Squamous Cell Carcinoma of the Prostate
Case Review
RiU_Apr2011_p56-60.qxd 4/13/11 10:53 AM Page 56 CASE REVIEW Squamous Cell Carcinoma of the Prostate Rena D. Malik, BS/BA,1 George Dakwar, MD,1 Matthew E. Hardee, MD, PhD,2 Nicholas J. Sanfilippo, MD,2 Andrew B. Rosenkrantz, MD,1 Samir S. Taneja, MD1 1 Department of Urology and 2Department of Radiation Oncology, New York University Langone Medical Center, New York, NY Squamous cell carcinoma of the prostate is a rare tumor, making up 0.5% to 1% of all prostate carcinomas. It is typically described as an aggressive cancer, with a median postdiagnosis survival of 14 months. Presented here is a case of primary squamous cell carcinoma of the prostate, with a complicated presentation of metastatic disease. Due to the extent of the patient’s disease, he was treated with palliative radiation therapy using a four-field technique (AP/PA and left and right lateral fields) with 18 mV photons prescribed to the 100% isodose line. The prescription dose was 4000 cGy in 16 fractions of 250 cGy per fraction. No definitive treatment of squamous cell carcinoma of the prostate exists but varying approaches including surgical intervention, chemotherapy, and radiation therapy have been implemented without durable response. However, multimodal treatments appear to be the most promising with longer durations of survival. [Rev Urol. 2011;13(1):56-60 doi: 10.3909/riu0494] © 2011 MedReviews®, LLC Key words: Squamous cell carcinoma • Prostate adenocarcinoma • Lower urinary tract symptoms • Multimodal treatments quamous cell carcinoma of the prostate is a rare tumor, making up 0.5% to 1% of all prostate carcinomas.1 Hence, information regarding clinical presentation, diagnostic workup, treatment, and prognosis is gathered via anecdotal descriptions. Presenting symptoms range from lower urinary tract symptoms (ie, obstructive) to bony metastases. It is typically described as an aggressive cancer, with a median postdiagnosis survival of approximately 14 months.2 No definitive treatment exists, although varying approaches including surgical intervention, multimodal chemotherapy, and radiation therapy have been implemented without durable response. We present a case of primary squamous cell carcinoma of the prostate, with a complicated presentation of metastatic disease, treated with palliative radiation therapy. S 56 VOL. 13 NO. 1 2011 REVIEWS IN UROLOGY RiU_Apr2011_p56-60.qxd 4/13/11 10:53 AM Page 57 Squamous Cell Carcinoma of the Prostate Case Report A 77-year-old white man, with a past medical history of chronic lymphocytic leukemia (CLL), initially presented in January 2008 with hematospermia and was diagnosed with epididymoorchitis. He was treated with a course of antibiotics with complete resolution of his symptoms. In October 2008, the patient developed progressive difficulty with urination and was found to have a uniformly thickened bladder wall on abdominopelvic computed tomography (CT) scan, consistent with benign prostatic hypertrophy. Given a benign digital rectal examination and normal serum prostate specific antigen (PSA) levels, he underwent transurethral microwave thermotherapy in November 2008 with minimal relief. During the ensuing months, the patient continued to complain of dysuria and worsening lower urinary symptoms. In January 2009, he developed gross hematuria with clot retention, requiring hospitalization for a period of 4 days, during which time a two-way Foley catheter was placed and he was put on continuous bladder irrigation. During this time, the patient required a blood transfusion. Upon evaluation at an outside institution in February 2009, he was noted to have a firm prostate potentially consistent with cancer. A cystoscopic examination demonstrated indentation of the bulbar urethra, but poor visualization of the bladder precluded any diagnosis of bladder cancer. Transrectal ultrasound-guided prostate biopsy was performed demonstrating anaplastic squamous cell carcinoma in multiple cores. An abdominopelvic CT scan at this point demonstrated multiple enlarged lymph nodes throughout the retroperitoneum and chest consistent with his previous diagnosis of CLL, small pulmonary nodules, a low attenuation region within the right central prostate gland likely representing necrosis from microwave thermotherapy, posterior lateral extension of the prostate gland, and two nodules along the penile shaft likely within the corpus cavernosum. The patient was referred to our institution in March 2009. Here, he was found to have an unintentional loss of 10 lbs and severe pelvic and penile pain over the previous 2 months. On physical examination, the patient was noted to have lower abdominal and suprapubic tenderness. A firm nodule was palpated at the base of his penis at the left penoscrotal junction, and digital rectal examination revealed a diffusely firm prostate with induration extending beyond the apex. A cystoscopic examination revealed urethral indentation secondary to external compression by the palpable nodule, a hyperemic prostate with luminal necrosis, and a normal-appearing bladder despite multiple clots within bladder. A magnetic resonance imaging (MRI) scan of the visceral pelvis performed the following week showed a large infiltrative neoplasm replacing the prostate with invasion of the bladder base and left seminal vesicle with areas of necrosis and hemorrhage (Figure 1). Additional soft tissue deposits near the glans penis, extensive pelvic lymphadenopathy, and right iliac wing and right sacral alae osseous metastasis were observed (Figure 2). Positron emission tomography (PET) tumor imaging demonstrated markedly increased fluorodeoxyglucose (FDG) uptake seen in the base of the penis, extensive FDG uptake seen throughout the prostate gland extending into and involving the bladder, multiple FDG avid pulmonary foci, increased metabolic uptake in T12, sacrum, and right iliac bone, all consistent with osseous metastatic disease. Diffusely increased activity was seen in the right bicep Figure 1. Sagittal turbo spin-echo T2-weighted magnetic resonance image demonstrates a T2-hypointense soft tissue mass replacing the entire prostate (solid arrow) with central necrosis (asterisk) and extension into the bladder base (dashed arrow). There is a Foley catheter (F) within the urinary bladder. Penile soft tissue mass (white arrowhead) is better demonstrated in Figure 2. Figure 2. Axial turbo-spin echo T2-weighted magnetic resonance image demonstrates well-circumscribed T2-hypointense soft tissue masses (solid arrows) within both corpora cavernosa, consistent with penile metastases. muscle. Brain MRI revealed no metastatic disease. Based on the metastatic nature of the disease as confirmed by PET imaging, the patient was no longer considered for surgical intervention (pelvic exoneration). He was hospitalized for VOL. 13 NO. 1 2011 REVIEWS IN UROLOGY 57 RiU_Apr2011_p56-60.qxd 4/13/11 10:53 AM Page 58 Squamous Cell Carcinoma of the Prostate continued management of his gross hematuria and for the initiation of local palliative radiotherapy. The patient underwent CT simulation and was treated in the supine position with a Vac-Loc for immobilization. A course of palliative radiation therapy was delivered to the pelvic mass using a four-field technique (AP/PA and left and right lateral fields) with 18 mV photons prescribed to the 100% isodose line. The prescription dose was 4000 cGy in 16 fractions of 250 cGy per fraction. Port films were obtained every 5 days to verify patient positioning. The patient tolerated the treatment well without any interruptions due to treatment-related side effects. During the treatment, he did not develop significant skin reactions or gastrointestinal (nausea, vomiting, diarrhea, abdominal pain) symptoms. His pain improved throughout the treatment and he developed no further episodes of bleeding through the Foley catheter. Following completion of radiation therapy, the patient was admitted to hospice care and died 3 months following his initial presentation to our institution. Discussion Primary squamous cell carcinoma (PSCC) of the prostate continues to be an infrequent and aggressive malignancy found in less than 1% of men worldwide. The first accepted criterion used to define the histologic characteristics of PSCC was described by Mott and colleagues. It included (1) a clearly malignant neoplasm as judged by invasion, disordered growth, and cellular anaplasia; (2) definite squamous features of keratinization, squamous pearls, and/or numerous distinct intercellular bridges; (3) lack of any glandular or acinar pattern; (4) no prior estrogen therapy; and (5) the absence of PSCC elsewhere, particularly in the 58 VOL. 13 NO. 1 2011 bladder.1 These criteria are important to differentiate between PSCC and nonneoplastic squamous metaplasia that can occur secondary to infarct, acute/chronic prostatitis, granulomatous prostatitis due to Bacillus Calmette-Guérin, estrogen therapy, or radiation therapy.2,3 The histogenesis of squamous cell carcinoma has long been a topic for debate. Some have thought the origin infection, hematuria, and bony pain secondary to metastases. A total of 56% of patients were found to have metastases to varying locations including bone, lungs, liver, and lymph nodes with survival ranging from 0 to 60 months with an average survival of 11.9 months. Because PSCC remains a rare occurrence, no specific treatment modality has been widely accepted. Surgical The histogenesis of squamous cell carcinoma has long been a topic for debate. Some have thought the origin to be of prostatic urethral urothelium, although others believe it arises from the transitional epithelium of periurethral ducts or the basal cells of prostatic acini. to be of prostatic urethral urothelium,4 although others believe it arises from the transitional epithelium of periurethral ducts5 or the basal cells of prostatic acini.6 Lager and associates concluded that squamous cell carcinoma developed due to adverse stimuli affecting columnar cells causing them to lose their ability to produce PSA and prostatic acid phosphatase (PAP), although retaining the ability to produce keratin.7 Clinically, PSCC remains distinctly different from its more common counterpart, prostate adenocarcinoma (ADC). The presenting symptoms are often similar to advanced ADC including lower urinary tract symptoms (LUTS) and bony metastasis. In terms of clinical markers, the squamous variant typically does not result in elevated levels of PAP or PSA. In addition, bone metastases are found to have an osteolytic rather than the osteoblastic appearance seen in adenocarcinoma.1 In a review of the scientific literature, 22 cases of PSCC with detailed clinical information were found (Table 1). Patients with PSCC ranged in age from 42 to 85 years with presenting symptoms including LUTS, acute urinary retention, urinary tract REVIEWS IN UROLOGY treatment and multimodal approaches are most commonly used with varying degrees of success (Table 1). Recently, Munoz and colleagues showed a 60-month survival rate using a multimodal approach in a patient presenting with extracapsular disease. Their patient underwent three courses of chemotherapy with cisplatin (CDDP), 75 mg/m2, on day 1 and continuous infusion with 5-fluorouracil (5-FU), 750 mg/m2, on days 1 to 5. This was followed by a full course of radiation therapy using a linear accelerator (19 MV photons) with a conventional four-field box technique up to 46 Gy to the pelvis with a 20 Gy boost dose to the prostate bed and 6 Gy to the prostate gland.8 Similarly, Imamura and associates treated a patient with radical cystoprostatectomy followed by adjuvant chemotherapy using the methotrexate (MTX), peplomycin (PEP), and CDDP regimen with a 60-month survival rate.9 Another promising outcome using multimodal therapy from Uchibayashi and coauthors resulted in a 21-month survival rate in a patient with organ-confined disease. This patient received 54 Gy of radiotherapy to his pelvis and intravenous (IV) administration of RiU_Apr2011_p56-60.qxd 4/13/11 10:53 AM Page 59 Squamous Cell Carcinoma of the Prostate Table 1 Overview of Cases of Primary Squamous Cell Carcinoma Age (years) Author Presenting Symptoms Metastases Length of Survival (Months) Treatment Multimodal Treatment 1 Mott LJ 59 Bony pain Osteolytic bone Bilateral orchiectomy, chemotherapy: DES, cobalt irradiation 5 Sarma DP et al15 69 AUR Local, late liver & pulmonary Pelvic exeneration pelvic and inguinal lymphadenectomy Majeed F et al11 71 Painless hematuria None RRP pelvic lymphadenectomy, mitoxantrone, cisplatin, XRT 18 6 Okada E et al12 65 AUR Iliac LNs Linac RT, PEP, CDDP 18 Uchibayashi T et al10 72 LUTS None Pelvic irradiation, bleomycin, cisplatinum 21 Imamura M et al9 54 Local Radical cystoprostatectomy, MPD regimen 60 Munoz F et al8 76 Pelvic relapse CDDP/5-FU, RT 60 AUR Surgical Treatment 16 Sharma SK et al 65 AUR None Bilateral orchiectomy 0 Di Pietro C et al17 72 AUR, prostatic abscess Iliac LN, liver TURP 0 Moskovitz B et al2 65 AUR, renal failure Local late pulmonary RRP, TURP of urethral mass 5 65 LUTS Perineal relapse TURP, APR, sigmoid colostomy, excision of pubic symphysis 12 5 Gray G et al Ulloa SA et al3 83 AUR Late pulmonary TURP 13 13 Little NA et al 56 Obstruction Periaortic/ pelvic LNs Bilateral pelvic lymphadenectomy, radical cystoprostatectomy, Kock pouch urinary diversion 25 Little NA et al13 55 Obstruction, hematuria None TURP, pelvic lymphadenectomy, radical cystoprostatectomy, total urethrectomy, and ileal conduit urinary diversion Mott LJ1 65 LUTS, weight loss Osteolytic bone Kanthan R et al18 (6 patients) 42-85 LUTS (2), obstruction (4), AUR (1) UTI (1) Lung (2), bone (1) Mohan H et al19 69 AUR Unknown Unknown Total 42-85 AUR/obstruction (15), LUTS (5), UTI (1), hematuria (2), bony pain (1) Bone (3), liver (2), lung (3), lymph nodes (3) CT (0), RT (1), surgery (8), multimodal (6) 40 Radiation Therapy Cobalt irradiation 8 Other RT (1), multimodal chemotherapy (4), TURP (3) 1-13 0-60 APR, abdomino-perineal resection; AUR, acute urinary retention; CDDP, cisplatin; CT, computed tomography; DES, diethylstilbestrol; 5-FU, 5-fluorouracil; LUTS, lower urinary tract symptoms; LN, lymph nodes; MPD, methotrexate, peplomycin, cisplatin; PEP, peplomycin; RRP, radical retropubic prostatectomy; RT, radiotherapy; TURP, transurethral resection of the prostate; UTI, urinary tract infection. VOL. 13 NO. 1 2011 REVIEWS IN UROLOGY 59 RiU_Apr2011_p56-60.qxd 4/13/11 10:53 AM Page 60 Squamous Cell Carcinoma of the Prostate continued bleomycin, 45 mg, with interarterial administration of CDDP.10 Both Majeed and colleagues and Okada and associates observed an 18-month disease-free survival rate with multimodal treatment. Majeed and colleagues used radical retropubic prostatectomy, bilateral pelvic lymphadenectomy with evidence of positive surgical margins followed by six cycles of mitoxantrone, 10 mg/m2, CDDP, 60 mg/m2, and external beam radiation, 2520 cGy, to the prostate bed.11 Okada and associates treated a patient with T3NIM0 PSCC with 50 Gy linac irradiation to the pelvis, and a boost to the prostate 10 Gy along with two cycles of chemotherapy consisting of an IV injection of PEP, 15 mg, weekly up to 150 mg, and CDDP, 80 mg/m2, every fourth week.12 Surgical treatment, reported by Little and associates, resulted in a 40-month and 25-month survival rate in two cases. Patients, one with organ-confined disease and one with lymph node involvement, underwent aggressive surgical treatment including radical cystoprostatectomy and bilateral pelvic lymphadenectomy. The patient with organ-confined disease underwent an additional total urethrectomy and ileal conduit urinary diversion, whereas the patient with metastatic disease had a Kock pouch urinary diversion.13 Experience using radiation therapy for the treatment of PSCC is limited. Some have even suggested that squamous cell carcinoma of the prostate may arise from metaplastic foci following previous radiation therapy.14 Only one case has been reported by Mott where a patient with findings of an osteolytic lesion on his right femur was treated with cobalt irradiation to the pelvis and femur with a survival of 8 months after presentation.1 From a recent review of reported cases, Munoz and colleagues concluded that radiation alone as a curative treatment of early-stage disease was only investigational.8 For locally advanced and metastatic disease, radiation therapy could be useful as part of a multimodal approach. Guidelines for doses of radiation therapy can be extrapolated from squamous cell carcinomas from other anatomic sites with similar patterns of behavior (ie, head and neck squamous cell carcinoma). Based on our patient’s unique presentation with extensive metastases and end-stage disease, a decision to use palliative radiation therapy was made. Although this treatment was not adequate to treat his extensive disease, it did provide symptomatic relief for the patient. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. References 1. 2. 3. Mott LJ. Squamous cell carcinoma of the prostate: report of 2 cases and review of the literature. J Urol. 1979;121:833-835. Moskovitz B, Munichor M, Bolkier M, Livne PM. Squamous cell carcinoma of the prostate. Urol Int. 1993;51:181-183. Ulloa SA, Iturregui JR, Amézquita M, Ortiz VN. Squamous cell carcinoma of the prostate: case 17. 18. 19. report and review of literature. Bol Asoc Med P R. 1997;89:192-194. Thompson GJ, Albers DD, Broders AC. Unusual carcinomas involving the prostate gland. J Urol. 1953;69:416-425. Gray GF Jr, Marshall VF. Squamous carcinoma of the prostate. J Urol. 1975;113:736-738. Sieracki JC. Epidermoid carcinoma of the human prostate, report of three cases. Lab Invest. 1955;4:232-240. Lager DJ, Goeken JA, Kemp JD, Robinson RA. Squamous metaplasia of the prostate. An immunohistochemical study. Am J Clin Pathol. 1988;90:597-601. Munoz F, Franco P, Ciammella P, et al. Squamous cell carcinoma of the prostate: long-term survival after combined chemo-radiation. Radiat Oncol. 2007;2:15. Imamura M, Nishiyama H, Ohmori K, Nishimura K. Squamous cell carcinoma of the prostate without evidence of recurrence 5 years after operation. Urol Int. 2000;65:122-124. Uchibayashi T, Hisazumi H, Hasegawa M, et al. Squamous cell carcinoma of the prostate. Scand J Urol Nephrol. 1997;31:223-224. Majeed F, Javed TA, Khan AU, Koerber RK. Primary squamous cell carcinoma of the prostate: a novel chemotherapy regimen. J Urol. 2002; 168:640. Okada E, Kamizaki H. Primary squamous cell carcinoma of the prostate. Int J Urol. 2000;7:347-350. Little NA, Wiener JS, Walther PJ, et al. Squamous cell carcinoma of the prostate: 2 cases of a rare malignancy and review of the literature. J Urol. 1993;149:137-139. Moyana TN. Adenosquamous carcinoma of the prostate. Am J Surg Pathol. 1987;11:403-407. Sarma DP, Weilbaecher TG, Moon TD. Squamous cell carcinoma of prostate. Urology. 1991;37: 260-262. Sharma SK, Malik AK, Bapna BC. Squamous cell carcinoma of prostate. Indian J Cancer. 1980;17:134-135. Di Pietro C, Celia A, De Stefani S, et al. Squamous cell carcinoma of the prostate. Arch Ital Urol Androl. 2006;78:75-76. Kanthan R, Torkian B. Squamous cell carcinoma of the prostate. A report of 6 cases. Urol Int. 2004;72:28-31. Mohan H, Bal A, Punia RP, Bawa AS. Squamous cell carcinoma of the prostate. Int J Urol. 2003;10:114-116. Main Points • Squamous cell carcinoma of the prostate is a rare tumor, making up 0.5% to 1% of all prostate carcinomas. Presenting symptoms range from lower urinary tract symptoms (ie, obstructive) to bony metastases. It is typically described as an aggressive cancer, with a median postdiagnosis survival of approximately 14 months. • Clinically, prostatic squamous cell carcinoma remains distinctly different from its more common counterpart, prostate adenocarcinoma. • Surgical treatment and multimodal approaches are most commonly used with varying degrees of success. 60 VOL. 13 NO. 1 2011 REVIEWS IN UROLOGY