Urological Flashcards

(18 cards)

1
Q

Renal cell carcinoma epidemiology? Signs and symptoms?

A

Worldwide, renal cell carcinoma represents the 6th most frequently diagnosed cancer in men and the 10th in women, accounting for 5% and 3% of all oncological diagnoses, respectively.

Signs and symptoms : heterogenous therefore difficult to make a diagnosis only based on clinical signs. They include flank pain, hematuria, a mass, hypertension, hypercalcemia, sedimentation rate elevation, anemia, fever.

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2
Q

Different types of renal masses?

A

Benign :
- Oncocytoma is the most frequent one and is an indolent tumor which is borderline.
- Angiomyolipoma.

Malignant :
- RCC : include clear cell RCC (70-80%), papillary I and II RCC (10-15%), chromophobe RCC.
- Upper tract transitional cancer.
- Sarcoma.
- Wilms tumor.

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3
Q

Renal cell carcinoma diagnosis? Staging and grading?

A

Diagnosis is made usually incidentally while performing a CT scan.

Staging is made by TNM. Grading is done according to shape of nuclei, nucleoli and sarcomatoid features. The Fuhman classification is used but is being replaced by the WHO/ISUP grading system.

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4
Q

Molecular pathways in RCC and their relevance for targeted therapies?

A

Clear cell RCC is the most common histological subtype of RCC and it is molecular driven by angiogenesis related pathway such as HIF-2alpha, loss of VHL tumor suppressor gene 90%, upregulation of VEGF. Also PBRM1 mutations in 40%.

Targeted therapies include drugs such as sunitinib (VEGFR), belzutifan, zutifan (HIF-2alpha i).

Papillary RCC is mostly associated to MET mutations in around 40% of cases. The implication is that MET inhibitors like crizotinib are effective in papillary RCC where MET is a driver mutation.

VHL syndrome caused by germline mutation in the VHL gene. It is characterized by multiple bilateral clear cell RCCs, hemangioblastomas, pheochromocytomas.

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5
Q

Different stages of kidney cancer and recommend treatment?

A
  • Stage I (less than 7 cm) and II (more than 7 cm) consist in small tumors confined to the kidneys in which surgery is the standard option for treatment. Surgical procedure like partial or radical nephrectomy are used.
  • Stage III consists of primary tumor and lymph node involvement, or a typical feature that is renal/caval vein thrombus. Stage III is still surgical, primary indication is radical surgery.

-In stage IV (metastatic disease), obviously the first indication is systemic therapy. Then, in selected cases, surgical resection of the remaining primary lesion can be performed, known as
cytoreductive nephrectomy.

Surgery (either radical or partial nephrectomy) has been the only option for a long time, but in more recent times, it has become an organ sparing approach, as in robotic surgery or laparoscopy.
There are also non-surgical procedures, such as:
- Radiological procedures as cryoablation
- Thermo-ablation
- Local tumor ablation for which we have the same results of surgical removal.

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6
Q

Mutations in RCC and their implication in immunotherapy?

A

There is a relationship between mutation and tumor that we can quantify as tumor mutational burden. This is useful to understand if we can benefit from the use of immunotherapy.

RCC is in between a highly mutated cancer (bladder cancer) and a low mutational cancer (testicular cancer).

PDL1 is expressed by tumor cells and binds to PD1 on T cells inhibiting T cell activation. By using PDL1 inhibitor we block this interaction restoring T cell mediated killing. Drugs like pemprolizumab or nivolumab affect PD1 on T cells, durvalumab and avelumab affect the PDL1 on tumor cells.

For papillary tumors there is the possibility to target MET, we can use drugs like crizotinib.

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7
Q

Prostate adenocarcinoma epidemiology? Grading? Metastasis?

A

It is the second leading cause of cancer death in men, predominantly in western countries. PSA screening is controversial due to risk of over diagnosis and overtreatment.
BRCA screening can be done in patients with metastatic prostate cancer, men with high risk of developing cancer, men with family history of breast, ovarian, pancreatic and prostate cancer.

Histological grading is done by using the Gleason score which combines the two most prevalent histological patterns.

Common sites of metastasis spread include pelvic lymph nodes and bone. Bone only metastases can occur.

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8
Q

Molecular alteration and targeted therapy in prostatic cancer?

A

There is evidence of
- DNA damage repair genes, in particular BRCA 1 and 2 so we can potentially use PARPi. 20/25% of cases. Olaparib has been recently approved for prostate cancer.
- PI3K/AKT/mTOR pathway alterations 40% , use of AKTi like Ipatasertib.
- TP53 and RB1 mutations, frequently mutated in advanced and castration resistant prostate cancer.
- ETS gene rearrangements, common in early prostate cancer.
- Microsatellite instability, we can use pembrolizumab.

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9
Q

Androgen and its role in prostate cancer progression?

A

Prostate cancer cells rely on androgen receptor signaling. Therapeutically we can affect it in two ways :
- Central blockade using gonadotropin releasing hormone agonist/antagonist.
- Peripherically by using antiandrogen therapies.

We now have second generation anti androgen receptor inhibitors orally available such as :
- Abitarone decrease aldosterone and cortisol levels.
- Enzalutamide blocks AR binding, nuclear translocation and DNA binding.

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10
Q

Clinical states of prostatic cancer? Treatment?

A

In Castration sensitive prostate cancer : the disease still responds to androgen deprivation therapy.

Castration resistant prostate cancer : the disease progresses (rising PSA) despite castrate levels of testosterone. It is important to remember that PSA rise alone does not define CRPC , it must happen while on androgen deprivation therapy.

Both CSPC and CRPC can be metastatic or non metastatic.

Localized prostate cancer RT or prostatectomy.

In cases of CRPC we can use chemo like docetaxel, PARPi like olaparib, anti PDL1 like pembrolizumab.

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11
Q

Bladder carcinoma epidemiology? Risk factors? Classification? Mutations?

A

It is a very frequent malignancy especially in smoker. It is most common in western countries and often asymptomatic until advanced stage.

Classification :
- Non muscle invasive bladder cancer which is confined to mucosa or submucosa and is treated mainly by urologists with TURBT. Mutations include FGFR3 in 60/70% of cases, HRAS (RAS/MAPK pathway) and PIK3CA

  • Muscle invasive bladder cancer invades the muscle layer and is treated but oncologist as it requires systemic chemotherapy and then possible surgery. Mutations include TP53 in 50/60% of cases, RB1, HER2 and ERCC2.
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12
Q

Diagnosis and staging of bladder cancer? Common lymph node metastasis sites?

A

Most common symptoms is painless hematuria. Diagnostic procedures include cystoscopy which detects lesion and TURBT which confirms malignancy and depth of invasion.

Staging is done with CT scan for MIBC but has limitations in accuracy, MRI better than CT for local tumor staging, FDG-PET is superior for distant metastasis.

Common lymph node metastasis sites include external iliac, obturator fossa, internal iliac and common iliac.

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13
Q

Neoadjuvant vs adjuvant treatment for bladder cancer?

A

Neoadjuvant treatment : given before cystectomy and uses cisplatin.

Adjuvant treatment : given after cystectomy and cisplatin or carboplatin which is less toxic is used. Immunotherapy is being investigated in particular with pembrolizumab and nivolumab.

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14
Q

Treatment for metastatic bladder cancer?

A

First line :
- if cisplatin eligible then cisplatin + gemcitabine.
- if ineligible for cisplatin then gemcitabine + carboplatin.

If after first line the patient is responsive then first line maintenance is avelumab, if not responsive use pembrolizumab.

Second line :
- pembrolizumab.
- erdafitinib which is a FGFR inhibitor used in patients with FGFR 2 or 3 mutations, still in experimental/clinical trials.

Third line :
- enfortumab vedotin which is an antibody drug conjugate, The target is for nectin-4, a transmembrane cell adhesion molecule overexpressed in epithelial cancers.
- sacituzumab targets Trop-2, epithelial cell surface glycoprotein expressed in muscle invasive disease, not yet used as not reimbursed.

mTOR inhibitors like everolimus are being identified as possible therapies for tuberous sclerosis 1 mutated bladder cancers.

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15
Q

Testicular cancer types?

A

Type 1 are very infrequent and are prepubertal teratoma and yolk sac tumor. Type 2 which are the most common and includes seminomas and embryonal carcinoma. Type III spermatocytic tumors.

Stage I : orchiectomy is enough in most cases, sometimes we may consider adjuvant therapy in patient with risk factors like tumor size and invasion of rete testis. In seminomas 1 cycle of carboplatin in non seminomas 1 cycle of PEB (platinum based + etoposide + bleomycin).

Stage II : treatment is more complex and is divided in IIa with adenopathy less than 2 cm and IIb between 2 and 5 cm.

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16
Q

Treatment strategy from testicular cancer? Staging?

A

Stage I : orchiectomy is enough in most cases, sometimes we may consider adjuvant therapy in patient with risk factors like tumor size and invasion of rete testis. In seminomas 1 cycle of carboplatin in non seminomas 1 cycle of PEB (platinum based + etoposide + bleomycin).

Stage II : treatment is more complex and is divided in IIa with adenopathy less than 2 cm and IIb between 2 and 5 cm.
If non seminoma then most used option is chemotherapy followed by surgery as chemo theory reduces the tumor burden and makes surgery easier.
If seminoma first line is RT :
- if IIa then RT to para aortic + ipsilateral iliac LN field.
- if IIb 30 Gy + boost to enlarged LN.

17
Q

Metastatic testicular cancer? Treatment?

A

The most common location of metastasis are the lymph nodes followed by the liver, lung and brain. Seminomas always have better prognosis than non seminomas.

Treatment of metastatic disease is similar to the stage II treatment. PEB is used, 3 cycles for good prognosis patients, 4 cycles for intermediate/poor prognosis patients.
Second lime we may use VIP (vinecristine, isofamide and platinum based).

18
Q

Most important markers for testicular cancer?

A

Chorionic gonadotropin, alpha fetoprotein, LDH.