242 CHAPTER 6 Urological neoplasia
Palliative management of prostate cancer
Involvement of the acute pain team, palliative care physicians, and nurses is often necessary in the terminal phase of the illness to optimize quality of life.
Pain
Pain is undoubtedly the most debilitating symptom of advanced prostate cancer. The pathogenesis of this pain is poorly understood, but there is known to be increased osteoclastic and osteoblastic activity. Table 6.7 categorizes the pain syndromes and their management.
Radiation can be given for palliation of painful bony metastases rather than for curative intent (typical treatment 300 cGy in 10 divided doses). Strontium-89 and samarium-153 can palliate bone pain and are most useful for diffuse metastasis, but they can have an adverse effect on platelets in particular.
Spinal cord compression (see p. 457)
Lower urinary tract symptoms/urinary retention
A TURP may be required for bladder outflow obstruction (BOO) or retention. Instrumentation can be difficult if there is a bulky fixed prostate cancer. The bladder may be contracted due to disease involvement, causing misery even after relief of BOO. This may respond to anticholinergic therapy.
A long-term urethral or suprapubic catheter may be required for difficult voiding symptoms or recurrent retention.
Ureteral obstruction (see p. 456)
This is a urological oncological emergency. Locally advanced prostate cancer and bladder cancer may cause bilateral ureteral obstruction. The patient presents with symptoms and signs of renal failure or is anuric without a palpable bladder. Renal ultrasound will demonstrate bilateral hydronephrosis and an empty bladder.
After treating any life-threatening metabolic abnormalities such as hyperkalemia, the treatment options include bilateral percutaneous nephrostomies or ureteral stents. Insertion of retrograde ureteral stents in this scenario is often unsuccessful because tumor on the trigone obscures the location of the ureteral orifices.
Antegrade ureteral stenting following placement of nephrostomies is usually successful.
Unilateral ureteral obstruction
This is occasionally observed at presentation or on progression. If asymptomatic, this may be managed conservatively provided there is a normal contralateral kidney.
PALLIATIVE MANAGEMENT OF PROSTATE CANCER 243
Anemia, thrombocytopenia, and coagulopathy
For some patients, hemoglobin levels drop rapidly and they become symptomatic on a regular basis. Some of this drop may be due to the androgen ablation. In more advanced disease, bone marrow replacement is the cause. This tends to be normochromic and normocytic and often occurs without other symptoms and with normal renal function.
Such patients require regular transfusions. Platelet transfusions are rarely required for bleeding.
Terminal patients may develop a clinical picture similar to disseminated intravascular coagulation (DIC) leading to problematic hematuria.
Table 6.7 Pain syndromes and their management
Pain type |
Initial management |
Other options |
|
|
Focal bone pain |
Medical: simple, NSAIDs, |
Surgical fixation of |
|
|
|
opiates Single-shot |
pathological fracture |
|
|
|
radiotherapy, 800 cGy (75% |
or extensive lytic |
|
|
|
respond up to 6 months) |
metastasis |
|
|
|
|
|||
Diffuse bone pain |
Medical: NSAIDs, opiates |
Steroids; |
|
|
|
||||
|
Multishot radiotherapy or |
bisphosphonates; |
|
|
|
radiopharmaceutical (e.g., |
chemotherapy |
|
|
|
Strontium89) |
|
|
|
Epidural metastasis and |
See p. 457 |
|
|
|
cord compression |
|
|
|
|
Plexopathies (rare— |
Medical: NSAIDs, opiates |
Tricyclics; |
|
|
caused by direct tumor |
Radiotherapy; nerve blocks |
anticonvulsants |
|
|
extension) |
|
|
|
|
Other pain syndromes: |
Radiotherapy Medical: |
Intrathecal |
|
|
skull/cranial nerve, liver, |
NSAIDs, opiates, steroids |
chemotherapy for |
|
|
rectum/perineum |
|
meningeal involvement |
|
|
|
|
|
|
|
244 CHAPTER 6 Urological neoplasia
Prostate cancer: prevention; complementary and alternative therapies
As many as 27% of men in their third decade have histological prostate cancer, even though the disease is rarely detected clinically <50 years of age. Further, a likely premalignant lesion (high-grade PIN) has been identified. This suggests there may be opportunity for preventative strategies.
Dietary intervention
There are many epidemiological and laboratory data supporting dietary interventions, though randomized prospective trials are awaited.
High-fat diets, particularly those rich in saturated fat and omega-6 fatty acids, are linked to increased risk of prostate cancer diagnosis.
Soy products contain phytoestrogens including the isoflavone genistein. Genistein is a natural inhibitor of tyrosine kinase receptors and inhibits prostate cancer cell lines. Chinese Americans have a 24-fold risk of developing prostate cancer compared to that of native Chinese, perhaps because of a difference in their respective diets.
Lycopene, present in cooked tomatoes and tomato products, is thought to reduce risk of prostate cancer progression and inhibit cell lines.
Vitamins A (retinoids) and D both inhibit growth of prostate cell lines, and vitamin D receptor polymorphisms appear to predispose certain individuals to prostate cancer.
The SELECT Trial is the largest cancer prevention trial to date that studied the effect of selenium and vitamin E, alone and in combination, on reducing the risk of prostate cancer. Preliminary data suggested that these agents might be effective. Unfortunately, the trial did not demonstrate an advantage for these agents; there was an early suggestion of an increased health risk with these agents.1
Studies from the UK, Europe, and the United States have shown that 25–40% of prostate cancer patients are taking some form of complementary therapy, most without informing their doctor. These can occasionally be harmful: for example, a Chinese herb mixture called PC-SPES, now withdrawn, frequently caused thromboembolism to contamination with estrogenic compounds that likely accounted for some of its reported activity.
Smoking has been shown in population studies to be significantly associated not with prostate cancer diagnosis but with fatal prostate cancer. No definite link exists between alcohol consumption, vasectomy, or sexual activity and prostate cancer.
Studies have suggested an increased risk associated with early sexual activity and a reduced risk associated with frequent masturbation, but these require substantiation.
1 Lippman SM, Klein EA, Goodman PJ, .et al. (2009). Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA 301(1):39–51.
PROSTATE CANCER 245
Chemoprevention with antiandrogens
Given that prostate cancer is believed to start as an androgen-dependent disease, interest in its prevention has also focused on antiandrogens. While nonsteroidal antiandrogens would have unacceptable side effects and cost, the 5-A reductase inhibitors could be feasible chemoprevention agents as they are already used for the treatment of symptomatic BPH.
The Prostate Cancer Prevention Trial (PCPT) recruited 18,000 men who had no clinical or biochemical evidence of prostate cancer. They were randomized to placebo or finasteride 5 mg daily for up to 7 years. The men were offered biopsy if they developed a rising PSA or an abnormality on DRE, or at end of study.
Prostate cancer was detected in 24% and 18% of participants in placebo and finasteride arms, respectively, a 25% reduction in prostate cancer. However, Gleason 7+ cancers were significantly more frequent in the finasteride arm. This increase in high-grade cancer has been ascribed to sampling artifact due to the reduction in the size of the prostate.
The REDUCE trial in over 8000 men used the 5-A reductase inhibitor dutasteride in a placebo-controlled trial to attempt to reduce the risk of prostate cancer in a group of high-risk men (i.e., previous negative biopsy). Follow-up biopsy was performed at 2 and 4 years and for cause (i.e., rising PSA, new prostate nodule). The study demonstrated a 23% reduction in cancer with improvements in BPH-related outcomes. There was no suggestion of increased Gleason score cancers.
A 2008 joint recommendation of the American Society of Clinical Oncology (ASCO) and the American Urological Association states that healthy men who have a prostate-specific antigen score of 3.0 or lower, have no signs of prostate cancer, and plan to be screened regularly for the disease should discuss with their physician whether to take 5-Areductase inhibitors to decrease their risk of developing prostate cancer.2
2 Kramer BS, et al. (2009). Use of 5-A-reductase inhibitors for prostate cancer chemoprevention: American Society of Clinical Oncology/American Urological Association 2008 Clinical Practice Guideline. J Urol 181:1642–1657.