Treating Locally Advanced Prostate Cancer: What the Latest Research Shows

Table of Contents

• Key Points
• Background: Why This Research Matters
• What Is Locally Advanced Prostate Cancer?
• How the Researchers Conducted the Review
• Key Findings: The Six Major Themes
• Hormonal Therapy and Chemotherapy
• Radiotherapy Innovations
• Surgical Management
• Emerging Therapies and Biomarkers
• Advanced Imaging Techniques
• Real-World Practice and Implementation
• Clinical Implications: What This Means for Patients
• Limitations: What the Review Could Not Prove
• Recommendations and Future Directions
• Frequently Asked Questions
• Source Information

Key Points

• Locally advanced prostate cancer has grown outside the prostate (stage T3-T4) and may involve seminal vesicles or nearby lymph nodes, but has not spread to distant organs (M0).
• In the STAMPEDE trial, adding docetaxel to androgen deprivation therapy improved overall and progression-free survival in men with high-risk non-metastatic and metastatic disease.
• In the HYPO-RT-PC trial, seven-session ultra-hypofractionated radiotherapy was not worse than 39 sessions for failure-free survival at five years, with no significant rise in late side effects.
• In the SPCG-15 trial, surgery and radiotherapy with hormone therapy gave similar cancer control, but surgery was linked more to urinary and sexual problems, radiotherapy more to bowel effects.
• In the Avidity trial, PSMA PET/CT found metastases missed by routine scans, changing treatment for many men; the PROTEUS trial showed apalutamide plus hormone therapy before surgery increased pathologic complete response.

Background: Why This Research Matters

Prostate cancer is one of the most common cancers in men. It is also a leading cause of illness and death from cancer worldwide. Many prostate cancers are found early and grow slowly. However, a significant number of patients are diagnosed when the cancer has already grown beyond the prostate. This stage is called locally advanced prostate cancer (LAPC).

LAPC is defined as cancer that has extended outside the prostate capsule (stages T3 to T4). It may also involve the seminal vesicles (the glands that produce semen) or nearby lymph nodes. Importantly, at this stage the cancer has not spread to distant organs (called M0 disease).

The incidence of LAPC varies by region. These differences are mostly due to screening availability, diagnostic practices, and hospital infrastructure. In high-income countries, the introduction of prostate-specific antigen (PSA) testing led to a stage shift, meaning more cancers were caught earlier. PSA is a protein made by the prostate gland; a blood test measures its level to help detect prostate cancer.

More recently, PSA screening has become more conservative because of concerns about overdiagnosis. Overdiagnosis means finding cancers that would never have caused symptoms or harm during a man's lifetime. As a result, there is growing evidence that LAPC cases are increasing again in recent years.

In low- and middle-income countries (LMICs), the situation is different. Limited resources often lead to delayed diagnoses. As a result, LAPC remains a common way that prostate cancer first appears in these regions. The authors emphasize that understanding new treatment approaches across different clinical settings and geographical regions is essential to address the global burden of this disease.

The management of LAPC is complex. It involves several treatment types used together. These include radical prostatectomy (surgical removal of the prostate) and external beam radiotherapy (EBRT, which uses high-energy X-rays to kill cancer cells). They also include androgen deprivation therapy (ADT). Sometimes they include brachytherapy (placing radioactive seeds directly inside the prostate) or chemotherapy.

ADT is a systemic treatment. It reduces or blocks the production or action of androgens (male hormones, primarily testosterone) that fuel the growth of prostate cancer cells. These treatments may be used alone or in combination, depending on the tumor's characteristics, the patient's other health conditions, and the doctor's clinical judgment.

Combination therapies have been shown to improve cancer outcomes. However, they are also linked to an increased risk of adverse effects. These include urinary incontinence (loss of bladder control), bowel dysfunction, and sexual health problems. All of these can seriously compromise quality of life. This creates a difficult balance for doctors. They must weigh the benefits of aggressive treatment against the risk of long-term damage.

Recent developments in imaging, molecular profiling, and targeted therapy are changing prostate cancer treatment. Advances such as prostate-specific membrane antigen (PSMA) PET imaging and genomic classifiers are improving risk assessment and treatment planning. This is especially helpful in ambiguous or borderline LAPC cases. PSMA is a protein found on the surface of prostate cancer cells; PET imaging uses a radioactive tracer that binds to PSMA to find cancer in the body. Genomic classifiers are tests that analyze the genes within a tumor to predict how aggressive it is.

Additionally, second-generation androgen receptor inhibitors and immunotherapeutic agents are being investigated for use in locally advanced disease. These drugs were historically used only for metastatic prostate cancer (cancer that has spread to distant organs). These developments highlight the need for continued assessment of both established and emerging treatment options.

The authors note that although many reviews exist, most focus on early-stage or metastatic prostate cancer. Very few are devoted to the locally advanced stage alone. Furthermore, current reviews tend to focus on individual treatment types or outcomes, rather than examining the full range of interventions and patient experiences. This scoping review was designed to fill that gap.

The review was guided by three central research questions:

1. What are the current treatment strategies for LAPC, and how are they being implemented across different clinical and geographical contexts?
2. What emerging methods and innovations are being explored in the management of LAPC?
3. Where do gaps exist in terms of clinical evidence, treatment outcomes, and patient-centered care?

What Is Locally Advanced Prostate Cancer?

LAPC refers to tumors that have extended beyond the prostate capsule but have not metastasized (spread) to distant organs. This stage is classified as T3-T4, N0-N1, M0. The "T" refers to tumor size and extent, the "N" refers to lymph node involvement, and the "M" refers to metastasis. In LAPC, the cancer may involve the seminal vesicles or regional lymph nodes, but it has not reached distant sites such as bones or other organs.

This stage of disease presents a distinct therapeutic dilemma. The biological behavior of LAPC is highly variable. Some tumors respond well to treatment, while others are more aggressive. Treatment outcomes also differ widely between patients. Therefore, doctors need a management strategy that addresses the tension between controlling the disease and maintaining the patient's quality of life.

How the Researchers Conducted the Review

This scoping review followed the methodology framework developed by Arksey and O'Malley. The researchers adapted this framework using guidelines from the Joanna Briggs Institute (JBI). They reported their findings according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR).

A scoping review is a type of study that maps the breadth and nature of evidence on a topic. Unlike a systematic review, it does not evaluate the quality of individual studies or combine their results statistically. The primary goal is to identify what research exists, what it covers, and where the gaps are.

The review protocol was developed before the search strategy was adopted. However, it was not placed on an open repository because of institutional rules.

The researchers did not conduct a risk-of-bias assessment. This is consistent with JBI and PRISMA-ScR guidance for scoping reviews. The purpose was to map the breadth of evidence, not to judge the quality or synthesize results from individual studies. No formal statistical analysis or meta-analysis was performed.

Eligibility criteria: The review included studies that examined the management of LAPC in adult males aged 18 years and older. Specifically, these were patients with clinical stage T3-T4, N0-N1, M0 disease. Studies focusing exclusively on early-stage or metastatic (M1) prostate cancer were excluded.

Included studies described clinical interventions or care pathways, treatment outcomes (either cancer-related or quality-of-life-related), or explored novel and emerging therapeutic approaches. Eligible studies covered treatments such as radiotherapy, surgery, ADT, and innovative treatments.

To ensure contemporary relevance, only peer-reviewed primary research published in English between January 2013 and April 2025 was included. This encompassed randomized controlled trials (RCTs), observational studies (such as cohort studies), qualitative research, and mixed-methods studies.

Studies not addressing treatment strategies were excluded. This included research focused solely on epidemiology (how diseases spread), screening, or diagnostic techniques. The review also excluded editorials, commentaries, letters to the editor, conference abstracts without complete data, study protocols, and other reviews.

Studies from any healthcare setting and all geographic regions were considered, provided they met the other inclusion criteria.

The Population-Concept-Context (PCC) framework: The researchers used this framework to guide their eligibility criteria and focus the evidence mapping.

• Population: Adult males with LAPC
• Concept: Clinical management strategies, including surgical, radiotherapeutic, systemic, and emerging approaches
• Context: All healthcare settings, across both high-income and low- and middle-income countries (LMICs)

Information sources and search strategy: A thorough search strategy was developed with the help of an academic librarian. The electronic databases searched included MEDLINE (through PubMed), Embase, CINAHL Plus, Web of Science, and Scopus. Additional gray literature was found through Google Scholar and institutional repositories. Gray literature refers to research materials that are not formally published in commercial journals.

Search terms were created using controlled vocabulary (such as MeSH terms) and keywords about LAPC and its management. Examples include "locally advanced prostate cancer," "radiotherapy," "androgen deprivation therapy," "PSMA," and "novel therapies." Boolean operators, truncations, and filters were used to increase the sensitivity of the search. The last search was conducted in April 2025. All search results were exported to EndNote for de-duplication and screening.

Selection of sources: After de-duplication, two reviewers independently screened all titles and abstracts. Full-text screening was performed on all studies considered potentially eligible. Discrepancies were resolved through discussion or by consultation with a third reviewer.

Data charting: A standardized data extraction form guided the charting process. The following key items were extracted from each included study:

• Citation details (authors and year)
• Country of study
• Study design (e.g., RCT, cohort, case-control, qualitative)
• Sample size and participant characteristics
• Study setting (e.g., hospital, cancer center, outpatient facility)
• Type of intervention(s) examined
• Comparator(s) where applicable
• Reported outcomes (e.g., survival rates, recurrence, treatment-related toxicity, and quality of life)
• Key findings
• Any stated gaps or recommendations for future research

Two reviewers extracted data from the included studies separately. Inconsistencies were resolved through discussion and consensus. The extracted data were summarized in tables to facilitate thematic synthesis.

Synthesis of results: The review used a descriptive and thematic synthesis approach. The extracted data were grouped based on major intervention categories such as radiotherapy, surgery, systemic therapy, and novel treatments. Subthemes were developed using iterative reading and coding of the findings. Each theme generated a narrative summary with frequency counts of study type, location, and outcome where applicable. The researchers also identified changing trends in clinical management approaches.

Key Findings: The Six Major Themes

The comprehensive literature search yielded 800 records. Of these, 782 came from databases and 18 from trial registers. After removing 178 records due to duplication or automation ineligibility, 622 studies remained for title and abstract screening. Of these, 82 full-text articles were assessed for eligibility. After further exclusions, 6 studies met all inclusion criteria and were retained for final synthesis.

To ensure rigor and reduce selection bias, two reviewers independently screened titles and abstracts. Any disagreements were resolved through discussion or consultation with a third reviewer. This approach aligns with the JBI scoping review methodology and ensures transparency and reliability in study selection.

The six final studies were grouped thematically by their primary research focus. These studies spanned diverse methodologies, including RCTs, observational studies, and diagnostic evaluations. The six themes were:

• Theme 1: Systemic Treatment — Hormonal/Chemotherapy. Use of androgen deprivation therapy (ADT) and systemic therapies (e.g., docetaxel, apalutamide) in managing LAPC. Key study: James et al. (2016).
• Theme 2: Radiotherapy Advances. Innovations in dose scheduling, particularly ultra-hypofractionation. Key study: Widmark et al. (2019).
• Theme 3: Surgical Management. Comparative evaluation of radical prostatectomy versus radiotherapy. Key study: Stranne et al. (2018).
• Theme 4: Emerging Therapies and Biomarkers. The efficacy of the combination of apalutamide and standard ADT. Key study: Shore et al. (2024).
• Theme 5: Diagnostic Imaging. Use of PSMA PET for staging and therapy planning. Key study: Houshmand et al. (2023).
• Theme 6: Real-World Practice and Implementation. Observational data on treatment variability and adherence to guidelines. Key study: Freedland et al. (2023).

To structure the analysis, the PICO (Population, Intervention, Comparison, Outcome) framework was applied.

Hormonal Therapy and Chemotherapy

Hormonal therapy remains a mainstay of treatment for LAPC. Its purpose is to reduce androgen levels and thereby suppress tumor progression. The most influential study in this area is the STAMPEDE trial by James et al. This trial assessed the effect of adding docetaxel (a chemotherapy drug) to standard ADT.

The STAMPEDE trial was carried out at multiple sites. It involved men with high-risk, non-metastatic and metastatic prostate cancer. This provided powerful information about systemic cancer treatment strategies.

The results showed significant improvement in overall survival and progression-free survival with docetaxel plus ADT compared with ADT alone. Overall survival means how long patients live. Progression-free survival means how long patients live without the cancer getting worse.

Since these results were published, they have redefined the standard of care. They encourage early integration of chemotherapy in eligible LAPC patients. Critically, the trial demonstrated that early intensification of treatment leads to better outcomes. This finding favors a move to combination approaches rather than sequential treatments in high-risk prostate cancer. Sequential treatment means using one treatment after another, rather than together.

Radiotherapy Innovations

Radiotherapy has seen great development in recent years, especially in fractionation techniques. Fractionation refers to how the total radiation dose is divided into individual treatment sessions. These techniques are designed to deliver optimal doses while reducing patient inconvenience and side effects.

A landmark study in this area is the HYPO-RT-PC trial performed by Widmark et al. This was a phase 3, non-inferiority randomized controlled trial. "Non-inferiority" means the study aimed to show that the new treatment was not worse than the standard treatment. The trial enrolled men with intermediate- to high-risk prostate cancer, including a subset of men with locally advanced disease.

The study compared two radiation schedules:

• Ultra-hypofractionated (UHF) radiotherapy: A total dose of 42.7 Gy (gray, the unit of radiation dose) spread over just seven sessions over two and a half weeks.
• Conventional fractionation: A total dose of 78.0 Gy in 39 fractions over eight weeks.

Results showed that the UHF radiotherapy schedule was non-inferior to conventional fractionation for failure-free survival at five years. This means the shorter schedule worked as well as the longer one. Importantly, there was no significant increase in late toxicity (side effects that appear months or years after treatment).

Most significantly, this approach provides practical benefits. These include a shortened duration of therapy, increased patient compliance, and more efficient use of resources in real clinical settings. Based on these observations, UHF radiotherapy can be integrated into the treatment plan for LAPC. This is particularly relevant when limited healthcare infrastructure or patient preference makes a shorter schedule preferable.

Surgical Management

Surgical intervention, especially radical prostatectomy (RP), is now being considered more achievable in the management of LAPC. This is especially true when surgery is incorporated into a multimodal approach (using multiple treatment types together).

The SPCG-15 (Scandinavian Prostate Cancer Group Study Number 15) trial provides valuable comparative information. This was a prospective randomized controlled study by Stranne et al. It compared radical prostatectomy versus radiotherapy with ADT. The trial included patients with LAPC and sought to establish whether surgery could offer the same or better cancer outcomes in the long term.

Preliminary outcomes showed that the two treatment arms achieved similar cancer control. This was mostly measured by biochemical recurrence (a rise in PSA levels after treatment that may indicate the cancer is returning). This was also measured by metastasis-free survival (how long patients live without the cancer spreading to distant organs).

However, the side effect profiles were notably different between the two groups:

• Radical prostatectomy was more often linked with urinary incontinence and sexual dysfunction.
• Radiotherapy was more often linked with digestive tract side effects, including bowel urgency and rectal bleeding.

These findings emphasize the value of shared decision-making. In this process, doctors individualize treatment plans based on patient-specific factors. These factors include age, other health conditions (comorbid diseases), baseline function, and the patient's personal values regarding quality of life.

The authors also note that robotic-assisted prostatectomy is being adopted more widely around the world. Evidence suggests this approach may lead to lower blood loss and shorter hospital stays. Future reviews may further investigate the comparative effectiveness of open, laparoscopic, and robot-assisted surgical approaches in LAPC. However, such comparisons were not the focus of the SPCG-15 trial and remain underrepresented in current LAPC literature.

Although outside the scope of this review's inclusion criteria, early-phase studies on stereotactic radiotherapy and PARP inhibitors (such as olaparib for BRCA1/2 mutations) are emerging. Stereotactic radiotherapy delivers highly precise, high-dose radiation. PARP inhibitors are drugs that block a specific enzyme used by cancer cells to repair their DNA; they are particularly effective in cancers with BRCA1 or BRCA2 gene mutations. These approaches could potentially expand the therapeutic landscape for LAPC. The authors state that these approaches warrant separate systematic exploration as more clinical outcome data become available.

Emerging Therapies and Biomarkers

The recent development of systemic therapies and molecular diagnostics has created new opportunities for treating LAPC in the neoadjuvant setting. Neoadjuvant means treatment given before the main treatment (in this case, before surgery).

The PROTEUS trial, as reported by Shore et al., tested the efficacy of combining apalutamide (an androgen receptor inhibitor) with standard ADT. Androgen receptor inhibitors are drugs that block the action of male hormones on cancer cells. The trial enrolled patients with high-risk localized or locally advanced disease who were candidates for radical prostatectomy.

Apalutamide has already shown proven activity in castration-resistant situations. Castration-resistant means the cancer continues to grow even when testosterone levels are very low. This trial aimed to test apalutamide's efficacy in earlier stages of the disease.

The findings showed that adding apalutamide substantially increased pathologic complete response (pCR) rates. A pathologic complete response means no cancer cells were found in the tissue removed during surgery. The combination also reduced residual tumor volume at surgery compared with ADT alone. Residual tumor volume refers to the amount of cancer remaining after treatment.

These results support the use of intensified neoadjuvant therapy to enhance surgical outcomes and reduce recurrence risk. The trial also demonstrates the growing reliance on individualized systemic treatment before definitive local therapy. Future investigations may consider the long-term survival effects of this approach. They may also incorporate genomic biomarkers to guide patient selection for such enhanced treatment strategies.

Advanced Imaging Techniques

Staging accuracy plays a vital role in the treatment of LAPC. It is equally important for treatment planning and for prognosis (predicting how the disease will progress). Traditional imaging modalities, such as CT scans and bone scans, are known to have limitations in detecting micrometastatic disease. Micrometastatic disease refers to tiny clusters of cancer cells that have spread but are too small to be seen on standard scans.

The Avidity trial, conducted by Houshmand et al., studied the clinical relevance of PSMA PET/CT in patients with high-risk or locally advanced prostate cancer. PSMA PET/CT is an advanced imaging technique that uses a radioactive tracer to find prostate cancer cells throughout the body. This trial was designed to determine whether PSMA PET/CT provided more sensitivity and specificity in detecting nodal and distant metastases than standard imaging. Sensitivity refers to how well a test finds cancer when it is present. Specificity refers to how well a test correctly identifies when cancer is not present.

Early results indicated that PSMA PET/CT was able to identify metastatic lesions not visible on routine scans. This finding led to significant changes in treatment choices in many cases. These changes included:

• Increasing the intensity of systemic therapy
• Adding targeted radiotherapy to oligometastatic sites (a small number of distant cancer deposits)
• Reclassifying patients as non-surgical candidates

The trial supports the growing role of advanced imaging in guiding treatment decisions for LAPC patients.

Real-World Practice and Implementation

The sixth theme focused on real-world practice and implementation. Freedland et al. provided observational data on treatment variability and adherence to guidelines. Observational data means information gathered by observing patients in routine clinical practice, rather than assigning them to specific treatments in a trial.

This theme highlights that how treatments are actually used in everyday practice may differ from how they are used in clinical trials. Variability in treatment and differences in how closely doctors follow guidelines can affect patient outcomes. The authors note that regional disparities in access to treatments remain a significant concern.

Clinical Implications: What This Means for Patients

The management of LAPC is moving toward a precision-based, multimodal paradigm. Precision-based means treatment is tailored to the specific characteristics of each patient's cancer. Multimodal means using several treatment types together.

Several key implications emerge from this review for patients and their families:

• Combination therapy improves cancer control. The STAMPEDE trial showed that adding docetaxel to ADT improved overall survival and progression-free survival. The PROTEUS trial showed that adding apalutamide to ADT increased pathologic complete response rates.
• Shorter radiotherapy schedules work as well as longer ones. The HYPO-RT-PC trial showed that a seven-session radiation schedule was as effective as a 39-session schedule at five years.
• Surgery and radiotherapy offer similar cancer control but different side effects. The SPCG-15 trial showed that radical prostatectomy and radiotherapy with ADT achieved similar cancer outcomes, but each had a distinct side effect profile.
• Advanced imaging changes treatment decisions. PSMA PET/CT detected metastases that standard scans missed, leading to changes in treatment for many patients.
• Quality of life matters. More aggressive treatment comes with a higher risk of urinary, bowel, and sexual side effects. Patients and doctors must weigh cancer control against quality of life.

Although current knowledge supports more aggressive and individualized therapy, there are still data gaps. These gaps include long-term outcomes, global uptake of new treatments, and patient-reported measures (how patients themselves describe their symptoms and well-being).

Limitations: What the Review Could Not Prove

This scoping review has several important limitations that patients and clinicians should understand.

First, the review included only six studies. This is a small number relative to the broad scope of the topic. The findings represent a mapping of available evidence rather than a comprehensive synthesis of all possible data.

Second, the researchers did not conduct a risk-of-bias assessment. This means they did not evaluate the methodological quality of the included studies. As a result, the review cannot comment on the strength or reliability of individual study findings.

Third, no formal statistical analysis or meta-analysis was performed. The purpose was to map the breadth of existing literature rather than to assess effect sizes. This means the review cannot provide combined numerical estimates of treatment benefits.

Fourth, the review was limited to studies published in English between January 2013 and April 2025. Research published in other languages or outside this timeframe was not included. This may have excluded relevant evidence.

Fifth, the review excluded editorials, commentaries, conference abstracts without complete data, and study protocols. While this ensures that only complete primary research was included, it may have excluded emerging findings that had not yet been fully published.

Finally, the authors note that comparisons of different surgical approaches (open, laparoscopic, and robot-assisted) were not the focus of the included trials. These comparisons remain underrepresented in current LAPC literature.

Recommendations and Future Directions

The authors make several recommendations for future research and clinical practice.

For researchers:

1. Conduct inclusive longitudinal studies that span the gap between clinical innovation and real-world application. Longitudinal means following patients over a long period of time.
2. Investigate the long-term survival effects of intensified neoadjuvant therapy, such as the apalutamide plus ADT combination tested in the PROTEUS trial.
3. Incorporate genomic biomarkers to guide patient selection for enhanced treatment approaches.
4. Explore the comparative effectiveness of open, laparoscopic, and robot-assisted surgical approaches in LAPC.
5. Conduct separate systematic explorations of stereotactic radiotherapy and PARP inhibitors (such as olaparib for BRCA1/2 mutations) as more clinical outcome data become available.
6. Address data gaps in long-term outcomes, global uptake of new treatments, and patient-reported measures.

For clinicians:

1. Consider early integration of chemotherapy in eligible LAPC patients, based on STAMPEDE trial results.
2. Consider ultra-hypofractionated radiotherapy as an option, especially when limited healthcare infrastructure or patient preference makes a shorter schedule preferable.
3. Engage in shared decision-making with patients. Individualize treatment plans based on age, other health conditions, baseline function, and the patient's personal values regarding quality of life.
4. Use PSMA PET/CT imaging for more accurate staging when available, as it can detect metastases that standard scans miss.

For policymakers:

1. Address regional disparities in access to treatments. The review found that access to care varies significantly between high-income countries and low- and middle-income countries.
2. Support the development of healthcare infrastructure that enables the delivery of advanced treatments, including PSMA PET imaging and ultra-hypofractionated radiotherapy.

The authors conclude that the management of LAPC is moving toward a precision-based, multimodal paradigm. Current knowledge supports more aggressive and individualized therapy. However, significant data gaps remain. Future research must be based on inclusive longitudinal studies that bridge clinical innovation and real-world application.

Frequently Asked Questions

What is locally advanced prostate cancer?

It is cancer that has grown just outside the prostate capsule, classified as stage T3 to T4, and may involve the seminal vesicles or nearby lymph nodes. Importantly, it has not spread to distant organs, which is called M0 disease. Because tumour behaviour varies widely between men, treatment must balance cancer control against quality of life.

Does adding chemotherapy to hormone therapy help?

In the STAMPEDE trial, which included men with high-risk non-metastatic and metastatic prostate cancer, adding docetaxel chemotherapy to standard androgen deprivation therapy improved overall survival and progression-free survival compared with hormone therapy alone. These results changed standard care and support starting chemotherapy early in eligible patients rather than using treatments one after another.

Can a shorter course of radiotherapy work as well?

In the HYPO-RT-PC trial, men with intermediate- to high-risk prostate cancer, including some with locally advanced disease, received either seven sessions over two and a half weeks or 39 sessions over eight weeks. At five years the shorter schedule was not worse for failure-free survival, with no significant increase in late side effects.

How do surgery and radiotherapy side effects differ?

In the SPCG-15 trial, radical prostatectomy and radiotherapy with hormone therapy achieved similar cancer control, measured by biochemical recurrence and metastasis-free survival. However, surgery was more often linked with urinary incontinence and sexual dysfunction, while radiotherapy was more often linked with bowel problems such as urgency and rectal bleeding. This is why shared decision-making matters.

What is PSMA PET/CT imaging and why is it used?

PSMA PET/CT is an advanced scan using a radioactive tracer that binds to a protein on prostate cancer cells to find cancer throughout the body. In the Avidity trial of men with high-risk or locally advanced disease, it detected metastatic lesions that routine scans missed, leading to treatment changes such as intensified systemic therapy, targeted radiotherapy, or reclassification as non-surgical.

What is apalutamide and how is it used before surgery?

Apalutamide is an androgen receptor inhibitor that blocks male hormones acting on cancer cells. In the PROTEUS trial, men with high-risk localized or locally advanced disease who were candidates for radical prostatectomy received apalutamide plus standard hormone therapy before surgery. This combination substantially increased pathologic complete response rates and reduced residual tumour volume compared with hormone therapy alone.

What are the limitations of this review?

Only six studies met the inclusion criteria, all published in English between January 2013 and April 2025. No risk-of-bias assessment or statistical analysis was performed, so the review maps existing evidence rather than judging study quality or combining results. Comparisons of open, laparoscopic, and robot-assisted surgery remain underrepresented, and long-term outcomes and global access gaps persist.

If I have locally advanced prostate cancer and my doctor recommends either surgery or radiotherapy, when should I get a second opinion?

Radical prostatectomy and radiotherapy with androgen deprivation therapy achieve similar cancer control in locally advanced disease, but their side effects differ: surgery is more often linked with urinary incontinence and sexual dysfunction, while radiotherapy is more often linked with bowel urgency and rectal bleeding. Because treatment plans should be individualized by age, other health conditions, baseline function, and personal quality-of-life values, a second opinion can help confirm which option fits your situation. Diagnostic Detectives Network provides independent expert second opinions.

Source Information

Original article title: Management of Locally Advanced Prostate Cancer: A Scoping Review of Contemporary Evidence and Emerging Approaches.

Authors: Adefehinti M, George AO, Enemoh O, Adenipekun B, Akinwale M, Akintayo A, Sanni QA, Adebisi AA, Erewele E, Onipede O, Oore-Ofe O, Ibikunle TP, Ajani OO.

Publication: Cureus, Volume 17, Issue 8, Article e89863. Published August 12, 2025.

DOI: 10.7759/cureus.89863

Review timeline: Review began July 13, 2025; Review ended August 8, 2025; Published August 12, 2025.

Author affiliations: The authors are affiliated with institutions in the United Kingdom and Nigeria, including Peterborough City Hospital, The Royal London Hospital, Chesterfield Royal Hospital, William Harvey Hospital, University Hospital Southampton NHS Foundation Trust, South Warwickshire University NHS Foundation Trust, Epsom and St. Helier University NHS Foundation Trust, Olabisi Urgent Care Hospital (Lagos), University of Ilorin, Lagoon Hospital (Lagos), Atlantis Pediatrics Hospital (Lagos), and London Metropolitan University.

Categories: Urology

Keywords: Advanced locally prostate cancer (LAPC), androgen deprivation therapies, apalutamide, multimodal treatments, precision oncology, PSMA PET, radical prostatectomy, radiotherapy, scoping review

This patient-friendly article is based on peer-reviewed research. The original article is an open-access publication distributed under the terms of the Creative Commons Attribution License CC-BY 4.0, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.