Abstract
Purpose:
In 2022 the American Urological Association (AUA) requested an Update Literature Review (ULR) to incorporate new evidence generated since the 2020 publication of this guideline. The resulting 2023 Guideline Amendment addresses updated recommendations for patients with advanced prostate cancer.
Materials and Methods:
The ULR addressed 23 of the original 38 guideline statements and included an abstract-level review of eligible studies published since the 2020 systematic review. Sixteen studies were selected for full text review. The current summary presents the updates made to the Guideline as a result of that new literature.
Results:
The Advanced Prostate Cancer Panel amended evidence- and consensus-based statements based on an updated review to aid clinicians in the management of patients with advanced prostate cancer. These statements are detailed herein.
Conclusion:
This Guideline Amendment provides a framework designed to improve a clinician’s ability to treat patients diagnosed with advanced prostate cancer with the most current evidence-based information. Further research and publication of high-quality clinical trials will be essential to continue to improve the quality of care for these patients.
| 95%CI |
95% confidence interval |
| ADT |
Androgen deprivation therapy |
| ARSI |
Androgen receptor signaling inhibitor |
| ART |
Androgen receptor-targeted therapy |
| AUA |
American Urological Association |
| CRPC |
Castration-resistant prostate cancer |
| CT |
Computed tomography |
| DDR |
DNA-damage response |
| FDA |
U.S. Food and Drug Administration |
| GINA |
Genetic Information Nondiscrimination Act |
| HR |
Hazard ratio |
| mCRPC |
Metastatic castration-resistant prostate cancer |
| MDT |
Metastasis-directed therapy |
| mHSPC |
Metastatic hormone-sensitive prostate cancer |
| MRI |
Magnetic resonance imaging |
| MSI |
Microsatellite instability |
| MSI-H |
Microsatellite instability-high |
| nmCRPC |
Non-metastatic castration-resistant prostate cancer |
| OS |
Overall survival |
| PARP |
Poly-ADP ribose polymerase |
| PET |
Positron emission tomography |
| PFS |
Progression-free survival |
| PSA |
Prostate-specific antigen |
| PSADT |
PSA doubling time |
| PSMA |
Prostate-specific membrane antigen |
| QOL |
Quality of life |
| SABR |
Stereotactic ablative radiotherapy |
| SBRT |
Stereotactic body radiotherapy |
| SOC |
Standard of care |
| SUO |
Society of Urologic Oncology |
| ULR |
Update Literature Review |
BACKGROUND
Epidemiology
Prostate cancer is the most common solid organ malignancy among men in the U.S. and remains the second leading cause of cancer deaths for this population. In fact, approximately 288,300 new diagnoses of prostate cancer and 34,700 deaths are estimated in the U.S. in 2023.1 The incidence of prostate cancer is 70% higher in Black men as compared to White men for reasons that remain unclear.1 Importantly, the incidence of advanced stage disease including metastatic hormone-sensitive prostate cancer (mHSPC) has been increasing by about 5% per year in recent years. Unfortunately, prostate cancer mortality among Black men is approximately double that of men in most other groups. This disproportionate impact of prostate cancer morbidity and mortality on Black men is an area of active investigation that includes new approaches to screening, access to care, and treatment considerations among these men.2 While metastatic prostate cancer remains a lethal disease, improvements in overall survival (OS) through combination therapies have resulted in a renaissance in the entire landscape for clinicians caring for men with advanced metastatic prostate cancer. At present, there is limited data-driven evidence regarding optimal agent combination or sequence. It is against this backdrop that the Panel provides evidence-based guidance for treatment of men with advanced prostate cancer.
Figure 1. AUA/SUO Advanced Prostate Cancer Algorithm.
GUIDELINE STATEMENTS
The 2020 guideline organized statements into 6 sections to cover the 4 advanced prostate cancer disease states, as defined in the Guideline, in addition to separate sections on evaluation and bone health. Through this update, the Panel determined that statement changes were not needed for the “Early Evaluation and Counseling” and “Bone Health” sections; however, the Panel did update supporting text to note the recommended inclusion of mental health professionals as 1 of many experts who may be included in the multidisciplinary care team for patients with advanced prostate cancer. The full Guideline is summarized in Figure 1 with 2023 updates detailed herein.
Biochemical Recurrence Without Metastatic Disease after Exhaustion of Local Treatment Options
Prognosis
-
In patients with prostate-specific antigen (PSA) recurrence after failure of local therapy who are at higher risk for the development of metastases (eg, PSA doubling time [PSADT] <12 months), clinicians should perform periodic staging evaluations consisting of cross-sectional imaging (computed tomography [CT], magnetic resonance imaging [MRI]) and technetium bone scan, and/or preferably prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging. (Clinical Principle)
-
Clinicians should utilize PSMA PET imaging preferentially, where available, in patients with PSA recurrence after failure of local therapy as an alternative to conventional imaging due to its greater sensitivity, or in the setting of negative conventional imaging. (Expert Opinion)
Based on the evolution of novel imaging techniques, PSMA PET is now included as an option for staging evaluation in this patient population. There are now 2 FDA approved PSMA PET agents for patients with advanced prostate cancer (68Ga-PSMA-11 and Piflufolastat F-18 [18F-DCFPyL]),3,4 which demonstrate greater sensitivity than conventional imaging in patients, including those with suspected recurrence based on rising PSA levels.
Similarly, PSMA PET is also now recommended, where available, for patients as an alternative to conventional imaging or in the setting of negative conventional imaging. While advanced imaging techniques may enhance detection of metastatic lesions, the impact on patients and OS has yet to be fully demonstrated. To date, there is limited evidence suggesting benefit in terms of a delay in disease progression (ORIOLE)5 or improvement in OS (SABR-COMET).6 Further, limited evidence remains that metastasis-directed therapy (MDT) confers a survival benefit.7
Treatment
-
For patients with a rising PSA after failure of local therapy and no demonstrated metastatic disease by imaging, clinicians should offer observation or clinical trial enrollment. (Clinical Principle)
As other imaging techniques become available, the Panel felt it was appropriate to update this statement to reflect that conventional imaging is no longer the only imaging modality available to detect metastatic disease amongst patients with a rising PSA.
Currently, there are no systemic treatments with proven efficacy in men without metastatic disease who have received maximal local therapy. The overall course of a rising PSA after failure of local therapy is highly variable with earlier recurrences indicative of more aggressive disease.
Any potential benefit of early initiation of systemic therapy must also be weighed against the impact of treatment of adverse events and quality of life (QOL). In the TOAD trial, men in the early androgen deprivation therapy (ADT) arm had higher rates of hormone-treatment-related symptoms and inferior QOL related to sexual activity.8
While observation or a clinical trial is preferred, it is recognized that ADT is sometimes given to men with rapid PSA rises in the absence of radiographic metastases in an attempt to delay the appearance of metastases. There currently is no evidence to determine the best time to start ADT in the absence of radiographic metastases.
Metastatic Hormone-Sensitive Prostate Cancer (mHSPC)
Prognosis
-
Clinicians should assess the extent of metastatic disease (lymph node, bone, and visceral metastases) in newly diagnosed mHSPC patients. (Clinical Principle)
This statement was updated to reflect the availability of non-conventional imaging modalities to assess metastatic disease.
The presence and extent of metastatic disease plays a central role in determining therapeutic options. Patients without metastatic disease have not been shown to benefit from aggressive systemic therapy. Studies of systemic therapy have demonstrated that extent of metastatic disease influences response. As a result, presence of metastatic disease, its burden, and precise locations should be assessed prior to treatment.
Patients diagnosed with aggressive cancer defined by D’Amico risk factors (cT3a or greater, Grade Group 4/5, or PSA >20ng/mL) should undergo routine bone scan and cross-sectional imaging (CT or MRI) or PET imaging at the time of diagnosis. PSMA PET availability is increasing in the U.S. and detects metastatic disease at low PSA values.
Both 68Ga-PSMA-11 and 18F-DCFPyL are indicated for patients with suspected prostate cancer metastasis, considering local therapy, as well as for patients with suspected prostate cancer recurrence based on elevated serum PSA levels. Utilization of PSMA PET may lead to the diagnosis of metastatic disease not previously detected with conventional imaging.
-
In patients with mHSPC, clinicians should offer germline testing, and consider somatic testing and genetic counseling. (Clinical Principle)
This statement was updated to note the value of germline testing in this patient population and the consideration for somatic testing. Germline testing should include, when possible, counseling by someone knowledgeable about the implications of testing. Counseling may include a discussion of possible test results; implications for patients; discussion of the Genetic Information Nondiscrimination Act (GINA); possible impact of test results on life, disability, and long-term care insurance; and potential role of cascade testing of family members if a pathogenic or likely pathogenic mutation is identified. Post-test counseling with a genetic counselor is necessary for anyone who is found to have 1 of these mutations.
Treatment
-
In patients with mHSPC, clinicians should offer ADT in combination with either androgen pathway directed therapy (abiraterone acetate plus prednisone, apalutamide, enzalutamide) or chemotherapy (docetaxel). (Strong Recommendation; Evidence Level: Grade A)
The Panel determined that this statement needed a small modification to remove “continued” ADT as some patients may have not previously received ADT.
mHSPC remains an incurable manifestation of the disease. While ADT, with or without non-steroidal antiandrogens, has been the backbone of mHSPC treatment for many decades, ADT alone is no longer considered sufficient treatment for mHSPC. In just the past 5 years, multiple studies have shown that additional therapy significantly extends OS and progression-free survival (PFS) in mHSPC patients.
Docetaxel
In the STAMPEDE trial,9 ADT plus docetaxel significantly improved median OS compared to ADT alone. The durability of these results was supported in an update of this trial. At a median follow-up of 78.2 months, there were 494 deaths on standard of care (SOC). There was good evidence of benefit in docetaxel over SOC on OS (HR=0.81; 95% CI: 0.69 to 0.95; P = .009). Analysis of other outcomes found evidence of benefit for docetaxel over SOC in failure-free survival (HR=0.66; 95% CI: 0.57 to 0.76; P < .001) and PFS (HR=0.69; 95% CI: 0.59 to 0.81; P < .001).10
Like many chemotherapy agents, docetaxel has a significant toxicity profile that needs consideration. In the STAMPEDE trial, the most frequently reported adverse events in the SOC plus docetaxel group included febrile neutropenia (15%), general disorder (including lethargy, fever, asthenia—7%), and gastrointestinal disorder (including diarrhea, abdominal pain, constipation, vomiting—8%).9
Abiraterone Acetate
Abiraterone acetate is a nonsteroidal irreversible inhibitor of CYP17A1, which catalyzes the conversion of C21 progesterone precursors to C19 adrenal androgens, DHEA, and androstenedione.11 In essence, abiraterone acetate is similar to ADT, but it is more potent, inhibiting gonadal and extragonadal androgen synthesis.
In the double-blind, placebo-controlled, phase 3 LATITUDE trial,12 1,199 patients were randomly assigned to receive either ADT plus abiraterone acetate (1,000mg given once daily as four 250mg tablets) plus prednisone (5mg daily) or ADT plus placebo. The primary endpoints were OS and radiographic PFS. Updated results on this trial continue to confirm benefit in this trial. The final analysis of this trial, at a median follow-up of 51.8 months, OS was significantly longer in the abiraterone acetate plus prednisone group (median 53.3 months [95% CI: 48.2 to not reached (NR)]) compared to the placebo group (36.5 months [33.5 to 40.0]), with an HR of 0.66 (95% CI: 0.56 to 0.78; P < .0001).13
Apalutamide
Apalutamide is a novel androgen receptor signaling inhibitor (ARSI). In the double-blind, phase 3 TITAN study,14 525 patients were assigned to receive apalutamide (240mg daily) with ADT compared to 527 patients receiving placebo plus ADT. Primary endpoints included radiographic PFS and OS. At the time of final analysis (44.0 months median follow-up), a total of 405 deaths had occurred (170 in the apalutamide arm, 235 in the placebo arm). An improvement in median OS was observed: NR in the apalutamide group versus 52.2 months in the placebo group (HR=0.65; 95% CI: 0.53 to 0.79; P < .0001), with a 35% reduction in risk of death.15 Rash of any grade was more common among patients who received apalutamide compared to those who received placebo (27.1% versus 8.5%).
Enzalutamide
Enzalutamide is a novel ARSI. It is a competitive inhibitor of androgen binding and also inhibits nuclear translocation of the androgen receptor, DNA binding, and coactivator recruitment.16
In an update on the phase 3 ARCHES trial, the final pre-specified analysis of OS, which was a key secondary end point, and an update on radiographic PFS was reported. Following unblinding, 180 (31.3%) progression-free patients randomly assigned to placebo plus ADT crossed over to open-label enzalutamide plus ADT. At a median follow-up of 44.6 months, 154 of 574 patients randomly assigned to enzalutamide plus ADT and 202 of 576 patients randomly assigned to placebo plus ADT had died. Enzalutamide plus ADT reduced risk of death by 34% versus placebo plus ADT (median NR in either group; HR=0.66; 95% CI: 0.53 to 0.81; P < .001).17
Enzalutamide, apalutamide, and darolutamide do present a small risk of seizures, so patients with a seizure disorder should instead choose a drug like abiraterone acetate plus prednisone or docetaxel.
Therapeutic Decision-making in mHSPC
Unfortunately, no comparative data on efficacy exist between the previously discussed options. The clinician should consider factors like age and comorbidities when choosing chemotherapy, where toxicity might be more difficult for older patients than fit younger patients. Duration of treatment may also influence choice. Further, in select patients with metastatic presentations, particularly de novo metastatic patients, triplet therapy is recommended (see following statement).
Given all of the recent data suggesting that additional therapy (chemotherapy or androgen receptor-targeted therapy [ART]) added to continuous ADT significantly improves OS, the Panel generally advises against intermittent ADT in otherwise healthy patients with mHSPC.
-
In selected patients with de novo mHSPC, clinicians should offer ADT in combination with docetaxel and either abiraterone acetate plus prednisone or darolutamide. (Strong Recommendation; Evidence Level: Grade A [Abiraterone]/Grade B [Darolutamide]
The Panel developed a new statement based on results of 2 phase 3 randomized trials demonstrating improvement in OS of patients receiving either abiraterone acetate (with prednisone) or darolutamide in addition to ADT and docetaxel in selected patients with de novo metastatic prostate cancer.
It is noted that the optimal patient for consideration of “dual intensification” or “triplet therapy” are best represented by the patients enrolled in the following 2 completed trials who are patients with de novo disease and are free of major comorbidities.
The PEACE-1 trial enrolled 1,173 patients with de novo metastatic prostate cancer who were randomized to receive ADT plus docetaxel (considered the SOC) plus radiotherapy, SOC plus abiraterone/prednisone or SOC plus abiraterone/prednisone and radiotherapy. In the initial analysis of the study, patients treated with SOC plus abiraterone/prednisone had an improvement in both OS (HR=0.82; 95.1% CI: 0.69 to 0.98; P = .030) and radiographic PFS (HR=0.54; 99.9% CI: 0.41 to 0.71; P < .0001) with some increase in toxicity in the abiraterone group, primarily being more hypertension. Data from the radiotherapy arms are anticipated in the near future.18
The ARASENS phase 3 study enrolled 1,306 patients with mHSPC (86.1% of enrolled patients had de novo metastatic disease) and randomized them to receive either darolutamide or placebo in combination with ADT and docetaxel. The trial demonstrated that the combination of darolutamide plus ADT/docetaxel resulted in improved OS, with the risk of death reduced by 32.5% (HR=0.68; 95% CI: 0.57 to 0.80; P < .001). The frequency of grade 3/4 events was similar between the treatment arms.19
As the majority of patients treated in both PEACE-1 and ARASENS had de novo metastatic disease, the role of “dual intensification” or “triplet therapy” in patients with mHSPC with progression following curative-intent local therapy remains undefined.
Non-Metastatic Castration-Resistant Prostate Cancer (nmCRPC)
Prognosis
-
Clinicians should assess nmCRPC patients for development of metastatic disease using conventional or PSMA PET imaging at intervals of 6 to 12 months. (Expert Opinion)
The Panel updated this statement to note the inclusion of PSMA PET imaging when monitoring the disease status of men with nmCRPC in addition to monitoring PSA. The suggested interval for imaging is 6 to 12 months, with the exact interval determined by the PSADT calculation, the development of symptoms, and patient/clinician preference. A PSADT of ≤10 months is associated with a high risk of developing metastatic disease or dying from prostate cancer.20
Once a patient has started ART therapy for nmCRPC, the imaging intervals can be extended to annually in the absence of other indicators of progression.
Metastatic Castration-Resistant Prostate Cancer (mCRPC)
Prognosis
-
In mCRPC patients without PSA progression or new symptoms, clinicians should perform imaging at least annually. (Expert Opinion)
The Panel determined that this statement needed a revision to emphasize that clinicians should perform imaging at least annually for mCRPC patients without PSA progression or new symptoms. It is recommended that men with mCRPC undergo imaging at least annually owing to the fact that, in patients with mCRPC treated with enzalutamide prior to chemotherapy in the PREVAIL trial, radiographic progression occurred in 24.5% of patients without PSA progression. This suggests routine imaging can identify a significant portion of patients with radiographic progression who would otherwise not be identified.21
-
In mCRPC patients with disease progression (PSA or radiographic progression or new disease related symptoms) having previously received docetaxel and androgen pathway inhibitor, who are considering 177Lu-PSMA-617, clinicians should order PSMA PET imaging. (Expert Opinion)
A new statement was warranted based on the phase 3 VISION study. The study enrolled 831 men with mCRPC previously treated with at least 1 androgen pathway inhibitor and 1 or 2 prior taxane regimens who had PSMA-positive 68Ga-PSMA-11 PET/CTs. Patients were randomized 2:1 to receive either 177Lu-PSMA-617 every 6 weeks for 4 to 6 cycles plus protocol-permitted SOC versus SOC alone. At a median follow-up of approximately 21 months, 177Lu-PSMA-617 plus SOC improved both PFS and OS compared to SOC alone (median, 8.7 versus 3.4 months; HR=0.40; 99.2% CI: 0.29 to 0.57; P < .001 and median, 15.3 versus 11.3 months; HR for death= 0.62; 95% CI: 0.52 to 0.74; P<.001, respectively). The incidence of grade 3 or higher adverse events was 52.7% versus 38% for 177Lu-PSMA-617 versus SOC, respectively; however, QOL was no different between the treatment arms.22
-
In patients with mCRPC, clinicians should offer germline (if not already performed) and somatic genetic testing to identify DNA repair deficiency, microsatellite instability (MSI) status, tumor mutational burden, and other potential mutations that may inform prognosis and familial cancer risk as well as direct potential targeted therapies. (Clinical Principle)
This statement underwent minor updates to note that clinicians should offer germline testing, if not already performed, and somatic genetic testing to identify several factors that may inform prognosis and prostate cancer risk. Germline testing may also be used to counsel patients regarding their family risk of associated malignancies. The landscape of evidence detailing the interactions between mutations and treatment individualization continues to evolve, and the use of genetic testing may ultimately enable the treating clinician to offer a personalized approach to prostate cancer treatment.
Treatment
-
In newly diagnosed mCRPC patients who have not received prior androgen receptor pathway inhibitors, clinicians should offer continued ADT with abiraterone acetate plus prednisone, docetaxel, or enzalutamide. (Strong Recommendation; Evidence Level: Grade A [abiraterone acetate plus prednisone and enzalutamide]/Grade B [docetaxel])
This statement was modified to specify mCRPC patients who have not received prior androgen receptor pathway inhibitors. Abiraterone acetate plus prednisone, enzalutamide, and docetaxel chemotherapy all have an FDA indication for use in men with mCRPC. For each agent, there are randomized clinical trials that show a survival benefit for men with mCRPC.23-30
-
Clinicians should offer 177Lu-PSMA-617 to patients with progressive mCRPC having previously received docetaxel and androgen pathway inhibitor with a positive PSMA PET imaging study. (Strong Recommendation; Evidence Level: Grade B)
A new statement was added on offering 177Lu-PSMA-617 to patients with progressive mCRPC as previously discussed. Patients receiving 177Lu-PSMA-617 plus SOC in the phase 3 VISION study showed improved PFS and OS compared to patients receiving SOC alone at a median follow-up of approximately 21 months.22
FUTURE DIRECTIONS
Advanced PET Imaging and Theranostics
PSMA PET imaging can identify sites of prostate cancer with superior specificity and sensitivity compared to conventional imaging.31-33 These findings are already impacting treatment planning by altering clinician decision-making, but they have yet to demonstrate a clear benefit specific to patient outcomes.34 With recent expanded indications for PSMA PET imaging in newly diagnosed high-risk individuals, the impact and implications of additional findings remains to be determined. Use of these imaging agents will allow for identification of metastatic sites not otherwise seen with conventional imaging.
To date, there is a lack of prospective randomized data evaluating PET as a staging study for untreated prostate cancer, mHSPC, or CRPC.35
PSMA-based therapeutics, or theranostics, are a new treatment emerging from the ability to target PSMA expressed on the surface of cancer cells. These use the homing ability of PSMA-targeted antibodies or small molecules coupled to radioligands, such as 177Lutetium, to target prostate cancer cells systemically.36 Given the positive results of the VISION trial in advanced CRPC, research is now turning to its earlier use within the CRPC disease state as well as investigation into mHSPC, biochemical recurrence, and possibly even neoadjuvant therapy for high-risk localized disease. The durability of these treatments is being evaluated in multiple prospective clinical studies. This is another area in which integrated multidisciplinary care will be important and will require the expertise of multiple specialties (eg, medical oncology, nuclear medicine, radiation oncology).
MDT
Given the ability to identify metastatic sites earlier than was previously possible using newer PET imaging modalities, there has been renewed interest in the concept of MDT with radiation, surgery, or ablative technologies. The majority of data consists of retrospective studies to date.37 However, in M1 patients with hormone-sensitive oligometastatic disease (defined as <3 sites) after local treatment, 2 small randomized phase 2 trials tested whether MDT delays systemic treatment. Utilizing PET choline imaging in 62 patients, the STOMP trial found that median ADT-free survival was 13 months for the surveillance group and 21 months for the MDT group (HR=0.6; 80% CI: 0.40 to 0.90; P = .11).38 QOL was comparable at baseline, 3 months, and 1 year of follow-up. In the phase 2 ORIOLE trial 54 patients were randomized to receive stereotactic ablative radiotherapy (SABR) or observation alone using PSMA PET imaging. The primary endpoint was progression after 6 months, which was significantly lower with stereotactic body radiotherapy (SBRT) than with surveillance (19% versus 61%, P = .005). It was also found that consolidation of all PSMA-positive disease decreased the risk of new lesions at 6 months (16% versus 63%; P = .006).5
PSMA and choline PET contribute to directing MDT. However, there is a lack of data regarding OS as well as selection criteria to identify those patients who will benefit. Therefore, MDT is not recommended outside of clinical trials until the results of several ongoing randomized trials become available. SOC (systemic therapy and prostate radiotherapy (RT) if low volume)±SBRT to metastatic sites is being prospectively analyzed in phase 3 trials, including START MET(NCT05209243) and PRESTO (NCT04115007).
Biomarkers and Other Systemic Therapies
Currently, the most promising markers are those associated with clinical interventions such as identification of germline or somatic alterations within DNA-damage response (DDR) genes (eg, BRCA1, BRCA2, and ATM) providing evidence for poly-ADP ribose polymerase (PARP) inhibitor use and MSI-high (MSI-H) status providing evidence of immune checkpoint inhibitor use.
The potential importance of germline and somatic tumor testing, covered in the guideline statements, largely surrounds their promise for predicting responses to PARP inhibitors such as olaparib, rucaparib, niraparib, veliparib, and talozaparib. Because PARP inhibitors, such as FDA approved agents olaparib and rucaparib, target the DNA replication machinery, tumors with deficiencies in homologous recombination repair (eg, BRCA1 or BRCA2 mutations) are uniquely sensitive to PARP inhibition, a phenomenon termed synthetic lethality. In addition to PARP inhibitors, immunotherapies have also emerged as a key therapeutic modality in a large number of solid tumors. Aside from sipuleucil-T, these treatments have generally shown less efficacy in advanced prostate cancer compared to other malignancies, in part related to the relatively low tumor mutational burden of most prostate cancers.39
Unmet Needs
While advances have been made, there are many unmet needs in prostate cancer management. Black patients with advanced prostate cancer demonstrate worse outcomes, and understanding the societal and biological underpinnings of these disparities is a critical area of need. Personalized care with predictive markers for treatment selection based on tumor and host biology have not yet been achieved. PSMA imaging is changing the landscape of advanced prostate cancer. As we learn more about its utility in the management of these patients, we will soon also be able to treat these patients with precision guided therapy. The emerging field of theranostics will add further benefit and complexity to the sequencing dilemmas. Emerging evidence supports the use of SBRT as MDT for oligometastatic genitourinary cancers in phase 2 trials.6 With the widening use of next-generation imaging, application of MDT as SOC requires definitive trials. Improving responses by treating high-risk patients in a neoadjuvant approach prior to surgery based on tumor susceptibilities is another area of developing interest.
There are many additional unmet needs. These include high-level evidence directed at understanding the optimal sequencing of advanced prostate cancer therapies. Further, we need additional studies and data to guide clinicians and patients in terms of treatment intensification and combinations of therapy. Improving access to care for those who are socioeconomically disadvantaged is also a future goal.
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