Microscopic Description:

In this case, radiation treatment effect is notable throughout the prostate which appears as alterations in gland architecture, including epithelial cell atrophy with a reduction of gland cellularity, the presence of pleomorphic and enlarged nuclei without nucleoli, as well as increased collagen density and fibrosis in the stroma. However, among the radiation-induced changes, there are also cells with large amounts of vacuolated cytoplasm forming misshapen glands with a straighter/more angulated border. Interestingly, these nuclei are smaller, darker, and somewhat more regular than their treatment effect counterparts, although occasional nucleoli are observed.

The IHC more definitively reveals a mix of prostatic adenocarcinoma intermixed with benign radiation changes. The carcinomatous glands show a loss of p63/CK5 staining, indicating a loss of the basal layer, as well as positive red cytoplasmic staining for AMACR, revealing the diagnosis of prostatic adenocarcinoma with radiation changes.

The other differentials can be ruled out as a Gleason grade should not be assigned in the setting of significant radiation treatment effect. The IHC reveals that while yes, benign treatment effect, including possibly those of androgen deprivation, is present, the presence of adenocarcinoma must be described in the report. Ductal adenocarcinoma is a variant that arises in the ducts of the prostate gland which shows tall columnar cell morphology, most commonly with cribriform, papillary, or solid architecture.

Discussion:

Prostate biochemical recurrence develops in approximately 1/3 of men who are treated with local therapy. The Phoenix criteria is used to define biochemical recurrence following radiation therapy which requires that the PSA increase by at least 2ng/mL above the post-radiation PSA nadir.1 Thus, in this case, the patient did not actually meet the Phoenix criteria of biochemical recurrence, despite the presence of adenocarcinoma observed in this biopsy.

Localized prostate adenocarcinoma classically can be treated with either brachytherapy or external beam radiotherapy (EBRT).2 Prostate brachytherapy involves placement of radioactive seeds nearby or even inside of the tumor via a hollow needle, which are often permanently left inside of the prostate. However, the accuracy of needle placement is crucial to providing effective treatment, which has the potential to be improved through surgical robotic systems.3

Currently, no randomized control trial has been successful in evaluating the difference in effectiveness of brachytherapy compared to EBRT. One retrospective study focusing on intermediate-risk prostate cancer did show that no differences in biochemical recurrence was detected between either brachytherapy or EBRT. However, GU side effects were more prevalent following brachytherapy whereas GI side effects were more prevalent among those treated with EBRT, although both types of side effects were noted to decrease over time.2

Unfortunately, prostate cancer recurrence following either form of radiation therapy may be difficult to treat with focal therapy following radiation failure, based on an analysis of pathological features shown following radical prostatectomy specimens. In general, prostate cancer recurrence is often high grade, close to the urethra, and is often bulky or involving multiple zones.4

In general, when reporting prostate adenocarcinoma in the presence of radiation treatment effects, a grade should not be assigned unless marked radiation changes are absent or if the patient has received androgen deprivation due to its induction of gland distortion and should be reported as not gradable. In addition to the IHC findings described in this case, PSA and PSAP is normally retained following radiation, but GATA3 may be falsely positive in benign radiated glands.55

References:

Simon NI, Parker C, Hope TA, Paller CJ. Best Approaches and Updates for Prostate Cancer Biochemical Recurrence. Am Soc Clin Oncol Educ Book. 2022;42:1-8. doi:10.1200/EDBK_351033

Moll M, Renner A, Kirisits C, Paschen C, Zaharie A, Goldner G. Comparison of EBRT and I-125 seed brachytherapy concerning outcome in intermediate-risk prostate cancer. Strahlenther Onkol. 2021;197(11):986-992. doi:10.1007/s00066-021-01815-z

Li, Y., et al.: A review on the techniques used in prostate brachytherapy. Cogn. Comput. Syst. 4(4), 317–328 (2022). https://doi.org/10.1049/ccs2.12067

Leibovici D, Chiong E, Pisters LL, et al. Pathological characteristics of prostate cancer recurrence after radiation therapy: implications for focal salvage therapy. J Urol. 2012;188(1):98-102. doi:10.1016/j.juro.2012.02.2571

Iczkowski KA. Prostate gland & seminal vesicles: Acinar/ductal adenocarcinomas: Treatment effect. Pathology Outlines. 2021. Available from: https://www.pathologyoutlines.com/topic/prostatetreatmenteffect.html

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