Archive

Prostate cancer stands as the second most prevalent cancer affecting males worldwide. Various risk factors contribute to its development, including familial predisposition, advancing age, lifestyle choices such as diet, and environmental influences. The onset of prostate cancer can often be traced back to cellular inflammation or genetic mutations.
Awareness of the key symptoms is crucial for early detection. Individuals may notice signs such as blood in urine or semen, significant unintended weight loss, or discomfort during ejaculation. Diagnosis typically involves a PSA blood test or a digital rectal examination. If there is a suspicion of cancer, advanced diagnostic tools, such as MRI or biopsy, can provide essential insights into the type and stage of the disease.
The treatment landscape for prostate cancer is diverse, tailored to the specific type and stage of the cancer diagnosed. While some therapeutic approaches may carry potential side effects such as urinary or fecal incontinence and sexual dysfunction, this complexity underscores the importance of comprehensive care and informed decision-making.
In anticipation of possible sexual dysfunction, sperm banking is an invaluable option for those considering future parenthood through IVF. Furthermore, specialized treatments remain available for challenging scenarios, such as castration-resistant prostate cancer or bone metastasis.
This evolving field continuously presents new avenues of hope through targeted therapies and innovative treatments.It is essential to approach the journey of diagnosis and treatment with resilience and a proactive mindset. By educating males, seeking timely medical advice, and relying on support networks, the challenges posed by prostate cancer can be navigated, and a pathway toward recovery and well-being can be fostered. Together, through awareness and advocacy, we can inspire hope and drive progress in the fight against this disease.

Epidemiology

 

  •  Prostate cancer is the second most common cancer among men worldwide and the eighth leading cause of death.
  • In Asia, it ranks second in prevalence and first in mortality.
  • Prostate cancer has emerged as a major public health concern in Saudi Arabia, being the second most prevalent cancer, and in the United Arab Emirates being the first most prevalent cancer, particularly among elderly males [1, 2].

Risk Factors

  • Various risk factors are associated with the incidence of prostate cancer, which can be categorized into non-modifiable and modifiable factors.

2.1.Modifiable Risk Factors

Smoking

  • Several studies indicate that smoking may increase the risk of prostate cancer. In addition, prostate cancer patients have poor survival and a higher risk of recurrence, increasing overall mortality [11].
  • Smokeless tobacco, such as chewing tobacco, snuff, and a mixture of chewing tobacco with other ingredients, also increases the prostate cancer risk  [12]  .

Dietary intake

Plant-based nutrition is associated with a lower risk of prostate cancer and a better prognosis during treatment [13].

 Lycopene rich in tomatoes, is associated with reduced prostate cancer risk [14] . A high consumption of vegetables, fruits, fish, and whole grain products exerts protective and/or therapeutic effects [15] .

Phytoestrogens are found in foods such as soybeans, lentils, tofu, peanuts, chickpeas, and kidney beans in addition to specific phytoestrogens found in daidzein, genistein, and glycitein were possible protective factors against prostate cancer [16] .

While increased risk of prostate cancer is associated with a high intake of total dairy products, milk, cheese, low-fat milk, and skim milk combined, total calcium, dietary calcium, and dairy calcium, but not whole milk [17] . In addition, inflammatory and hyper-insulinemic dietary patterns such as processed meat, sugar, refined grains, and saturated fats are linked to an increased risk of prostate cancer and prostate carcinogenesis [18] since they lead to the disruption of prostate hormonal regulation, induction of oxidative stress and inflammation, and alteration of growth factor signaling and lipid metabolism [15] .

Environmental exposure

Exposure to industrial chemicals and carcinogens, such as polychlorinated biphenyls (PCBs), polyhalogenated aromatic hydrocarbons (like dioxins, bisphenol A (BPA), and dibenzofurans), and inorganic arsenic, disrupts androgens, increasing the risk of prostate cancer and accelerating prostate carcinogenesis [19] .

Body mass index

Obesity increases prostate cancer risk in addition to aggressiveness. Obesity also causes recurrence and treatment failure [20] .

Infections

There is an increased association between human papillomavirus (HPV) and prostate cancer[21]. Syphilis and gonorrhea increase the risk of prostate cancer  [22] .

Drugs

Consistent aspirin use is associated with a lower risk of the development of prostate cancer [23].

5-Alpha-reductase inhibitors, which are used for enlarged prostate and scalp hair loss, are associated with reduced prostate cancer risk [24] .

2.2.Non Modifiable Risk Factors

AGE

Screening reveals that 40% of unscreened Asian men older than 60 harbor prostate cancer, which increases to 60% in men older than 80 [3]. While the incidence of prostate cancer generally increases with age, it is important to note that Saudi men under the age of 45 can also be diagnosed with prostate cancer [4, 5].

Family History

  • Family history significantly influences prostate cancer risk, with about 58% of cases linked to genetic factors.

Key elements affecting risk: [6].

1.Number of affected relatives.

2.Degree of relationship (first-degree vs. second-degree).

3.Age of diagnosis and death from prostate cancer.

4.Presence of high-grade disease and history of other cancers (e.g., breast, ovarian).

  • Brothers and sons of prostate cancer patients have a 2.5-fold increased risk of developing the disease [6].
  • A family history of prostate cancer may increase the likelihood of severe forms of the disease.
  • Men with relatives diagnosed with high-grade or metastatic prostate cancer face greater risks than those with low-grade cases [6].
  • Risk of developing prostate cancer:
  • Doubles with one affected relative [7]
  • .Increases nearly fourfold with two or more affected relatives, especially if diagnosed before age 60 [7].
  • Although family history may potentiate the early incidence of prostate cancer, the raised awareness of early detection and treatment of positive family history results in a better prognosis [8].

Genetic Mutation

  • It is beneficial to recognize that men with a family history of breast or ovarian cancer may also have an increased risk of prostate cancer due to mutations in the BRCA1 and BRCA2 genes [9, 10].

Pathogenesis

  •  The prostate gland, located at the base of the penis, produces a significant portion of seminal fluid and relies on androgens like testosterone for optimal function.
  • Initially, prostate cancer begins with mutations in normal glandular cells and can be detected through procedures like digital rectal examinations (DRE).
  • While some tumors respond to hormonal treatments, others may resist castration by producing their own androgens [25].
  • Prostate cancer, primarily classified as adenocarcinoma, originates from glandular cells in the peripheral zone of the prostate gland.
  • It often starts with small clusters of cancer cells, sometimes referred to as carcinoma in situ or prostate intraepithelial neoplasia (PIN).
  • Histologically, the transition from normal epithelium to PIN involves nuclear atypia, epithelial cell crowding, and some components of basal cell loss.
  • Autopsy studies suggest that PIN lesions precede the appearance of carcinoma.
  • High-grade PIN lesions are often spatially associated with carcinoma and may exhibit molecular alterations like those found in prostate tumorscells [26].
  • Over time, these cells can multiply, invade surrounding tissue, and form tumors that may spread to nearby organs such as the seminal vesicles and rectum.
  • Metastasis commonly occurs in the bones and lymph nodes, with a believed venous pathway due to the connection between the prostatic venous plexus and the vertebral veins [27].

 

3.1 Inflammation and Oxidative Stress

  • Chronic inflammation in the prostate, caused by infections, diet, or environmental factors, can lead to the production of reactive oxygen species (ROS), which damage DNA and trigger mutations in androgen-regulated genes, potentially initiating prostate cancer[28].
  • Conditions like glandular atrophy and Proliferative Inflammatory Atrophy (PIA) are commonly associated with prostate cancer. Glandular atrophy, often seen in aging prostates, may act as a precursor to cancer. PIA lesions are highly proliferative, linked to inflammation, and can progress to high-grade PIN or rarely carcinoma [26]. Chronic inflammation due to hormonal changes or carcinogen exposure is responsible for initiating prostate cancer [29].

3.2 Molecular Mechanisms

  •  Androgen is essential for prostate development; however, prostate cancer is dependent on androgen receptor activation.
  • Although androgen deprivation therapy may be used, it is not curative since prostate cancer cells reactivate Androgen Receptor (AR) signaling and resume proliferation despite very low levels of circulating testosterone, a stage termed castrate-resistant prostate cancer (CRPC) [30].
  • Mutations in the AR gene result in the development of metastatic CRPC (mCRPC) [31] and impart resistance to androgen deprivation therapy; Abiraterone [32].
  • Mutations in the PI3K/AKT/mTOR pathway enhance prostate carcinogenesis [33].
  • While genetic mutations, found in PTEN (phosphatase and tensin homolog on chromosome 10) tumor suppressors, are common in prostate cancer, especially metastatic castration-resistant prostate cancer (CRPC) [34].

Symptoms of Prostate Cancer

4.1 Symptoms of prostate cancer [35, 36].

  • Fatigue, excessive weight loss.
  • Difficulty starting urination.
  • Weak urine flow or flow that starts and stops.
  • Blood urine (hematuria).
  • Pain or burning urination (dysuria).
  • Loss of bladder control (urinary incontinence).
  • Loss of bowel control (fecal incontinence).
  • Painful ejaculation and erectile dysfunction.
  • Blood in semen (hemato-spermia).
  • Bone pain, especially in the back, hip, or chest, if it metastasizes into bone.

Classification

5.1 Classification of prostate cancer

  •  Prostate cancer is primarily classified based on histological and molecular characteristics.
  • In 2022, WHO classified prostate cancer into epithelial and mesenchymal tumors.
  • Epithelial prostate cancer is subclassified into glandular or squamous neoplasms according to the International Classification of Diseases for Oncology (ICD-O) [37].

Epithelial Prostate Cancer - Glandular

1.Cystadenoma

 Benign tumors (ICD-O:0)

Prostatic cystadenoma is a rare, benign epithelial tumor of variably sized cysts lined by bland cuboidal cells. It is commonly centered within seminal vesicles that occur in a wide age distribution (23 66 years old).

 2.High-Grade Prostatic Intraepithelial Neoplasia (HGPIN):

Carcinoma in situ (ICD-O:2) HGPIN refers to the proliferation of prostate glandular epithelial cells that display significant cytological atypia within the confines of prostatic ducts and acini. A HGPIN diagnosis in biopsies indicates a ~25% risk of detection of cancer in repeat biopsies. It has been accepted as the main precursor lesion to invasive carcinoma [38].

 3.Intraductal carcinoma

Intraductal carcinoma is an intraglandular/ductal neoplastic proliferation of prostatic glandular epithelial cells, characterized by marked expansion of glandular architecture and nuclear atypia that often exceeds that in invasive carcinoma. Only a small minority of intraductal prostate lesions are thought to be truly “in situ” in nature (ie, originating through a progression from an HGPIN precursor). The great majority of intraductal prostate lesions develop as late events in tumor progression, where high-grade invasive prostate cancer spreads into pre-existing benign prostatic ducts or acini [38].

4. Adenocarcinoma

Malignant cancer (ICD-O:3)

Adenocarcinoma is the most common type of prostate cancer, classified into two types: Acinar adenocarcinoma and ductal adenocarcinoma. However, ductal adenocarcinoma tends to grow and spread more quickly than acinar adenocarcinoma [39].

4.1. Acinar adenocarcinoma

  •  Acinar adenocarcinoma originates in the glands lining the prostate and exhibits histological patterns, including atrophic adenocarcinoma (with aberrant p63+), pseudo-hyperplastic adenocarcinoma, foamy gland adenocarcinoma, microcystic adenocarcinoma, and mucinous (colloid) adenocarcinoma.
  • The subtypes of acinar adenocarcinoma include signet ring cell–like adenocarcinoma, pleomorphic giant cell adenocarcinoma, sarcomatoid carcinoma, and PIN-like carcinoma subtype [37].

4.2. Ductal adenocarcinoma

  •  Pure ductal adenocarcinoma is rare and accounts for 1.3% of prostate carcinomas, composed of large glands lined by tall columnar cells with pseudostratified nuclei.
  • Ductal adenocarcinoma is considered a more aggressive disease than acinar carcinomas and is associated with a higher stage and greater risk of prostate-specific antigen (PSA) recurrence and mortality [37, 38].

5. Treatment-related neuroendocrine prostatic carcinoma

  •  Treatment-related neuroendocrine prostatic carcinoma is considered a distinct clinical entity with a spectrum of histologic features ranging from pure neuroendocrine morphology to mixed neuroendocrine tumors with poorly differentiated adenocarcinoma components.
  • The histologic and immunohistochemical staining features of treatment-related neuroendocrine prostatic carcinoma overlap with those of primary prostatic small cell carcinoma.
  • Patients undergoing androgen deprivation therapy who develop treatment-related neuroendocrine prostatic carcinoma, on average, do so in <24 months.
  • Unfortunately, they will then be destined to a dismal median survival of up to 12 months [37].

Epithelial Prostate Cancer - Squamous neoplasia

 Malignant cancer (ICD-O:3)

 1.Squamous cell carcinoma of the prostate

  •  These cancers develop from flat cells that cover the prostate.
  • They tend to grow and spread more quickly than the adenocarcinoma of the prostate [39].
  • It may be purely prostatic with a transformation of adenocarcinoma, derived from pluripotent stem cells, or a clonal evolution of adenocarcinoma under pressure after estrogen therapy, glutamine therapy, or radiation seed implantation [40]. 

2.Adenosquamous carcinoma of the prostate

  •  Adenosquamous carcinoma of the prostate is characterized by the presence of both glandular/acinar and squamous components.
  • Adenosquamous prostatic carcinoma is a very rare, aggressive tumor.
  • 67% of cases are associated with prior androgen deprivation therapy or radiotherapy [40].

3.Adenoid cystic (basal cell) carcinoma

  • Adenoid cystic (basal cell) carcinoma is a rare, malignant neoplasm that is thought to be derived from basal cells of the prostate.
  • Nonspecific symptoms of urinary tract obstruction, hematuria, nocturia, pollakiuria, or pelvic pain are associated with adenoid cystic (basal cell) carcinoma [40].

Mesenchymal Prostate Cancer

 1. Prostatic stromal tumor of uncertain malignant potential (STUMP)

 Benign tumors (ICD-O:0)

  • STUMP is a rare prostatic tumor that never metastasizes with stromal degenerative atypia featuring vacuolated nuclei.
  • Some cases have cyst spaces (need to rule out phyllodes tumor) that may recur rapidly after incomplete resection; rarely progress to stromal sarcoma.

2.Stromal sarcoma

Malignant cancer (ICD-O:3)
  • Prostatic stromal sarcoma (PSS) is a rare entity that usually presents with urinary retention; also, abnormal digital rectal examination, hematuria or hematospermia, and palpable rectal mass.
  • It includes phyllodes tumors. The most common presentation is bladder outlet obstruction, followed by an abnormal digital rectal exam, hematuria, and rectal fullness.
  • It is diagnosed with Cellular pleomorphism, necrosis, mitotic activity, extension outside the prostate, and metastasis, ruling out benign mimics [40].

Transitional cell carcinoma of the prostate (Urothelial cancer)

  •  Transitional cell carcinoma of the prostate starts in the urethra and spreads into the prostate.
  • But it can rarely begin in the prostate and may spread into the bladder entrance and nearby tissues.
  • This is sometimes called urothelial carcinoma of the prostate. 2-4% of prostate cancers are this type [39].
  • However, the WHO classification for 2022 has transferred urothelial cancer to urinary tract cancers [40].

Diagnosis

  • Warning signs of prostate cancer can be detected early, before symptoms develop, with the prostate-specific antigen (PSA) blood test and a digital rectal exam (DRE).

1.DRE examination

  •  This is a physical examination to check the size and shape of the prostate through the rectum to check if there are any abnormalities.
  • DRE examination is not specific for prostate cancer but for prostate enlargement or changes in the shape, such as the presence of nodules [41].

2.PSA test

  • Prostate-specific antigen (PSA) is useful in the early stages of prostate cancer; however, it is specific to the organ and not to cancer itself.
  • PSA levels can also rise in the case of benign prostatic hypertrophy (BPH) or benign prostatic enlargement (BPE).
  • Individuals at high risk due to a family history of breast or prostate cancer or genetic mutations should begin regular PSA testing at age 40 or 10 years before the youngest prostate cancer diagnosis in the family (for example, start at age 35 if your father or brother is diagnosed with prostate cancer at age (45).
  • Individuals at average risk should undergo baseline PSA testing at age 45 to have a reference for results in later years.
  • Regular testing should continue at intervals of one to four years based on your baseline or previous PSA level, age, and risk factors. If the initial PSA test shows a level of 1.0 ng/mL or higher, follow-up testing should occur every one to two years. If the level is below 1.0 ng/mL, follow-up testing can be conducted every two to four years.
  • For individuals over 70, PSA testing may be discontinued unless they are in very good health with a life expectancy of 10 years or more. 
  • The recommended PSA thresholds are age-adjusted to 2.5, 3.5, 4.5, and 6.5 ng/mL in men in their 40s, 50s, 60s, and 70s, respectively [42].
  • PSA velocity, or the doubling time of PSA levels more than the previous reading, indicates prostate cancer [42].

 3.Multiparametric Magnetic Resonance Imaging (mpMRI)

  •  The NICE guideline offers multiparametric MRI (mpMRI) as the first-line investigation for people with suspected clinically localized prostate cancer, and the results are reported using a 5-point Likert scale. [43]
  • If the Likert score is 1 or 2, consider omitting a prostate biopsy, but only after discussing the risks and benefits with the person and reaching a shared decision.
  • If necessary, a systematic prostate biopsy is better.
  • If the Likert score is 3 or more, mpMRI-influenced prostate biopsy is offered [43].
  • The NICE guidelines do not routinely offer mpMRI to people with prostate cancer who are not going to be able to have radical treatment [43].

4.Prostate biopsy

  • Prostate biopsies aim to confirm the diagnosis and assess the histological architecture using the Gleason grade, which is used to create a Gleason score [44].

1. Transrectal ultrasound-guided (TRUS) biopsy

  • The most common biopsy approach [43].
  • TRUS has a low accuracy for detecting prostate cancer [45]. 
  • Antibiotics may be used for prophylaxis against bacterial infections in TRUS [46].

2. Systematic Biopsy

  • There are several systematic biopsy protocols. Initially, when transrectal prostate biopsy was developed, it used a sextant pattern, with 3 cores taken from each side of the prostate. It was superior to targeting lesions identified using TRUS [47].
  • However, the sextant protocol has been found to have a high false negative rate, particularly in missing apical and lateral lesions.

3.Targeted prostate biopsy

  • Whilst systematic biopsies are useful for sampling the prostate, targeting abnormal lesions directly has become more relevant with the increasing use of mpMRI [44].
  • The current guidance is to offer combined systematic and targeted biopsies [48].

4. Robotic Biopsy

  • The robotic-assistance biopsies increase the cancer targeting and success rate. 
  • Transrectal in-bore MRI robotic biopsy is more commonly used. 
  • The advantages: a short MRI room, and the speed and ease of needle positioning [44, 51] . 

5.Grading and Staging

 1.Gleason grading system: Grades 1-5, predicts aggressiveness

  •  The most common grading system is called the Gleason grading system.
  • The Gleason score measures How quickly cancer cells can grow and affect other tissues.
  • The Gleason prostate cancer score has proven to be the most reliable and predictive histological grading system over time.The Gleason scoring system is based on the microscopic arrangement, architecture, or pattern of the glands in the prostate [52].
  • In clinical practice, Grade Group 1 is histologically considered low-grade, Grade Group 2 is intermediate-grade, and Grade Group 3 or higher is a high-grade disease.

 2.Staging:

Tumor, Nodes, and Metastasis (TNM) is the system used for tumor staging. The TNM score is a measure of how far prostate cancer has spread in the body [53, 54].

The T (tumor) score rates the size and extent of the original tumor.

The N (nodes) score rates whether the cancer has spread into nearby lymph nodes.

The M (metastasis) score rates whether the cancer has spread to distant sites.

Early-stage prostate cancer remains confined to the prostate. It is also known as localized prostate cancer and may be referred to as stage I or II.

Regional prostate cancer (locally advanced prostate cancer) has extended beyond the prostate to nearby areas, such as the seminal vesicles or lymph nodes. Some forms of regional or locally advanced prostate cancer are classified as stage III.

Metastatic prostate cancer (advanced prostate cancer), or stage IV cancer, has spread (metastasized) beyond the prostate and pelvis to other parts of the body [53].

Treatment

7. Treatment [55-59]

  •  Treatment for prostate cancer will depend on individual circumstances.
  • When treatment is necessary, the aim is to cure or control the disease, so it affects everyday life as little as possible and does not shorten life expectancy.
  • Sometimes, if the cancer has already spread, the aim is not to cure it but to prolong life and delay symptoms.
  • Different treatments could be provided depending on the grading of the Gleason score [55-59].
  • Note: Sperm Banking is recommended before any kind of treatment that may cause erectile dysfunction or impotence. It will be possible to have IVF anytime then.

1- Watchful waiting or active surveillance:

  •  Watchful waiting and active surveillance are different approaches to keeping an eye on cancer and starting treatment only if it shows signs of getting worse or causing symptoms.

Active surveillance

  • Closely monitoring prostate cancer by performing DRE, PSA tests, and prostate biopsies regularly and treating the cancer only if it grows or causes symptoms.

Watchful waiting.

  • No tests are done. Your doctor treats any symptoms when they develop. This is usually recommended for men who are not expected to live for more than 10 more years.

2. Surgery:

  •  Patients in good health whose tumor is in the prostate gland only may be treated with surgery to remove the tumor.
  • The following types of surgery are used:

a.Radical prostatectomy

 A surgical procedure to remove the prostate, surrounding tissue, and seminal vesicles. Removal of nearby lymph nodes may be done at the same time. The rate of maintenance of sexual potency with radical prostatectomy was 10% to 40%.

b.Pelvic lymphadenectomy:

  • A surgical procedure to remove the lymph nodes in the pelvis.
  • A pathologist views the tissue under a microscope to look for cancer cells. If the lymph nodes contain cancer, the doctor will not remove the prostate and may recommend other treatment. 

c.Transurethral resection of the prostate (TURP):

A surgical procedure to remove tissue from the prostate using a resectoscope inserted through the urethra.

This procedure is done to treat benign prostatic hypertrophy, and it is sometimes done to relieve symptoms caused by a tumor before other cancer treatment is given.

TURP may also be done in men whose tumor is in the prostate only and who cannot have a radical prostatectomy.

This is carried out under general anesthetic or a spinal anesthetic (epidural).

d.Nerve-sparing prostatectomy:

  • Nerve-sparing surgery is for prostate cancer that hasn’t spread outside the prostate gland. This surgery aims to avoid the nerves that control erections.
  • The surgeon cuts the prostate tissue away from the nerve bundles without damaging them.

Possible problems after prostate cancer surgery include:

  • Impotence or erectile dysfunction
  • Urinary incontinence
  • Fecal incontinence
  • Shortening of the penis
  • Inguinal hernia may occur more often in men treated with radical prostatectomy within the first 2 years.

3. Radiation Therapy:

 Using high-energy rays (like x-rays) to kill the cancer. Hormonal therapy may be used before undergoing radiotherapy to increase the chance of successful treatment and/or after radiotherapy to reduce the chances of cancerous cells recurrence.

Short-term effects of radiotherapy can include:

  • Discomfort
  • Diarrhea
  • Loss of pubic hair
  • Tiredness
  • Bladder cystitis

4.Focal therapy:

  •  Focal therapy is a new form of treatment that destroys tumors inside the prostate.

5.Hormone therapy (Androgen Deprivation Therapy (ADT))

  •  Hormone therapy blocks cancer cells from getting the hormones they need to grow.
  • It doesn’t cure prostate cancer on its own. But it canlower the risk of early prostate cancer coming back when it is combined with other treatments.
  • Hormone therapy is also a possible treatment for metastatic or advanced prostate cancer.
  • There are 3 main ways of having hormone therapy theyinclude injections, tablets, surgery, or combinations

The main side effects are:

  •  Erectile dysfunction (occurs more with injections than tablets)
  • Hot flushes and sweating
  • Feeling tired and weak
  • Breast tenderness
  • Tumor flare

Side effects of long-term treatment are:

  • Weight gain
  • Memory problems
  • Mood swings and depression
  • Bone thinning (Osteoporosis)
  • Risk of early heart failure

6.Novel Hormone therapy:

Enzalutamide significantly decreased the risk of radiographic progression and death and delayed the initiation of chemotherapy in men with metastatic prostate cancer [63].

Apalutamide exerts its action by directly inhibiting the androgen receptor at the ligand-binding domain.

This action allows for the inhibition of Androgen receptor nuclear translocation, DNA binding, and impedes AR-mediated transcription [64].

Apalutamide’s major metabolite, N-desmethyl apalutamide, is a less potent inhibitor of the androgen receptor. The inhibitory actions of apalutamide allow for decreased tumor cell proliferation and increased apoptosis, leading to decreased tumor volume. It is approved for nonmetastatic and metastatic CRPC [64].

 

7.Other therapies under investigation

Treatment Options for Recurrent Prostate Cancer

1. Chemotherapy

  • uses anticancer drugs to destroy cancer cells. Docetaxel and prednisone are the drugs used most often. They are used along with hormone therapy.
  • Other chemotherapy regimens reported to produce subjective improvement in symptoms and reduction in PSA level include:
  • Paclitaxel.
  • Estramustine/etoposide.
  • Estramustine/vinblastine.
  • Estramustine/paclitaxel.

2. Targeted therapy:

  • Targeted therapy uses drugs to target specific molecules (such as proteins) on cancer cells or inside them to stop the growth and spread of cancer and limit harm to normal cells.
  • Targeted therapy may be used to treat recurrent prostate cancer that has certain BRCA genetic mutations, such as Olaparib and rucaparib.
  • Olaparib and rucaparib.
  • They inhibit poly(ADP‐ribose) polymerase (PARP), thereby blocking the repair of single‐strand DNA breaks. This results in synthetic lethality in BRCA‐associated cancer cells, which have a dysfunction of another DNA repair pathway – homologous recombination [69].
  • One potential advantage of Rucaparib over Olaparib could be the eventual availability of a blood test, called a liquid biopsy, that can identify men with BRCA1 or BRCA2 alterations (as well as other genetic alterations) who are candidates for the drug [70].
  • FDA has approved the combinational therapy of Olaparib (Lynparza, AstraZeneca Pharmaceuticals LP) with abiraterone and prednisone (or prednisolone) for adult patients with deleterious or suspected deleterious BRCA-mutated (BRCAm) metastatic castration-resistant prostate cancer (mCRPC) [71].
  • The most common adverse reactions (≥10%) in patients receiving olaparib plus abiraterone were anemia, fatigue, nausea, diarrhea, decreased appetite, lymphopenia, dizziness, and abdominal pain [71].
  • Talazoparib
  • Talazoparib, a potent PARP inhibitor, is used for advanced mCRPCs with DNA damage response (DDR) alterations in genes involved directly or indirectly in homologous recombination repair (HRR) who had been heavily pretreated [72].
  • Recently FDA approved talazoparib with enzalutamide for HRR gene-mutated mCRPC [73].

3. Immunotherapy :

  • Immunotherapy, also called biological therapy, strengthens your immune system so it’s better able to identify and fight cancer cells.
  • Sipuleucel-T, an autologous cellular immunotherapy manufactured from antigen-presenting cells primed to recognize prostatic acid phosphatase, was the first immunotherapy product approved by the US FDA.
  • It was approved for men with asymptomatic or minimally symptomatic mCRPC.
  • Sipuleucel-T has increased overall survival [74].
  • Side effects are generally consistent with cytokine release and include chills, fever, headache, myalgia, sweating, and influenza-like symptoms, usually within the first 24 hours of infusion.
  • No increase in autoimmune disorders or secondary malignancies.

Treatments for bone metastases

  •  The most common treatments for prostate cancer that has spread to the bones are:
  • Bisphosphonates, such as zoledronic acid
  • Denosumab, which is a type of monoclonal antibody therapy
  • Corticosteroids, such as prednisone and dexamethasone
  • External radiation therapy
  • Systemic radiation therapy with radium-223 dichloride
  • A procedure to stabilize a collapsed bone (called kyphoplasty)
  • Pain relief medicines

Prevention for prostate cance

 

  • Adopt an anti-inflammatory diet that is low in red meat, sugar, processed foods, and dairy products, and high in foods that combat inflammation, such as brightly colored vegetables.
  • More physical activity is needed to maintain a healthy weight. Vigorous exercise, tailored to fitness level, has been shown to reduce a man’s risk of developing lethal forms of prostate cancer. Obesity is linked to a higher risk of fatal prostate cancer and recurrence.
  • Monitor your calcium intake. Reduce dairy intake. Excessive amounts of calcium may increase the risk of aggressive prostate cancer.
  • Aim to obtain most of your calcium from plant-based sources, such as almonds, tofu, and leafy greens, rather than supplements unless advised otherwise by your doctor.
  • Substitute red meat with plant-based proteins and fish. Saturated fat found in red meat contributes to inflammation, which is associated with cancer and other chronic diseases. Steer clear of trans fatty acids, found in items like margarine and packaged baked goods.
  • Incorporate lycopene through cooked tomatoes (prepared with olive oil) and cruciferous vegetables, like broccoli and cauliflower, into your meals throughout the week; they may offer health benefits.
  • Avoid smoking.
  • Manage high blood pressure, diabetes, high cholesterol, and depression to enhance your survivorship with prostate cancer.
  • Manage stress since research indicates that the stress hormone cortisol can impede cancer cell death. Lowering stress at work and home can improve your survivorship and contribute to a longer, happier life.
  • For men aged 45 or older (and 40 or older for Black men or those with a family history of prostate cancer), regular screening of the PSA test and, if appropriate, a rectal examination is required.

References

1-Abbas, N., et al., The Silent Burden of De Novo Metastatic Prostate Cancer in the Middle East: A Call for Region-Specific Screening Guidelines. Société Internationale d’Urologie Journal, 2025. 6(1): p. 4.

2-Observatory), G.G.C. 2024; Available from: https://gco.iarc.who.int/today/ https://gco.iarc.who.int/media/globocan/factsheets/cancers/27-prostate-fact-sheet.pdf.

3-Zlotta, A.R., et al., Prevalence of prostate cancer on autopsy: cross-sectional study on unscreened Caucasian and Asian men. Journal of the National Cancer Institute, 2013. 105(14): p. 1050-1058.

1. Abbas, N., et al., The Silent Burden of De Novo Metastatic Prostate Cancer in the Middle East: A Call for Region-Specific Screening Guidelines. Société Internationale d’Urologie Journal, 2025. 6(1): p. 4.
2. Observatory), G.G.C. 2024; Available from: https://gco.iarc.who.int/today/ https://gco.iarc.who.int/media/globocan/factsheets/cancers/27-prostate-fact-sheet.pdf.
3. Zlotta, A.R., et al., Prevalence of prostate cancer on autopsy: cross-sectional study on unscreened Caucasian and Asian men. Journal of the National Cancer Institute, 2013. 105(14): p. 1050-1058.
4. Institute, N.C. Cancer Stat Facts: Prostate Cancer. Available from: https://seer.cancer.gov/statfacts/html/prost.html.
5. Arafa, M.A. and D.M. Rabah, With increasing trends of prostate cancer in the Saudi Arabia and Arab World: Should we start screening programs? World Journal of Clinical Oncology, 2017. 8(6): p. 447.
6. Bergengren, O., et al., 2022 Update on Prostate Cancer Epidemiology and Risk Factors—A Systematic Review. European Urology, 2023. 84(2): p. 191-206.
7. foundation, P.c. Risk factors. Available from: https://www.pcf.org/patient-resources/family-cancer-risk/prostate-cancer-risk-factors/.
8. Rajwa, P., et al., Positive family history as a predictor for disease outcomes after radical prostatectomy for nonmetastatic prostate cancer. Arab Journal of Urology, 2023. 21(4): p. 241-247.
9. Barber, L., et al., Family History of Breast or Prostate Cancer and Prostate Cancer Risk. Clin Cancer Res, 2018. 24(23): p. 5910-5917.
10. D’Elia, G., et al., Increased Risk of Hereditary Prostate Cancer in Italian Families with Hereditary Breast and Ovarian Cancer Syndrome Harboring Mutations in BRCA and in Other Susceptibility Genes. Genes (Basel), 2022. 13(10).
11. Darcey, E. and T. Boyle, Tobacco smoking and survival after a prostate cancer diagnosis: A systematic review and meta-analysis. Cancer Treatment Reviews, 2018. 70: p. 30-40.
12. Gupta, S., et al., Relationship between type of smokeless tobacco & risk of cancer: A systematic review. Indian Journal of Medical Research, 2018. 148(1).
13. Gupta, N., et al., Systematic review of the impact of a plant-based diet on prostate cancer incidence and outcomes. Prostate Cancer and Prostatic Diseases, 2022. 25(3): p. 444-452.
14. Rowles, J.L., et al., Increased dietary and circulating lycopene are associated with reduced prostate cancer risk: a systematic review and meta-analysis. Prostate Cancer and Prostatic Diseases, 2017. 20(4): p. 361-377.

15. Oczkowski, M., et al., Dietary Factors and Prostate Cancer Development, Progression, and Reduction. Nutrients, 2021. 13(2).
16. Zhang, Q., et al., Phytoestrogens and risk of prostate cancer: an updated meta-analysis of epidemiologic studies. International journal of food sciences and nutrition, 2017. 68(1): p. 28-42.
17. Aune, D., et al., Dairy products, calcium, and prostate cancer risk: a systematic review and meta-analysis of cohort studies23. The American Journal of Clinical Nutrition, 2015. 101(1): p. 87-117.
18. Fu, B.C., et al., Insulinemic and Inflammatory Dietary Patterns and Risk of Prostate Cancer. European Urology, 2021. 79(3): p. 405-412.
19. Prins, G.S., Endocrine disruptors and prostate cancer risk. Endocr Relat Cancer, 2008. 15(3): p. 649-56.
Saha, A., M.G. Kolonin, and J. DiGiovanni, Obesity and prostate cancer — microenvironmental roles of adipose tissue. Nature Reviews Urology, 2023. 20(10): p. 579-596.
Russo, G.I., et al., Human papillomavirus and risk of prostate cancer: a systematic review and meta-analysis. The Aging Male, 2020. 23(2): p. 132-138.
22. Hayes, R.B., et al., Sexual behaviour, STDs and risks for prostate cancer. Br J Cancer, 2000. 82(3): p. 718-25.
23. Qiao, Y., et al., Associations between aspirin use and the risk of cancers: a meta-analysis of observational studies. BMC cancer, 2018. 18: p. 1-57.
24. Hu, X., et al., Association of 5-alpha-reductase inhibitor and prostate cancer incidence and mortality: a meta-analysis. Translational andrology and urology, 2020. 9(6): p. 2519.
25. Alukal, J.P. and H. Lepor, Testosterone Deficiency and the Prostate. Urol Clin North Am, 2016. 43(2): p. 203-8.
26. Bethel, C.R., A.M. De Marzo, and W.G. Nelson, Chapter 25 – Molecular Pathogenesis of Prostate Cancer: Somatic, Epigenetic, and Genetic Alterations, in Essential Concepts in Molecular Pathology, W.B. Coleman and G.J. Tsongalis, Editors. 2010, Academic Press: San Diego. p. 335-340.
27. Leslie, S.W., T.L. Soon-Sutton, and W.P. Skelton, Prostate Cancer, in StatPearls. 2025, StatPearls Publishing
Copyright © 2025, StatPearls Publishing LLC.: Treasure Island (FL).
28. Mani, R.S., et al., Inflammation-Induced Oxidative Stress Mediates Gene Fusion Formation in Prostate Cancer. Cell Reports, 2016. 17(10): p. 2620-2631.

29. Sfanos, K.S. and A.M. De Marzo, Prostate cancer and inflammation: the evidence. Histopathology, 2012. 60(1): p. 199-215.
30. Grossmann, M., A.S. Cheung, and J.D. Zajac, Androgens and prostate cancer; pathogenesis and deprivation therapy. Best Practice & Research Clinical Endocrinology & Metabolism, 2013. 27(4): p. 603-616.
31. Azad, A.A., et al., Androgen receptor gene aberrations in circulating cell-free DNA: biomarkers of therapeutic resistance in castration-resistant prostate cancer. Clinical cancer research, 2015. 21(10): p. 2315-2324.
32. Romanel, A., et al., Plasma AR and abiraterone-resistant prostate cancer. Sci Transl Med, 2015. 7(312): p. 312re10.
33. Shorning, B.Y., et al., The PI3K-AKT-mTOR Pathway and Prostate Cancer: At the Crossroads of AR, MAPK, and WNT Signaling. Int J Mol Sci, 2020. 21(12).
34. Jamaspishvili, T., et al., Clinical implications of PTEN loss in prostate cancer. Nat Rev Urol, 2018. 15(4): p. 222-234.
35. Drudge-Coates, L., et al., Recognizing Symptom Burden in Advanced Prostate Cancer: A Global Patient and Caregiver Survey. Clinical Genitourinary Cancer, 2018. 16(2): p. e411-e419.
36. (CDC), C.f.D.C.a.P. Prostate cancer. Available from: https://www.cdc.gov/prostate-cancer/symptoms/index.html.
37. Netto, G.J., et al., The 2022 World Health Organization Classification of Tumors of the Urinary System and Male Genital Organs—Part B: Prostate and Urinary Tract Tumors. European Urology, 2022. 82(5): p. 469-482.
38. Zhou, M., High-grade prostatic intraepithelial neoplasia, PIN-like carcinoma, ductal carcinoma, and intraductal carcinoma of the prostate. Modern Pathology, 2018. 31(1): p. 71-79.
39. UK, C.R. Prostate cancer Available from: https://www.cancerresearchuk.org/about-cancer/prostate-cancer/stages/types
40. Pires Gama A, C.B. WHO classification of prostate cancer March 18th, 2025.]; Available from: https://www.pathologyoutlines.com/topic/prostateWHO.html.
41. Kirby, M., et al., Is the digital rectal exam any good as a prostate cancer screening test? British Journal of General Practice, 2024. 74(740): p. 137.
42. Descotes, J.-L., Diagnosis of prostate cancer. Asian Journal of Urology, 2019. 6(2): p. 129-136.

43. guidlines, N. Prostate cancer. Available from: https://www.nice.org.uk/guidance/ng131/chapter/Recommendations#assessment-and-diagnosis.
44. Paul Gravestock, B., et al., Prostate cancer diagnosis: Biopsy approaches. Exon Publications, 2022: p. 141-168.
45. Grups, J.W., et al., Diagnostic Value of Transrectal Ultrasound in Tumor Staging and in the Detection of Incidental Prostatic Cancer. Urologia Internationalis, 2010. 45(1): p. 38-40.
46. Zani, E.L., O.A. Clark, and N. Rodrigues Netto, Jr., Antibiotic prophylaxis for transrectal prostate biopsy. Cochrane Database Syst Rev, 2011(5): p. Cd006576.
47. Hodge, K.K., et al., Random systematic versus directed ultrasound guided transrectal core biopsies of the prostate. The Journal of urology, 1989. 142(1): p. 71-74.
48. Mottet, N., et al., EAU-EANM-ESTRO-ESUR-SIOG Guidelines on Prostate Cancer—2020 Update. Part 1: Screening, Diagnosis, and Local Treatment with Curative Intent. European Urology, 2021. 79(2): p. 243-262.
49. Costa, D.N., et al., Magnetic Resonance Imaging-guided In-bore and Magnetic Resonance Imaging-transrectal Ultrasound Fusion Targeted Prostate Biopsies: An Adjusted Comparison of Clinically Significant Prostate Cancer Detection Rate. Eur Urol Oncol, 2019. 2(4): p. 397-404.
50. Altok, M., et al., Cost and efficacy comparison of five prostate biopsy modalities: a platform for integrating cost into novel-platform comparative research. Prostate Cancer and Prostatic Diseases, 2018. 21(4): p. 524-532.
51. Barral, M., et al., In-Bore Transrectal MRI–Guided Biopsy With Robotic Assistance in the Diagnosis of Prostate Cancer: An Analysis of 57 Patients. American Journal of Roentgenology, 2019. 213(4): p. W171-W179.
52. Chen, N. and Q. Zhou, The evolving Gleason grading system. Chin J Cancer Res, 2016. 28(1): p. 58-64.
53. cancer, Z.p. Staging of prostate cancer. Available from: https://zerocancer.org/stages-and-grading#risk.
54. foundation, U.c. Prostate staging Available from: https://www.urologyhealth.org/urology-a-z/p/prostate-cancer.

55. (CDC), C.f.D.C.a.P. Prostate cancer treatment Available from: https://www.cdc.gov/prostate-cancer/treatment/index.html.
56. Institute, N.C. Prostate Cancer Treatment (PDQ®)–Health Professional Version. Available from: https://www.cancer.gov/types/prostate/hp/prostate-treatment-pdq.
57. (NHS), N.h.S.U. Prostate cancer treatment Available from: https://www.nhs.uk/conditions/prostate-cancer/treatment/.
58. research, C. Prostate cancer treatment. Available from: https://www.cancerresearchuk.org/about-cancer/prostate-cancer/treatment.
59. clinic.org, C. Prostate cancer managment and treatment Available from: https://my.clevelandclinic.org/health/diseases/8634-prostate-cancer#management-and-treatment.
60. center, J.H. Proton Therapy for Prostate Cancer. Available from: https://www.hopkinsmedicine.org/health/conditions-and-diseases/prostate-cancer/proton-therapy-for-prostate-cancer#:~:text=Proton%20beam%20therapy%20for%20prostate%20cancer%20is%20a%20noninvasive%20external,and%20organs%20from%20radiation%20exposure.

61. Brogden, R.N. and P. Chrisp, Flutamide. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in advanced prostatic cancer. Drugs Aging, 1991. 1(2): p. 104-15.
62. Schellhammer, P.F. and J.W. Davis, An Evaluation of Bicalutamide in the Treatment of Prostate Cancer. Clinical Prostate Cancer, 2004. 2(4): p. 213-219.
63. Beer, T.M., et al., Enzalutamide in Metastatic Prostate Cancer before Chemotherapy. New England Journal of Medicine, 2014. 371(5): p. 424-433.
64. Patel, U.J. and S. Caulfield, Apalutamide for the Treatment of Nonmetastatic Castration-Resistant Prostate Cancer. J Adv Pract Oncol, 2019. 10(5): p. 501-507.
65. Yamaoka, M., et al., Orteronel (TAK-700), a novel non-steroidal 17, 20-lyase inhibitor: effects on steroid synthesis in human and monkey adrenal cells and serum steroid levels in cynomolgus monkeys. The Journal of steroid biochemistry and molecular biology, 2012. 129(3-5): p. 115-128.
66. He, Y., et al., Targeting signaling pathways in prostate cancer: mechanisms and clinical trials. Signal Transduction and Targeted Therapy, 2022. 7(1): p. 198.
67. Taplin, M.-E., et al., Androgen receptor modulation optimized for response—Splice variant: A phase 3, randomized trial of galeterone versus enzalutamide in androgen receptor splice variant-7–expressing metastatic castration-resistant prostate cancer. European urology, 2019. 76(6): p. 843-851.
68. Madan, R.A., et al., Phase 2 Study of Seviteronel (INO-464) in Patients With Metastatic Castration-Resistant Prostate Cancer After Enzalutamide Treatment. Clin Genitourin Cancer, 2020. 18(4): p. 258-267.e1.
69. Goulooze, S.C., A.F. Cohen, and R. Rissmann, Olaparib. Br J Clin Pharmacol, 2016. 81(1): p. 171-3.

70. Institute, N.C. With Two FDA Approvals, Prostate Cancer Treatment Enters the PARP Era. 2020; Available from: https://www.cancer.gov/news-events/cancer-currents-blog/2020/fda-olaparib-rucaparib-prostate-cancer.
71. FDA. FDA approves olaparib with abiraterone and prednisone (or prednisolone) for BRCA-mutated metastatic castration-resistant prostate cancer. 2023; Available from: https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-olaparib-abiraterone-and-prednisone-or-prednisolone-brca-mutated-metastatic-castration#:~:text=On%20May%2031%2C%202023%2C%20the,mCRPC)%2C%20as%20determined%20by%20an.
72. de Bono, J.S., et al., Talazoparib monotherapy in metastatic castration-resistant prostate cancer with DNA repair alterations (TALAPRO-1): an open-label, phase 2 trial. The Lancet Oncology, 2021. 22(9): p. 1250-1264.
73. FDA. FDA approves talazoparib with enzalutamide for HRR gene-mutated metastatic castration-resistant prostate cancer. Available from: https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-talazoparib-enzalutamide-hrr-gene-mutated-metastatic-castration-resistant-prostate.
74. Handy, C.E. and E.S. Antonarakis, Sipuleucel-T for the treatment of prostate cancer: novel insights and future directions. Future Oncol, 2018. 14(10): p. 907-917.
75. Prostate cancer prevention. Available from: https://www.pcf.org/patient-resources/family-cancer-risk/prostate-cancer-prevention/.

Paving the path to a future free from genitourinary cancer

Site Map

Contact us

LinkedIn

All Rights Reserved to Indigoarabia.com