What is desmoplastic resistant prostate cancer?
Prostate cancer is often effective when initially treated with denervation because the prostate cancer cells are still androgen-dependent. As the treatment lengthens, the prostate cancer cells begin to become androgen-independent, and thus develop into denervation-resistant prostate cancer (CRPC).
CRPC is defined in professional prostate cancer guidelines as prostate cancer that progresses despite initial continuous androgen deprivation therapy (ADT). 2 conditions need to be met simultaneously:
- Serum testosterone at depleted levels (<50 ng/mL or <1.7 nmol/L);
- 3 consecutive PSA rises at 1-week intervals of more than 50% from the nadir.
Statistically, metastatic prostate cancer tends to become progressively non-dependent on hormones and develop CRPC after a median remission of 18 to 24 months on endocrine therapy, although there are certainly some prostate cancer cells that are non-dependent on androgens at the time of initial treatment that can also become CRPC.
Principles of treatment for desmoplastic-resistant prostate cancer
Although desmoplastic-resistant prostate cancer becomes androgen non-dependent, the androgen receptor remains active and androgen suppressive therapy must be continued. Therefore, the principles of systemic therapy for CRPC are continuation of endocrine agents to ensure that serum testosterone is maintained at depot levels, chemotherapy to improve symptoms such as pain and malaise and prolong survival, and bisphosphonates to prevent bone-related events in patients with bone metastases.
There are several regimens of chemotherapy, including docetaxel regimens and mitoxantrone regimens. Chemotherapy kills normal cells in addition to cancer cells, so its adverse effects are heavy, causing diarrhea, hair loss, fatigue, and increased risk of infection, which can be hard on the body. The new drug abiraterone acetate, developed in recent years, blocks androgen biosynthesis including testicular, adrenal, and prostate cancer cell sources, thereby minimizing androgen levels in the body and even within tumor cells, altering previous CRPC treatment decisions.
Below we talk about the current principles of treatment, which is a complex section and you can consult your physician if you need more detail.
- Treatment of patients with non-metastatic CRPC: Chemotherapy and immunotherapy are not recommended, and second-line endocrine therapies may be observed or chosen. This includes addition of anti-androgens, anti-androgen drug replacement, discontinuation of anti-androgens, addition of adrenal androgen inhibitors (ketoconazole, aminophenazone, corticosteroids such as dexamethasone, etc.), estrogenic compounds (with caution for thrombotic risk), and new therapies.
- Metastatic CRPC without chemotherapy, asymptomatic or mildly symptomatic but in good health: Second-line endocrine therapy and treatment with abiraterone acetate in combination with prednisone, docetaxel, and Sipuleucel-T (the first effective tumor vaccine for CRPC) are options.
- Patients with metastatic CRPC who are symptomatic but in good health without chemotherapy: can be treated with docetaxel, abiraterone acetate in combination with prednisone, ketoconazole in combination with corticosteroids, mitoxantrone, or radionuclides.
- Patients with metastatic CRPC without chemotherapy who are symptomatic and in poor physical condition: treatment with abiraterone acetate in combination with prednisone is recommended.
- Patients with metastatic CRPC who have received prior docetaxel chemotherapy but are in good health: treat with abiraterone acetate in combination with prednisone, cabazitaxel, or enzalutamide (MDV3100, a new anti-androgen drug), or ketoconazole in combination with corticosteroids if there is difficulty obtaining these drugs. Docetaxel chemotherapy can be retried for patients who have previously responded to docetaxel chemotherapy.
- Patients with metastatic CRPC who have received prior docetaxel chemotherapy but are in poor health: The primary treatment is palliative, with selective administration of abiraterone acetate in combination with corticosteroids, enzalutamide, ketoconazole in combination with corticosteroids, or radionuclides in some patients.