College of American Pathologists



Pitfalls in the Diagnosis of Treated Prostate Cancer

Posted Decemeber 6, 2013

Tarren Vyas, MD

In American men, prostate cancer is the most commonly diagnosed nonskin cancer and the second most common cause of cancer-related death.1 Pathologists receive prostatic tissues in the form of needle biopsies, transurethral resections, and radical prostatectomy specimens. Specimens are assessed for a variety of factors, including Gleason grade, extra-prostatic extension, surgical margin status, and treatment effect. This information allows clinicians to determine extent of disease, effectiveness of treatment, need for additional treatment, risk of recurrence, and long-term survival. In some cases, the pathologist receives a specimen from a patient who has been previously treated for prostate cancer. While these therapies are beneficial to the patient, they also cause morphologic changes that can present a diagnostic challenge for the pathologist. It is therefore essential that clinicians provide an accurate patient history, as well as detailed information about the use of prior therapies.

For patients with locally advanced or metastatic prostate cancer, a common form of therapy is androgen deprivation, a form of hormone therapy. This can also be used as neoadjuvant therapy prior to a radical prostatectomy or radiation.2 The histologic effects vary with the type of agent, size of dose, and duration of therapy.3 In general, there is a reduction in gland size and density, along with a relative increase in stromal tissue. One common finding is the dissolution of glandular architecture, including acini with compressed or collapsed lumens, single cells with cleared cytoplasm, small hyperchromatic nuclei, and inconspicuous nucleoli. Cancer glands with these changes may look deceptively bland and be overlooked. Furthermore, they can resemble cancer cells of higher grades and can lead to a spuriously high Gleason score.3-10

Radiation therapy may also cause significant changes in neoplastic tissue. The appearance is highly variable, ranging from no obvious effect to profound changes, often within the same specimen. Marked effects manifest as haphazardly scattered glands or single cells with pale, vacuolated cytoplasm and enlarged nuclei with prominent nucleoli. Distinguishing between benign glands with radiation-induced atypia and malignant glands can often be difficult. These changes also affect the overall architecture, which alters the Gleason grade. Since Gleason grading can be misleading, a Gleason score is generally not assigned.5,6

Other treatments such as thermal ablation, cryotherapy, and high-intensity focused ultrasound cause various changes in tissue largely confined to the targeted areas. These include well-demarcated areas of coagulative necrosis, haemorrhage, inflammation, and fibrosis. However, when residual adenocarcinoma is identified outside of the areas of treatment effect, no specific effects are generally noted allowing a Gleason score to be assigned.2,5,6

In summary, treatment modalities other than surgical resection have become increasingly important for prostate cancer management. However, treatment options often render significant morphologic changes. Knowledge of such treatment is essential in order to ensure accurate diagnosis and Gleason grading of specimens. Thus, it is essential that clinicians provide this information when submitting a prostate biopsy.


  1. American Cancer Society. What are the key statistics about prostate cancer? Published March 15, 2013. Accessed July 15, 2013.
  2. Petraki CD, Sfikas CP. Histopathological changes induced by therapies in the benign prostate and prostate adenocarcinoma. Histol Histopathol. 2007;22(1):107–118.
  3. Evans AJ, Ryan P, Van derKwast T. Treatment effects in the prostate including those associated with traditional and emerging therapies. Adv Anat Pathol. 2011;18(4):281–293. doi:10.1097/PAP.0b013e318220f5b1.
  4. Têtu B. Morphological changes induced by androgen blockade in normal prostate and prostatic carcinoma. Best Pract Res Clin Endocrinol Metab. 2008;22(2):271–283. doi:10.1016/j.beem.2008.01.005.
  5. Armas OA, Aprikian AG, Melamed J, et al. Clinical and pathological effects of neoadjuvant total androgen ablation therapy on clinically localized prostatic adenocarcinoma. Am J Surg Pathol. 1994;18(10):979–991.
  6. Srigley JR, Delahunt B, Evans AJ. Therapy-associated effects in the prostate gland. Histopathology.2012;60(1):153–165. doi:10.1111/j.1365-2559.2011.04079.x
  7. Efstathiou E, Abrahams NA, Tibbs RF, et al. Morphologic characterization of preoperatively treated prostate cancer: toward a post-therapy histologic classification. Eur Urol. 2010;57(6): 1030–1038. doi:10.1016/j.eururo.2009.10.020.
  8. Schulman CC, Debruyne FM, Forster G, Selvaggi FP, Zlotta AR, Witjes WP. 4-Year follow-up results of a European prospective randomized study on neoadjuvant hormonal therapy prior to radical prostatectomy in T2-3N0M0 prostate cancer. European Study Group on Neoadjuvant Treatment of Prostate Cancer. Eur Urol. 2000;38(6):706-713.

Download this article in Microsoft Word format.
Download this article in PDF format.

NewsPath® Editor: Kyle L. Eskue, MD, FCAP
This newsletter is produced in cooperation with the College of American Pathologists Member and Public Communications Committee and the NewsPath Editorial Board and may be reproduced in whole or in part as a service to the medical community. Copyright © 2013 by the College of American Pathologists.
Please e-mail any comments to


Related Links