Advanced Prostate Cancer Survivorship Challenges and Issues

73 Advanced Prostate Cancer Survivorship Challenges and Issues

Jesus H. Hermosillo-Rodriguez and Nicholas Mitsiades

INTRODUCTION

Patients with metastatic prostate cancer can develop side effects from therapy that can impact their quality of life and potentially limit their lifespans. This chapter focuses on these issues.

METABOLIC AND CARDIOVASCULAR EFFECTS OF ANDROGEN DEPRIVATION THERAPY

Patients with prostate cancer on androgen deprivation therapy (ADT) can develop insulin resistance, diabetes mellitus, hyperlipidemia, osteoporosis, and cardiovascular disease (1). However, increased cardiac death related to ADT has been difficult to prove in randomized controlled trials. Regardless, men initiating ADT should be counseled on lifestyle modifications, including diet, exercise, smoking cessation, and weight loss. Pharmacologic therapy for these comorbidities should also be initiated if indicated and reasonable within the clinical setting.

COMMON PALLIATIVE CARE CHALLENGES IN PATIENTS WITH METASTATIC PROSTATE CANCER

• Fatigue: Frequently reported in patients receiving ADT. Multiple factors like the loss of lean muscle mass and increase in fat mass, chronic pain, psychological distress, and depression are potential contributors. Exercise with muscle-strengthening programs have been shown to reduce 74the frequency and severity of fatigue, and a combination of resistance training with aerobic training (15–20 minutes of cardiovascular exercise at 65%–80% of maximum heart rate—two to three times a week) can be recommended.

• Pain from bone metastases: The most common type of bone lesions are osteoblastic, causing pain and functional impairment and contributing to fatigue (2). Besides antitumor systemic therapy and bone-directed therapies that have been discussed in previous subchapters, other adjunct therapies can be used. Factors that are taken into account in the selection of therapy include performance status, life expectancies, disease state, and effect on quality of life:

▪ Analgesics: Usually the frontline therapy.

– Nonsteroidal anti-inflammatory drugs (NSAIDs).

– Opiates.

– Corticosteroids (3): The mechanism of action is likely related to decreased inflammation. The ideal agent, dose, and duration is unknown, but dexamethasone is commonly used due to its lower mineralocorticoid effect and long half-life, allowing once daily dosing (e.g., dexamethasone 4–8 mg PO daily).

– Neuropathic pain agents (4): Some patients with bone pain have neuropathic pain features and these agents may be a useful adjunct therapy in this setting.

▪ Surgery: Reserved typically for patients with impending or pathologic fracture. Bracing can be used for patients who are not candidates for surgery or have limited life expectancies.

▪ Radiation therapy: Usually indicated for focal symptomatic bone metastases. A single dose of 8 Gy may be sufficient for pain control.

▪ Nerve blocks: For special situations of focal pain, such as rib metastases.

▪ Ablation: Usually considered for patients who are not candidates for surgery or reirradiation.

▪ Percutaneous vertebral augmentation: May be prescribed for patients with pathologic vertebral fractures.

• Vasomotor symptoms: Most men on ADT will experience hot flashes. Although there are concerns that agents that are 75effective in women may not be as effective in men, agents that have shown some benefit in men with ADT-related hot flashes include:

▪ Progestins: Results superior to venlafaxine on a randomized, double-blind trial.

– Medroxyprogesterone 20 mg/day.

– Cyproterone 100 mg/day.

▪ Venlafaxine 75 mg/day.

▪ Gabapentin 900 mg daily.

▪ Clonidine at doses of 0.1, 0.2, or 0.4 mg daily (5).

• Sexual dysfunction: Counseling the patient and his partner regarding the expectations of the impact of ADT in sexual function is key. Although therapies including phosphodiesterase inhibitors, vacuum erection devices, intracorporal injection therapy, or penile prosthesis are beneficial for some patients with erectile dysfunction related to ADT, the evidence is limited regarding the effectiveness of such therapies in this setting.

• Osteoporosis: Men on chronic androgen ablation may develop osteoporosis. Supplementation with calcium and vitamin D and monitoring with serial bone density scans can help to prevent complications.

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