Prostate Cancer Symptoms, Stages and Treatment
In this article
What Is Prostate Cancer?
Prostate cancer is an adenocarcinoma arising from the glandular tissue of the prostate and is the most common cancer in men when skin cancers are excluded. Its clinical course spans an extremely broad range: in some patients it progresses slowly enough to be safely monitored for years without treatment, while in others it can progress rapidly and become life-threatening. Prostate cancer also has one of oncology's richest and fastest-evolving treatment histories — in just the past few years, new treatment approvals have arrived in succession at nearly every stage, from the earliest to the most advanced disease. This guide comprehensively covers all details, from diagnosis to current treatment options (including 2026).
The Prostate Cancer Working Group 4 (PCWG4) consensus published in early 2026 recommends gradually replacing the long-used terms "hormone-sensitive (HSPC/CSPC)" and "castration-resistant (CRPC)" with "androgen pathway modulation-sensitive/resistant (APM-sensitive/APM-resistant)", based on patient feedback. This guide continues to use traditional terms (hormone-sensitive, castration-resistant), which still predominate in current Turkish and international clinical literature, while drawing attention to this terminology change readers may encounter in the future.
Prostate Anatomy
The prostate is a walnut-sized gland just below the bladder, surrounding the urethra (urinary passage). It produces a substantial proportion of the fluid component of semen and secretes PSA (prostate-specific antigen). Anatomically, it has three main zones: the vast majority of prostate cancers (approximately %70-75) arise in the peripheral zone (closest to the rectum — hence palpable on digital rectal examination), the main site of benign prostatic hyperplasia (BPH) is the transition zone, and a smaller region is the central zone. This zonal anatomy explains both why digital rectal examination (DRE) can assess only a limited portion and the diagnostic value of multiparametric MRI.
How Common Is It? (Current Statistics)
According to the International Agency for Research on Cancer's (IARC) "Global cancer statistics 2024" report (Sung H, et al., CA: A Cancer Journal for Clinicians, published 8 July 2026, DOI: 10.3322/caac.70090), 2024 data show approximately 1.546.112 new prostate cancer cases (ranking 4th in incidence among all cancers), and 419.849 prostate cancer deaths were reported worldwide (ranking 8th among cancer deaths). Regionally, %29,9 of cases occur in Europe, %27,6 in Asia and %19,9 in North America; an estimated 5,18 million men worldwide are currently living with prostate cancer.
According to the American Cancer Society's "Cancer Statistics, 2026" report (Siegel RL, et al., CA: A Cancer Journal for Clinicians, published 13 January 2026, DOI: 10.3322/caac.70043), in 2026 approximately 333.830 new prostate cancer cases and 36.320 deaths are expected in the US; prostate cancer is the most common cancer in men excluding skin cancers, and after lung cancer it is the 2nd most common cause of cancer death in men. Median age at diagnosis is approximately 67, and about %60 of cases occur at age 65 or older. Lifetime risk is approximately a diagnosis in 1 of every 8 men and death from this disease in 1 of every 44 men. Stage-specific 5-year relative survival (SEER, 2015-2021 diagnosis cohort) offers a striking contrast: in localised and regional disease it is over %99 , while in distant metastatic disease it falls to only %38 — clearly demonstrating why early diagnosis is so valuable in this disease.
According to the GLOBOCAN 2024 country profile for Türkiye, prostate cancer is the 2nd most common cancer among Turkish men (approximately 18.749 new cases annually, %14,0 of all cancer cases in men), and ranks 4th among all cancers (both sexes combined). Annual deaths are approximately 4.851 , placing prostate cancer 7th among all causes of cancer death. The cumulative risk of diagnosis by age 75 is %4,3.
Risk Factors
- Advanced age — the strongest risk factor, increasing markedly above age 50
- African ancestry/race/ethnicity — higher incidence and a tendency towards more aggressive disease
- Family history of prostate cancer (particularly in a first-degree relative)
- Family history of breast/ovarian cancer (a hereditary BRCA association may be present)
- A high-fat diet rich in processed red meat (the evidence is weaker than for other risk factors)
Hereditary Syndromes and Germline Genetic Testing
| Gene / Syndrome | Clinical Significance |
|---|---|
| BRCA2 | The most clinically significant germline gene in prostate cancer — it not only increases risk but is also associated with younger age at diagnosis, more aggressive histology and poorer prognosis; determines eligibility for PARP inhibitor treatment |
| BRCA1 | Associated with a weaker but still significant increase in risk compared with BRCA2 |
| HOXB13 (G84E variant) | A relatively recently identified hereditary risk variant specific to prostate cancer; contributes to familial prostate cancer clustering, particularly in populations of Northern European ancestry |
| ATM, CHEK2, PALB2 (other HRR genes) | Mutations in these genes involved in the homologous recombination repair (HRR) pathway form part of a broad panel determining eligibility for PARP inhibitor treatment in metastatic disease |
| Lynch syndrome (MLH1, MSH2, MSH6, PMS2) | Associated with the rare MSI-H/dMMR prostate cancer subgroup — potential for an exceptional response to tumour-agnostic immunotherapy |
Current guidelines recommend germline genetic testing for all patients diagnosed with metastatic prostate cancer, as well as those with high-risk/very-high-risk localised disease or a strong family history. These tests guide both treatment selection (BRCA2/HRR positivity determines eligibility for PARP inhibitor combinations) and risk assessment and screening of first-degree relatives.
Screening: PSA and Its Controversial History
PSA (prostate-specific antigen) screening has been one of oncology's most controversial topics: elevated PSA is not specific to prostate cancer (it can also rise in benign prostatic hyperplasia, prostatitis and even activities such as cycling), and PSA screening may lead to unnecessary detection of clinically insignificant cancers that would never cause symptoms (overdiagnosis), and to unnecessary treatment. Therefore, rather than automatic screening at a particular age, the current approach recommends a process of shared decision-making between patient and physician, considering the patient's life expectancy, family history and personal preferences.
To clarify how strongly an elevated PSA alone supports a biopsy decision, the free PSA ratio, PSA density (PSA relative to prostate volume) and newer multibiomarker panels (4Kscore, Prostate Health Index/PHI) are increasingly used in clinical practice; these tests may help reduce unnecessary biopsies. Our separate article on the free PSA test discusses this topic in detail.
Symptoms
Early-stage prostate cancer generally causes no symptoms — therefore most cases are detected during routine PSA screening. The following symptoms may develop as disease progresses:
- Frequent urination (particularly at night)
- Weak urine flow or intermittent urination
- Difficulty starting urination
- Blood in urine or semen
- Erectile dysfunction
- In advanced disease: bone pain (particularly lower back/hip — the most common metastatic site), unexplained weight loss
Most of these symptoms may arise from noncancerous causes such as benign prostatic hyperplasia (BPH); however, they must be assessed, particularly when accompanied by new bone pain.
How Is It Diagnosed?
Digital Rectal Examination (DRE) and PSA
Digital rectal examination detects firmness/nodules in the peripheral zone but can assess only part of the prostate; its diagnostic value increases when used with PSA.
Multiparametric MRI and PI-RADS
In current practice, after elevated PSA/an abnormal DRE, performing multiparametric MRI (mpMRI) before biopsy has become standard. MRI findings are classified using the PI-RADS (Prostate Imaging Reporting and Data System) score from 1 (very low probability) to 5 (high probability), directly guiding both the biopsy decision and the regions to target during biopsy.
Prostate Biopsy
The current biopsy approach combines systematic biopsy sampling the entire prostate systematically with MRI-fusion (targeted) biopsy directly targeting regions suspicious on MRI — this combination improves detection of clinically significant cancers compared with systematic biopsy alone. To reduce infection risk, there is also a growing shift from the traditional transrectal approach towards the lower-infection-risk transperineal biopsy approach.
Pathology: Gleason Score and ISUP Grade Group
The Gleason grading system developed by pathologist Donald Gleason in the 1960s remains a cornerstone of prostate cancer pathology — although its interpretation has evolved substantially over time. In the original system, the two most common growth patterns in tumour tissue (from 1 to 5) are added to obtain a Gleason score (for example, 3+4=7). In 2014, however, the International Society of Urological Pathology (ISUP) sought to clarify a system that was confusing for patients (for example, "Is Gleason 6 cancer?") and insufficiently distinguished two subtypes with the same total score (7) but very different prognoses — 3+4 and 4+3 — by defining the ISUP Grade Group 1-5 system.
| ISUP Grade Group | Gleason Score | Clinical Meaning |
|---|---|---|
| Grade Group 1 | ≤6 (3+3) | Low-grade; often a suitable candidate for active surveillance |
| Grade Group 2 | 7 (3+4) | Intermediate group with a better-differentiated dominant pattern — important in favourable intermediate-risk classification |
| Grade Group 3 | 7 (4+3) | Intermediate group with a more poorly differentiated dominant pattern — markedly worse prognosis than 3+4 |
| Grade Group 4 | 8 (4+4, 3+5 or 5+3) | High-grade |
| Grade Group 5 | 9-10 | Highest-grade, most aggressive course |
This is a frequent question in patient education and a controversial topic: although Grade Group 1 (Gleason 6) tumours contain cancer cells by definition, their metastatic capacity is extremely low, and almost all large series have failed to demonstrate that they alone cause death. Consequently, many centres consider Grade Group 1 disease ideal for active surveillance and openly discuss this nuance with patients.
Molecular and Genomic Tests
| Test | Use | Clinical Significance |
|---|---|---|
| Germline BRCA1/2, ATM, CHEK2, PALB2 (HRR panel) | Metastatic disease (recommended for all patients) | Determines eligibility for PARP inhibitor treatment (as monotherapy or combined with abiraterone/enzalutamide) |
| MSI-H / dMMR | Metastatic disease (rare subgroup) | Potential for an exceptional response to tumour-agnostic treatment with pembrolizumab |
| PTEN loss (immunohistochemistry) | Metastatic hormone-sensitive disease | A new companion diagnostic test approved in 2026 determining eligibility for capivasertib (AKT inhibitor) + abiraterone |
| Decipher Genomic Classifier | Localised disease (active surveillance decision, postoperative radiotherapy timing) | Gene expression test recommended in NCCN guidelines; helps predict aggressive/high-risk biology |
| Oncotype DX Genomic Prostate Score (GPS), Prolaris | Newly diagnosed low/favourable-intermediate-risk disease | Complementary genomic tests to predict active surveillance suitability and adverse pathology risk |
PSMA PET/CT: A Revolution in Imaging
PSMA (Prostate-Specific Membrane Antigen)is a protein expressed much more densely on prostate cancer cell surfaces than in normal tissue. Imaging performed with radiolabelled agents targeting this protein, PSMA PET/CT imaging, has revolutionised prostate cancer staging and recurrence assessment over the past few years — it can detect very small metastatic sites missed by conventional CT/bone scintigraphy, even at particularly low PSA levels.
| Agent | FDA Approval Date | Note |
|---|---|---|
| ⁶⁸Ga-PSMA-11 (academic, UCSF/UCLA) | 1 December 2020 | The first approved PSMA PET agents |
| ¹⁸F-DCFPyL (Pylarify) | 26 May 2021 | The first widely commercially available PSMA PET agent |
| ⁶⁸Ga-PSMA-11 (commercial kit, Illuccix) | 19 December 2021 | Made 68Ga-PSMA-11 more widely accessible |
| ¹⁸F-flotufolastat (Posluma) | 25 May 2023 | The first "radiohybrid" (rhPSMA) PSMA PET agent |
| Ga-68 gozetotide (Gozellix) | 20 March 2025 | Next-generation PSMA PET kit |
PSMA PET's clinical impact is evident in two main areas: (1) initial staging — it has begun to replace/complement conventional imaging, particularly in intermediate-to-high-risk disease; (2) biochemical recurrence assessment — it can locate recurrence even at very low PSA levels, enabling more accurate planning of salvage treatment (such as salvage RT). PSMA PET positivity is also now a prerequisite for eligibility for 177Lu-PSMA-617 radioligand therapy (see below). Our separate article on Gallium-68 PSMA-PET discusses this topic in detail.
Staging and Risk Classification
While AJCC TNM determines formal staging, NCCN risk groups more directly guide treatment decisions in everyday clinical practice — this classification combines PSA level, Grade Group and clinical T stage:
| NCCN Risk Group | General Features |
|---|---|
| Very low risk | T1c, Grade Group 1, PSA <10, limited biopsy involvement |
| Low risk | T1-T2a, Grade Group 1, PSA <10 |
| Favourable intermediate (intermediate-favourable) | Grade Group 1-2 with only one intermediate-risk feature (T2b-c, PSA 10-20 or Grade Group 2), without Grade Group 2 predominance |
| Unfavourable intermediate (intermediate-unfavourable) | More than one intermediate-risk feature or Grade Group 3, or biopsy involvement above %50 |
| High risk | T3a or Grade Group 4-5 or PSA >20 |
| Very high risk | T3b-T4, primary Gleason pattern 5, or multiple high-risk features |
This risk classification forms the framework of the treatment sections below.
Active Surveillance in Low-Risk Localised Disease
In low- and very-low-risk localised disease, active surveillance — close monitoring through regular PSA follow-up, periodic mpMRI and repeat biopsies, initiating treatment only if signs of progression appear — has become the preferred approach. This makes it possible to avoid adverse effects of active treatment (surgery/radiotherapy), such as urinary incontinence and erectile dysfunction, without compromising survival.
According to the ProtecT study (Hamdy FC, et al., New England Journal of Medicine, 21 March 2023), comparing active surveillance, radical prostatectomy and radiotherapy in localised prostate cancer, at 15-year follow-up no significant difference in prostate cancer-specific mortality was found (active surveillance %3,1, prostatectomy %2,2, radiotherapy %2,9; p=0,53) — all-cause mortality (%21-23) was also similar across the three arms. Although the metastasis rate in the active surveillance arm (%9,4) was approximately twice that in the other two arms (%4,7 and %5,0), this difference did not translate into mortality. This study provides the strongest randomised evidence that active surveillance is safe in low-risk disease. Our separate article on the active observation approach discusses this topic in detail.
Current AUA/ASTRO guidelines (2022, updated in 2026) strongly recommend active surveillance as the preferred approach for low-risk disease; in favourable intermediate-risk disease, they present active surveillance, radiotherapy and surgery as three equally reasonable options within shared decision-making.
Definitive Treatment in Localised Disease
When active treatment is chosen, two main definitive treatment options are available and generally offer similar oncological outcomes; selection largely depends on adverse-effect profiles, patient preference and centre expertise:
- Radical prostatectomy: complete removal of the prostate by open, laparoscopic or (now most commonly) robot-assisted laparoscopic techniques
- External beam radiotherapy (EBRT): generally delivered using IMRT/VMAT today; stereotactic body radiotherapy (SBRT) can complete treatment in less time (usually 5 sessions)
- Brachytherapy: placing radioactive sources directly inside the prostate (using permanent low-dose-rate or temporary high-dose-rate techniques); usable alone or with EBRT
Targeting only the tumour-bearing region instead of removing the prostate, focal therapies (such as high-intensity focused ultrasound/HIFU and cryotherapy) remain investigational/in limited clinical use in selected low-to-intermediate-risk patients and have not yet replaced standard treatment.
Treatment in High-Risk/Locally Advanced Disease
In high- and very-high-risk localised disease, local treatment alone (surgery or radiotherapy) is generally insufficient; radiotherapy is combined with long-term androgen deprivation therapy (ADT) (generally 18-36 months). If surgery is preferred, lymph node dissection is extended, and postoperative pathology may prompt adjuvant/salvage radiotherapy. Our separate article on hormone therapy for prostate cancer discusses ADT's mechanism and modes of use in detail.
Management of Biochemical Recurrence
A renewed rise in PSA after definitive treatment (biochemical recurrence/BCR) indicates recurrence even without disease yet detectable on imaging. PSMA PET/CT has now become the gold standard for locating recurrence at these low PSA levels, directly influencing treatment decisions (salvage radiotherapy to the prostate bed alone or metastasis-directed treatment). Options include salvage radiotherapy for postoperative BCR and, in suitable patients, salvage surgery, cryotherapy or HIFU for BCR after radiotherapy. Our separate article on biochemical recurrence discusses this topic in detail.
Treatment of Metastatic Hormone-Sensitive Disease (mHSPC)
In patients presenting with distant metastases (bone, lymph nodes, rarely visceral organs), or developing metastatic disease after localised treatment, who are not yet resistant to hormone therapy, treatment has changed fundamentally over the past decade: from ADT alone to intensified treatment adding a second (doublet) or third (triplet) agent to ADT.
According to CHAARTED (in the high-volume disease subgroup), early addition of docetaxel to ADT significantly prolonged overall survival compared with ADT alone (median 51,2 versus 34,4 months; HR 0,63). STAMPEDE's docetaxel arm showed similar survival benefit. These studies established early addition of docetaxel to ADT in mHSPC as a guideline standard — because docetaxel has long been a generic chemotherapy drug, this change entered clinical practice through guideline adoption rather than a new FDA approval.
According to LATITUDE, adding abiraterone+prednisolone to ADT in high-risk mHSPC significantly prolonged overall survival (HR 0,621; p<0,0001), and this combination received FDA approval on 7 February 2018 . STAMPEDE's abiraterone arm reported similar results.
According to ARCHES, adding enzalutamide to ADT significantly prolonged radiographic progression-free survival (HR 0,39; p<0,0001), and received FDA approval on 16 December 2019 . The independent ENZAMET study also reported significant benefit in 3-year overall survival (with or without early docetaxel) (%80 versus %72; approximately %33 reduction in death risk).
According to TITAN, adding apalutamide to ADT significantly prolonged overall survival (HR 0,67; p=0,0053) and markedly improved radiographic progression-free survival (HR 0,48; p<0,0001); this combination received FDA approval on 17 September 2019 .
According to ARASENS, adding darolutamide to ADT + docetaxel ("triplet" treatment) significantly prolonged overall survival (HR 0,68; p<0,0001 — approximately %32 reduction in death risk), and received FDA approval on 5 August 2022 . This established triplet treatment as a standard option in chemotherapy-eligible patients with high-volume/high-risk disease.
According to ARANOTE, the ADT+darolutamide doublet without docetaxel significantly prolonged radiographic progression-free survival (HR 0,54; p<0,0001), and received FDA approval on 3 June 2025 — overall survival analysis has not yet reached statistical significance (HR 0,78). This approval provides a chemotherapy-free darolutamide-based doublet option for patients unable or unwilling to receive docetaxel.
In one of the latest and most important developments in the field, PSMAddition showed that in PSMA PET-positive mHSPC, adding to standard ADT+next-generation hormonal agent (ARPI) treatment 177Lu-PSMA-617 (Pluvicto) significantly prolonged radiographic progression-free survival (HR approximately 0,67-0,72), and received FDA approval on 31 July 2026 — overall survival data remain immature but show a favourable trend (HR 0,80). This approval means that radioligand therapy, previously used only in castration-resistant disease, is now available much earlier in the hormone-sensitive phase — substantially expanding the eligible patient population.
Treatment of Nonmetastatic Castration-Resistant Prostate Cancer (nmCRPC)
In patients whose PSA continues to rise under ADT without detectable metastases on imaging (development of castration resistance), adding a third-generation androgen receptor inhibitor to ADT has become standard when the PSA doubling time is short (high risk); all three agents significantly prolonged metastasis-free survival in similarly designed randomised trials:
Apalutamide received FDA approval based on SPARTAN on 14 February 2018; enzalutamide based on PROSPER on 13 July 2018; darolutamide based on ARAMIS on 30 July 2019 for nmCRPC. In ARAMIS, darolutamide increased metastasis-free survival from 18,4 to 40,4 months (HR 0,41; p<0,0001) — approximately %59 reduction in metastasis/death risk. Although no head-to-head study compares the three drugs, darolutamide is thought to cross the blood-brain barrier relatively less, with fewer reported central nervous system adverse effects (fatigue, falls, cognitive effects) than the other two.
Treatment of Metastatic Castration-Resistant Prostate Cancer (mCRPC)
When disease becomes resistant to ADT (and prior ARPI/chemotherapy, if given) and progresses metastatically, treatment is largely personalised according to previous therapies, symptoms and biomarker profile. This is prostate cancer's stage with the richest range of treatment options:
Based on IMPACT, sipuleucel-T received FDA approval for asymptomatic/minimally symptomatic mCRPC on 29 April 2010 , becoming the first therapeutic cancer vaccine in history (median overall survival benefit approximately 4,1 months). It is personalised cellular immunotherapy requiring processing and reinfusion of the patient's own immune cells.
Abiraterone was approved first for post-docetaxel mCRPC based on COU-AA-301 (28 April 2011), then extended to pre-chemotherapy mCRPC based on COU-AA-302 (10 December 2012). Enzalutamide received approval in post-docetaxel mCRPC based on AFFIRM on 31 August 2012 . These drugs became the backbone of mCRPC treatment by targeting androgen receptor signalling at different points (abiraterone blocks androgen synthesis, while enzalutamide directly blocks the androgen receptor).
Docetaxel has been standard chemotherapy with proven overall survival benefit in mCRPC since the era before ARPIs. Cabazitaxel is a second-line taxane option in docetaxel-resistant mCRPC, particularly preferred in rapidly progressing disease resistant to ARPI treatment.
Based on ALSYMPCA, radium-223 received FDA approval in mCRPC with symptomatic bone metastases (without visceral metastases) on 15 May 2013 , becoming the first approved alpha-particle-emitting radiopharmaceutical; it selectively binds to bone, causing localised radiation damage and providing overall survival benefit.
Olaparib, based on PROfound (BRCA1/2/ATM-mutated cohort: rPFS 7,4 versus 3,6 months, HR 0,34; OS 19,1 versus 14,7 months, HR 0,69), received FDA approval on 19 May 2020 . Rucaparib received accelerated approval based on TRITON2 on 15 May 2020, converted following the confirmatory TRITON3 results (rPFS 11,2 versus 6,4 months, HR 0,50) on 17 December 2025 to full approval. PARP inhibitors are also used earlier, in first-line mCRPC, in combination with ARPIs: niraparib+abiraterone (Akeega) was approved based on MAGNITUDE on 11 August 2023 in BRCA-mutated mCRPC; talazoparib+enzalutamide was approved based on TALAPRO-2 (rPFS not reached versus 13,8 months, HR 0,45) on 20 June 2023 in HRR-mutated mCRPC.
According to VISION, in PSMA PET-positive mCRPC previously treated with an ARPI and taxane-based chemotherapy, 177Lu-PSMA-617 reduced death risk by %38 and received FDA approval on 23 March 2022 . Subsequently, based on PSMAfore (rPFS 9,3 versus 5,6 months, HR 0,41), its use was expanded on 28 March 2025 to pre-chemotherapy mCRPC (after only one ARPI) — demonstrating that radioligand therapy can also be used at an earlier disease stage. Our separate article on Pluvicto (lutetium therapy) discusses this topic in detail.
According to CAPItello-281, in PTEN-deficient mHSPC (identified by immunohistochemistry using a companion diagnostic), adding the AKT inhibitor capivasertib to standard abiraterone+ADT significantly prolonged radiographic progression-free survival (33,2 versus 25,7 months; HR 0,81; p=0,034), and received FDA approval on 12 June 2026 . This approval is important as the first use of the AKT inhibitor class in prostate cancer and for introducing PTEN testing into clinical practice as a companion diagnostic.
Treatment Side Effects
| Treatment | Common Side Effects |
|---|---|
| Radical prostatectomy | Urinary incontinence (generally improves over time), erectile dysfunction, rarely anastomotic stricture |
| Radiotherapy (EBRT/brachytherapy) | Radiation proctitis (rectal irritation), radiation cystitis (bladder irritation), erectile dysfunction (usually delayed), rarely secondary malignancy risk |
| ADT (hormone therapy) | Hot flushes, reduced bone mineral density/osteoporosis, reduced muscle mass, weight gain, increased cardiometabolic risk (diabetes, cardiovascular disease), cognitive effects, loss of libido, mood changes |
| Docetaxel/cabazitaxel | Bone marrow suppression (febrile neutropenia risk), fatigue, peripheral neuropathy, nail changes, fluid retention |
| PARP inhibitors (olaparib, rucaparib, niraparib, talazoparib) | Anaemia, fatigue, nausea; rare myelodysplastic syndrome/leukaemia risk with long-term use (class effect) |
| ¹⁷⁷Lu-PSMA-617 (radioligand therapy) | Dry mouth (xerostomia — because salivary glands also express PSMA), nausea, fatigue, bone marrow suppression, need to monitor renal function |
| Capivasertib (AKT inhibitor) | Hyperglycaemia, diarrhoea, rash — requires close metabolic monitoring |
Supportive Treatments
Bone Health
Long-term ADT reduces bone mineral density and increases fracture risk; regular bone density measurement and calcium/vitamin D supplementation when necessary are recommended. In metastatic disease spread to bone with a high fracture/compression risk, skeletal-related events (such as pathological fractures and spinal cord compression) may be reduced using denosumab or zoledronic acid .
Sexual Function and Continence Rehabilitation
Erectile dysfunction and urinary incontinence after surgery or radiotherapy can substantially affect quality of life; pelvic floor exercises, phosphodiesterase-5 inhibitors, vacuum devices and urological/andrological support when necessary play an important role in managing these adverse effects.
Genetic Counselling
Genetic counselling is recommended for patients with a germline BRCA2 or other HRR gene mutation, both for treatment decisions and risk assessment of first-degree relatives. Our separate article on BRCA1 and BRCA2 mutations discusses this topic in detail.
Global Approval and Evidence Timeline
The following timeline shows how rapidly and broadly prostate cancer treatment has developed over the past fifteen years — new approvals have arrived in succession at nearly every disease stage (from nmCRPC to mHSPC and mCRPC, through the latest radioligand/AKT inhibitor classes).
Sipuleucel-T (Provenge) FDA ApprovalMilestone
The first therapeutic cancer vaccine in history.
Abiraterone FDA Approval (mCRPC, post-docetaxel)
Based on COU-AA-301.
Enzalutamide FDA Approval (mCRPC)
Based on AFFIRM.
Radium-223 (Xofigo) FDA ApprovalMilestone
Based on ALSYMPCA; the first alpha-particle-emitting radiopharmaceutical approval.
Abiraterone FDA Approval (mHSPC, high risk)
Based on LATITUDE.
Apalutamide (Erleada) FDA Approval (nmCRPC)
Based on SPARTAN.
Darolutamide (Nubeqa) FDA Approval (nmCRPC)
Based on ARAMIS.
Apalutamide FDA Approval (mHSPC)
Based on TITAN.
Enzalutamide FDA Approval (mHSPC)
Based on ARCHES.
Olaparib FDA Approval (BRCA/HRR-mutated mCRPC)Milestone
Based on PROfound; the first biomarker-directed targeted treatment in prostate cancer.
¹⁷⁷Lu-PSMA-617 (Pluvicto) FDA ApprovalMilestone
Based on VISION; the birth of PSMA-targeted radioligand therapy.
Darolutamide + Docetaxel FDA Approval (mHSPC Triplet)
Based on ARASENS.
Niraparib + Abiraterone (Akeega) FDA Approval
Based on MAGNITUDE, BRCA-mutated mCRPC.
Talazoparib + Enzalutamide FDA Approval
Based on TALAPRO-2, HRR-mutated mCRPC.
Pluvicto FDA Approval Expanded (Pre-Chemotherapy mCRPC)
Based on PSMAfore.
Darolutamide + ADT FDA Approval (Chemotherapy-Free mHSPC)
Based on ARANOTE.
Rucaparib Converted to Full Approval
Transition from accelerated to full approval following the confirmatory TRITON3 study.
Capivasertib (Truqap) FDA Approval
Based on CAPItello-281; the first AKT inhibitor approval in PTEN deficiency.
Pluvicto FDA Approval Expanded (mHSPC)Latest
Based on PSMAddition; radioligand therapy is now also available in hormone-sensitive disease.
Situation in Türkiye: TİTCK Licensing and SGK Reimbursement
Standard LHRH agonists such as Lökoprolid (Lucrin), goserelin (Zoladex) and triptorelin (Decapeptyl) have been TİTCK-licensed and widely reimbursed by SGK in Türkiye for many years — this is the most readily accessible component of prostate cancer treatment.
Under SUT article 4.2.14.u, SGK reimburses abiraterone, enzalutamide and cabazitaxel only "in patients with metastatic prostate cancer who have progressed on hormonal therapy and subsequent docetaxel-based chemotherapy" (post-docetaxel mCRPC), based on a 6-month medical board report signed by at least one medical oncology specialist. An important restriction: the same article explicitly states that these three drugs cannot be used sequentially — SGK funds only one of these treatments and does not support sequential transitions. This research found no current text separately providing SUT reimbursement for abiraterone/enzalutamide in pre-chemotherapy mCRPC or mHSPC (LATITUDE/ARCHES-type use); this is an important open issue requiring verification.
Apalutamide (Erleada) and darolutamide (Nubeqa) are TİTCK-licensed and marketed in Türkiye. However, this research found no verified information about SGK/SUT reimbursement coverage for either drug (for any nmCRPC or mHSPC indication). Patients and physicians should directly confirm current reimbursement with SGK/TİTCK sources or their treating centre.
No evidence was found that sipuleucel-T, which requires personalised cellular processing, is commercially available in Türkiye or licensed by TİTCK.
This research found no evidence that radium-223 is TİTCK-licensed in Türkiye; this is a lack of verification rather than a definitive finding of "unlicensed" status — the current situation should be confirmed through TİTCK sources.
No evidence was found of TİTCK licensing in Türkiye for Novartis's commercial "Pluvicto" product. However, Lu-177-PSMA radioligand therapy is actually administered at many major private hospitals and nuclear medicine centres in Türkiye — through patient-specific preparation in nuclear medicine departments combining a TİTCK-licensed Lu-177 chloride solution (Mon.Lutec) with a PSMA-617 peptide kit (compounded radiopharmaceutical preparation). This differs from an "imported ready-made drug" model but enables actual access to treatment. This research could not clearly verify the extent of SGK coverage; patients are advised to confirm costs/coverage directly with their treating centre.
Olaparib is TİTCK-licensed in Türkiye, and its current Summary of Product Characteristics (KÜB) explicitly lists BRCA1/2- or ATM-mutated metastatic castration-resistant prostate cancer as an indication. However, according to two independent legal sources, SGK reimbursement is limited to maintenance in BRCA-mutated platinum-sensitive ovarian cancer; prostate (and breast, pancreatic) indications are outside standard SGK coverage. Nevertheless, in a decision of Istanbul Anatolian Labour Court dated 7 April 2026 , SGK's refusal to reimburse olaparib was annulled for a stage 4 prostate cancer patient carrying a germline BRCA mutation whose disease progressed after docetaxel and abiraterone, and uninterrupted payment was ordered — a concrete precedent showing that access through litigation may also be possible for the prostate indication.
Docetaxel has long been readily available and reimbursed in Türkiye as a generic chemotherapy drug. PSMA PET/CT imaging is generally covered by SGK at contracted centres (the exact tariff/article number could not be verified in this research). Denosumab is explicitly listed in SUT under "hormone-refractory prostate cancer" and reimbursed with a 6-month medical board report for patients with bone metastases at high fracture/compression risk who have not previously used zoledronic acid (no previous zoledronic acid use is required); zoledronic acid is reimbursed as standard supportive care without an additional restriction.
Frequently Asked Questions
- Does elevated PSA always indicate prostate cancer?
- No. PSA may also rise due to benign prostatic hyperplasia, prostatitis and even certain physical activities. Elevated PSA requires further assessment (free PSA ratio, MRI) but is not diagnostic alone.
- Is Gleason 6 (Grade Group 1) prostate cancer dangerous?
- Grade Group 1 tumours have extremely low metastatic capacity and are generally suitable for active surveillance; large series have rarely demonstrated that they alone cause death.
- Is active surveillance a safe option?
- In low-risk disease, yes — ProtecT's 15-year data showed no significant disadvantage of active surveillance compared with surgery or radiotherapy in prostate cancer-specific mortality.
- How different is PSMA PET/CT from conventional imaging?
- PSMA PET can detect very small metastatic sites missed by conventional CT/bone scintigraphy, even at particularly low PSA levels; this has substantially improved both initial staging and biochemical recurrence assessment.
- Why is the PSMAddition approval considered important?
- This approval enables Lu-177-PSMA radioligand therapy, previously used only in castration-resistant (advanced-stage) disease, to be used much earlier in the hormone-sensitive metastatic phase, substantially expanding the eligible population.
- Should all metastatic prostate cancer patients undergo genetic testing?
- Yes — current guidelines recommend germline genetic testing for all patients with metastatic disease; this determines PARP inhibitor eligibility and guides family risk assessment.
References:
- Sung H, et al. Global cancer statistics 2024. CA Cancer J Clin. 2026. DOI: 10.3322/caac.70090.
- Siegel RL, et al. Cancer Statistics, 2026. CA Cancer J Clin. 2026. DOI: 10.3322/caac.70043.
- Hamdy FC, et al. Fifteen-year outcomes after monitoring, surgery, or radiotherapy for prostate cancer (ProtecT). N Engl J Med. 2023.
- Kantoff PW, et al. Sipuleucel-T immunotherapy (IMPACT). N Engl J Med. 2010.
- de Bono JS, et al. Abiraterone and increased survival in metastatic prostate cancer (COU-AA-301). N Engl J Med. 2011.
- Scher HI, et al. Increased survival with enzalutamide (AFFIRM). N Engl J Med. 2012.
- Parker C, et al. Alpha emitter radium-223 (ALSYMPCA). N Engl J Med. 2013.
- Fizazi K, et al. Abiraterone plus prednisone in metastatic, castration-sensitive prostate cancer (LATITUDE). N Engl J Med. 2017.
- Smith MR, et al. Apalutamide treatment and metastasis-free survival (SPARTAN). N Engl J Med. 2018.
- Fizazi K, et al. Darolutamide in nonmetastatic CRPC (ARAMIS). N Engl J Med. 2019.
- Chi KN, et al. Apalutamide for metastatic, castration-sensitive prostate cancer (TITAN). N Engl J Med. 2019.
- Armstrong AJ, et al. Enzalutamide in metastatic hormone-sensitive prostate cancer (ARCHES). J Clin Oncol. 2019.
- de Bono J, et al. Olaparib for metastatic castration-resistant prostate cancer (PROfound). N Engl J Med. 2020.
- Smith MR, et al. Darolutamide and survival in metastatic, hormone-sensitive prostate cancer (ARASENS). N Engl J Med. 2022.
- Sartor O, et al. Lutetium-177-PSMA-617 for metastatic castration-resistant prostate cancer (VISION). N Engl J Med. 2021.
- Chi KN, et al. Niraparib and abiraterone acetate for metastatic castration-resistant prostate cancer (MAGNITUDE). J Clin Oncol. 2023.
- Agarwal N, et al. Talazoparib plus enzalutamide in HRR-mutated prostate cancer (TALAPRO-2). Lancet. 2023.
- Sartor O, et al. Lutetium-177-PSMA-617 in taxane-naive patients (PSMAfore). Lancet. 2025.
- FDA approval announcements: darolutamide (ARANOTE), rucaparib (TRITON3 full approval), capivasertib (CAPItello-281), Pluvicto (PSMAddition).
- Relevant articles of Türkiye's Healthcare Implementation Communiqué (SUT), TİTCK drug licensing lists.
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