007; 33: 167-173.
25. Abbas F, Hochberg D, Civantos F, et al. Incidental prostatic adenocarcinoma in patients undergoing radical cystoprostatectomy for bladder cancer. Eur Urol 1996; 30: 322-326.
26. Zhu YP, Ye DW, Yao XD, et al. Prevalence of incidental prostate cancer in patients undergoing radical cystoprostatectomy: data from China and other Asian countries. Asian J Androl 2009; 11: 104-108.
27. Epstein JI, Walsh PC, Carmichael M, et al. Pathologic and clinical findings to predict tumor extent of nonpalpable (stage T1c) prostate cancer. JAMA 1994; 271: 368-374.
28. van der Kwast TH, Amin MB, Billis A, et al.; ISUP Prostate Cancer Group. International Society of Urological Pathology (ISUP) Consensus Conference on Handling and Staging of Radical Prostatectomy Specimens. Working group 2: T2 substaging and prostate cancer volume. Mod Pathol 2011; 24: 16-25.
29. Buse S, Höfner T, Müller SC, et al. Characterization and risk stratification of prostate cancer in patients undergoing radical cystoprostatectomy. Int J Urol 2013; 20: 866-871.
30. Pignot G, Salomon L, Neuzillet Y, et al. Clinicopathological characteristics of incidental prostate cancer discovered from radical cystoprostatectomy specimen: a multicenter French study. Ann Surg Oncol 2014; 21: 684-690.
31. Bruins HM, Djaladat H, Ahmadi H, et al. Incidental prostate cancer in patients with bladder urothelial carcinoma: comprehensive analysis of 1,476 radical cystoprostatectomy specimens. J Urol 2013; 190: 1704-1709.

Address for correspondence

Metka Volavšek
Institute of Pathology
Faculty of Medicine
University of Ljubljana
Korytkova 2
1000 Ljubljana, Slovenia
e-mail: metka.volavsek@mf.uni-lj.si
Copyright: © 2016 Polish Association of Pathologists and the Polish Branch of the International Academy of Pathology This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) License (http://creativecommons.org/licenses/by-nc-sa/4.0/), allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.
Quick links
© 2022 Termedia Sp. z o.o. All rights reserved.
Developed by Bentus.