Prostatic sarcoma after conservative treatment with brachytherapy for low-risk prostate cancer

To the Editor,

The oncological history of the patient, a 71-year-old man, started 10 years before when he was diagnosed with organ-confined Gleason 6 prostate cancer. Serum prostate specific antigen (PSA) was < 10 ng/ml. The patient was treated with interstitial permanent brachytherapy using I125 with a total dose planned of 145 Gy. PSA nadir of < 0.1 ng/ml was achieved 38 months after treatment, and no urinary or digestive toxicity were observed.

Urinary symptoms characterized by dysuria, nocturia, tenesmus and perineal pain started to appear nine years after brachytherapy treatment. Obstructive symptomatology rapidly evolved despite treatment with alpha-blockers for six months with substantial increase in nocturia and stranguria, as well as pelvic and lumbar pain, constipation and toxic syndrome. Digital rectal examination showed a large and heterogeneous prostate mass. Acute renal failure (creatinine of 393 μmol/l) was detected in the blood test and PSA levels continued to be below the levels of detection. Abdominal computed tomography (CT) scan revealed bilateral grade III ureteral ectasia due to a large prostate with irregular contours. Thorax CT-scan did not find lung dissemination. Transrectal ultrasound-guided biopsies and prostatic transurethral resection were performed. Prostate high-grade sarcoma with bladder extension was suspected and the patient underwent radical cystoprostatectomy with urinary derivation and extended pelvic lymphadenectomy.

Gross pathological examination of the surgical specimen showed the prostate to be entirely replaced by grayish tumor tissue, which extended into the bladder wall (Figure 1A and B), surrounded the seminal vesicles and invaded the perivesical fat and both terminal ureters. Metastatic peritoneal nodules and bilateral pelvic lymph nodes were found as well.

Figure 1. Macroscopic performance of prostatic sarcoma. (A) Black arrows show brachytherapy implants into the prostate tissue. (B) Sectional profile of excised specimen. Prostate is replaced by grayish tumor tissue, which extended into the bladder wall.

On histological examination, the tumor tissue ranged from bland myxoid areas with a heavy inflammatory component to frankly malignant ones, made up of bundles of ovoid to spindle large atypical cells admixed with occasional lymphocytes and plasma cells (Figure 2). Mitoses and vascular invasion were easily found, and there were multiple foci of necrosis. On immunohistochemistry, the tumor cells were positive for vimentin and, focally, for cytokeratin AE1/AE3, CD68, and CD31, and negative for a number of other cytokeratins, EMA, muscle markers, CD21, CD23, CD30, CD34, CD117, S-100 protein, PSA and ALK-1.

Figure 2. Histologic findings of prostatic sarcoma (HE, 400×). Atypical ovoid-spindle tumor cells with large vesicular nuclei and high mitotic index, accompanied by inflammatory cells.

On the basis of these results, the tumor was classified as a high-grade spindle cell sarcoma with features of inflammatory myofibroblastic tumor. The patient had a torpid postsurgical evolution and died three months after surgery due to surgical complications and disease progression.

Discussion

Radiation-induced sarcomas are rare tumors, more malignant than prostatic adenocarcinoma, representing less than 0.2% of all irradiated patients [1–3]. Local symptoms are the most common clinical presentation for this disease. In the case described herein, a progressive intensive dysuria for several months that worsened to cause acute retention of urine and acute renal failure were the main symptoms that lead to diagnosis. CT-scan is essential for diagnosis, because even if the sarcoma has a non-specific radiological appearance, it will help the study loco regional and distant spread of the disease [4]. However, the definitive diagnosis of prostate sarcoma is usually established with ultrasound-guided biopsy or transurethral resection.

Prostate cancer is not clearly associated with an increased number of additional malignancies, but radiation is known to cause malignant transformation. In this context, several publications suggest that there is an increased risk for secondary tumors after prostate radiotherapy or brachytherapy [5–8]. The diagnosis of postradiation neoplasm, established by Cahan et al. in 1948 is generally based on the following criteria [9]: 1) The second neoplasm is located within the radiation field; 2) The latent period (period between initiation of radiation treatment and histological diagnosis of second neoplasm) should be longer than four years; 3) The histological features of the original lesion and the second tumor must be completely different; and 4) The patient should not have a genetic predisposition for tumors.

Our patient accomplished the first three preceding criteria, although he was not tested for genetic predisposing syndrome because his familial history did not suggest a potential hereditary genetic disorder.

Brenner et al. reported that approximately one of 70 patients undergoing radiation for prostate cancer and surviving more than 10 years will develop secondary cancers [1]. The most common sites of secondary tumors are located in the radiation field or adjacent to it, such as bladder, rectum or in-field sarcomas [1,10], but also second neoplasms are reported in distant sites such as the lung [1,11]. The relative risk of occurrence of radiation-induced sarcomas is doubled at five years, and then increases rapidly. Its onset depends more on the irradiated tissue volume [12,13] and is proportional to the beam-on time [14]. Experimental studies suggest that intensity-modulated radiation therapy may be associated with up to three times higher risk of secondary malignancy [14].

There are few cases of radiation-induced prostatic sarcoma reported in the medical literature, always after external radiotherapy and one case in association with brachytherapy [15]. Despite the low incidence, it is expected to be seen more frequently, due to an increased life expectancy with progressively improved survival in cancer patients as a result of a better cancer treatment.

To the best of our knowledge, this is the first case in the medical literature of a prostatic sarcoma in a patient treated with prostate permanent brachytherapy and without history of external radiotherapy. The cases of second malignancy after brachytherapy are still limited and additional studies with long-term follow-up are needed to confirm a potential cause-and-effect relationship.

Acknowledgements

The authors would like to thank Carlos García- Echeverría for review of the report and the technical support.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.