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Clinical Features, Prognosis, and Outcome of Patients with Pure Squamous Cell Carcinoma of the ProstateDaniel Brunnhoelzl, and Jue Wang1,2*
1Creighton University School of Medicine, St. Joseph's Hospital and Medical Center, USA
2Genitourinary Oncology Section, University of Arizona Cancer Center at Dignity Health, St. Joseph’s Hospital and Medical Center, USA
*Corresponding author: Jue Wang, MD, Professor of Medicine, Director of Genitourinary Oncology Section, University of Arizona Cancer Center at Dignity Health St. Joseph’s, Phoenix, AZ, 625 N 6th Street, Phoenix, AZ 85004, USA, Tel: +1 602-406-8222; E-mail: email@example.com
Received: February 15, 2017; Accepted: April 26, 2018; Published: April 30, 2018
Copyright: ©2018 Brunnhoelzl D, et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Citation: Brunnhoelzl D, Wang J (2018) Clinical Features, Prognosis, and Outcome of Patients with Pure Squamous Cell Carcinoma of the Prostate. J Compr Cancer Res 2(1): 100008.
Background: Pure squamous cell carcinoma of the prostate is a rare entity. Data regarding clinical features, management, and treatment outcomes are limited. As such, management of this cancer has been variable throughout the reported literature, and with limited success.
Methods: A systematic review of the literature and secondary data analysis was performed to characterize clinical features, management, and survival outcomes.
Results: In total 47 cases of histological confirmed pure squamous cell carcinoma of the prostate were included in analysis. Pure squamous cell carcinoma of the prostate is a disease of older males with mean age at diagnosis of 68.5 years (range 42-85). Urinary obstruction was reported as a presenting symptom in 60% of cases. PSA was usually normal with a mean value of 1.6 (n=11). The disease was metastatic at diagnosis in 32% of patients among cases that stage was reported (n=31). In terms of management, chemotherapy was attempted in 28% of cases, radiation in 30%, and surgery (excluding transurethral resection of the prostate TURP) in 25.5%. Hormone therapy was rarely attempted (4%). Metastatic disease was associated with a significant decrease in survival when compared to localized disease, p=0.006. Surgical management was associated with significantly increased survival, p=0.041. Overall 1-year survival was 32%, while 3-year survival was 9%.
Conclusions: Squamous cell carcinoma of the prostate has an aggressive clinical course and is associated with poor prognosis. There is urgent need for early detection and the development of novel treatment options.Keywords: squamous cell carcinoma of prostate, prostate-specific antigen, chemotherapy, prostatectomy, transurethral resection of the prostate, radiotherapy, multimodal therapy, prognosis, survival
Pure squamous cell carcinoma (SCCA) of the prostate is a rare entity with a very poor prognosis. Early series suggested it represented about 0.5-1% of all prostatic malignancies . However, more recently an incident of 0.04% was reported on a survey of Saskatchewan Cancer Agency over a 30-year period (13,497 cases) using strict diagnostic criteria . This discrepancy in incidence reported is probably due in part to the development of more rigorous diagnostic criteria  and clarification of the specific histology of pure SCCA of the prostate.
In contrast to well-described histopathological findings, data regarding clinical features, management, and treatment outcomes are limited to case reports, and thus, are generally anecdotal. As such, diagnosis and management of this cancer has been variable throughout the reported literature, and with limited success.
The aim of this report is to describe the clinical characteristics, diagnostic features, prognosis, and outcome of patients with SCC of prostate using a pooled sample from published literature.
Materials and Methods
Published data Search
A systematic search of the literature was performed by first querying PubMed and Google Scholar for “squamous cell carcinoma of prostate.” Case reports were reviewed, and additional articles of interest were identified from reference lists. No randomized controlled trials or systematic review articles were identified. Thirty-five articles were identified for a total of 83 cases. Thirty-six of the initial 83 cases were excluded because the studies were autopsy or otherwise non-clinical. In total, 47 cases of pure squamous cell carcinoma of the prostate were included in analysis [1-30].
The process of data extraction was conducted independently by two reviewers who used a standard data extraction checklist to extract data from each study. Clinical features including demographic data, presenting symptoms, laboratory findings, grade and stage at diagnosis were reviewed. Treatments provided including chemotherapy, surgery, or radiation were also collected and analyzed in an attempt to ascertain patterns in management.
Descriptive statistics, such as frequency counts, medians, and ranges, were used to characterize the pooled sample. Survival data was collected where available, and used to plot Kaplan-Meier survival curves, as well as determine 3-year and 1-year survival.
Patient and tumor characteristics
Pure SCCA of the prostate is a disease of older men with a mean age at diagnosis of 68.5 years and a range of 42-85 years. The usual presentation of primary squamous carcinoma of the prostate is urinary obstruction (60%), sometimes with dysuria (19%). Hematuria is reported in 9% of cases, while bone pain (due to bony metastatic disease) is rarely reported in the literature (4%). In contrast to primary adenocarcinoma, serum Prostate-specific antigen (PSA) is generally within normal limits, even in the setting of metastasis. Average serum PSA is 1.6 in the reported literature (n=11).
Histologic grade was found to be moderately or poorly differentiated in the majority of cases (40% and 45%, respectively) among cases that grade was reported (Table 1). Metastatic disease is present at the time of diagnosis in 32% of patients among cases that stage was reported (n=31). Similar to prostate adenocarcinoma, bone and lymph nodes metastases are most common. In addition, bone metastases are found to have an osteolytic rather than the osteoblastic appearance seen in adenocarcinoma.  Liver and brain metastasis have been reported (Table 2).
Given the rarity of this condition, there is no consensus for the best way to manage these patients with pure SCCA of the prostate. Several therapeutic approaches have been employed in an effort to treat prostate pure squamous cell carcinoma, including radical surgery, radiotherapy, chemotherapy and hormonal therapy (Table 1). Chemotherapy was used in 28% of cases, radiation in 30%, and surgery (excluding TURP) in 25.5%. Hormone therapy was rarely attempted (4%).
Aggressive surgical approaches, consisting of radical cysto-prostatectomy and bilateral pelvic lymphadenectomy with an additional total urethrectomy have been used in patients with organ-confined disease in order to assure negative distal urethral margins. Radiation therapy as a single modality treatment in limited-stage disease has been used as investigative approach. For locally advanced and metastatic disease, radiation therapy has been used as part of a multimodal approach to achieve local control with organ functional preservation.
Various chemotherapy regimens have been used in setting of metastatic disease or in a combined modality approach in locally advanced disease. (Table 3). CDDP-based regimens are the most established ones, possibly combined with bleomycin (BLM), peplomycin (PEP) and methotrexate (MTX).
Combined-modality treatments have been used with some degree of success, as evidenced by prolonged disease control, and consistent survival time [4,8,11,14,21].
In this cohort, one-year survival is 32%, while 3-year survival is just 9% (Figure 1a). Metastatic disease was associated with a significant decrease in survival when compared to localized disease, p=0.006 (Figure 1b). Surgical management was associated with significantly increased survival, p=0.041 (Figure 1c).
Because of the rarity of SCCA of the prostate, previously published information has been based on case series and anecdotal experiences. The clinical significance and biologic behavior of this subtype of prostate cancer requires further characterization by performing more extensive studies with long-term follow-up. This study took advantage of the published literature to examine the largest series of pure SCCA of the prostate reported to date.
The presenting symptoms are often similar to advanced adenocarcinoma including lower urinary tract symptoms (LUTS) and bony metastasis. From a diagnostic standpoint, serum Prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) commonly show values within the normal range, even in metastatic disease. Unlike adenocarcinoma of the prostate, SCCA of the prostate typically has a normal PSA (average of 1.6 in this study). However, squamous cell carcinoma (SCC) antigen might be elevated, allowing a serologic monitoring of disease status . Patients with SCCA of the prostate present with aggressive disease. Among patients with known histologic grade, 45% and 40% had poorly and moderately differentiated disease, respectively. SCCA of the prostate commonly metastasizes to the bone (mainly with osteolytic lesions), liver and lungs.
Our review of the literature yields sparse reporting of treatment data and associated outcome. Many different treatment options have been reported: surgical resection with or without adjuvant chemotherapy/radiotherapy. While radical prostatectomy and radiation are the only potentially curative options for prostate adenocarcinomas, there is no established optimal treatment strategy for SCCA of the prostate because there are no clinical trials specifically designed for these patients. Prostatectomy, chemotherapy, radiation therapy, and, less commonly, hormone therapy has been used alone or as part of multimodal management. In this study, patients treated with prostatectomy had improved survival compared to those who did not. Our finding is in line with previous reports [7,17,32], where long-term survivors after surgical treatment for localized tumors have been reported.
Various chemotherapy regimens have been reported (Table 3). CDDP-based regimens are the most established, possibly combined with bleomycin (BLM), peplomycin (PEP) and methotrexate (MTX). Chemotherapy did demonstrate some improvement in survival, although it did not demonstrate statistical significance. This might be due to the limited number of patients in this study. There are a number of cases in which chemotherapy was used as part of therapy, and there was relatively good response [2,3,5,8,11,13,14,21]. So far, the most encouraging results came from multimodal treatment including surgery, radiotherapy and chemotherapy. Munoz et al. reported an encouraging result after treating with concurrent chemo-radiotherapy using cisplatin and 5-FU, similar to the regimen used in SCC of anal origin . The patient remained disease free for 5 years when he relapsed locally and died. Similarly, several investigators also reported long term survival cases with combined chemo radiotherapy [8,14,21,33].
The prognosis of this tumor remains poor, with 1-year and 3-year survival rates of 32% and 9%, respectively. Advanced stage disease usually confers a worse prognosis. These survival rates are significantly lower than the near unanimous 3-year and 1-year survival rates of adenocarcinoma . Novel therapeutic approach is urgently needed for this aggressive disease.
Strengths of this study include a large sample size and the inclusion of patients with a wide range of age, and racial groups treated in different setting. Large sample size is of particular importance for analysis of rare tumors such as squamous cell carcinoma of the prostate, where it is nearly impossible for a single institution to collect enough cases to make meaningful predictions regarding important prognostic factors and treatment recommendations.
Limitations of the study include of the lack central review of pathology. In addition, information regarding patients' comorbidities and performance status are not available in published reports, all of which may influence survival in cancer patients. Finally, sample size in our study may still not be enough to fully describe the factors that affect the incidence, treatment choice, and survival of this rare tumor.
Our large retrospective study of pooled data from published literature showed pure SCCA of the prostate is an aggressive subtype of prostate cancer in elderly man. A better understanding of the natural history of the disease and prognostic factors as provided herein are necessary to allow physicians and patients to accurately assess the risks and potential benefits of treatment. Development of early diagnosis methods and novel therapeutics are important for prevention and mortality reduction. Further study of the molecular biology of the tumor is needed to better understand its aggressive course and may help guide individualized therapeutic management.
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