Small Cell Carcinoma of the Prostate in an Elderly Patient: A Case Report and Review of the Literature.

Prostate cancer is the most common malignancy of men in the United States. Small-cell carcinoma (SCC), which typically presents as an aggressive lung malignancy, is a rare diagnosis within the setting of prostate cancer pathology. Due to its limited prevalence, little information regarding the treatment and prognosis of this disease in large populations is available. To date our current knowledge base is largely limited to case reports and retrospective case reviews. The mainstay of treatment for this particular histology most often involves a multimodality approach utilizing chemotherapy in conjunction with radiation therapy, androgen deprivation therapy, or prostatectomy. Here we present the case of an elderly 89-year-old Caucasian male who was diagnosed with SCC of the prostate. Despite proceeding with a course of definitive radiotherapy, the patient experienced rapid progression of disease and ultimately elected to discontinue radiation therapy and receive hospice care.

Introduction

Small cell carcinoma (SCC) is an uncommon and aggressive neoplasm most commonly diagnosed within the lung. Extrapulmonary SCC can be present in multiple organs, and its presence in the prostate accounts for approximately 10% of these cases.[1,2] It was initially described in 1977 by Wenk and colleagues, and remains infrequently discussed within the medical literature.[3,4] Due to its limited incidence, standard treatment guidelines remain undeveloped and most current treatment approaches are based largely on case reports and retrospective review series.[5,6] Notably SCC of the prostate is known for its highly aggressive nature with a median survival of approximately 10 months.[3,7] Prostate specific antigen (PSA) screening and progressively more effective treatment options have led to an increased prevalence of prostate cancer.[4,8] Despite these advances, the value of PSA screening remains indeterminate at best for SCC of the prostate, with most reviews showing limited positivity <25%.[3,9] The utilization of chemotherapy as the basis of treatment for SCC of the prostate has been well documented, with etoposide/cisplatin regimes derived from the treatment of SCC of the lung showing the greatest efficacy.[2,4,5,10] While the diagnosis of prostate cancer remains common, SCC of the prostate accounts for less than 2%.[4,8] Here, we present the case of an elderly 89-year-old Caucasian male diagnosed with SCC of the prostate following a transurethral resection of the prostate (TURP) procedure for urinary hesitancy. The patient’s age was a major factor in limiting his choice of treatment, and in his overall outcome.

Case Report

An 89-year-old Caucasian male who presented with urinary obstructive symptoms was found to have a normal digital rectal exam and a PSA of 0.72. His past medical history was significant for a stage 1, pT1N0M0, noninvasive, high-grade papillary urothelial cell carcinoma of the bladder three years prior, for which he had undergone transurethral resection of bladder tumor. He subsequently was treated with six cycles of intravesical bacillus Calmette-Guérin immunotherapy. Repeat biopsy of the bladder had revealed no evidence of malignancy. The patient had undergone close follow-up by his urologist consisting of abdominal/pelvic computed tomography (CT) scans, cystoscopy, and urine cytology which remained negative. After presenting with his new symptoms, the patient was recommended TURP for relief of his obstructive symptoms. The final pathology showed small cell carcinoma. Immunohist-ochemistry showed the tumor cells were strongly positive for synaptophysin and chromogranin, but negative for PSA, p63, and CK5/6. The pathologist did not identify adenocarcinoma or urothelial carcinoma in the TURP specimen. Further staging workup with a positron emission tomography/CT scan did not reveal any concerning evidence for metastatic disease, and a magnetic resonance imaging of the brain was also negative for evidence of intracranial metastasis. The patient’s urinary obstructive symptoms resolved following this procedure. The patient was discussed at length in a multidisciplinary tumor board, and not felt to be an optimal candidate for chemotherapy due to his advanced age and medical comorbidities.

The patient proceeded to treatment with radiation therapy alone, which was initiated with a definitive intent to deliver a dose of 7560 cGy with image guided radiotherapy (Figure 1). During his radiation therapy the patient experienced rapidly worsening constipation, and was noted to have an increased prostate size on digital rectal exam. He presented to the emergency department for worsening constipation where a CT of the abdomen and pelvis noted new celiac, periportal, and peripancreatic adenopathy along with moderate ascites consistent with metastatic disease (Figure 2). The patient discontinued his radiation therapy at that time, after completing 9 of his 42 scheduled treatments. The patient and his family decided to proceed with hospice treatment, and the patient passed away 3 months after his initial diagnosis.

Figure 1.

Axial computed tomography image showing the respective 7560, 7400, 7000, and 5000 cGy isodose lines for the patient’s planned course of image guided radiotherapy.

Figure 2.

Computed tomography image showing development of progressive metastatic disease with new periportal, periaortic, and peripancreatic adenopathy.

Discussion and Conclusions

SCC of the prostate is a rare malignancy with very low incidence (<2% of all prostate cancers) and continues to have a dismal prognosis despite advances in systemic therapy.[3,7,9] To date our knowledge of SCC of the prostate relies largely on retrospective institutional case series or larger retrospective database reviews (Table 1).[1,11-13] In a study by the University of Nebraska, 73.7% of patients with SCC of the prostate were diagnosed over the age of 65, and 39% were 75 or older when diagnosed.[12] Signs and symptoms often include obstructive uropathy, neurologic/constitutional symptoms, paraneoplastic syndromes, bone pain, hydronephrosis, abdominal pain, hematochezia, and hematuria depending on the involvement of malignancy. Additional clinical features of SCC of the prostate consist of an enlarged prostate, disproportionately low PSA levels in the presence of metastatic disease, limited response to hormone therapy, visceral metastases, and a high proportion of lytic bone lesions.[8,9] While value of testing PSA expression remains largely uncertain for SCC of the prostate, other markers including CD 56, chromogranin, synaptophysin, TTF-1, and CD 44 show much better specificity for SCC when compared to conventional immunohistochemical markers used for adenocarcinoma.[3,8,11]

Table 1.

Significant findings given for major database review articles, institutional reviews, and limited prospective studies.

Authors	Type of study	N	Median age	Median survival	Conclusions (months)	P value
Wang and Wang[12]	Retrospective SEER registry review (1973-2004).	259	72	CSS=19	Older age >75, concomitant high-grade adenocarcinoma, no prostatectomy were significant predictors of poor CSS.	≤0.007
Weiner et al.[6]	National Cancer Database review - localized SCC prostate (1998-2011).	287	70	OS=14.8	Local therapy (surgery or radiation) improved survival, advanced disease ≥cT3 negative prognostic factor.	≤0.011
Cohen et al.[4]	National Cancer Database review - metastatic SCC prostate (1998-2011).	379	70	OS=7.6	Older age and distant metastases increased risk of death, chemotherapy usage decreased the risk of death.	≤0.010
Guo et al.[2]	Clinicopathological Analysis, Chinese database review (1999-2011).	26	61	OS=8	CT only prognostic factor, 1 year survival 50.0% CT – 9.0% no CT.	≤0.007
Wang and Epstein[13]	Retrospective single Institution pathology review.	95	69	NA	Morphologic and immunohistochemical patterns of SCC. PSA, P501S, PSMA all negative ~60%.	NA
Papandreou et al.[10]	Phase II Study.	38	65	OS=10.5	Doxorubicin addition to etoposide/cisplatin increased toxicity without improving outcome, 7.9% grade-5 toxicity.	NA

CSS, cancer-specific survival; SCC, small-cell carcinoma; OS, overall survival; CT, chemotherapy; NA, not available; PSA, prostate-specific antigen; P501S, positive for prostein; PSMA, prostate-specific membrane antigen.

It is known that small cell lung carcinoma responds well to chemotherapy and radiation based on previous randomized control trials. We have extrapolated this data when treating SCC of the prostate to typically include chemotherapy with a platinum-containing doublet (i.e. cisplatin/etoposide).[9,10] Due to the aggressive nature of SCC of the prostate, chemotherapy remains the mainstay of treatment with radiation therapy/surgery more often utilized for limited stage disease or increased local control, which may improve survival based on some data.[3,6] Additional randomized trials have explored the addition of other systemic agents with limited to no benefit.[2,10] A research report that explored the clinical and pathological characteristics of SCC of the prostate found statistical evidence that survival time was closely related to chemotherapy administration. The one-year survival rate for patients treated with chemotherapy was 50% while those who did not receive treatment was 9%. Other factors, including age, were not statistically significant when correlated with survival time.[2,6]

While the statistical significance of the correlation of age to clinical outcome depends on the paper reviewed, it played a central role in the determination of our patient’s ability to undergo chemotherapy.[6,12] Due to our patient’s inability to receive chemotherapy, his clinical outcome was clearly affected. He had rapid progression of metastatic disease requiring hospital admission and discontinuation of radiation therapy altogether. If the patient were younger with a sufficient performance status to tolerate a multimodality approach with radiation and chemotherapy, it may have prolonged his life.