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Most hormone dependent cancers become resistant to treatment after one to three years and resume growth despite hormone therapy. Previously considered "hormone-refractory prostate cancer" or "androgen-independent prostate cancer", the term castration-resistant has replaced "hormone refractory" because while they are no longer responsive to castration treatment (reduction of available androgen/testosterone/DHT by chemical or surgical means), these cancers still show reliance upon hormones for androgen receptor activation.
The cancer chemotherapic docetaxel has been used as treatment for CRPC with a median survival benefit of 2 to 3 months. A second-line chemotherapy treatment is cabazitaxel. A combination of bevacizumab, docetaxel, thalidomide and prednisone appears effective in the treatment of CRPC.
The immunotherapy treatment with sipuleucel-T in CRPC increases survival by 4 months. The second line hormonal therapy abiraterone increases survival by 4.6 months when compared to placebo. Enzalutamide is another second line hormonal agent with a 5-month survival advantage over placebo. Both abiraterone and enzalutamide are currently being tested in clinical trials in those with CRPC who have not previously received chemotherapy.
Only a subset of people respond to androgen signaling blocking drugs and certain cells with characteristics resembling stem cells remain unaffected. Therefore, the desire to improve outcome of people with CRPC has resulted in the claims of increasing doses further or combination therapy with synergistic androgen signaling blocking agents. But even these combination will not affect stem-like cells that do not exhibit androgen signaling. It is possible that for further advances, a combination of androgen signaling blocking agent with stem-like cell directed differentiation therapy drug would prove ideal.
Palliative care is medical care which focuses on treatment of symptoms of serious illness, like cancer, and improving quality of life. One of the goals of treatment in palliative care is symptom control rather than a cure of the underlying cancer. Pain is common in metastatic prostate cancer, and cancer pain related to bone metastases can be treated with bisphosphonates, medications such as opioids, and palliative radiation therapy to known metastases. Spinal cord compression can occur with metastases to the spine and can be treated with steroids, surgery, or radiation therapy. Other symptoms that can be addressed through palliative care include fatigue, delirium, lymphedema in the scrotum or penis, nausea, vomiting, and weight loss.
Selective α-blockers are the most common choice for initial therapy. They include alfuzosin, doxazosin, silodosin, tamsulosin, and terazosin. They have a small to moderate benefit. All five are equally effective but have slightly different side effect profiles. Alpha blockers relax smooth muscle in the prostate and the bladder neck, thus decreasing the blockage of urine flow. Common side effects of alpha blockers include orthostatic hypotension (a head rush or dizzy spell when standing up or stretching), ejaculation changes, erectile dysfunction, headaches, nasal congestion, and weakness.
Tamsulosin and silodosin are selective α1 receptor blockers that preferentially bind to the α1A receptor in the prostate instead of the α1B receptor in the blood vessels. Less-selective α1 receptor blockers such as terazosin and doxazosin may lower blood pressure. The older, less selective α1-adrenergic blocker prazosin is not a first line choice for either high blood pressure or prostatic hyperplasia; it is a choice for patients who present with both problems at the same time. The older, broadly non-selective alpha blocker medications such as phenoxybenzamine are not recommended for control of BPH. Non-selective alpha blockers such as terazosin and doxazosin may also require slow dose adjustments as they can lower blood pressure and cause syncope (fainting) if the response to the medication is too strong.
The 5α-reductase inhibitors finasteride and dutasteride may also be used in men with BPH. These medications inhibit the 5α-reductase enzyme, which, in turn, inhibits production of DHT, a hormone responsible for enlarging the prostate. Effects may take longer to appear than alpha blockers, but they persist for many years. When used together with alpha blockers, no benefit was reported in short-term trials, but in a longer term study (3–4 years) there was a greater reduction in BPH progression to acute urinary retention and surgery than with either agent alone, especially in patients were more severe symptoms and larger prostates. Other trials have confirmed reductions in symptoms, within 6 months in one trial, an effect that was maintained after withdrawal of the alpha blocker. Side effects include decreased libido and ejaculatory or erectile dysfunction. The 5α-reductase inhibitors are contraindicated in pregnant women because of their teratogenicity due to interference with fetal testosterone metabolism, and as a precaution, pregnant women should not handle crushed or broken tablets.
The goals of the treatment for bone metastases include pain control, prevention and treatment of fractures, maintenance of patient function, and local tumor control. Treatment options are determined by multiple factors, including performance status, life expectancy, impact on quality of life, and overall status of clinical disease.
Pain management
The World Health Organization's pain ladder was designed for the management of cancer-associated pain, and mainly involves various strength of opioids. Mild pain or breakthrough pain may be treated with nonsteroidal anti-inflammatory drugs.
Other treatments include bisphosphonates, corticosteroids, radiotherapy, and radionucleotides.
Percutaneous osteoplasty involves the use of bone cement to reduce pain and improve mobility. In palliative therapy, the main options are external radiation and radiopharmaceuticals. High-intensity focused ultrasound (HIFU) has CE approval for palliative care for bone metastasis, though treatments are still in investigatory phases as more information is needed to study effectiveness in order to obtain full approval in countries such as the USA.
Thermal ablation techniques are increasingly being used in the palliative treatment of painful metastatic bone disease. Although the majority of patients experience complete or partial relief of pain following external radiation therapy, the effect is not immediate and has been shown in some studies to be transient in more than half of patients. For patients who are not eligible or do not respond to traditional therapies ( i.e. radiation therapy, chemotherapy, palliative surgery, bisphosphonates or analgesic medications), thermal ablation techniques have been explored as alternatives for pain reduction. Several multi-center clinical trials studying the efficacy of radiofrequency ablation in the treatment of moderate to severe pain in patients with metastatic bone disease have shown significant decreases in patient reported pain after treatment. These studies are limited, however, to patients with one or two metastatic sites; pain from multiple tumors can be difficult to localize for directed therapy. More recently, cryoablation has also been explored as a potentially effective alternative as the area of destruction created by this technique can be monitored more effectively by CT than radiofrequency ablation, a potential advantage when treating tumors adjacent to critical structures.
Monthly injections of radium-223 chloride (as Xofigo, formerly called Alpharadin) have
been approved by the FDA in May 2013 for castration-resistant prostate cancer (CRPC) with bone metastases.
A Cochrane review of calcitonin for the treatment of metastatic bone pain indicated no benefit in reduction of bone pain, complications, or quality of life.
HGPIN in isolation does not require treatment. In prostate biopsies it is not predictive of prostate cancer in one year if the prostate was well-sampled, i.e. if there were 8 or more cores.
The exact timing of repeat biopsies remains an area of controversy, as the time required for, and probability of HGPIN transformations to prostate cancer are not well understood.
Tamoxifen, a selective estrogen receptor modulator (SERM) with antiestrogenic actions in breast tissue and estrogenic actions in bone, has been found to be highly effective in preventing and reversing bicalutamide-induced gynecomastia in men. Moreover, in contrast to analogues (which also alleviate bicalutamide-induced gynecomastia), tamoxifen poses minimal risk of accelerated bone loss and osteoporosis. For reasons that are unclear, anastrozole, an aromatase inhibitor (or an inhibitor of estrogen biosynthesis), has been found to be much less effective in comparison to tamoxifen for treating bicalutamide-induced gynecomastia. A systematic review of -induced gynecomastia and breast tenderness concluded that tamoxifen (10–20 mg/day) and radiotherapy could effectively manage the side effect without relevant adverse effects, though with tamoxifen showing superior effectiveness. Surgical breast reduction may also be employed to correct bicalutamide-induced gynecomastia.
These lesions rarely require surgery unless they are symptomatic or the diagnosis is in question. Since these lesions do not have malignant potential, long-term observation is unnecessary. Surgery can include the removal of the head of the pancreas (a pancreaticoduodenectomy), removal of the body and tail of the pancreas (a distal pancreatectomy), or rarely removal of the entire pancreas (a total pancreatectomy). In selected cases the surgery can be performed using minimally invasive techniques such as laparoscopy.
Combination of bicalutamide with medical (i.e., a analogue) or surgical castration modifies the side effect profile of bicalutamide. Some of its side effects, including breast pain/tenderness and gynecomastia, are far less likely to occur when the drug is combined with a analogue, while certain other side effects, including hot flashes, depression, fatigue, and sexual dysfunction, occur much more frequently in combination with a analogue. It is thought that this is due to the suppression of estrogen levels (in addition to androgen levels) by analogues, as estrogen may compensate for various negative central effects of androgen deprivation. If bicalutamide is combined with a analogue or surgical castration, the elevation of androgen and estrogen levels in men caused by bicalutamide will be prevented and the side effects of excessive estrogens, namely gynecomastia, will be reduced. However, due to the loss of estrogen, bone loss will accelerate and the risk of osteoporosis developing with long-term therapy will increase.
The treatment of choice for main-duct IPMNs is resection due to approximately 50% chance of malignancy. Side-branch IPMNs are occasionally monitored with regular CT or MRIs, but most are eventually resected, with a 30% rate of malignancy in these resected tumors. Survival 5 years after resection of an IPMN without malignancy is approximately 80%, 85% with malignancy but no lymph node spread and 0% with malignancy spreading to lymph nodes. Surgery can include the removal of the head of the pancreas (a pancreaticoduodenectomy), removal of the body and tail of the pancreas (a distal pancreatectomy), or rarely removal of the entire pancreas (a total pancreatectomy). In selected cases the surgery can be performed using minimally invasive techniques such as laparoscopy or robotic surgery. A study using Surveillance, Epidemiology, and End Result Registry (SEER) data suggested that increased lymph node counts harvested during the surgery were associated with better survival in invasive IPMN patients.
In ES-SCLC, combination chemotherapy is the standard of care, with radiotherapy added only to palliate symptoms such as dyspnea, pain from liver or bone metastases, or for treatment of brain metastases, which, in small-cell lung carcinoma, typically have a rapid, if temporary, response to whole brain radiotherapy.
Combination chemotherapy consists of a wide variety of agents, including cisplatin, cyclophosphamide, vincristine and carboplatin. Response rates are high even in extensive disease, with between 15% and 30% of subjects having a complete response to combination chemotherapy, and the vast majority having at least some objective response. Responses in ES-SCLC are often of short duration, however.
If complete response to chemotherapy occurs in a subject with SCLC, then prophylactic cranial irradiation (PCI) is often used in an attempt to prevent the emergence of brain metastases. Although this treatment is often effective, it can cause hair loss and fatigue. Prospective randomized trials with almost two years follow-up have not shown neurocognitive ill-effects. Meta-analyses of randomized trials confirm that PCI provides significant survival benefits.
Thyroidectomy and neck dissection show good results in early stages of SCTC. However, due to highly aggressive phenotype, surgical treatment is not always possible. The SCTC is a radioiodine-refractory tumor. Radiotherapy might be effective in certain cases, resulting in relatively better survival rate and quality of life. Vincristine, Adriamycin, and bleomycin are used for adjuvant chemotherapy, but their effects are not good enough according to published series.
In cases of LS-SCLC, combination chemotherapy (often including cyclophosphamide, cisplatinum, doxorubicin, etoposide, vincristine and/or paclitaxel) is administered together with concurrent chest radiotherapy (RT).
Chest RT has been shown to improve survival in LS-SCLC.
Exceptionally high objective initial response rates (RR) of between 60% and 90% are seen in LS-SCLC using chemotherapy alone, with between 45% and 75% of individuals showing a "complete response" (CR), which is defined as the disappearance of all radiological and clinical signs of tumor. However, relapse rate remains high, and median survival is only 18 to 24 months.
Because SCLC usually metastasizes widely very early on in the natural history of the tumor, and because nearly all cases respond dramatically to chemotherapy and/or radiotherapy, there has been little role for surgery in this disease since the 1970s. However, recent work suggests that in cases of small, asymptomatic, node-negative SCLC's ("very limited stage"), surgical excision may improve survival when used prior to chemotherapy ("adjuvant chemotherapy").
In urologic pathology, high-grade prostatic intraepithelial neoplasia, abbreviated HGPIN, is an abnormality of prostatic glands and believed to precede the development of prostate adenocarcinoma (the most common form of prostate cancer).
It may be referred to simply as prostatic intraepithelial neoplasia (abbreviated as PIN). It is considered to be a pre-malignancy, or carcinoma in situ, of the prostatic glands.
Identifying and treatment the underlying malignancy constitutes an uptime approach. Topical 5-fluorouracil may occasionally be help, as may oral retinoids, topical steroids, vitamin A acid, urea, salicylic acid, podophyllotoxin, and cryodestruction employing liquid.
As the condition is quite rare, opinions among experts about how to treat OKCs differ.
Treatment options:
- Wide (local) surgical excision.
- Marsupialization - the surgical opening of the (OKC) cavity and a creation of a marsupial-like pouch, so that the cavity is in contact with the outside for an extended period, e.g. three months.
- Curettage (simple excision & scrape-out of cavity).
- Peripheral ostectomy after curettage and/or enucleation.
- Simple excision.
- Carnoy's solution - usually used in conjunction with excision.
- Enucleation and cryotherapy
Improvement usually parallels that of the cancer, whether surgical or chemotherapeutic. Generalization of the associated visceral malignancy may worsen the eruption.
Treatment of a thyroid nodule depends on many things including size of the nodule, age of the patient, the type of thyroid cancer, and whether or not it has spread to other tissues in the body.
If the nodule is benign, patients may receive thyroxine therapy to suppress thyroid-stimulating hormone and should be reevaluated in 6 months. However, if the benign nodule is inhibiting the patient's normal functions of life; such as breathing, speaking, or swallowing, the thyroid may need to be removed.
Sometimes only part of the thyroid is removed in an attempt to avoid causing hypothyroidism. There's still a risk of hypothyroidism though, as the remaining thyroid tissue may not be able to produce enough hormones in the long-run.
If the nodule is malignant or has indeterminate cytologic features, it may require surgery. A thyroidectomy is a medium risk surgery that can result complications if not performed correctly. Problems with the voice, nerve or muscular damage, or bleeding from a lacerated blood vessel are rare but serious complications that may occur. After removing the thyroid, the patient must be supplied with a replacement hormone for the rest of their life. This is commonly a daily oral medication prescribed by their endocrinologist.
Radioactive iodine-131 is used in patients with papillary or follicular thyroid cancer for ablation of residual thyroid tissue after surgery and for the treatment of thyroid cancer. Patients with medullary, anaplastic, and most Hurthle cell cancers do not benefit from this therapy. External irradiation may be used when the cancer is unresectable, when it recurs after resection, or to relieve pain from bone metastasis.
A urogenital neoplasm is a tumor of the urogenital system.
Types include:
- Cancer of the breast and female genital organs: (Breast cancer, Vulvar cancer, Vaginal cancer, Cervical cancer, Uterine cancer, Endometrial cancer, Ovarian cancer)
- Cancer of the male genital organs (Carcinoma of the penis, Prostate cancer, Testicular cancer)
- Cancer of the urinary organs (Renal cell carcinoma, Bladder cancer)
A hormone-sensitive cancer, or hormone-dependent cancer, is a type of cancer that is dependent on a hormone for growth and/or survival. Examples include breast cancer, which is dependent on estrogens like estradiol, and prostate cancer, which is dependent on androgens like testosterone.
IgG4-related disease responds well, and often dramatically, to glucocorticoid therapy, provided that advanced fibrotic lesions have not resulted in irreversible damage, and this has included resolution of radiologic findings. Men given glucocorticoids to treat IgG4-related disease at other anatomical sites sometimes report relief of their lower urinary tract symptoms, suggesting that IgG4-related prostatitis may be underdiagnosed.
Cases are however likely to get misdiagnosed as benign prostatic hyperplasia and to get treated alternatively with medications such as alpha blockers. The efficacy of alpha blockers in IgG4-related prostatitis remains unclear.
A number of medications can be used to treat this disorder. Alpha blockers and/or antibiotics appear to be the most effective with NSAIDs such as ibuprofen providing lesser benefit.
- Treatment with antibiotics is controversial. Some have found benefits in symptoms while others have questioned the utility of a trial of antibiotics. Antibiotics are known to have anti-inflammatory properties and this has been suggested as an explanation for their partial efficacy in treating CPPS. Antibiotics such as fluoroquinolones, tetracyclines, and macrolides have direct anti-inflammatory properties in the absence of infection, blocking inflammatory chemical signals (cytokines) such as interleukin-1 (IL-1), interleukin-8 and tumor necrosis factor (TNF), which coincidentally are the same cytokines found to be elevated in the semen and EPS of men with chronic prostatitis.
- The effectiveness of alpha blockers (tamsulosin, alfuzosin) is questionable in men with CPPS. A 2006 meta-analysis found that they are moderately beneficial when the duration of therapy was at least 3 months.
- An estrogen reabsorption inhibitor such as mepartricin improves voiding, reduces urological pain and improves quality of life in patients with chronic non-bacterial prostatitis.
- Therapies that have not been properly evaluated in clinical trials although there is supportive anecdotal evidence include gabapentin, benzodiazepines, and amitriptyline.
Breast diseases can be classified either with disorders of the integument, or disorders of the reproductive system. A majority of breast diseases are noncancerous.
Surgical excision of the lesion is done, and depending upon the clinical circumstances, this may or may not involve removal of the involved tooth. With incomplete removal, recurrence is common; some surgeons advocate curettage after extraction of teeth to decrease the overall rate of recurrence.
Transurethral needle ablation of the prostate (TUNA) has been shown to be ineffective in trials.