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Keywords:

  • penile cancer;
  • centralization;
  • histology

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Material and Methods
  5. Results
  6. Discussion
  7. Conflict of Interest
  8. References

Objective

  • To assess the role of centralized pathological review in penile cancer management.

Materials and Methods

  • Newly diagnosed squamous cell carcinomas (SCC) of the penis, including squamous cell carcinoma in situ (CIS), from biopsy specimens were referred from 15 centres to the regional supra-network multidisciplinary team (Sn-MDT) between 1 January 2008 and 30 March 2011.
  • Biopsy histology reports and slides from the respective referring hospitals were reviewed by the Sn-MDT pathologists.
  • The biopsy specimens’ histological type, grade and stage reported by the Sn-MDT pathologist were compared with those given in the referring hospital pathology report, as well as with definitive surgery histology.
  • Any changes in histological diagnosis were sub-divided into critical changes (i.e. those that could alter management) and non-critical changes (i.e. those that would not affect management).

Results

  • A total of 155 cases of squamous cell carcinoma or CIS of the penis were referred from 15 different centres in North-West England.
  • After review by the Sn-MDT, the histological diagnosis was changed in 31% of cases and this difference was statistically significant. A total of 60.4% of the changes were deemed to be critical changes that resulted in a significant change in management.
  • When comparing the biopsy histology reported by the Sn-MDT with the final histology from the definitive surgical specimens, a good correlation was generally found.

Conclusions

  • In the present study a significant proportion of penile cancer histology reports were revised after review by the Sn-MDT. Many of these changes altered patient management.
  • The present study shows that accurate pathological diagnosis plays a crucial role in determining the correct treatment and maximizing the potential for good clinical outcomes in penile cancer.
  • In the case of histopathology, centralization has increased exposure to penile cancer and thereby increased diagnostic accuracy, and should therefore be considered the ‘gold standard’.

Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Material and Methods
  5. Results
  6. Discussion
  7. Conflict of Interest
  8. References

In the UK, centralization of cancer services is standard practice. It is believed that centralization consolidates the service infrastructure, providing specialized multidisciplinary teams, which delivers improved cancer management outcomes. Urological malignancies are no exception and, in particular, outcomes in rare conditions such as penile cancer should improve with centralization of care.

Penile cancer is a rare urological cancer; the data for male urological cancers in England show that its incidence is 1.3 in 100 000, with 315 new cases each year [1]. The National Institute for Health and Care Excellence (NICE) guidelines (2002) suggested that the management of rare urological cancers by local district general hospitals resulted in a low caseload and was no longer acceptable. Specialist services at a supra-network level were to be set up to manage rare urological cancers such as penile cancer. This supra-network specialist centre should serve a population of at least 4 million people, with the expectation of managing at least 25 new penile cancer cases per year [2].

The supra-network multidisciplinary team (Sn-MDT) set-up should include urologists, oncologists, radiologists, pathologists, clinical nurse specialists and extended team members in psychology, counselling and plastic surgery. The expected benefits of such a network were improved patient care with more consistent and appropriate management, and better subsequent outcomes.

One of the functions of the Sn-MDT is centralized pathological review. This should ensure that the diagnosis is accurate, thereby preventing unnecessary aggressive treatment for early disease and ensuring that more advanced disease receives adequate treatment. The NICE guidelines for ‘Improving Outcomes in Urological Cancers’ suggest that all patients with newly diagnosed penile cancers should be referred to a specialist Sn-MDT and the diagnostic slides made available for pathology review [2]. There is currently no evidence to support the benefit of Sn-MDT pathology review in penile cancer outcomes.

Penile carcinomas are morphologically heterogeneous and there is a correlation between histological type and tumour behaviour and management, making accurate histological diagnosis highly important [3].

This study will assess how centralized pathological review can effect penile cancer management decisions.

Material and Methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Material and Methods
  5. Results
  6. Discussion
  7. Conflict of Interest
  8. References

Data were collected retrospectively for all newly diagnosed squamous cell carcinomas of the penis, including squamous cell carcinoma in situ (CIS), from punch, incision and excision biopsy specimens. These cases were referred to the regional Sn-MDT from 15 centres between 1 January 2008 and 30 March 2011. All data were retrieved from computerized records made and filed prospectively.

The histology reports, slides and unsectioned paraffin-embedded tissue from the respective referring hospitals were sent to the supra-network centre and reviewed by the Sn-MDT pathologists.

The Sn-MDT pathologists re-reported all the histology slides and, where needed, fresh sections were taken from paraffin-embedded tissue for further analysis. The histological type, grade and stage reported by the Sn-MDT pathologist were compared with the report of the pathologist from the referring hospital to determine if there were significant differences in the histological diagnosis. Statistical analysis was performed using R statistical software (http://www.r-project.org/). The null hypothesis of the study was that there would be no difference between the local pathology report and Sn-MDT pathology report. A chi-squared test was used and a difference with a P value of <0.05 was considered statistically significant. Any histological changes were further divided into critical changes or non-critical changes i.e. those leading to alterations in patients’ management and those that did not alter patients’ management, respectively. The changes to the initial biopsy report generated by the Sn-MDT were then compared with the definitive surgery histological results to further evaluate whether the Sn-MDT changes were accurate.

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Material and Methods
  5. Results
  6. Discussion
  7. Conflict of Interest
  8. References

In the study period, a total of 155 cases of squamous cell carcinomas or squamous cell CIS of the penis were referred to the Sn-MDT from 15 different centres in North-West England (hospitals A–O). All cases underwent histopathology review. The referral pattern is shown in Fig. 1. The mean (range) patient age at diagnosis was 65.8 (21–98) years.

figure

Figure 1. Local hospital referral pattern.

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The data show that after Sn-MDT histology review, there was a significant change in pathology results, with 48 out of 155, i.e. 31% (chi-squared = 22.458, degrees of freedom = 1, P < 0.001) of individual cases showing changes in the final histological diagnosis compared with the initial local hospital histology report.

The percentages of cases for individual referring hospitals A–O that had a histopathological change were 33, 0, 33, 29, 38, 14, 35, 33, 50, 42, 25, 40, 0, 14 and 0%, respectively. The median (range) percentage was 33 (0–50)%. The majority of referring hospitals lie close to the median and the outliers, with 0% histological changes, appeared to be the low-volume centres with only one penile cancer referral during the study period.

Among the 48 cases where histology was changed, the changes were deemed to be critical in 29 (60.4%) cases; these results led to some patients requiring more extensive and invasive treatment for local penile cancer management, and/or sentinel lymph node staging/lymph node dissection in the pathology upgrade group and, in some cases, a change to a more conservative treatment approach in the pathologically downgraded group as shown below. There were 19 (39.6%) cases in which the changes were deemed to be non-critical.

Among all the histological changes, we found the Sn-MDT generated more upgrades (38 cases) than downgrades (10 cases) in disease. The upgrades included: four cases a change in diagnosis from dysplasia to CIS; 10 cases a change from dysplasia or CIS to invasive squamous cell carcinoma; in 19 cases an increase in tumour grade and in five cases an increase in tumour stage. The downgrades included four cases of downgrading from CIS to dysplasia; three cases of downgrading from invasive squamous cell carcinoma to no tumour; two cases of a decrease in tumour grade and one case of a decrease in tumour stage.

Histological upgrades from dysplasia to CIS or dysplasia/CIS to invasive tumours led to more aggressive treatment strategies, such as the use of topical chemotherapy (5-fluorouracil) and circumcision for CIS disease, and debilitating penile surgery such as amputation surgery for invasive disease. An increase in grade or stage of the disease in some circumstances led to the use of more aggressive lymph node management, such as sentinel node biopsy and/or inguinal lymph node dissection. A downgrade of specimen from CIS or invasive tumour to a benign lesion led to the avoidance of unnecessary treatment. A decrease in grade or stage of disease, in some cases, avoided unnecessary lymph node surgery (Tables 1, 2).

Table 1. Histological changes: upgrades
Type of histological change (made to the initial local hospital histology report after review by the Sn-MDT)NumberCritical change?Definitive treatments (histology) as recommended by Sn-MDT
  1. *Discrepancy between changes made by the Sn-MDT to initial biopsy histology specimen and the definitive treatment histology.

  2. SNB, sentinel node biopsy; LND, lymph node dissection.

UpgradesDysplasia/other to CIS4Yes4 × circumcision and 5-fluorouracil
Dysplasia/other to invasive SCC6Yes1 × partial penectomy (G1T1)
3 × glansectomy (G1T1)
1 × glansectomy + SNB (G2T1)
1 × circumcision + SNB (G2T1)
CIS to invasive SCC4Yes1 × glansectomy (G1T1)
2 × glansectomy + SNB (G2T1)
1 × circumcision (G1T1)
G1 to G2 invasive SCC5Yes2 × partial penectomy + SNB (G3T2)*
1 × partial penectomy + SNB (G2T2)
1 × glansectomy + SNB (G3T2)*
1 × circumcision + SNB (G2T1)
G2 to G3 invasive SCC14No3 × partial penectomy + LND (G3T3)
5 × partial penectomy + SNB (G3T2)
6 × circumcision + SNB (G3T1)
G1T1 to T2 SCC2Yes1 × partial penectomy + SNB (G2T2)*
1 × partial penectomy + SNB (G1T2)
G2T1 to G3T2 SCC3No3 × partial penectomy + SNB (G3T2)
Table 2. Histological changes:downgrades
Type of histological change (made to the initial local hospital histology report after review by the Sn-MDT)NumberCritical change?Definitive treatments (histology) as recommended by Sn-MDT
  1. SNB, sentinel node biopsy.

DowngradesCIS to dysplasia4YesSurveillance
Invasive SCC to no tumour3YesSurveillance
G2T2 to G1T2 invasive SCC1No1 × partial penectomy + SNB (G1T2)
G2T1 to G1T1 invasive SCC1Yes1 × glansectomy (G1T1)
T3 to T2 invasive SCC1No1 × partial penectomy + SNB (G2T2)

When comparing the initial biopsy histological changes made by the Sn-MDT with the final histology from the definitive surgical specimens, a good correlation was generally shown; however, there were four patients who had an even higher grade disease in the final definitive surgery histology than the initial biopsy specimens suggested, and this was despite Sn-MDT review. This finding may be merely a reflection of the heterogeneity of penile cancer and the inherent problem of small initial biopsy samples not fully representing the ultimate penile cancer histology rather than inaccuracy on the part of the Sn-MDT pathologists (Tables 1, 2).

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Material and Methods
  5. Results
  6. Discussion
  7. Conflict of Interest
  8. References

The NICE first issued guidance on ‘Improving Outcomes in Urological Cancer’ in 2002 [2]. At that time, although there was evidence suggesting improved outcomes in high-volume centres for prostate, bladder and testis cancer [4, 5], there was little evidence to support the centralization of penile cancer services. Since then reports from the UK have suggested that the introduction of Sn-MDTs in the management of penile cancer has led to an increasing trend towards penile-preserving surgery, prophylactic inguinal lymph node sampling and a reduced mortality rate [6]. While these results are highly encouraging, the main factors responsible for the improvement in outcomes are yet to be determined.

In the present study, we have provided evidence that accurate pathological staging and grading may play a crucial role in determining the most appropriate treatment for the patient, thus ensuring good clinical outcomes. Indeed, one of the main aims of centralization of penile cancer services was to allow healthcare professionals to develop expertise in what is a very rare disease. In the case of histopathology it is evident that increased exposure to these cases has helped to improve the accuracy of histological staging. Our results therefore strongly suggest that penile cancer care should be centralized.

Given the significant number of pathology reports from referring hospitals that were reclassified on subsequent Sn-MDT review, this raises the question as to whether all suspicious penile biopsies should be sent directly to the Sn-MDT histopathologists for preparation and reporting. This would streamline the service by reducing duplication of work. Further research is needed, involving larger multicentre collaboration, to address this question fully and make recommendations regarding acceptable reporting errors from referring hospitals.

One of the potential limitations of the present retrospective study is that the Sn-MDT pathologists were not blinded to the original referring hospital report. This could, of course, lead to the introduction of bias in subsequent Sn-MDT reporting. In addition, the authors accept that a second blinded review by a Sn-MDT pathologist from a different network would enhance the validity of these results; however, our Sn-MDT process does to some extent provide a degree of internal validation, as two Sn-MDT pathologists were present for each case discussion. Again, these issues could be addressed by a larger, prospective multicentre trial.

In conclusion, a significant proportion of penile cancers in histology reports are upgraded or upstaged after review in the Sn-MDT. Many of these histological changes can alter patient management. All cases of suspected or proven penile cancer, including penile intraepithelial neoplasia and premalignant lesions, should therefore be referred immediately to a specialist centre. These data support the value of the supra-network pathology review in achieving accurate histological diagnosis and correct treatment in penile cancer, and should therefore be considered the European, if not global, standard.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Material and Methods
  5. Results
  6. Discussion
  7. Conflict of Interest
  8. References
  • 1
    National Cancer Intelligence Network. Rare Urological Cancer. London 2012. Available at: http://www.ncin.org.uk/publications. Accessed August 2013
  • 2
    National Institute for Clinical Excellence. Improving Outcomes in Urological Cancers. London 2002. Available at: http://www.nice.org.uk. Accessed August 2013
  • 3
    Solsona E, Iborra I, Rubio J, Casanova JL, Ricós JV, Calabuig C. Prospective validation of the association of local tumor stage grade as a predictive factor for occult lymph node micrometastasis in patients with penile carcinoma and clinically negative inguinal lymph nodes. J Urol 2001; 165: 15061509
  • 4
    Hillner BE, Smith TJ, Desch CE. Hospital and physician volume or specialization and outcomes in cancer treatment: important in quality of cancer care. J Clin Oncol 2000; 18: 23272340
  • 5
    Tiesberg P, Hansen F, Hotvedt R et al. Patient Volume and Quality: A Methodologically Based International Literature Review. Oslo: SINTEF Unimed, 2001
  • 6
    Bayles AC, Sethia KK. The impact of improving outcomes guidance on the management and outcomes of patients with carcinoma of the penis. Ann R Coll Surg Engl 2010; 92: 4445
Abbreviations
CIS

carcinoma in situ

Sn-MDT

supra-network multidisciplinary team

NICE

National Institute for Health and Care Excellence