Introduction
Methodology
Category, grade | Criteria |
---|---|
Quality of evidence | |
I | Evidence from at least 1 properly randomized, controlled trial * |
II | Evidence from at least 1 well-designed clinical trial without randomization, from cohort or case-controlled analytical studies (Preferably from more than 1 centre), or from multiple time-series or dramatic results from uncontrolled experiments |
III | Evidence from opinions of respected authorities based on clinical Experience, descriptive studies, or reports of expert committees |
Strength of recommendation | |
A | Both strong evidence of efficacy and substantial clinical benefit Support recommendation for use. Should always be offered |
B | Moderate evidence of efficacy—or strong evidence of efficacy but only limited clinical benefit—supports recommendation for use Should generally be offered |
C | Evidence of efficacy is insufficient to support a recommendation For or against use, or evidence for efficacy might not outweigh adverse consequences (e.g., drug toxicity, drug interactions) or Cost of the chemoprophylaxis or alternative approaches Optional |
D | Moderate evidence of lack of efficacy or of adverse outcome supports a recommendation against use Should generally not be offered |
E | Good evidence of lack of efficacy or of adverse outcome supports a recommendation against use Should never be offered |
Molecular features and biomarkers.
Recommendations
-
Tumor testing for BRCA1 and BRCA2 is recommended for patients with metastatic prostate cancer [I, A].
-
The assessment of other potential biomarkers of response should be steadily incorporated in clinical practice as further evidence emerges. Consider a broad panel including other HHR and MMR genes (and/or perform MSI assessment) (II, B).
Therapeutic approach in metastatic hormone-naive prostate cancer patients (mHNPC)
-
In symptomatic metastatic patients, ADT should be offered immediately to palliate symptoms and prolong survival (I, A).
-
Deferred ADT could be considered in selected well-informed asymptomatic patients to minimize long-term adverse effects (II,A).
-
Combination of LHRH with first generation anti-androgens for longer than one month to avoid androgen flare, does not offer clinical benefit (I, D).
b1. ADT plus Docetaxel in mHNPC
b2. ADT plus Abiraterone—prednisone in mHNPC
b3. ADT plus new generation anti-androgens
b4. Radiotherapy in mHNPC
Recommendations:
-
In high-risk or high-volume mHNPC patients, ADT should be combined with docetaxel, abiraterone, enzalutamide or apalutamide, rather than using ADT alone (I, A).
-
In low-volume mHNPC patients, RT to the primary tumor combined with systemic therapy is recommended (I, B).
Definition of castration-resistant prostate cancer (CPRC).
Recommendations:
-
Standard of care imaging for patients with nmCRPC is still conventional CT and bone scan. Perform new imaging techniques if results may condition the therapy (III,C).
-
Risk stratification can define the frequency of imaging (III;B).
Therapeutic options for nmCRPC
-
ADT should be continued in patients with CRPC (III, C).
-
For patients with high-risk nmCRPC ADT plus enzalutamide, darolutamide or apalutamide prolong MFS and OS. Selection of systemic therapy should be based on toxicity profile and an overall strategy. In view of the long-term treatment with these AR targeted agents in asymptomatic patients, potential adverse events need to be taken into consideration and the patient informed accordingly (I, A).
Criteria for selecting the therapeutic sequence in mCPRC
-
Docetaxel—prednisone should be the first option for symptomatic patients who have received ADT alone. For asymptomatic or mildly symptomatic patients, docetaxel, abiraterone–prednisone or enzalutamide are recommended (I, A)
-
In mCRPC patients who have progressed to docetaxel, abiraterone–prednisone, enzalutamide or cabazitaxel are recommended (I, A).
-
In mCRPC patients who have progressed to a new generation anti-androgen therapy docetaxel-prednisone are recommended (I, B).
-
Cabazitaxel is indicated as third line after a sequence of docetaxel and an androgen-signaling-targeted inhibitor (I, A).
-
In mCRPC patients with symptomatic bone metastases and contraindication or progression to docetaxel, radium-223 may be considered (I, B).
Aggressive variants
1. Histological evidence of small-cell prostate carcinoma |
2. Exclusively visceral metastasis |
3. Predominantly lytic bone metastasis |
4. Bulky (> 5 cm) lymphadenopathy or primary tumor with Gleason score of 8 or more at diagnosis |
5. Low PSA (< 10 ng/ml) plus high volume (≥ 20) bone metastasis at initial presentation |
6. Elevated (> 2 × ULN) LDH or CEA |
7. Short interval response (< 6 months) to androgen deprivation therapy |
-
Platinum-based chemotherapy should be considered the first option in mCRPC with clinicopathological characteristics of AVPC (II, B).
New strategies in metastatic prostate cancer (MPC)
-
Olaparib is recommended in BRCA1/BRCA2 mutated mCRPC patients after progression on at least one new generation AR targeted therapy [I, A]
-
Immune checkpoint inhibitors may be considered in patients with microsatellite instability or mismatch repair deficiency [II, B]
-
Currently, insufficient evidence is available in mCRPC to recommend Akt inhibitors [I, C] or radioligand therapy [II, B].
Criteria for genetic testing
-
Germline testing for BRCA1/2 and other genes associated with cancer predisposition syndromes is recommended for patients with a family history of cancer [I,A] as well as in all patients with metastatic prostate cancer [III, A].
-
Patients with somatic pathogenic/likely pathogenic mutations in genes linked to cancer predisposition syndromes (i.e., BRCA2) should undergo germline testing [III, A].
-
Genetic counseling by clinicians with specific training or expertise should always be offered before ordering germinal testing [III, A]