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Prostatic carcinosarcoma 15 years after combined external beam radiation and brachytherapy for prostatic adenocarcinoma: a case report

Abstract

A 65-year-old man with a history of combined pelvic external beam radiation therapy (EBRT) and brachytherapy for prostatic adenocarcinoma 15 years prior underwent total pelvic exenteration for presumed rectal sarcoma with prostatic invasion. Pathology revealed carcinosarcoma of prostatic origin. This patient exhibited the longest reported interval between initial presentation with prostatic adenocarcinoma and development of carcinosarcoma. This case is also the first reported case of prostatic carcinosarcoma occurring after combined EBRT and brachytherapy. The increasing use of such combination high-dose radiation therapy may potentially lead to an increased incidence of secondary malignancies such as prostatic carcinosarcoma in the future.

Introduction

Unlike prostatic epithelial malignancies, neoplasms of prostatic stromal tissue occur infrequently. Such sarcomas constitute approximately 0.1% of all prostatic neoplasms.1, 2 As prostatic sarcoma occurs more commonly at an earlier age than adenocarcinoma, it is extremely rare for a patient to have both neoplasms.3 When these do occur together as carcinosarcoma, half of the patients have a history of prostatic adenocarcinoma.4 We report an unusually delayed occurrence of prostatic carcinosarcoma after combined external beam radiation therapy (EBRT) and brachytherapy.

Case report

A 65-year-old male presented with rapidly progressive overflow incontinence and obstipation 15 years after high-dose brachytherapy and EBRT for prostate adenocarcinoma. Pre-treatment prostate-specific antigen (PSA) had been 10 ng/ml. At 6 years after irradiation, the patient's PSA had risen slightly and the patient had been maintained on leuprolide.

On physical examination, the patient had a rectal mass. Cystoscopy demonstrated prostatic fossa occlusion and endoscopic ultrasound revealed a 2 cm anterior rectal mass with prostate and seminal vesicle invasion. Computed tomography (CT) scan showed a rectal mass invading the prostate, bilateral hydronephrosis and no evidence of metastatic disease. Bone scan and chest X-ray were also negative for metastases. Trans-rectal biopsy demonstrated poorly differentiated tumor. Cytokeratin and PSA stains were negative, arguing against recurrent prostatic adenocarcinoma. Vimentin staining was strongly positive, indicating the presence of sarcoma.

The patient underwent total pelvic exenteration with ileal loop diversion for presumed rectal sarcoma. Prostate-specific antigen at the time of surgery was 2.2 ng/ml. Pathology demonstrated focal heterologous cartilage stained by S-100 and vimentin-positive spindled cells consistent with sarcoma. However, a small cytokeratin-positive component of Gleason 4+5 adenocarcinoma was present, making the final diagnosis prostatic carcinosarcoma (see Figure 1.). Although all lymph nodes were negative, there was significant extracapsular extension. Repeat staging CT scan demonstrated metastatic disease with enlarged thoracic and abdominal lymph nodes. Docetaxel therapy was initiated for the adenocarcinoma component of this patient's metastatic disease. This will be followed by liposomal doxorubicin to treat the sarcoma component of the tumor should the disease progress.

Figure 1
figure1

(a) Hematoxylin–eosin staining of the prostate tumor showing predominantly high-grade spindle cell neoplasm with a small focus of adenocarcinoma (asterisk). Original magnification, × 100. (b) Hematoxylin–eosin staining demonstrating cartilaginous differentiation within the sarcomatous component. Original magnification, × 400.

Discussion

This case is unique because it represents only the fourth reported case of prostatic carcinosarcoma after radiation therapy and is the first reported case after combined EBRT and brachytherapy. The 15-year latency period from adenocarcinoma to development of carcinosarcoma is also the longest in the reported literature. The change in final diagnosis to prostatic carcinosarcoma highlights the diagnostic difficulties these tumors present. Biopsies that contain only one of the two components of a carcinosarcoma can be misleading. Furthermore, without sampling of differentiating features, the tissue source of a sarcomatous neoplasm can be indeterminate by pathology.

Carcinosarcoma is exceedingly rare and generally presents after the age of 40 years. The mean age at diagnosis was 66 years among all published cases.2, 5 In the largest published series on prostatic carcinosarcoma, Dundore et al. found that, among their 21 patients, 48% had a previous diagnosis of prostatic adenocarcinoma. The mean time to development of carcinosarcoma was 33 months (range 2–73 months). The presenting symptom was urinary obstruction in 85% of patients. Other symptoms associated with prostatic sarcomas include pelvic and perineal pain, suprapubic or lower abdominal mass and urinary frequency.6, 7 Consistent with the substantial non-epithelial component of many of these malignancies, PSA in carcinosarcoma is usually normal. As with other adult prostatic sarcomas, overall survival is poor. Dundore et al.4 found that 5-year survival was 41% while 7-year survival was 14%. In this series, disease progression and survival were unaffected by the histologic pattern of the sarcomatous component.

Metastases to lung, bone, liver, and lymph nodes occur early in prostatic carcinosarcomas. Twenty-five percent of patients have metastatic disease at diagnosis, and an additional 39% subsequently develop metastases.8 No studies have shown a survival advantage for any adjuvant or neoadjuvant therapy.4 However, as with other prostatic sarcomas with uniformly poor outcomes, multimodality therapy may be applied. Surgery generally involves anterior exenteration with urinary diversion. For patients with bulky disease who may be at higher risk for positive surgical margins, small series have demonstrated that neoadjuvant doxorubicin and cisplatin can produce significant tumor necrosis. Adjuvant therapies include doxorubicin-based chemotherapy and radiation therapy.6, 9 Patients with post-irradiation malignancies, however, may have already received their maximum dose of pelvic irradiation. In patients who present with metastatic disease, palliative surgery to relieve urinary or bowel obstruction may be appropriate.

As a result of the association between prostatic carcinosarcoma and a previous diagnosis of prostatic adenocarcinoma, it is thought that carcinosarcoma represents a ‘dedifferentiation’ of an initial adenocarcinoma, possibly induced by androgen ablation and/or radiation therapy.2 Some investigators discount androgen deprivation therapy because a multitude of patients have been treated with androgen ablation without development of these rare tumors.4 Others discount radiation therapy as an inciting event as only a small proportion of reported carcinosarcoma patients have a history of irradiation. In any case, the rarity of this malignancy precludes any compelling statistical analysis.

Our patient received both brachytherapy and EBRT as initial therapy for prostatic adenocarcinoma. Such combination high-dose radiation therapy was introduced in the 1990s when PSA testing demonstrated poor biochemical cure rates with conventional irradiation.10 Our patient's prolonged latency period of 15 years is consistent with reports of other radiation-induced malignancies which have mean latency periods of 5–15 years.11 As high-dose irradiation is increasingly used to treat prostate cancer, it would be unsurprising if the incidence of secondary radiation-induced malignancies were to rise.

Conclusions

Carcinosarcoma of the prostate is a rare and aggressive malignancy that can develop many years after initial presentation with prostatic adenocarcinoma. In addition to long-term surveillance for disease recurrence, there should be suspicion for the development of secondary malignancies when obstructive symptomatology occurs in the absence of biochemical recurrence, particularly in a patient with a history of pelvic irradiation.

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Correspondence to K E Maloney.

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Tseng, T., Sevilla, D., Moul, J. et al. Prostatic carcinosarcoma 15 years after combined external beam radiation and brachytherapy for prostatic adenocarcinoma: a case report. Prostate Cancer Prostatic Dis 9, 195–197 (2006). https://doi.org/10.1038/sj.pcan.4500870

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Keywords

  • brachytherapy
  • carcinosarcoma
  • case reports
  • prostatic neoplasms
  • radiotherapy

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