PSA Testing and Robotic Surgery in Prostate Cancer

Introduction: Confronting the Silent Threat

Prostate cancer remains the most commonly diagnosed cancer in men worldwide, excluding skin cancers. In 2020, over 1.4 million new cases were diagnosed globally, with incidence growing approximately 3% annually. In advanced stages, this growth rate climbs to 5%. As Turkey's population ages, the number of diagnosed cases continues to rise, making public awareness and clinical excellence critically important.

The primary goal of this article is to provide a comprehensive, evidence-based guide — written in accessible language — for both healthcare professionals and individuals interested in prostate health. From the correct interpretation of PSA testing to MR fusion biopsy, from robotic surgical techniques to active surveillance protocols, you will find the latest 2026 guideline data in a single resource.

1. What Is Prostate Cancer? Epidemiology and Risk Factors

1.1 Definition and Biology

The prostate gland is a walnut-sized male reproductive organ located just below the bladder and surrounding the urethra. Its primary function is to produce a portion of seminal fluid.

Prostate cancer originates from the epithelial cells of this gland, most commonly as acinar adenocarcinoma. The majority of cases follow an indolent course; however, tumors with high Gleason/Grade Group scores can exhibit an aggressive clinical trajectory.

Cancer cells are initially confined within the prostate capsule. In advanced stages, spread to seminal vesicles, lymph nodes, and most commonly bones — followed by lung and liver — is observed. When diagnosed at an early stage, the five-year survival rate exceeds 90% significantly, underscoring the life-saving role of screening programs.

1.2 Current Statistics

The American Cancer Society's 2026 Cancer Statistics Report marks a critical milestone in the fight against cancer. The report reveals that the five-year relative survival rate across all cancer types and stages combined has reached 70%. This figure reflects diagnoses from the 2015-2020 period, before the full clinical impact of immunotherapy and targeted therapies had been captured in survival data. The results obtained with today's treatments are therefore expected to appear even more favorable in future reports.

Since 1991, cancer-related mortality rates have declined by 35%. This remarkable reduction is attributable to early screening programs, advances in surgical techniques, and next-generation pharmacological therapies.

1.3 Risk Factors

The principal risk factors currently recognized in prostate cancer can be summarized as follows:

• Advanced age: The vast majority of diagnoses occur in men aged 65 and older. It is extremely rare under 40.
• Family history: The risk is approximately doubled in men with a first-degree relative (father, brother) diagnosed with prostate cancer.
• Genetic predisposition: BRCA2 gene mutation and other DNA repair gene variants are associated with elevated risk. A history of breast or ovarian cancer in first-degree female relatives also increases prostate cancer risk.
• Ethnicity: African American men have significantly higher incidence and mortality compared to other ethnic groups.
• Diet and lifestyle: A strong correlation between excessive saturated fat consumption, obesity, and cancer has been demonstrated. Red meat consumption is also associated with elevated risk. Diets rich in tomatoes (lycopene), soy products, and cruciferous vegetables represent potentially protective dietary patterns.

2. PSA Testing: A Comprehensive Guide

2.1 What Is PSA?

PSA (Prostate-Specific Antigen) is a glycoprotein produced exclusively by the prostate gland. Normally present in blood at low concentrations, any pathological process in prostatic tissue disrupts this balance and increases PSA serum levels. The detection of PSA and its introduction into routine clinical practice represented a revolution in the early diagnosis of prostate cancer.

PSA exists in blood in two distinct forms: total PSA and free PSA. The ratio of free PSA to total PSA (f/t PSA) carries critical diagnostic value particularly in the gray zone of 4-10 ng/mL, helping distinguish cancer from benign prostatic hyperplasia (BPH).

2.2 Age-Specific Normal PSA Values

2.3 Other Factors That Influence PSA

It is critically important to emphasize that not every PSA elevation indicates cancer. The following conditions can temporarily or persistently elevate PSA levels:

• Acute prostatitis: Can raise PSA values into the 10-50 ng/mL range.
• Chronic prostatitis: Causes persistent mild elevation due to low-grade inflammation.
• Benign prostatic hyperplasia (BPH): PSA rises proportionally with prostate volume.
• Prior to biopsy or bladder catheterization: Transient elevations may occur.
• Cycling and prostate massage: Can cause short-term PSA increases.
• 5-alpha reductase inhibitors (finasteride, dutasteride): Reduce PSA by approximately 50%; interpretation must account for this effect.

2.4 PSA Density and PSA Velocity

In modern urological practice, a single PSA value is no longer considered sufficient. Two additional parameters have been incorporated into routine assessment:

PSA density: Calculated by dividing the PSA value by prostate volume. Plays a critical role in distinguishing cancer from BPH in the gray zone of 4-10 ng/mL. The threshold is generally accepted at 0.15 ng/mL/cc.

PSA velocity: An annual PSA increase exceeding 0.75 ng/mL strengthens the indication for biopsy. This parameter significantly influences clinical decision-making independently of absolute PSA values.

3. Diagnostic Methods: From MR Fusion Biopsy to Liquid Biopsy

3.1 Multiparametric Prostate MRI (mpMRI)

The most fundamental transformation in prostate diagnosis over the past decade has been the introduction of multiparametric MRI into clinical practice. mpMRI — combining T2-weighted imaging, diffusion-weighted imaging (DWI), and dynamic contrast-enhanced sequences — renders suspicious lesions within the prostate visible. Standardized through the PI-RADS (Prostate Imaging Reporting and Data System) v2.1 scoring system using a 1-5 scale, PI-RADS 4-5 lesions carry high suspicion for clinically significant cancer.

The 2026 European Association of Urology (EAU) guidelines strongly recommend performing mpMRI prior to systematic biopsy in biopsy-naive patients with elevated PSA. This approach both reduces unnecessary biopsies and prevents the over-diagnosis of clinically insignificant cancers.

3.2 Targeted MR Fusion Biopsy

MR fusion biopsy involves targeting suspicious lesions identified on mpMRI by co-registering MRI images with real-time ultrasound using fusion mapping software. Either perineal or transrectal approach can be used; perineal access is increasingly preferred in contemporary practice due to its lower infection risk.

Compared with conventional 12-core systematic biopsy, fusion biopsy detects clinically significant cancer at higher rates, reduces the diagnostic frequency of clinically insignificant low-risk cancers, and improves the patient biopsy experience. Antibiotic prophylaxis protocols prior to biopsy are clearly defined in both EAU and American Urological Association (AUA) guidelines.

3.3 Liquid Biopsy and Future Perspectives

Liquid biopsy — based on the detection of circulating tumor DNA (ctDNA) and tumor-derived exosomes in blood — is assuming increasing importance in prostate cancer diagnosis and monitoring. As of 2026, clinical use remains largely investigational; however, it holds enormous potential for the early detection of treatment resistance mechanisms and evaluation of minimal residual disease.

Specific biomarkers such as the miR-371a-3p test, which has entered clinical practice in testicular cancer, are expected to advance in the prostate cancer space as well. Integration of liquid biopsy panels into standard follow-up protocols is anticipated in the near future.

4. Staging and the Gleason/Grade Group Classification

4.1 TNM Staging System

Prostate cancer staging defines the extent of tumor spread and directly shapes treatment decisions. The current UICC/AJCC TNM staging system encompasses the following categories:

• T1: Clinically inapparent cancer, not palpable or visible on imaging — incidentally detected
• T2: Cancer confined within the prostate capsule (T2a: less than half of one lobe; T2b: more than half of one lobe; T2c: both lobes)
• T3: Extension beyond the capsule (T3a: extracapsular extension; T3b: seminal vesicle invasion)
• T4: Invasion of bladder neck, rectum, or pelvic wall
• N0/N1: No regional lymph node involvement / regional lymph node metastasis
• M0/M1: No distant metastasis / distant metastasis present (M1a: non-regional lymph nodes; M1b: bone; M1c: other)

4.2 Gleason Score and Grade Group System

While the traditional Gleason score forms the foundation of pathological grading, the 2016 WHO classification introduced the Grade Group (GG) scale as a more prognostically accurate system:

• Grade Group 1 (Gleason 6): Low risk — generally an active surveillance candidate
• Grade Group 2 (Gleason 3+4=7): Intermediate-favorable risk
• Grade Group 3 (Gleason 4+3=7): Intermediate-unfavorable risk
• Grade Group 4 (Gleason 8): High risk
• Grade Group 5 (Gleason 9-10): Very high risk — requires aggressive management

5. Treatment Options: From Active Surveillance to Robotic Surgery

5.1 Active Surveillance

The recognition that not all prostate cancers require immediate treatment represents one of the most significant clinical paradigm shifts of the past decade. For low-risk (GG1) and selected intermediate-favorable (GG2) patients, the standard active surveillance protocol consists of annual PSA measurements, regular digital rectal examinations, and repeat mpMRI-guided biopsies at 1-3 year intervals. Avoiding the serious side effects of surgery or radiation therapy (incontinence, erectile dysfunction) in men who do not require treatment is of paramount importance.

Randomized controlled trials such as the ProtecT study have demonstrated the oncological safety of active surveillance in carefully selected patients through 15-year follow-up data. Patient selection, psychosocial factors, and protocol adherence remain critical determinants of success.

5.2 Robot-Assisted Radical Prostatectomy (RARP)

Robotic surgery has undoubtedly constituted the greatest technical revolution in prostate cancer treatment over the past fifteen years. The robotic platform -now in its fourth and fifth generations are available- provides three-dimensional magnified visualization, tremor-free instruments, and ergonomic positioning, enabling surgeons to apply nerve-sparing techniques with greater precision.

The advantages of robot-assisted radical prostatectomy can be summarized as follows:

• Significantly reduced intraoperative blood loss and blood transfusion requirements
• Shorter hospital stay (typically 1-2 days)
• Faster return to continence compared to open surgery
• Potentially better erectile function outcomes with bilateral nerve-sparing technique
• Minimal transfusion rates and improved recovery profile

As of 2026, high-volume centers in Turkey are reporting outcomes in robotic prostatectomy that meet world-class standards. In the hands of experienced surgeons, oncological results -surgical margin positivity rates, biochemical recurrence rates- are comparable to or better than open surgery.

5.3 Radiation Therapy

Radiation oncology is an indispensable component of prostate cancer treatment. Radiotherapy, which can be used in combination with surgery or as an alternative to it in many patients, achieves tumor control rates between 80% and 90% in early-stage cancers — all delivered as a painless, non-invasive modality.

The principal radiation modalities currently in use include:

• External beam radiotherapy (EBRT): Specifically intensity-modulated radiation therapy (IMRT) and image-guided radiotherapy (IGRT), which have substantially reduced side effects.
• Stereotactic body radiotherapy (SBRT/SABR): Delivering high-dose conformal radiation over a limited number of fractions, with growing adoption worldwide.
• Brachytherapy: Provides localized radiation via radioactive seeds implanted within the prostate.

5.4 Hormone Therapy (ADT) and Next-Generation Antiandrogen Therapies

Androgen deprivation therapy (ADT) remains the cornerstone of advanced and metastatic prostate cancer management. Testosterone suppression is achieved through LHRH agonists/antagonists. However, prolonged ADT carries significant side effects including osteoporosis, metabolic syndrome, cardiovascular risk, and sexual dysfunction.

Since the early 2020s, next-generation antiandrogens (enzalutamide, apalutamide, darolutamide) — which have transformed clinical practice — have gained indications in both metastatic castration-resistant prostate cancer (mCRPC) and metastatic castration-sensitive disease (mCSPC) in combination with ADT. These agents provide far more potent androgen receptor blockade compared to classical antiandrogens and significantly extend overall survival.

5.5 Immunotherapy and CAR-T Cell Therapy

Prostate cancer retains relative resistance to immunotherapy; however, meaningful progress is being made in this domain. PARP inhibitors demonstrate significant efficacy in patients harboring BRCA2 or CDK12 mutations. Checkpoint inhibitors such as pembrolizumab have received FDA approval in metastatic prostate cancer with high microsatellite instability (MSI-H) or high tumor mutational burden (TMB-H).

While CAR-T cell therapy does not yet hold standard clinical approval in prostate cancer, research efforts aimed at overcoming the technical barriers in solid tumors have accelerated considerably. PSMA (prostate-specific membrane antigen)-targeted CAR-T approaches have shown promising results in early clinical trials.

6. 2026 EAU and AUA Guideline Updates

The principal updates in the 2026 European Association of Urology guidelines include:

• Mandatory mpMRI prior to systematic biopsy in biopsy-naive patients is now a Grade A recommendation.
• PSMA PET/CT is recommended as the standard imaging modality for staging in high-risk localized disease and at biochemical recurrence.
• Intensified combination (ADT + ARPI + docetaxel) triplet therapy protocol in metastatic castration-sensitive prostate cancer is supported by robust evidence.
• BRCA1/2 and CDK12 mutation testing has been incorporated into the mandatory genetic testing panel for metastatic disease.

7. The Patient Journey: From Screening to Follow-Up

7.1 Who Should Be Screened and When?

According to the 2023 American Urological Association guidelines:

• Men aged 55-69: Annual or biennial PSA screening is recommended following individualized risk assessment through a shared decision-making process with their physician.
• Men with a first-degree relative with a prostate cancer history: Screening should be initiated from age 45.
• BRCA2 mutation carriers and African American men: Evaluation is recommended starting at age 40.
• Men over 70: The screening decision should be individualized based on life expectancy and patient preferences.

7.2 Post-Treatment Follow-Up

Following radical prostatectomy, PSA levels are expected to become undetectable (<0.1 ng/mL). A subsequent rise in PSA is defined as biochemical recurrence and necessitates a second-line treatment plan. After radiotherapy, an increase of 2 ng/mL above the PSA nadir (Phoenix criteria) is recognized as a recurrence marker. The follow-up protocol encompasses PSA measurement every three months for the first two years, every six months for the subsequent three years, and annually thereafter.

8. Quality of Life and Supportive Care

The potential side effects of prostate cancer treatment — incontinence, erectile dysfunction, hot flashes, and bone loss — can profoundly affect patients' quality of life. Contemporary oncology mandates comprehensive discussion of these side effects not only after treatment but also during pre-treatment patient counseling.

Pelvic floor exercises (Kegel exercises), when performed before and after robotic prostatectomy, accelerate the return of continence. Erectile rehabilitation programs require a multimodal approach — primarily phosphodiesterase-5 inhibitors — and programs initiated early produce meaningfully better long-term outcomes. Bone mineral density monitoring and bisphosphonate/denosumab support in patients receiving ADT are standard components of the care protocol.

Psycho-oncological support must not be overlooked. The psychological burden of a cancer diagnosis and the associated uncertainty directly influence the patient's adjustment process, treatment adherence, and overall well-being.

Conclusion: Early Detection Saves Lives

Prostate cancer, under the right clinical circumstances, is a disease with an exceptionally high rate of curability. When the accurate interpretation of PSA screening, targeted biopsy guided by mpMRI, the precise application of robotic surgical technology, and next-generation pharmacological therapies are brought together, the prospect of the vast majority of patients living normal lives decades after diagnosis is no longer aspirational but increasingly achievable.

At ekonsey.com, our fundamental responsibility is to connect the most current, evidence-based knowledge in this field with healthcare professionals and patients alike. We strongly encourage you to share any questions or concerns regarding your prostate health with a specialist in urology.

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