Case 2: Adenocarcinoma of the Prostate
A 68-year-old retired chef initially complained of frequency of micturition, urinary urgency, and hesitancy associated with a weak stream. Over the past several weeks, he has reported a few episodes of hematuria and incontinence. In addition to his urologic symptoms, the patient complained of low-grade, constant back pain and bouts of constipation. A digital rectal examination revealed the patient has an enlarged prostate gland with several palpably discreet nodules. His past medical history was unremarkable.
Laboratory Studies
The patient had a prostate-specific antigen (PSA) level of 95 ng/mL (range: 0.0–4.0 ng/mL), while a similar determination 6 years earlier showed a PSA of 1.5 ng/mL. His hemoglobin was 15 g/dL (range: 13.2–17.1 g/dL), hematocrit 43% (range: 38.5–50%), white blood cell 7,500/mm3, normal differential, platelets 250,000/mm3, blood urea nitrogen 15 mg/dL (normal range: 7–30 mg/dL), and creatinine level 1.0 mg/dL (range: 0.5–1.4 mg/dL). Alkaline phosphatase and liver function tests were all within normal range.
Imaging Studies
A transrectal ultrasonography-guided biopsy was performed. During the biopsy procedure, the ultrasound revealed many hypoechoic or echopenic areas within the homogeneous parenchyma of the gland (Figure 1). MRI of the spine revealed a metastatic lesion at the level of T10, showing infiltration of the entire vertebral body marrow space, which was suggestive of metastasis (Figure 2). There was no evidence of cord compression; however, there was signal activity in proximity to the corresponding nerve root. Radionuclide scintigraphy demonstrated several areas along the spine suggestive of metastatic bone disease, which were consistent with evidence derived from MRI studies (Figure 3). Chest, abdominal, and pelvic CT scans demonstrated no evidence of nodal or visceral metastasis; however, the prostate was enlarged and irregular with extensive deformity of the bladder neck.
Figure 1
Figure 1
Sonogram of the patient’s prostate gland. Arrows indicate hypoechoic areas within the homogenous parenchyma, demonstrating widespread neoplastic disease, which has metastasized beyond the capsule.
Figure 2
Figure 2
MRI of spine revealing metastatic infiltration of entire T10 vertebral body marrow space.
Figure 3
Figure 3
Radionuclide bone scan showing metastatic bone disease secondary to prostatic adenocarcinoma. Osseous sites of increased uptake can be identified in the spine (T1 to T12) and ribs.
Staging
In the Tumor, Nodes, Metastases staging system, the tumor had extended bilaterally through the prostatic capsule (T3b), and metastasis was found in bone (M1b). The patient was staged as stage D2 with extensive local disease.
Biopsy Results
Histologic evaluation of the biopsy specimens revealed a Gleason score of 8 (4 + 4) and adenocarcinoma in 7 of 12 multiple cores, representing 60% of the biopsied material (Figure 4).
Figure 4
Figure 4
Biopsy specimen (hematoxylin and eosin 1000X) reveals adenocarcinoma of the prostate gland with a Gleason score 8 (4 + 4) representing 60% of the tissue sample. This neoplasm was characterized by well-defined acini arranged in a back-to- back formation. ...
Diagnosis
Based upon prostate biopsy evaluation and ultrasound images, radionuclide scintigraphy, and MRI studies, a diagnosis was made of advanced prostatic adenocarcinoma with metastases to the bone.
Treatment Options
In view of the advanced stage of the disease and evidence of distant metastasis, the primary treatment modality for this patient was systemic therapy. The pattern of metastatic disease, that is, extensive local involvement and likely extension into the bladder, as well as the virtual replacement of a vertebral body with disease in close anatomic proximity to the nerve root, suggested that in addition to the standard systemic approach, local palliative measures should be considered. Importantly, the constellation of signs and symptoms of this patient’s disease underscored the critical need to select a systemic treatment that produced a rapid decline of serum testosterone and consequently allowed prompt control of the disease. He was, therefore, treated with abarelix, 12 a gonadotropin-releasing hormone (GnRH) antagonist.
External Beam Radiation Therapy
The role of radiation therapy in the setting of this patient’s disease was primarily palliative and focused on the control of local obstructive problems. After a 3-month treatment with abarelix, the patient experienced a significant improvement of his urological symptoms. To further improve local control and relief of obstruction, a course of palliative external beam radiation was administered. A total of 40 treatments over an 8-week period consisted of 3-dimensional conformal radiation therapy, which delivered a total 6570 Gy dose of radiation to the prostate.
Treatment of Bone Metastases
Abarelix produced a rapid decline of the serum PSA to < 0.1 ng/mL after 3 months of treatment. This was associated with major improvements in pain. External beam radiation to the involved vertebral body was subsequently delivered to enhance local control and to minimize the possibility of future neurological complications resulting from spinal cord or nerveroot compression. To further improve the management of bone metastasis, the patient was initiated on bisphosphonate treatments with intravenous infusions of zoledronic acid.
Follow-Up
Follow-up at 6 months showed a healthy-looking patient with PSA level < 0.1 ng/mL. Long-term gonadal suppression with abarelix was planned and the patient was continued with serial physical exams, routine blood evaluations, including serum PSA determinations at regular intervals (every 2 to 3 months), and radiological assessments every 6 to 12 months or as clinically indicated.
Discussion
The use of androgen ablation in the treatment of advanced cancer of the prostate has been standard treatment for many years.13 The role for local radiation therapy in patients with distant metastasis is primarily palliative. In this case, it was elected to proceed with external beam radiation to metastatic sites primarily to increase local control of severely involved sites associated with major symptoms and impending serious life- and functionally threatening complications. Specifically, there was evidence of significant anatomic bladder-outlet obstruction and potentially impending neurological compromise due to local extension of disease to the radicular space. Furthermore, the patient demonstrated significant symptoms associated with these involved metastatic sites.13,14 Androgen ablative therapy with abarelix was shown to be highly effective in reducing the PSA to < 0.1 ng/mL in a short period of time. The use of a GnRH antagonist (abarelix) in this setting was critical in view of the severity of symptoms and need for rapid therapeutic effects. In addition, the flare phenomenon (reported in 10% to 30% of patients treated with luteinizing hormone-releasing hormone agonists) is avoided with abarelix, which is a major factor in the selection of GnRH antagonists as the initial treatment approach.13,15
The prognosis for this patient is poor due to the extensive degree of metastatic bone involvement.13 Data derived from large prospective randomized trials indicate that the median time to progression with conventional forms of androgen ablation approaches ranges between 12 to 18 months and the median survival is around 30 to 36 months.13,15 The main issue centers around the development of hormone resistance. Evolving data with new chemotherapeutic approaches suggest that nonhormonal treatment plays a significant role in the treatment of patients with hormone-resistant prostate cancer and may be a major addition to hormonal treatment in the initial management of patients with metastatic disease.
[Mario A. Eisenberger, MD]