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AUA 2021: AUA Guidelines: Advanced Prostate Cancer

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(UroToday.com) In this plenary session, Dr. William Thomas Lowrance summarized the 2021 AUA / ASTRO / SUO guidelines for advanced prostate cancer and highlighted important takeaway points.Complete two-part guidelines1,2 You can find it online. They are also listed in the Journal of Urology.

He reiterated that these guidelines were developed by an interdisciplinary panel of representatives from AUA, ASCO, ASTRO, and SUO. They also included defenders of the patient.

The purpose of the guidelines is to support clinical decision-making and to provide evidence-based guideline recommendations throughout the continuum of advanced prostate cancer.

They utilized a statement evidence assessment in the range A to C. A represents high certainty and C represents very low certainty.

He states that the treatment environment for advanced prostate cancer requires interdisciplinary patient care, including urologists, medical oncologists, radiation oncologists, pathologists, genetic counselors, and palliative care. Treatment includes a combination of systemic therapy with or without topical therapy, advanced diagnostic imaging, germline and somatic genetic testing.

As you can see in his slide below, the guidelines focus on four major patient populations. They exclude patients with localized prostate cancer and discuss only those who appear to have exhausted all topical treatment options. There is another set of guidelines for identifying prostate cancer.

He then reviewed the recommendations of the main guidelines for each of the above four categories summarized below.

1) Biochemically recurrent prostate cancer
In the hormonal sensitivity setting, PSA recurrence most often precedes clinical detection of metastases. For these patients, the guidelines recommend that:

  1. Clinicians should inform patients with PSA recurrence after depletion of topical therapy regarding the risk of developing metastatic disease.
  2. Serial PSA measurement
  3. Clinical evaluation
  4. Staging – Traditional Imaging (CT A / P or MRI and NM Bone Scintigraphy)

He states that while clinicians may consider radiographic evaluations based on overall PSA and PSA kinetics (clinical principles), patients may be risk stratified. For patients at high risk of developing metastases (such as PSADT <12 months), it is recommended that the clinician perform a regular staging assessment consisting of cross-sectional images (CT, MRI) and technetium bone scintigraphy. (Clinical principle)

For new PET-CT scans (eg, flucyclobin, choline, PSMA), the authors do not recommend these as routine tests. However, they can be considered as an alternative to traditional imaging or as a negative traditional imaging setting. (Expert opinion)

Regarding treatment:

  1. If traditional diagnostic imaging does not prove metastatic disease, the clinician should provide observation or enrollment in a clinical trial.
    -Recommended daily use of ADT with this setting
  2. ADT should not be started on a daily basis in this group (expert opinion). However, if ADT is initiated in the absence of metastatic disease, intermittent ADT may be offered instead of continuous ADT due to the low side effect profile.

2) Metastatic hormone-sensitive prostate cancer (mHSPC)

This category includes men with metastatic disease that are still hormone-sensitive and are clearly radiographed. The presence and extent of metastatic disease play a central role in determining which treatments are beneficial. Therefore, we recommend the following:

  1. Traditional radiographic assessment of the degree of disease burden (bone, lymph node, visceral metastases) – stratified into high and low metastatic loads
    -Massive is defined as four or more bone metastases with at least one metastasis outside the spine / pelvis and / or with visceral metastases. (Medium recommendation: Evidence level: Grade B)
  2. Symptom Discussion – Assess whether a patient is experiencing symptoms due to metastatic burden
  3. Baseline and Serial PSA-Clinicians should obtain baseline PSA and serial PSA at 3-6 intervals after the start of ADT in patients with mHSPC and consider regular conventional diagnostic imaging.
  4. Genetic counseling and germline germline testing – for all men regardless of age or family history

Clinicians should provide patients with mHSPC with either LHRH agonists or antagonists or ADT with surgical castration.

Treatment options for this patient population are:

  1. ADT with LHRH agonist / antagonist or surgical castration
  2. Continued ADT with androgen pathway-directed therapy (enzalutamide, appartamide, avilateron) or chemotherapy (docetaxel)
  • Tests supporting docetaxel: CHAARTED, STAMPEDE
  • Tests to support Avilateron: LATITUDE, STAMPEDE
  • Tests supporting enzalutamide: TITAN
  • Tests to support appartamide: ARCHES, ENZAMET
  1. ADT with first-line radiation therapy to the prostate – a small amount of disease.

They state that clinicians should not provide patients with mHSPC with first-generation antiandrogens (bicalutamide, flutamide, nilutamide) in combination with LHRH agonists, except to block testosterone flare. They also stated that clinicians should not provide patients with mHSPC with oral androgen pathway-directed therapies (eg, avilateron acetate and prednisone, appartamide, bicalutamide, dalortomid, enzalutamide, flutamide, nilutamide) without ADT. I am.

3) Non-metastatic castration-resistant prostate cancer (nmCRPC, cM0 CRPC)

This category includes men with elevated PSA but no visible metastatic disease on conventional images, despite medical or surgical castration. This represents a unique medical condition. For patients in this condition, monitoring includes:

  1. Serial PSA every 3-6 months
  2. Traditional imaging every 6-12 months

Recently, three androgen receptor antagonists have been approved for these patients because they have shown extended metastasis-free survival compared to ADT Plus placebo. These include avilateron, enzalutamide and appartamide. The data for the main exams are as follows:

image-1.jpg

He emphasized the fact that PSADT may be at risk of stratifying patients for receiving AR-oriented therapy.

  • Clinicians should provide patients with nmCRPC at high risk of developing metastatic disease (PSADT ≤ 10 months) with appartamide, dalortamide, or enzalutamide with continuous ADT.
  • Clinicians may recommend continuous ADT observations for patients with nmCRPC, especially those at low risk of developing metastatic disease (PSADT> 10 months).

Chemotherapy and immunotherapy should not be offered outside of clinical trials in the area of ​​this disease.

4) Metastatic castration-resistant prostate cancer (mCRPC)

Treatment of patients with mCRPC has changed dramatically over the last decade and now there are many treatment options for these patients.

Patients with mCRPC require a thorough prognostic assessment, including:

  1. Baseline Lab (psa, testosterone, LDH, Hgb, alkaline phosphatase)
  2. Assessment of disease-related symptoms
  3. Performance status
  4. Traditional staging images – at least annually or based on patient symptoms
  5. Germline and somatic tumor testing in all patients may help with prognosis and counseling on family risks and potential targeted therapies DNA repair deficiency mutations (DDR mutations) and microsatellite instability Identifies the status of (MSI).

Since the initial approval of docetaxel, there have been multiple drugs that have shown life-prolonging effects in the strength of randomized controlled trials. These drugs have been tested in multiple “disease states” within the mCRPC.

He did not dig into the details of the various trials that led to the approval of these drugs. But he summarized the important signs for using them.

  1. Continuous ADT – All Patients Must Maintain Continuous ADT
  2. Avilaterone, Enzalutamide, or Docetaxel-All patients should be provided with continuous ADT in combination with Avilaterone acetate with prednisone, docetaxel, or enzalutamide. (Strong Recommendation; Level of Evidence: Grade A [abiraterone acetate plus prednisone and enzalutamide]/ NS [docetaxel]).
  3. Sipaleucil-T-Can be provided to patients with mCRPC who are asymptomatic or minimally symptomatic
  4. Radium-223 – Can be provided to patients with bone metastases from mCRPC and no known visceral disease or lymphadenopathy> 3 cm.
  5. Cabazitaxel
    -Clinicians may provide cabazitaxel in patients with mCRPC who have previously received docetaxel chemotherapy with or without prednisone or enzalutamide for the treatment of CRPC
    -In patients with mCRPC who have previously received docetaxel chemotherapy and avilateron acetate and prednisone or enzalutamide, clinicians should recommend cabazitaxel rather than alternative androgen pathway-directed therapy.
  6. Olaparib / PARP Inhibitors-Clinicians inhibit PARP in patients with harmful or harmful germline or homologous recombinant repair gene mutations mCRPC after prior treatment with enzaltamide or avilateron acetate and / or taxan-based chemotherapy You need to provide the agent. If it cannot tolerate PARP inhibitors, these patients should consider platinum-based chemotherapy.
  7. Pembrolizumab – Patients with mCRPC with high mismatch repair deficiency or microsatellite instability should consider pembrolizumab.

When ordering the above treatments, clinicians should consider prior treatments and recommending treatments with different mechanisms of action. Therefore, if one AR-targeted drug fails, subsequent treatment should not be another AR-targeted drug.

5) Bone health

His last section of the guidelines focused on bone health. He states that several factors are colluding to put the average patient with metastatic prostate cancer at a higher risk of bone complications.

  • Patients with prostate cancer tend to be older and have an element of age-related osteoporosis
  • Patients with advanced prostate cancer are exposed to ADT, which has been shown to have a detrimental effect on bone mineral density
  • Pathological fractures are also a concern because prostate cancer tends to metastasize to bone

Based on these guidelines, we recommend the following:

  1. Clinicians should recommend preventative treatment for fracture and skeletal-related events such as calcium, vitamin D supplementation, quitting, and weight-bearing exercise in patients with advanced prostate cancer with ADT.
  2. In patients with advanced prostate cancer who are at high risk of fracture due to bone loss, clinicians recommend prophylactic treatment with bisphosphonates or denosumab and refer to doctors who are familiar with osteoporosis management as needed. is needed.
  3. Clinicians should prescribe a bone protectant (denosumab or zoledronic acid) to patients with mCRPC with bone metastases to prevent skeletal-related events.

Closing words:

Finally, he pointed out that there are some important areas of future research that are not fully integrated into the guidelines:

  • Interdisciplinary care integration
  • Advanced PET imaging
  • Biomarker
  • Other systemic therapies

These will need to be included in the future as the level of evidence increases.

Presenters: William Thomas Lowrance, MD, MPH, MBA, Associate Professor of Urology, University of Utah School of Medicine, Bon Secours Mercy Health

Author: Thenappan (Thenu) Chandrasekar, MD – Urological Oncology Associate Professor, Associate Professor of Urology, Sidney Kimmel Cancer Center, Thomas Jefferson University, @ tchandra_uromd on Twitter 2021 American Urological Association (AUA) Annual Meeting, Friday, September 10, 2021 to Monday, September 13, 2021.

reference:

1.1. Lowrance WT, Breau RH, Chou R et al: Advanced Prostate Cancer: AUA / ASTRO / SUO Guideline Part IJ Urol 2021; 205: 14
2.2. Lowrance WT, Breau RH, Chou R et al: Advanced Prostate Cancer: AUA / ASTRO / SUO Guideline Part II. J Urol 2021; 205: 22.

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2/ http://www.urotoday.com/conference-highlights/aua-2021-program/aua-2021-prostate-cancer/131951-aua-2021-aua-guidelines-advanced-prostate-cancer.html

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