This document summarizes hormonal therapy approaches for prostate cancer, including ablation of androgen sources, anti-androgens, LHRH agonists/antagonists, and inhibition of androgen synthesis. It describes various drugs and their mechanisms of action and side effects. It also discusses testosterone testing, PSA response to ADT, adverse effects like osteoporosis and hot flashes, and indications for ADT in localized, locally advanced, biochemical recurrence, and metastatic prostate cancer.
Hormonal therapy in prostate cancer involves androgen deprivation therapy (ADT) to slow cancer growth by lowering testosterone levels or blocking its effects. ADT can be achieved through surgical castration via orchidectomy, medical castration using LHRH agonists or antagonists to inhibit testosterone production, or anti-androgens to block the effects of testosterone. While effective, ADT can cause adverse effects like hot flashes, loss of libido, and increased risks of bone loss, diabetes, and cardiovascular disease. Principles of ADT indicate that LHRH agonists and surgical castration are equally effective, and that combined androgen blockade provides no additional benefit over castration alone for
This document discusses various treatment options for prostate cancer based on risk level. For low risk prostate cancer with a life expectancy under 10 years, observation is recommended. For intermediate risk prostate cancer, options include radiation therapy with a short course of hormone therapy or surgery with radiation and hormone therapy if high risk features are present. For high risk prostate cancer, initial treatment involves radiation therapy with a long course of hormone therapy or surgery with radiation and long course hormone therapy if high risk features or positive lymph nodes are present. Very high risk prostate cancer may be treated with hormone therapy alone or similarly to metastatic disease.
This document discusses locally advanced high risk prostate cancer and evolving treatment options. It provides an overview of risk stratification, guidelines for biopsy from the European Association of Urology, options for imaging with multiparametric MRI, and options for treatment including radical prostatectomy, radiation therapy, and hormonal therapy. New advances in radiation therapy include stereotactic body radiation therapy and hypofractionated regimens. Advances in hormonal therapy include gonadotropin-releasing hormone antagonists and oral options like relugolix. Neoadjuvant docetaxel chemotherapy is also discussed for high risk localized disease.
This document discusses hormone therapy for prostate cancer. It begins by providing global and Indian statistics on prostate cancer incidence and mortality. It then describes the roles of testosterone and dihydrotestosterone in prostate growth and cancer. Hormone therapy aims to suppress androgen production and is used in metastatic, locally advanced and some early-stage prostate cancers. Common hormone therapies include surgical castration, LHRH agonists and antagonists, antiandrogens, and androgen synthesis inhibitors. The document discusses the use, mechanisms, and side effects of these various hormone therapy options in detail.
Prostate carcinoma- Castrate Resistant Prostate Cancer (crpc)GovtRoyapettahHospit
This document discusses castrate resistant prostate cancer (CRPC). It defines CRPC and outlines various treatment options including androgen receptor directed therapies like abiraterone and enzalutamide, cytotoxic chemotherapies like docetaxel and cabazitol, immunotherapies, and targeted therapies. It also discusses mechanisms of castration resistance like AR amplification and activation by alternative ligands.
This document discusses the management of biochemical recurrence after definitive therapy for localized prostate cancer. It defines biochemical recurrence after radical prostatectomy and radiation therapy. Imaging options for detecting recurrence like PET/CT, MRI, and prostate-specific membrane antigen (PSMA) PET are discussed. The document reviews treatment options for recurrence including salvage radiation therapy, androgen deprivation therapy, salvage surgery, cryotherapy, brachytherapy, and high-intensity focused ultrasound. Guidelines for imaging and treatment of recurrence are provided.
Androgen Deprivation Therapy for Prostate CancerAlexander Small
This document summarizes a tumor board review on androgen deprivation therapy for prostate cancer. It begins with a case presentation of a patient with metastatic prostate cancer and then provides: 1) A brief history of the discovery of the connection between androgens and prostate cancer; 2) An overview of the androgen axis and various methods of androgen deprivation therapy including surgical castration, medical castration, anti-androgens, and GnRH agonists/antagonists; 3) A discussion of the adverse effects of androgen deprivation therapy including quality of life impacts, increased risks of osteoporosis and cardiovascular disease; 4) Considerations around treatment timing; and 5) Conclusions regarding optimal androgen deprivation therapy
This document discusses a trial investigating the role of local radiation therapy for metastatic prostate cancer. The main findings were:
1. No overall survival benefit was seen with radiation therapy, but survival improved in patients with low metastatic burden.
2. Failure-free survival improved with radiation therapy overall and in the low metastatic burden group.
3. Adverse effects from radiation therapy were modest.
The trial provides evidence that radiation therapy to the prostate improves outcomes for men with metastatic prostate cancer who have a low metastatic burden and does not negatively impact side effects.
Hormonal therapy in prostate cancer involves androgen deprivation therapy (ADT) to slow cancer growth by lowering testosterone levels or blocking its effects. ADT can be achieved through surgical castration via orchidectomy, medical castration using LHRH agonists or antagonists to inhibit testosterone production, or anti-androgens to block the effects of testosterone. While effective, ADT can cause adverse effects like hot flashes, loss of libido, and increased risks of bone loss, diabetes, and cardiovascular disease. Principles of ADT indicate that LHRH agonists and surgical castration are equally effective, and that combined androgen blockade provides no additional benefit over castration alone for
This document discusses various treatment options for prostate cancer based on risk level. For low risk prostate cancer with a life expectancy under 10 years, observation is recommended. For intermediate risk prostate cancer, options include radiation therapy with a short course of hormone therapy or surgery with radiation and hormone therapy if high risk features are present. For high risk prostate cancer, initial treatment involves radiation therapy with a long course of hormone therapy or surgery with radiation and long course hormone therapy if high risk features or positive lymph nodes are present. Very high risk prostate cancer may be treated with hormone therapy alone or similarly to metastatic disease.
This document discusses locally advanced high risk prostate cancer and evolving treatment options. It provides an overview of risk stratification, guidelines for biopsy from the European Association of Urology, options for imaging with multiparametric MRI, and options for treatment including radical prostatectomy, radiation therapy, and hormonal therapy. New advances in radiation therapy include stereotactic body radiation therapy and hypofractionated regimens. Advances in hormonal therapy include gonadotropin-releasing hormone antagonists and oral options like relugolix. Neoadjuvant docetaxel chemotherapy is also discussed for high risk localized disease.
This document discusses hormone therapy for prostate cancer. It begins by providing global and Indian statistics on prostate cancer incidence and mortality. It then describes the roles of testosterone and dihydrotestosterone in prostate growth and cancer. Hormone therapy aims to suppress androgen production and is used in metastatic, locally advanced and some early-stage prostate cancers. Common hormone therapies include surgical castration, LHRH agonists and antagonists, antiandrogens, and androgen synthesis inhibitors. The document discusses the use, mechanisms, and side effects of these various hormone therapy options in detail.
Prostate carcinoma- Castrate Resistant Prostate Cancer (crpc)GovtRoyapettahHospit
This document discusses castrate resistant prostate cancer (CRPC). It defines CRPC and outlines various treatment options including androgen receptor directed therapies like abiraterone and enzalutamide, cytotoxic chemotherapies like docetaxel and cabazitol, immunotherapies, and targeted therapies. It also discusses mechanisms of castration resistance like AR amplification and activation by alternative ligands.
This document discusses the management of biochemical recurrence after definitive therapy for localized prostate cancer. It defines biochemical recurrence after radical prostatectomy and radiation therapy. Imaging options for detecting recurrence like PET/CT, MRI, and prostate-specific membrane antigen (PSMA) PET are discussed. The document reviews treatment options for recurrence including salvage radiation therapy, androgen deprivation therapy, salvage surgery, cryotherapy, brachytherapy, and high-intensity focused ultrasound. Guidelines for imaging and treatment of recurrence are provided.
Androgen Deprivation Therapy for Prostate CancerAlexander Small
This document summarizes a tumor board review on androgen deprivation therapy for prostate cancer. It begins with a case presentation of a patient with metastatic prostate cancer and then provides: 1) A brief history of the discovery of the connection between androgens and prostate cancer; 2) An overview of the androgen axis and various methods of androgen deprivation therapy including surgical castration, medical castration, anti-androgens, and GnRH agonists/antagonists; 3) A discussion of the adverse effects of androgen deprivation therapy including quality of life impacts, increased risks of osteoporosis and cardiovascular disease; 4) Considerations around treatment timing; and 5) Conclusions regarding optimal androgen deprivation therapy
This document discusses a trial investigating the role of local radiation therapy for metastatic prostate cancer. The main findings were:
1. No overall survival benefit was seen with radiation therapy, but survival improved in patients with low metastatic burden.
2. Failure-free survival improved with radiation therapy overall and in the low metastatic burden group.
3. Adverse effects from radiation therapy were modest.
The trial provides evidence that radiation therapy to the prostate improves outcomes for men with metastatic prostate cancer who have a low metastatic burden and does not negatively impact side effects.
This presentation provides an overview of androgen deprivation therapy (ADT), also known as hormone therapy, for prostate cancer. It discusses the basic principles, including how prostate cancer cells rely on androgens like testosterone to grow. ADT aims to stop androgen production or block their effects. Methods include surgical removal of the testes, medications to reduce testosterone production, and anti-androgens to inhibit testosterone's action. Side effects from lowering testosterone levels can include hot flashes, fatigue, reduced libido and sexual dysfunction, as well as increased risks of osteoporosis, obesity, and cardiovascular issues over the long term.
The document discusses the role of radiation therapy in treating oligometastatic prostate cancer, noting that radiation can potentially achieve durable responses or even cure in some cases when metastases are limited. It reviews definitions of oligometastatic prostate cancer, the rationale for local and metastasis-directed radiation therapy, clinical evidence from studies on the use of external beam radiation therapy and stereotactic body radiation therapy to treat the primary tumor and metastases, and outcomes from these studies including local control rates, progression-free survival, and overall survival. The document concludes that radiation therapy plays an important role in the treatment of oligometastatic prostate cancer.
Locally advanced prostate cancer (LAPC) involves spread outside the prostate capsule or involvement of nearby structures. While no consensus exists on optimal treatment, combination therapy with radical prostatectomy (RP), radiation therapy (RT), and androgen deprivation (AD) provides the best outcomes. For selected patients with low-volume LAPC, RP alone may be sufficient, but extended pelvic lymph node dissection is important. Adjuvant or neoadjuvant RT and long-term AD after RP can improve local control and reduce recurrence rates. For patients unable to undergo surgery, RT with concurrent and adjuvant AD is the standard treatment and provides improved survival compared to monotherapy. Multimodal therapy increases side effects but provides superior outcomes over the
This document discusses the management of localized and locally advanced prostate cancer. It covers risk stratification methods including D'Amico, NCCN and EAU classifications. Treatment options for localized prostate cancer include active surveillance, radical prostatectomy, external beam radiotherapy and brachytherapy. Patient selection factors, follow-up protocols and potential complications are reviewed for different treatment modalities. Risk assessment tools like Partin tables, Kattan and Briganti nomograms are also described to guide treatment decisions in localized prostate cancer.
Metronomic chemotherapy involves administering lower doses of chemotherapy drugs more frequently to target tumor growth. This summary approach has three potential mechanisms of action - inhibiting angiogenesis, stimulating the immune system, and directly targeting tumor cells. It yields long-term improved outcomes despite slower initial decreases in tumor size compared to maximum tolerated dose regimens. Clinical trials have shown metronomic chemotherapy to be an effective treatment approach in several cancer types including breast, colon, ovarian and prostate cancer when used as a single agent or in combinations.
This document summarizes treatment approaches for metastatic castration-resistant prostate cancer (mCRPC). It discusses definitions of CRPC and mechanisms of resistance. For mCRPC patients with PSADT >10 months and no symptoms, secondary hormonal therapies are recommended, while those with PSADT <10 months receive second-generation antiandrogens. Docetaxel remains first-line for symptomatic mCRPC, while abiraterone, enzalutamide, radium-223, and sipuleucel-T are also options. Detection of AR-V7 in circulating tumor cells may help determine if taxanes or AR-targeted therapies are most suitable. Ongoing treatment, monitoring of
Bacille Calmette-Guérin (BCG) is an effective immunotherapy for bladder cancer that produces a local immune response. It is administered by reconstituting the powder with saline and instilling it into the bladder through a catheter. The patient must retain the fluid for 1-2 hours to allow the BCG to activate immune cells and cytokines in the bladder wall and urine. Common side effects include cystitis and flu-like symptoms. More severe complications like BCG sepsis require discontinuing treatment and using antimicrobials. BCG is given as a 6-week induction course followed by 1-3 years of maintenance therapy depending on cancer risk level to prevent recurrence and progression of bladder cancer. Radical cystectomy may
This document discusses radiation therapy options for prostate cancer. It notes that treatment depends on risk level: low risk may receive external beam radiation or seeds alone, intermediate risk should receive some external beam, and high risk should receive hormone therapy plus radiation. Newer techniques like IMRT and IGRT reduce side effects by more precisely targeting the prostate. Side effects of radiation include short term issues like urinary frequency and diarrhea as well as long term risks like radiation cystitis and impotence in some cases.
This document discusses management of prostate cancer through different treatment modalities including active surveillance, radical prostatectomy, radiation therapy, and hormonal therapy. It provides treatment recommendations based on cancer stage and risk level as well as 5-year outcomes. For low risk prostate cancer, active surveillance, radical prostatectomy, or radiation therapy are recommended depending on life expectancy. Radiation therapy techniques like 3D-CRT, IMRT, and brachytherapy are covered. Dose escalation studies showing improved outcomes with higher radiation doses are also summarized.
The document summarizes several clinical trials related to prostate cancer treatment. It provides details on trials such as PIVOT, ProtecT, TAX327 which compared radical prostatectomy vs observation, active monitoring vs surgery or radiation, and docetaxel vs mitoxantrone for advanced prostate cancer. It also summarizes larger ongoing trials like STAMPEDE and LATITUDE that are evaluating multiple treatment strategies for high risk or metastatic prostate cancer.
The document summarizes the treatment landscape for metastatic hormone-sensitive prostate cancer (mHSPC). It discusses several key trials that have established the benefit of primary intensification with the addition of docetaxel, abiraterone, enzalutamide, or apalutamide to androgen deprivation therapy (ADT). Trials like CHAARTED, LATITUDE, and STAMPEDE showed improved overall survival with these combinations compared to ADT alone. There is ongoing debate around the appropriate definition of high-volume versus low-volume disease and which patients most benefit from the triplet combination of ADT plus docetaxel plus a second agent. Overall, primary intensification beyond ADT alone is now
Advanced & metastatic bladder cancer - Dr Alok GuptaAlok Gupta
This document discusses four case scenarios of patients with advanced or metastatic bladder cancer and summarizes discussion points from an expert panel on their treatment.
The first case involves a 74-year-old male with metastatic high-grade urothelial carcinoma. The panel discusses options for first-line therapy including cisplatin-based chemotherapy or immunotherapy.
The second case involves the same patient but with diabetic nephropathy, limiting cisplatin. The preferred regimen in this setting is gemcitabine and carboplatin or immunotherapy.
The third case is an 85-year old with multiple comorbidities, where the preferred option would be immunotherapy rather than chemotherapy.
The fourth case discusses options after
This document summarizes information about anal canal cancer, including:
- It accounts for 1-2% of large bowel malignancies and is increasing in incidence. Risk factors include HPV infection and HIV infection.
- Screening high-risk groups like HIV+ individuals can detect early anal intraepithelial neoplasia, as HPV vaccines may help prevent cancers.
- Most anal canal cancers are squamous cell carcinomas. Clinical staging evaluates tumor extent, node involvement, and distant spread through digital exam, imaging and biopsy.
This document discusses the management of early HER2+ breast cancer. It defines early breast cancer and describes the HER2+ subtype, which accounts for around 25% of cases. For early HER2+ breast cancer, neoadjuvant chemotherapy plus trastuzumab improves pathological complete response rates and long-term outcomes compared to chemotherapy alone. Multiple trials demonstrate the benefit of adding pertuzumab or T-DM1 to neoadjuvant regimens. Post-neoadjuvant surgery may require close evaluation of margins due to heterogeneous response.
Localized prostate cancer is the most common cancer in men in Western countries. For patients with high risk localized prostate cancer, the current recommended treatment is androgen deprivation therapy combined with radiotherapy. Several large randomized controlled trials have shown this combination prolongs progression-free and overall survival compared to androgen deprivation alone. Additional treatment options for high risk localized prostate cancer currently being investigated include radical prostatectomy and chemotherapy with docetaxel. Erectile dysfunction is a common side effect of treatment that can be addressed with oral phosphodiesterase inhibitors or intracavernosal injections.
Radiation therapy can enhance anti-tumor immunity through several mechanisms like increasing antigen visibility and activating the cGAS-STING pathway. However, it can also induce immunosuppressive effects by modifying the tumor microenvironment. The combination of radiation therapy with immunotherapy may provide synergistic effects by stimulating both local and systemic tumor control. Some challenges in combining these approaches include optimizing the timing and dose of radiation therapy to maximize its immune stimulatory effects while minimizing direct effects on T cells. Further studies are still needed to determine the best approaches.
This document discusses stage IV prostate cancer and advanced or metastatic prostate cancer. It defines stage IV based on the TNM classification system and notes that approximately 10-20% of newly diagnosed prostate cancer cases involve locally advanced disease. For metastatic prostate cancer, median survival ranges from 9 to 24 months depending on whether metastases are asymptomatic or symptomatic. Main treatments discussed include androgen deprivation therapy and chemotherapy. The document also covers management of bone metastases, hormone-refractory prostate cancer, newer hormone therapies like abiraterone and enzalutamide, immunotherapy with sipuleucel-T, chemotherapy options including docetaxel and cabazitaxel, radiopharmaceuticals like radium-223, and bone-mod
Hypofractionation in early breast cancer is no more a research scholars topic. Multiple studies with robust data have proven its utility. It may hold an important role in many countries with constrained resources. This is a short presentation incorporating important completed and ongoing trials. Feel free to use this.
Molecular biology of Prostate cancer. There are three major pathways - the androgen receptor pathway, PI3K/Akt pathway, and Rb pathway. Other factors include TMPRSS2-ETS fusion, TGF-b1, PTEN loss, and aberrant E-cadherin expression. Risk factors include age, ethnicity, genetic mutations like BRCA1/2, and environmental exposures. Prostate cancer can metastasize, with bone and lymph nodes being common sites. Diagnosis involves tests like DRE, PSA, biopsy, and imaging. Hormone therapy targets the androgen receptor and includes surgical or medical castration as well as antiandrogens, but resistance eventually develops
This document discusses hormonal therapy for breast cancer. It notes that around 60-70% of breast cancer patients are estrogen receptor positive. Estrogen receptor positive tumors have a better survival rate than estrogen receptor negative tumors. The document discusses the molecular basis of estrogen receptor signaling and the genomic and non-genomic mechanisms of estrogen action. It describes the different types of hormonal therapies used in breast cancer including selective estrogen receptor modulators, aromatase inhibitors, antiestrogens, LHRH agonists, and progestins. It discusses the application of hormonal therapy in the adjuvant setting for premenopausal and postmenopausal patients.
This presentation provides an overview of androgen deprivation therapy (ADT), also known as hormone therapy, for prostate cancer. It discusses the basic principles, including how prostate cancer cells rely on androgens like testosterone to grow. ADT aims to stop androgen production or block their effects. Methods include surgical removal of the testes, medications to reduce testosterone production, and anti-androgens to inhibit testosterone's action. Side effects from lowering testosterone levels can include hot flashes, fatigue, reduced libido and sexual dysfunction, as well as increased risks of osteoporosis, obesity, and cardiovascular issues over the long term.
The document discusses the role of radiation therapy in treating oligometastatic prostate cancer, noting that radiation can potentially achieve durable responses or even cure in some cases when metastases are limited. It reviews definitions of oligometastatic prostate cancer, the rationale for local and metastasis-directed radiation therapy, clinical evidence from studies on the use of external beam radiation therapy and stereotactic body radiation therapy to treat the primary tumor and metastases, and outcomes from these studies including local control rates, progression-free survival, and overall survival. The document concludes that radiation therapy plays an important role in the treatment of oligometastatic prostate cancer.
Locally advanced prostate cancer (LAPC) involves spread outside the prostate capsule or involvement of nearby structures. While no consensus exists on optimal treatment, combination therapy with radical prostatectomy (RP), radiation therapy (RT), and androgen deprivation (AD) provides the best outcomes. For selected patients with low-volume LAPC, RP alone may be sufficient, but extended pelvic lymph node dissection is important. Adjuvant or neoadjuvant RT and long-term AD after RP can improve local control and reduce recurrence rates. For patients unable to undergo surgery, RT with concurrent and adjuvant AD is the standard treatment and provides improved survival compared to monotherapy. Multimodal therapy increases side effects but provides superior outcomes over the
This document discusses the management of localized and locally advanced prostate cancer. It covers risk stratification methods including D'Amico, NCCN and EAU classifications. Treatment options for localized prostate cancer include active surveillance, radical prostatectomy, external beam radiotherapy and brachytherapy. Patient selection factors, follow-up protocols and potential complications are reviewed for different treatment modalities. Risk assessment tools like Partin tables, Kattan and Briganti nomograms are also described to guide treatment decisions in localized prostate cancer.
Metronomic chemotherapy involves administering lower doses of chemotherapy drugs more frequently to target tumor growth. This summary approach has three potential mechanisms of action - inhibiting angiogenesis, stimulating the immune system, and directly targeting tumor cells. It yields long-term improved outcomes despite slower initial decreases in tumor size compared to maximum tolerated dose regimens. Clinical trials have shown metronomic chemotherapy to be an effective treatment approach in several cancer types including breast, colon, ovarian and prostate cancer when used as a single agent or in combinations.
This document summarizes treatment approaches for metastatic castration-resistant prostate cancer (mCRPC). It discusses definitions of CRPC and mechanisms of resistance. For mCRPC patients with PSADT >10 months and no symptoms, secondary hormonal therapies are recommended, while those with PSADT <10 months receive second-generation antiandrogens. Docetaxel remains first-line for symptomatic mCRPC, while abiraterone, enzalutamide, radium-223, and sipuleucel-T are also options. Detection of AR-V7 in circulating tumor cells may help determine if taxanes or AR-targeted therapies are most suitable. Ongoing treatment, monitoring of
Bacille Calmette-Guérin (BCG) is an effective immunotherapy for bladder cancer that produces a local immune response. It is administered by reconstituting the powder with saline and instilling it into the bladder through a catheter. The patient must retain the fluid for 1-2 hours to allow the BCG to activate immune cells and cytokines in the bladder wall and urine. Common side effects include cystitis and flu-like symptoms. More severe complications like BCG sepsis require discontinuing treatment and using antimicrobials. BCG is given as a 6-week induction course followed by 1-3 years of maintenance therapy depending on cancer risk level to prevent recurrence and progression of bladder cancer. Radical cystectomy may
This document discusses radiation therapy options for prostate cancer. It notes that treatment depends on risk level: low risk may receive external beam radiation or seeds alone, intermediate risk should receive some external beam, and high risk should receive hormone therapy plus radiation. Newer techniques like IMRT and IGRT reduce side effects by more precisely targeting the prostate. Side effects of radiation include short term issues like urinary frequency and diarrhea as well as long term risks like radiation cystitis and impotence in some cases.
This document discusses management of prostate cancer through different treatment modalities including active surveillance, radical prostatectomy, radiation therapy, and hormonal therapy. It provides treatment recommendations based on cancer stage and risk level as well as 5-year outcomes. For low risk prostate cancer, active surveillance, radical prostatectomy, or radiation therapy are recommended depending on life expectancy. Radiation therapy techniques like 3D-CRT, IMRT, and brachytherapy are covered. Dose escalation studies showing improved outcomes with higher radiation doses are also summarized.
The document summarizes several clinical trials related to prostate cancer treatment. It provides details on trials such as PIVOT, ProtecT, TAX327 which compared radical prostatectomy vs observation, active monitoring vs surgery or radiation, and docetaxel vs mitoxantrone for advanced prostate cancer. It also summarizes larger ongoing trials like STAMPEDE and LATITUDE that are evaluating multiple treatment strategies for high risk or metastatic prostate cancer.
The document summarizes the treatment landscape for metastatic hormone-sensitive prostate cancer (mHSPC). It discusses several key trials that have established the benefit of primary intensification with the addition of docetaxel, abiraterone, enzalutamide, or apalutamide to androgen deprivation therapy (ADT). Trials like CHAARTED, LATITUDE, and STAMPEDE showed improved overall survival with these combinations compared to ADT alone. There is ongoing debate around the appropriate definition of high-volume versus low-volume disease and which patients most benefit from the triplet combination of ADT plus docetaxel plus a second agent. Overall, primary intensification beyond ADT alone is now
Advanced & metastatic bladder cancer - Dr Alok GuptaAlok Gupta
This document discusses four case scenarios of patients with advanced or metastatic bladder cancer and summarizes discussion points from an expert panel on their treatment.
The first case involves a 74-year-old male with metastatic high-grade urothelial carcinoma. The panel discusses options for first-line therapy including cisplatin-based chemotherapy or immunotherapy.
The second case involves the same patient but with diabetic nephropathy, limiting cisplatin. The preferred regimen in this setting is gemcitabine and carboplatin or immunotherapy.
The third case is an 85-year old with multiple comorbidities, where the preferred option would be immunotherapy rather than chemotherapy.
The fourth case discusses options after
This document summarizes information about anal canal cancer, including:
- It accounts for 1-2% of large bowel malignancies and is increasing in incidence. Risk factors include HPV infection and HIV infection.
- Screening high-risk groups like HIV+ individuals can detect early anal intraepithelial neoplasia, as HPV vaccines may help prevent cancers.
- Most anal canal cancers are squamous cell carcinomas. Clinical staging evaluates tumor extent, node involvement, and distant spread through digital exam, imaging and biopsy.
This document discusses the management of early HER2+ breast cancer. It defines early breast cancer and describes the HER2+ subtype, which accounts for around 25% of cases. For early HER2+ breast cancer, neoadjuvant chemotherapy plus trastuzumab improves pathological complete response rates and long-term outcomes compared to chemotherapy alone. Multiple trials demonstrate the benefit of adding pertuzumab or T-DM1 to neoadjuvant regimens. Post-neoadjuvant surgery may require close evaluation of margins due to heterogeneous response.
Localized prostate cancer is the most common cancer in men in Western countries. For patients with high risk localized prostate cancer, the current recommended treatment is androgen deprivation therapy combined with radiotherapy. Several large randomized controlled trials have shown this combination prolongs progression-free and overall survival compared to androgen deprivation alone. Additional treatment options for high risk localized prostate cancer currently being investigated include radical prostatectomy and chemotherapy with docetaxel. Erectile dysfunction is a common side effect of treatment that can be addressed with oral phosphodiesterase inhibitors or intracavernosal injections.
Radiation therapy can enhance anti-tumor immunity through several mechanisms like increasing antigen visibility and activating the cGAS-STING pathway. However, it can also induce immunosuppressive effects by modifying the tumor microenvironment. The combination of radiation therapy with immunotherapy may provide synergistic effects by stimulating both local and systemic tumor control. Some challenges in combining these approaches include optimizing the timing and dose of radiation therapy to maximize its immune stimulatory effects while minimizing direct effects on T cells. Further studies are still needed to determine the best approaches.
This document discusses stage IV prostate cancer and advanced or metastatic prostate cancer. It defines stage IV based on the TNM classification system and notes that approximately 10-20% of newly diagnosed prostate cancer cases involve locally advanced disease. For metastatic prostate cancer, median survival ranges from 9 to 24 months depending on whether metastases are asymptomatic or symptomatic. Main treatments discussed include androgen deprivation therapy and chemotherapy. The document also covers management of bone metastases, hormone-refractory prostate cancer, newer hormone therapies like abiraterone and enzalutamide, immunotherapy with sipuleucel-T, chemotherapy options including docetaxel and cabazitaxel, radiopharmaceuticals like radium-223, and bone-mod
Hypofractionation in early breast cancer is no more a research scholars topic. Multiple studies with robust data have proven its utility. It may hold an important role in many countries with constrained resources. This is a short presentation incorporating important completed and ongoing trials. Feel free to use this.
Molecular biology of Prostate cancer. There are three major pathways - the androgen receptor pathway, PI3K/Akt pathway, and Rb pathway. Other factors include TMPRSS2-ETS fusion, TGF-b1, PTEN loss, and aberrant E-cadherin expression. Risk factors include age, ethnicity, genetic mutations like BRCA1/2, and environmental exposures. Prostate cancer can metastasize, with bone and lymph nodes being common sites. Diagnosis involves tests like DRE, PSA, biopsy, and imaging. Hormone therapy targets the androgen receptor and includes surgical or medical castration as well as antiandrogens, but resistance eventually develops
This document discusses hormonal therapy for breast cancer. It notes that around 60-70% of breast cancer patients are estrogen receptor positive. Estrogen receptor positive tumors have a better survival rate than estrogen receptor negative tumors. The document discusses the molecular basis of estrogen receptor signaling and the genomic and non-genomic mechanisms of estrogen action. It describes the different types of hormonal therapies used in breast cancer including selective estrogen receptor modulators, aromatase inhibitors, antiestrogens, LHRH agonists, and progestins. It discusses the application of hormonal therapy in the adjuvant setting for premenopausal and postmenopausal patients.
This document summarizes treatment approaches for metastatic prostate cancer and castration-resistant prostate cancer (CRPC). It discusses how initial treatments aim to reduce androgen levels via surgical or medical castration. While initial responses are good, cancer typically becomes resistant to castration after 2-3 years. For CRPC, options discussed include secondary hormonal therapies, bone-targeted agents, chemotherapy, immunotherapy, radiotherapy, and novel targeted therapies. Key mechanisms of CRPC resistance and clinical considerations for treatment are also reviewed.
This document discusses metastatic prostate cancer and androgen deprivation therapy (ADT). It is presented by the Department of Urology at Govt Royapettah Hospital and Kilpauk Medical College in Chennai. The document covers various aspects of ADT including ablation of androgen sources through bilateral orchidectomy or anti-androgens, inhibition of LHRH or LH through agonists or antagonists, and inhibition of androgen synthesis through drugs like abiraterone. It also discusses adverse effects of ADT, monitoring of PSA levels, and management of issues like osteoporosis and hot flashes.
The document discusses hormonal therapy for prostate cancer. It provides a history of hormonal therapy and discusses key figures like Charles Huggins who demonstrated that castration improved outcomes for advanced prostate cancer. It then discusses the molecular biology of the androgen axis and different therapeutic approaches to hormonal therapy including ablation of androgen sources, anti-androgens, LHRH agonists/antagonists, and inhibition of androgen synthesis. Specific drugs are discussed for each class. Adverse effects of hormonal therapy like osteoporosis and hot flashes are also summarized.
This document discusses various hormone therapies and antagonists used to treat cancers like breast cancer and prostate cancer. It describes several classes of drugs including glucocorticoids, estrogens, selective estrogen receptor modulators, aromatase inhibitors, antiandrogens, 5-α reductase inhibitors, and GnRH analogues. For each drug class or individual drug, it provides information on mechanism of action, pharmacokinetics, uses, and adverse effects. The goal of these hormone therapies is to block the effects of hormones like estrogen and androgen that can promote the growth of hormone-sensitive cancers.
This document summarizes the medical management of lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH). It discusses the components of bladder outlet obstruction, associated voiding and storage dysfunctions, and various treatment options including alpha blockers, 5-alpha reductase inhibitors, combination therapy, phytotherapy, minimally invasive techniques, and surgery. The goal of treatment is relieving LUTS, decreasing obstruction, and improving bladder emptying while preventing disease progression.
Docetaxel plus prednisone is the standard first-line chemotherapy for metastatic castration-resistant prostate cancer. Cabazitaxel is an option for second-line chemotherapy.
Other options include:
- Abiraterone acetate (CYP17 inhibitor) plus prednisone
- Enzalutamide (second-generation antiandrogen)
- Radium-223 (alpha particle-emitting radiopharmaceutical) for symptomatic bone metastases
- Investigational therapies through clinical trials
Close monitoring of response and side effects is important with any of these advanced therapies. Palliative care should also be incorporated to maximize quality of life.
1) Chemotherapy induced nausea and vomiting is a serious side effect that can negatively impact quality of life. The mechanisms involve the central nervous system including brainstem areas that control vomiting.
2) Antiemetic treatments target neurotransmitters like serotonin, substance P, and dopamine to prevent nausea and vomiting. Combination regimens are most effective depending on the emetogenicity of the chemotherapy.
3) Studies show the addition of newer drugs like NK1 receptor antagonists, olanzapine, and palonosetron to standard treatments improves control of both acute and delayed nausea and vomiting from chemotherapy.
This document discusses androgens and the male reproductive system. It describes the structure and function of the male reproductive system and the role of testosterone as the main hormone. Testosterone is produced in the testes and regulates sperm production and male characteristics. It binds to receptors in target tissues like muscle and bone. The effects, production, regulation, and clinical uses of testosterone are summarized along with descriptions of anti-androgen drugs that block testosterone's actions.
This document provides an overview of estrogens, progestins, and androgens. It discusses their synthesis, physiological effects, regulation, and therapeutic formulations and uses. Estrogens are involved in reproductive functions and non-reproductive tissues. Progestins are used in contraceptives and hormone replacement therapy. Androgens have roles in reproduction and behavior. Oral contraceptives contain estrogen and progestin combinations to suppress ovulation and prevent pregnancy.
Recent advances in the treatment of dermatological diseaseDRMOHITKHER
This document discusses recent advances in pharmacotherapy for various dermatological diseases. It covers treatment options for common conditions like vitiligo, acne, psoriasis, and androgenetic alopecia. For these conditions, it describes both topical and systemic drug therapy options, including corticosteroids, retinoids, antibiotics, isotretinoin, JAK inhibitors, and phototherapy. It also provides details on specific drugs, dosages, and mechanisms of action for treating various dermatological diseases.
This document discusses thyroid emergencies including thyroid storm and myxedema coma. It provides details on the synthesis and effects of thyroid hormones, diagnosis of thyroid storm using the Burch-Wartofsky Point Scale and Japan Thyroid Association criteria, and management principles for thyroid storm including beta blockers, antithyroid medications, corticosteroids, iodine, and definitive therapy. Precipitating factors and management of myxedema coma are also summarized.
This document provides guidelines for evaluating and treating male infertility. It discusses when to evaluate couples for infertility, how to perform semen analysis according to WHO guidelines, and how to differentiate between obstructive and non-obstructive azoospermia. It provides recommendations on treating varicoceles, lifestyle factors, oxidative stress, and infections. For non-obstructive azoospermia, it discusses evaluating genetic causes and techniques for sperm retrieval like microdissection testicular sperm extraction. Medical therapies for infertility including hormones, antioxidants, and supplements are discussed along with their effectiveness. The document concludes by discussing fertility preservation and future areas of research like gene therapy.
This document provides an overview of gonadal hormones and their inhibitors. It discusses the physiological functions and mechanisms of action of estrogens, including their natural and synthetic forms. It also covers estrogen biosynthesis, pharmacokinetics, effects on various body systems, clinical uses for hormone replacement and contraception, and potential adverse effects. Finally, it examines different classes of estrogen inhibitors like SERMs, aromatase inhibitors, and receptor antagonists, outlining their mechanisms of action and clinical applications.
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This document provides information about a KUB (kidney, ureter, bladder) x-ray performed at the Department of Urology, Government Royapettah Hospital and Kilpauk Medical College in Chennai. It lists the professors and assistant professors in the department and provides details on the history, physics, techniques, anatomical landmarks, disorders, and interpretations of renal calculi, ureter, bladder, and other findings that can be seen on a KUB x-ray.
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This patient presented with anterior urethral stricture and multiple abnormal connections (fistulas) between the prostate gland/urethra and the skin, resulting in urine leakage to the skin. Treatment will require surgical repair of the strictures and closure of all abnormal connections to restore normal urinary flow and continence.
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4. Ablation of Androgen sources
1. Bilateral orchidectomy (Total or subcapsular)
2. Bilateral adrenalectomy (Historical and Obsolete)
5. Bilateral orchidectomy
• Quickly reduces circulating testosterone levels to less
than 50 ng/dL (Castrate range).
• Classical castrate range – 50 ng/mL, now 15ng/mL
• Within 24 hours of surgical castration, testosterone
levels are reduced by greater than 90%.
7. Cyproterone acetate
• Classical steroidal antiandrogen with direct AR
blocking effects.
• Rapidly lowers testosterone levels to 70-80%
• Acts through progestational central inhibition.
• Dose 100 mg twice or thrice daily.
• Side effects:
Loss of libido,
Erectile dysfunction,
Lassitude.
8. Cyproterone acetate
• Cardiovascular complications in 10% of patients.
• Gynaecomastia in < 20% of patients.
• Used for the treatment of Hot flashes. Dose 50-100
mg/day.
9. Non steroidal antiandrogens
• Block testosterone feedback centrally.
• Cause LH and testosterone levels to increase.
• Testosterone levels reach 1.5 times the normal levels.
• Potency can be preserved. (< 20%)
• Peripheral aromatization to estradiol.
• Gynaecomastia and mastodynia.
• Liver toxicity requires periodic LFT monitoring
10. Flutamide
• First ‘Pure’ anti androgen.
• Half life 6 hrs.
• Dose 250 mg twice or thrice a day.
• Gastrointestinal toxicity – Diarrhoea is a common
complication.
11. Bicalutamide
• Half life 6 days
• Dose 150 mg once daily
• Equivalent efficacy to surgical or medical castration.
• Side effects: Gynaecomastia, mastalgia.
12. Nilutamide
• Half life 56 hours.
• Elimination via Cytochrome P450 system.
• Dose 300 mg daily for 1 month followed by 150 mg
daily.
• Adverse effects: Delayed adaptation to darkness
(25%), Interstitial pneumonitis (1%) progressing to
pulmonary fibrosis.
13. Enzalutamide
• AR antagonist inhibiting nuclear translocation and
DNA binding.
• Effective in castration resistant prostate cancer.
• Side effects: Fatigue, diarrhoea and hot flashes.
Seizures (1%)
• Indicated in patients with mCRPC.
• Efficacy equal to Abiraterone.
• Dose: 160 mg/day. (1 tab – 40 mg)
14. Apalutamide
• Oral, nonsteroidal antiandrogen
• Blocks the action of testosterone by binding to the
ligand-binding domain of the AR receptor.
• Used for the treatment of nonmetastatic CRPC.
• Adverse reactions: Fatigue, hypertension, rash, and
diarrhea.
• Dose: 240 mg/ day. ( 1 tab- 60 mg)
16. Leuprolide acetate
• Commonly used LHRH agonist
• Available as depot preparation for subcutaneous and
im injections.
• Lupron depot : Available with 1-,3-,4- and 6th
monthly depot preparations with 7.5 mg, 22.5 mg,
30 mg and 45 mg for im injections.
• Eligard: Same dosage available for SC injections.
• Leuprolide acetate 1 mg/0.2 mL/day SC
17. Mechanism of Action
• Exploits sensitization of LHRH receptors in ant
pituitary following chronic exposure to LHRH.
• After initial flare up, downregulation of LHRH
receptor occurs.
• LH and testosterone production shut down.
18. Flare up phenomenon
• Testosterone surge or Flare up phenomenon
associated with upto 10 fold increase in LH.
• May last for 10-20 days.
• Co administration of an antiandrogen functionally
blocks the increased levels of testosterone.
• Antiandrogen administration required for 3-4 weeks.
20. LHRH antagonists
• Competitively bind to LHRH receptors in the
pituitary, reducing LH concentrations by 84 % with in
24 hours.
• No LH and testosterone flare.
• No need for antiandrogen coadministration.
21. Abarelix
• Severe allergic reactions even after previous
uneventful treatment.
• Patient should be monitored for 30 minutes after
administration.
• Voluntarily withdrawn in 2005.
22. Degarelix
• No systemic allergic reactions.
• 1-month SC dose, requiring two initial injections (2 ×
3 mL for 240 mg) followed by monthly doses of 4 mL
(80 mg).
24. Aminoglutethimide
• Inhibits conversion of cholesterol to pregnenolone.
• Blocks production of aldosterone and cortisol also.
Hence should be replaced.
• Side effects: Anorexia, nausea, skin rash, lethargy,
vertigo, hypothyroidism and nystagmus.
• Dose: 1000 mg/day and Hydrocortisone acetate (40
mg/day).
25. Ketoconazole
• Interferes with two cytochrome P450 dependent
pathways.
• Blocks conversion of C21 to C19 steroids.
• Effect is rapid. Testosterone level drops to castrate
levels in 4 hours in some cases.
• Effect is immediately reversible.
• Dose: 400 mg 8 hrly. Usually with hydrocortisone 20
mg bd.
26. Ketoconazole
• With continuous use, testosterone levels begins to
rise and can reach low normal ranges with in 5
months of therapy.
• Used currently for castration resistant prostae cancer.
• Side effects:
– Gynaecomastia,
– lethargy, weakness,
– hepatic dysfunction, visual disturbance and
nausea.
27. Abiraterone
• Selective irreversible inhibitor of Cytochrome P17.
• Inhibits 17α hydroxylase and C17-20 lyase.
• Increase synthesis of aldosterone and its precursors.
• Suppress cortisol and increase ACTH secretion.
• Testosterone levels < 1 ng/mL.
• Side effects:
– Hypokalemia, hypertension, fluid overload.
• Dose: 1000 mg/day ( 1 tab – 250mg/500mg)
28. Abiraterone
• Co administration of prednisolone supresses ACTH.
• Can be used in Metastatic castration resistant
prostate cancer.
30. Darolutamide
• Oral, nonsteroidal antiandrogen with a similar mode
of action to enzalutamide and apalutamide.
Relugolix
• Oral, GnRH antagonist in phase 3 development.
• Reduced mean serum testosterone levels within 6 h of
dosing.
• However, a food effect reduced exposure by 50%
31. Orteronel (TAK-700)
• Mechanism of action similar to abiraterone.
• CYPP17 inhibitor with potentially greater 17,20 lyase
selectivity.
• Impairs androgen synthesis preferentially over
corticosteroid synthesis.
32. ARN-509
• Novel antiandrogen similar to enzalutamide
• Pure antagonist of AR while also inhibiting AR
nuclear translocation and DNA binding.
• Does not cross blood brain barrier. So no seizures.
33. Testosterone Testing
• Testosterone levels should be measured regularly to
ensure its suppression is being maintained to target.
• EAU guidelines recommendation: Test 3 months after
the first dose of ADT and repeated every 3−6 months
thereafter.
34. ADT and PSA Response
• Patients who had more than an 80% drop in PSA
within 1 month of initiating ADT survived significantly
longer free of disease progression.
• A rise in PSA, evidence of the emergence of
castration-resistant disease, preceded bone
metastatic progression by several months, with a
mean lead time of 7.3 months.
35. ADT and PSA Response
• In men with newly diagnosed metastatic prostate
cancer started on ADT, the absolute PSA level after 7
months of ADT was a strong, independent predictor
of survival.
37. Osteoporosis
• BMD criteria for osteopenia or osteoporosis-
– More than 2.5 standard deviations below an age
specific reference mean – Prior to the initiation of
ADT.
• After 5 yrs of ADT, fracture incidence 19.4 %.
• Over 15 years incidence 40%.
• 4 years of ADT will place the average man in
osteopenia range.
38. Osteoporosis
• Treatment begins with recognition.
• BMD of the hip for all men anticipated on long term
ADT.
• Smoking cessation, weight bearing exercise, Vitamin
D and calcium supplementation.
• Bisphosphonate pamidronate can be used for
prevention as demonstrated in some studies.
• Bisphosphonates to be used when evidence of
osteopenia or osteoporosis emerge.
40. Hot flashes
• Uncomfortable flushes of heat similar to that
experienced by women during menopause.
• Warmth in the upper torso and head followed by
objective perspiration.
• Experienced by 50-80% of patients.
• Mechanism: Increase in hypothalamic adrenergic
concentrations and alternations in endorphins and
CGRP acting on thermoregulating center in
hypothalamus.
41. Hot flashes
• Treatment reserved for bothersome patients.
• Megestrol acetate 20 mg bd can be used. Dose can
be reduced to 5 mg bd.
• Cyproterone acetate 50 mg/day titrated to 300
mg/day.
• DES and transdermal estradiol- Most effective.
• Clonidine – Centrally acting α agonist decreases
vascular reactivity.
42. Hot flashes
• Venlafaxime 12.5 mg bd can be used.
• Gabapentin decreased hot flashes to a moderate
degree in some studies.
43. Sexual Dysfunction
• 20% men on ADT have some sexual activity.
• 10-17% of men can have some erection adequate for
intercourse.
• Libido is highly compromised. Only 5% of men
maintain high level of sexual interest.
• Loss of penile volume and penile length loss of
noctural penile tumescence and loss of testicular
volume noted.
44. Sexual Dysfunction
• Treatment of libido is difficult.
• PDE 5 inhibitors or intracavernosal injections of
alprostadil can be used for erective dysfunction.
45. Cognitive function
• Hypogonadal state is associated with declines in
cognitive functioning.
• Short course of ADT is associated with increased
depression and anxiety scores.
• Major depressive disorder in 12.8% of men with ADT.
• Testosterone supplementation improves verbal
fluency.
46. Body Habitus
• Loss of muscle mass and increase in percent fat body
mass is common.
• More pronounced with initiation of ADT.
• Weight gain due to increase in body fat mass. (1.8-
3.8% increase in one year)
• Regular vigorous exercise may help to limit
accumulation of fat.
47. Diabetes and metabolic syndrome
• Present in 50% of men undergoing longterm ADT.
• Unlike visceral fat accumulation in classical metabolic
syndrome, fat accumulates in subcutaneous regions.
• HDL level is increased.
• Insulin sensitivity decreased.
48. Cardiovascular morbidity and
Mortality
• Effect more in low risk prostate cancer patients on
ADT.
• At 1 year of ADT, 20% higher risk of cardiovascular
morbidity compared to normal men.
49. Gynaecomastia
• Peripheral conversion of testosterone to estradiol
induces gynaecomastia and mastodynia.
• Bicalutamide: 66.3% Gynaecomastia, 72.7%
Mastodynia.
• Prophylactic radiation therapy (10 Gy) can be used to
prevent or reduce painful gynaecomastia.
• Liposuction and subcutaneous mastectomy can be
used for established gynaecomastia.
• Tamoxifen can be used for mastodynia.
50. Anaemia
• Normochromic, normocytic anaemia
• Decline in hemoglobin begin within 1 month of ADT
initiation. It continues for 24 months.
• Secondary to lack of testosterone stimulation of
erythroid precursors and decrease in erythropoietin
production.
• Recombinant erythropoietin can be used.
• After stopping ADT, anaemia reversal may take upto
1 year.
52. ADT Indications
1. In Localised Ca prostate
2. In Locally advanced Ca prostate
3. In Biochemical recurrence
4. In metastatic Ca prostate
53. ADT in Localised Prostate Cancer
• Preoperative ADT before RP
• Combination therapy ADT and RT
• Primary ADT (Obsolete)
54. Preoperative ADT before RP
• Preoperative ADT reduces the rate of positive
surgical margins.
• But there is no benefit in terms of progression free
survival.
• It may be beneficial in high risk disease.
55. Combination therapy ADT and RT
• Combination of ADT with external beam radiation
shows benefit in overall survival, cancer specific
survival or freedom from disease progression.
• Benefit noted in disease and/or high grade, high risk
disease.
• Low risk tumours have no benefit.
56. Combination therapy duration
• For high risk disease, Combination therapy with 3
years of ADT is superior to 6 months of ADT..
• For intermediate risk disease, 4-6 months of ADT
improves the survival relative to standard dose of
radiation alone.
57. Primary ADT
• Was used in the past extensively in the treatment of
localized prostate cancer in men with significant
comorbidities and those not willing for surgery.
• They did not live any longer than patients who
received no treatment.
• ADT as primary therapy for localised Ca prostate not
recommended.
58. ADT in Locally Advanced Ca Prostate
• Neoadjuvant ADT before RP
• Adjuvant ADT after RP
• Neoadjuvant and concurrent ADT and RT
• Adjuvant ADT and RT
59. Neoadjuvant ADT before RP
• Period was 3 months.
• Clinical downstaging of the tumour in 32% to 90%.
• Pathological downstaging observed in 8%-31%.
• Current data do not support a significant benefit of
NAD before surgery.
60. Adjuvant ADT after RP
• Not of much clinical significance.
• Recent studies shows benefit of early ADT after RP in
high risk men with locoregional disease spread.
61. Neoadjuvant ADT and RT
• 2 months before and 2 months during RT (RTOG)
• Causes reduction in target volume and potential
cytotoxic synergy of radiation and hormone
manipulation.
• Appropriate in high risk patients.
• Improvement in local control, disease free survival
and cancer specific mortality.
62. Adjuvant ADT and RT
Timing of ADT:
• RTOG (Goserelin)- Last week of RT and continued
indefinitely or at the time of relapse. (RTOG).
• EORTC (Goserelin) – Beginning of RT and continuing
for 3 years.
• Beneficial in both intermediate risk and high risk
cancers.
64. After RP
• Underevaluated, PSA value to start not known.
• High risk features show benefit-
– Gleason 8 or more,
– PSA level 15 ng/mL,
– Pathologic stage T3b, T4 or N1,
– Gleason 7 with concomitant PSA > 10 ng/mL or
– Positive surgical margin
65. After RT
• May be due to local vs distant metastatic disease.
• For local disease salvage local therapy is advised.
• 93.5% of men undergo ADT as second line therapy
after RT failure.
• PSA doubling time < 12 months- High risk of distant
failure - start ADT
• Early or delayed ADT? Unknown…Trials awaited.
• Continuous or Intermittent? May be intermittent.
68. Continuous ADT-
Immediate Vs Delayed
1. There is no survival benefit to immediate ADT in
low-risk, localized prostate cancer.
2. In locally advanced, asymptomatic metastatic and
clinically present but undefined prostate cancer
treated in a community setting with limited disease
monitoring, immediate ADT results in significantly
better prostate cancer–specific survival but not
better overall survival.
69. Continuous ADT-
Immediate Vs Delayed
3. On the other hand, in men deemed not suitable for
local treatment, immediate ADT improved overall
survival but not prostate cancer–specific survival.
4. In node-positive disease without primary treatment,
there is no significant advantage to immediate ADT.
5. In node-positive disease with radical prostatectomy,
there is a significant survival advantage favoring
immediate ADT, with a 2.6-year difference in median
overall survival.
70. Intermittent ADT - Rationale
• Intermittent ADT may lengthen the time to the
emergence of androgen-refractory cancer growth.
• Side effects of continuous ADT are severe.
• Intermittent ADT improves the quality of life of
patients.
72. Combined Androgen Blockade
• Idea is to remove the testicular and non testicular
source of androgens.
• Combination of antiandrogen with either castration
or an LHRH agonist, the results are conflicting.