Squamous cell carcinoma (SCC) of the prostate is a very rare and highly aggressive tumor, representing less than 1 % of prostatic carcinomas[1, 3]. The age of onset of SCC is mostly about 40 to 80 years old, and the median survival time after diagnosis is estimated to be 14 months[4]. The clinical features of SCC of the prostate and adenocarcinoma of the prostate are quite different, and the SCC of the prostate of patient's symptoms are similar to those of advanced prostatic adenocarcinoma, including lower urinary tract symptoms (LUTS), acute urinary retention, and bone metastases, among which bone metastases are mainly osteolytic rather than osteoblastic, which can lead to pain associated with bone metastases[5]. Due to SCC of the prostate differs from adenocarcinoma in its therapeutic response and prognosis. It usually with a poor response to conventional treatment and with a poor prognosis[6]. Because of high degree of malignancy, SCC of the prostate commonly metastasizes to other organs in early time. As well, the serum PSA may be within the normal range in SCC of the prostate, PSA and the Gleason grading system are of limited value in the diagnosis of SCC, histopathological can help its diagnosis[7–9].
The etiology of SCC remains unclear. It may originate from the prostatic or bladder urethral squamous cell, prostatic acini metaplasia, or squamous metaplasia of a prostatic urethral primary tumor[4, 10]. Regarding the occurrence and progression of cancer, it is proposed that cancer stem cells with the ability of self-replication, multi-differentiation and tumor formation are the origin, which can form pluripotent stem cells capable of multidirectional differentiation or metaplastic transformation of adenocarcinoma[11]. It has been suggested that SCC developed was a result of adverse stimuli affecting columnar cells causing them to express normal prostatic antigen such as PSA and prostatic acid prophatase (PAP), although retaining the ability to produce keratin[12]. Some reported transformation of adenocarcinoma to SCC occurred secondary to radiation or endocrine treatment. And the transformation often occurs in high-grade prostatic adenocarcinoma[7, 8]. Our case fits this situation. Recently, Hubert et al[13] detected a TMPRSS2-ERG fusion, among other genetic alterations, by comprehensive genomic profiling (CGP), supporting a diagnosis of metastatic SCC transformed from prostatic adenocarcinoma following androgen deprivation therapy (ADT).
Until now, there are a few cases about prostatic adenocarcinoma transformed into squamous cell carcinoma through endocrine therapy since Braslis et al[8] first reported in 1995. To our knowledge, our case is the first reported in China. In 2004, Parwani et al[4] reported 33 cases of prostate cancer with squamous differentiation, 21 of which had a history of adenocarcinoma diagnosis before treatment, and of these 21 cases, a total of 9 had a history of endocrine therapy (8 cases treated with endocrine therapy alone and 1 case treated with endocrine therapy and radiation). And in 2019, Hamza et al[2] retrospectively analyzed more than 70 cases of prostate cancer with squamous differentiation. 40 of these cases were caused by the transformation of prostatic adenocarcinoma into SCC after radiation therapy (RT) or endocrine therapy. There were 8 cases of purely epidermoid carcinoma alone and 32 cases of adenosquamous carcinoma. In their review, the further suggests a possible link between the transformation of prostatic adenocarcinoma into SCC and endocrine therapy. Our patient was diagnosed with metastatic prostatic adenocarcinoma that transformed into SCC of the prostate after 2 years of endocrine therapy. There are 6 cases reported in the English literature in the last 10 years of prostatic adenocarcinoma transformed into squamous cell carcinoma by endocrine therapy. We reviewed these cases and our case in Table 1. 4 of these cases did not undergo radical prostatectomy and received endocrine therapy and eventually transformed into SCC of the prostate. Moreover, the duration of treatment of endocrine therapy is different in each case, it is uncertain from which point in time differentiation to squamous epithelial carcinoma begins to occur. Leuprorelin and bicalutamide in our patient resulting a decrease in the level of androgens in the patient's blood. Which may affect the loss of the ability of the prostatic columnar cells to express PSA and PAP, while the ability of the prostate to produce keratin remains, thus facilitating transformation.
Table 1
Published cases about transformation of prostatic adenocarcinoma into SCC after endocrine therapy in the last 10 years
| | Reference | Year | Age (yr.) | Initial PSA(ng/ml) | GS | Rdical prostatectomy | Endocrine therapy therapy time |
| 1 | Al-Qassim et al[4] | 2014 | 65 | 84.5 | 4 + 5 = 9 | No | LHRH analogue (Leuprorelin) 18 months |
| 2 | Lee et al[1] | 2019 | 76 | 1.27 | 4 + 5 = 9 | No | LHRH analogue (goserelin) and antiandrogenagent(bicalutamide) 7 months |
| 3 | Ichaoui et al[2] | 2019 | 71 | 2.7 | 3 + 3 = 6 | Yes | LHRH ananlogue(Triptorelin) 6 months |
| 4 | Dizman et al[14] | 2020 | ① 76 | 44.7 | 4 + 4 = 8 | No | CYP17 inhibitor and LHRH analogue(Leuprorelin) 3 years |
| 5 | | | ② 60 | 9.9 | 5 + 4 = 9 | Yes | LHRH analogue (Leuprorelin)and CYP17 inhibitor(Abiraterone) 2 months |
| 6 | Lau et al[13] | 2020 | 68 | N/A | 3 + 4 = 7 | Yes | LHRH analogue (Leuprorelin) and antiandrogen agent (bicalutamide) 8 months |
| 7 | Our case | 2021 | 67 | 63.38 | 5 + 5 = 10 | No | LHRH analogue (Leuprorelin) and Bilateral Orchidectomy 27 months |
| N/A, not mentioned in literature; PSA, Prostate specific antigen; GS, Gleason score; LHRH: Luteinizing Hormone Releasing Hormone. |
Imaging diagnosis of SCC of the prostate is challenging due to it is extremely rare and lack of well-established imaging characteristics[1]. Currently, the treatment of primary SCC of the prostate is unclear and is mostly a combination of surgical therapy, radiotherapy and chemotherapy. For patients who have lost the opportunity for surgical therapy, a combination of chemotherapy and radiation therapy may be effective for SCC of the prostate. Biswas et al[15] reported a patient with primary SCC of the prostate staged as T4N1M0, who received chemotherapy regimen included Mitomycin C and 5-Fluoro-uracil (5FU) and low-dose radiotherapy. The patient is doing well after treatment, with no progression for 27 months of follow-up. Onoda M et al[16] reported a case of locally advanced SCC of the prostate treated with a combination of docetaxel, cisplatin, and 5-fluorouracil chemotherapy and radiotherapy. The patient showed good responsiveness after treatment with no progression for 24 months of follow-up. Recently, Hanna K et al[17] reported a case of primary SCC of the prostate staged as T4N1M1. The patient is currently undergoing four cycles of adjuvant docetaxel and carboplatin. There is also no optimal treatment for SCC of the prostate transformed from prostatic adenocarcinoma during endocrine therapy. Based on the pathological diagnosis and the imaging, the decision was made to pursue adjuvant chemotherapy, and the patient is currently undergoing two cycles of adjuvant docetaxel. Dizman N et al[14] have conducted CGP on the squamous transformation of prostate adenocarcinoma, suggested that CGP could play an essential role in clinical practice to identify the origin and targeted therapy of the squamous transformation.