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 LUTS, acute urinary retention, and bone metastases, among which bone metastases are mainly osteolytic rather than osteoblastic, which can cause a pain associated with bone metastases[5]. As SCC of the prostate differs from adenocarcinoma in its therapeutic response and prognosis. It usually indicates a poor response to conventional treatment and a poor prognosis[6]. Because of the high level of malignancy, SCC of the prostate commonly metastasizes to other organs in an early time. However, the serum PSA may be at the normal range in SCC of the prostate. PSA and the Gleason grading system are not of high value in the diagnosis of SCC [7–9].
The etiology of SCC remains unclear. The origin may be 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 suggested that the progress of SCC was possibly stemmed from a series of factors disabling columnar cells to produce the normal prostatic antigen, such as PSA and prostatic acid prophatase (PAP), whereas enabling them to produce keratin.[12]. Some reported that transformation of adenocarcinoma to SCC occurred secondary to radiation or endocrine treatment. And the transformation often occurs in high-grade prostatic adenocarcinoma[7, 8]. Similarly, the transformation occurring in our case belongs to 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).
As of now, there have been a few cases about prostatic adenocarcinoma transformation into squamous cell carcinoma through hormonotherapy with LHRH since Braslis et al[8] first reported in 1995. To our knowledge, our case is the first report 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 hormonotherapy (8 cases treated with hormonotherapy alone and 1 case treated with hormonotherapy 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 hormonotherapy. There were 8 cases of purely epidermoid carcinoma alone and 32 cases of adenosquamous carcinoma. Which above suggested that the transformation of prostatic adenocarcinoma into SCC may be associated with hormonotherapy. In addition, radiotherapy may also play an important role in transformation. Our patient was diagnosed with metastatic prostatic adenocarcinoma which transformed into SCC of the prostate after 2 years of hormonotherapy. Evidence revealed that there had been 6 cases of prostatic adenocarcinoma transforming into squamous cell carcinoma by hormonotherapy in the last decade. We reviewed these cases and our case in Table 1. Two of them underwent radiotherapy, 4 of these cases did not undergo radical prostatectomy but received hormonotherapy and eventually transformed into SCC of the prostate. However, the time of transformation from prostatic adenocarcinoma into squamous cell carcinoma was not yet clear. The Leuprorelin and bicalutamide for the treatment of our patient led to a decrease of the level of androgens in the blood, which may result in the inability of the prostatic columnar cells to express PSA and PAP. while remaining the ability of the prostate to produce keratin facilitates transformation.
Table 1
Published cases about transformation of prostatic adenocarcinoma into SCC after hormonotherapy in the last 10 years
| | Reference | Year | Age (yr.) | Initial PSA(ng/ml) | GS | Radical prostatectomy | Radiotherapy | Hormonotherapy and therapy time |
| 1 | Al-Qassim et al[4] | 2014 | 65 | 84.5 | 4 + 5 = 9 | No | No | LHRH analogue (Leuprorelin) 18 months |
| 2 | Lee et al[1] | 2019 | 76 | 1.27 | 4 + 5 = 9 | No | No | LHRH analogue (goserelin) and antiandrogenagent(bicalutamide) 7 months |
| 3 | Ichaoui et al[2] | 2019 | 71 | 2.7 | 3 + 3 = 6 | Yes | Yes | LHRH ananlogue(Triptorelin) 6 months |
| 4 | Dizman et al[14] | 2020 | ① 76 | 44.7 | 4 + 4 = 8 | No | Yes | CYP17 inhibitor and LHRH analogue(Leuprorelin) 3 years |
| 5 | | | ② 60 | 9.9 | 5 + 4 = 9 | Yes | No | LHRH analogue (Leuprorelin)and CYP17 inhibitor(Abiraterone) 2 months |
| 6 | Lau et al[13] | 2020 | 68 | N/A | 3 + 4 = 7 | Yes | No | LHRH analogue (Leuprorelin) and antiandrogen agent (bicalutamide) 8 months |
| 7 | Our case | 2022 | 67 | 63.38 | 5 + 5 = 10 | No | 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 because it is extremely scarce and lacks well-established imaging characteristics[1]. Currently, the treatment for primary SCC of the prostate is ineffective despite of 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 an effective treatment 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 including Mitomycin C and 5-Fluoro-uracil (5FU) and low-dose radiotherapy. No progression was seen in the 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 was 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 hormonotherapy. Based on the pathological diagnosis and the imaging, our patient had experienced two cycles of adjuvant chemotherapy (docetaxel). Dizman N et al[14] conducted CGP on the squamous transformation of prostate adenocarcinoma, suggesting that CGP could play an essential role in clinical practice to identify the origin and targeted therapy of the squamous transformation.