Quality of Individual Studies and Determination of Evidence Strength. The systematic review included 303 eligible studies that addressed the pre-identified questions of interest. A large body of evidence evaluated established chemotherapy agents such as docetaxel [19 Randomized controlled trials (RCTs)], estramustine (5 RCTs) and mitoxantrone (5 RCTs). Randomized evidence was also available for various immunotherapies (8 RCTs), therapies targeting the androgen signaling pathway (12 RCTs), radiotherapy and radiopharmaceuticals (4 RCTs) and bone-targeting therapies (6 RCTs). The quality of these trials was acceptable overall and ranged from moderate to low risk of bias. All the remaining studies were otherwise non-randomized (observational) and considered to be at high risk of bias.
During conventional pharmacologic dose corticosteroid therapy, ACTH production is inhibited with subsequent suppression of cortisol production by the adrenal cortex. Recovery time for normal HPA activity is variable depending upon the dose and duration of treatment. During this time the patient is vulnerable to any stressful situation. Although it has been shown that there is considerably less adrenal suppression following a single morning dose of prednisolone (10 mg) as opposed to a quarter of that dose administered every six hours, there is evidence that some suppressive effect on adrenal activity may be carried over into the following day when pharmacologic doses are used. Further, it has been shown that a single dose of certain corticosteroids will produce adrenal cortical suppression for two or more days. Other corticoids, including methylprednisolone, hydrocortisone, prednisone, and prednisolone, are considered to be short acting (producing adrenal cortical suppression for 1¼ to 1½ days following a single dose) and thus are recommended for alternate day therapy.
Steroid injections are commonly used to treat rotator cuff tendinopathy, but controlled studies have demonstrated modest benefit, particularly in the long term. 34 Steroid injections should be reserved for patients who have discomfort that would limit them from engaging in rehabilitative exercises. Injections into the gluteal muscle versus guided injections into the subacromial bursa have demonstrated similar levels of pain relief. 35 Surgical options are available for patients with persistent symptoms, or for patients in whom function cannot be maintained.