testicular tumors

testicular tumors

1. TESTICULAR CANCERS Dr. Ayush Garg

2. Overview Cancers of testis are relatively rare cancer accounting for approx. 1 % cancer in males. However it is important in field of oncology as it represents a highly curable neoplasm & the incidence is focused on young patients at their peak of productivity

3. Anatomy The testis is the male gonad. It is homologous with the ovary in female. It lies obliquely within the scrotum suspended by the spermatic cord The left testis is slightly lower than the right Shape: Oval Size:3.75 cm long, 2.5 cm broad, 1.8 cm thick Weight: about 10-15 gm. Has 2poles , 2surface, 2 borders

4. Skin DARTOS Muscle External Spermatic Fascia Cremastric Muscle Internal Spermatic Fascia Tunica Vaginalis Tunica Albuginea Coverings of testis

5. Blood Supply Areterial supply The testicular artery branch of abdominal aorta . The testis has collateral blood supply from the cremasteric artery artery to the ductus deferens Venous drainage The veins emerge from the back of the testis, and receive tributaries from the epididymis; they unite and form convoluted plexus, called the pampiniform plexus . plexus to form a single vein, which opens, on the right side, into the inferior vena cava ,on the left side into the left renal vein

6. Lymphatic Drainage Drain into the retroperitoneal lymph glands between the levels of T11 and L4 , but they are concentrated at the level of the L1 and L3 vertebrae Lymph nodes located lateral or anterior to the inferior vena cava are called paracaval or precaval nodes, respectively. Interaortocaval nodes are located between the inferior vena cava and the aorta. Nodes anterior or lateral to the aorta are preaortic or para- aortic nodes, respectively

7. On the right: Interaortocaval region, followed by the paracaval, preaortic, and para- aortic lymph nodes. On the left: Preaortic and para-aortic nodes and thence to the interaortocaval Metastatic nodal disease to the common iliac, external iliac, or inguinal lymph nodes is usually secondary to a large volume of disease with retrograde spread. If the patient has undergone a herniorrhaphy, vasectomy, or other transscrotal procedure , metastasis to the pelvic and inguinal lymph nodes is more likely Through the thoracic duct to lymph nodes in the posterior mediastinum and supraclavicular fossae and occasionally to the axillary nodes. Contralateral spread is mainly seen with right-sided tumors. In 15% to 20%, bilateral nodes are involved

8. INTRODUCTION Comprise a morphologically and clinically diverse group of tumors Predominantly affects young males 1 -2 % of all cancers in USA Testicular cancer forms about 1% of all malignancies in males in India. Incidence (ASR)– 0.6 per 100000 Mortality (ASR)– 0.3 per 100000 95% are Germ Cell Tumours (GCTs) 90% GCT are in testes,2-10% in extra gonadal (eg retropreitoneum, mediastinal) Cure rate increased with introduction of platinum based chemotherapy from 10 to 80%

9. EPIDEMOLOGY OF TESTICULAR CANCER Age : for GCT: median age at diagnosis is 34 years, with 50% of incident cases between 20 and 34 years. In a man age: 50 years or older solid testicular mass is usually lymphoma Age - 3 peaks 2 – 4 yrs 20 – 40 yrs above 50 yrs Geographic : Highest incidence in Denmark, Norway, and Switzerland and the lowest in eastern Europe and Asia. Race : more common in young white men ,less in African Americans

10. Predisposing Factors Cryptorchidism Klinefelter syndrome Positive family history Positive personal history Intratubular germ cell neoplasia Trauma Viral infection Hormonal factors Exposure to environmental oestrogen

11. Pathological classification 1:Intra tubular germ-cell neoplasia(IGCN) 2:GERM CELL TUMORS 95% Seminoma 40% Classic type anaplastic Spermatocytic type Non seminomatous germ-cell tumors 60% Embryonal carcinoma 20-25% Teratoma 25-35% Yolk sac (endodermal sinus) tumor Choriocarcinoma 1% Mixed germ-cell tumor 3:Classification of Sex-Cord Stromal Tumors of the Testis 2-3% Leydig cell tumor Sertoli cell tumor Granulosa cell tumor Fibroma-thecoma stromal tumor Gonadoblastoma Sex cord-stromal tumor unclassified type 4: others 5% lymphoma rabdomyosarcoma melanoma

12. Seminoma The commonest variety of testicular tumour Adults are the usual target (4 th and 5 th decade); never seen in infancy Right > Left Testis Starts in the mediastinum: compresses the surrounding structure. Patients present with painless testicular mass 30 % have metastases at presentation, but only 3% have symptoms related to metastases

13. Seminoma Serum alpha fetoprotein is normal Beta HCG is elevated in 30% of patients with Seminoma Classification classical Anaplastic Spermatocytic

14. Sp r ead Direct Spread: This spread occurs by invasion. Whole of testis in involved and restricted Tunica albuginea is rarely penetrated May be crossed by “blunder biopsy” Scrotal skin involvement Fungation on the anterior aspect Spread to spermatic cord and epidedymis may occur : points towards bad prognosis

15. Sp r ead Lymphatic spread: Seminoma metastasize exclusively through lymphatics They drain primarily to para-aortic lymph nodes From RPLN drain into cysterna chili, thoracic duct ,posterior mediastinum & left supraclavicular Lymph from medial side of testes run along the artery to the vas to drain to nodes at the bifurcation of common iliac No inguinal nodes until scrotal skin involvement

16. Sp r ead Blood Spread NSGCT spread through blood route Lungs, liver, bones and brain are the usual sites usually involved

17. Clinical Features Due to primary tumor Painless testicular lump Sensation of heaviness if size > than 2-3 times Rarely dragging pain is complained of (1/3 rd cases) May mimic epidedymo-orchitis Sudden pain and enlargement due to hemorrhage mimicking torsion History of trauma (co-incidental)

18. Clinical Features Due to metastasis Abdominal or lumbar pain (lymphatic spread) Dyspnoea, hemoptysis and chest pain with lung mets Jaundice with liver mets Hydronephrosis by para-aortic lymph nodes enlargement Pedal oedema by IVC obstruction Troiser’s sign

19. Clinical Features Clinical examination: Enlarged testis (except choriocarcinoma) Nodular testis Firm to hard in consistency Loss of testicular sensation Secondary hydrocele Flat and difficult to feel epididymis General examination for metastasis

20. Tumor markers TWO MAIN CLASSES Onco-fetal Substances : AFP & HCG AFP - Trophoblastic Cells HCG - Syncytiotrophoblastic Cells AFP, BHCG & LDH are included in TNM staging of testicular cancers

21. Staging Work Up General History (document cryptorchidism and previous inguinal or scrotal surgery) Physical examination Laboratory Studies CBC, LFT, RFT, LDH Serum assays Alpha fetoprotein (AFP) Beta human chorionic gonadotropin

22. Diagnostic Radiology Chest x-ray films, posterior/anterior and lateral views Computed tomography (CT) scan of abdomen and pelvis CT scan of chest for non seminomas and stage II seminomas Ultrasound of contralateral testis

23. LDH Beta HCG AFP (mIu/ml) (ng/ml) S1 < 1.5 x N <5000 <1000 S2 1.5-10 x N 5000-50000 1000-10000 S3 >10 x N >50000 >10000 Serum Tumor Markers (S)

24. Surgery Radical orchidectomy : all patients done via an inguinal incision, with cross clamping of spermatic cord vasculature and delivery of testis into the surgical field. Scrotal violation, increased local/regional recurrence, but no difference in distant recurrence rate or overall survival.

25. Retro peritoneal lymph node dissection( RPLND ): Indication: preferred treatment for low stage NSGCT Include the precaval , retrocaval , paracaval , interaortocaval , retroaortic , preaortic , para-aortic, and common iliac lymph nodes bilaterally. Disadv .: sympathetic nerve fibers are disrupted, resulting in loss of seminal emission. A modified RPLND developed that preserves ejaculation in up to 90%.

26. PRINCIPLES OF RADIOTHERAPY FOR PURE TESTICULAR SEMINOMA Linear accelerators with >6 MV photons should be used when possible. The mean dose ( Dmean ) and dose delivered to 50% of the volume (D50%) of the kidneys, liver, and bowel are lower with CT-based AP-PA 3D-CRT than IMRT. As a result, the risk of second cancers arising in the kidneys, liver, or bowel may be lower with 3D-CRT than IMRT, and IMRT is not recommended. 3D Planning 3D planning is preferred due to potential of marginal miss, with 2D planning based on bony anatomy . 3D planning improves target definition and kidney/small bowel shielding.

27. Para-aortic field: Contour IVC and aorta separately from 2 cm below the top of the kidneys down to the point where these vessels bifurcate. Use a 1.2 cm expansion radially around IVC and a 1.9 cm expansion around the aorta, excluding bone and bowel. Dogleg field : In addition to PA field, contour the ipsilateral common , external, and proximal internal iliac veins and arteries down to upper border of acetabulum . Use a 1.2 cm expansion on the iliac vessels, excluding bone and bowel . PTV=CTV+0.5 cm 0.7 cm margin on PTV to block edge to take penumbra into account 3D PLANNING

28. Dog Leg Field upper border of T10 or T11 left renal hilum is included for left-sided tumors (only) Traditionally , the inferior border was placed at the superior obturator foramen (indicated in orange) to include all external iliac nodes 10 cm wide in the para-aortic region and usually covers the transverse processes At the mid-L4 level, the field is extended laterally to cover the i /l external iliac

29. Dog Leg Field- Modified Superior border :bottom of body T11. Inferior border : top of the acetabulum . The medial border for the lower aspect of the modified dog-leg fields extends from the tip of the c/l transverse process of L5 toward the medial border of the i /l obturator foramen. The lateral border for the lower aspect of the modified dog-leg fields is defined by a line from the tip of the i /l transverse process of L5 to the superolateral border of the i /l acetabulum .

30. Radiation therapy Indications Adjuvant therapy for stages I– IIb diseases Salvage of loco-regional failure after surgery or chemotherapy Palliative treatment to loco-regional or distant metastatic sites Techniques EBRT to lymph nodes High-energy radiation (6 – 18 MV) Seminoma is extremely radiosensitive. Radiation therapy is often used for adjuvant therapy for early-stage seminoma, and its use in non-seminoma germ cell tumors (GCT) is limited.

31. Position and immobilization Supine, arms placed by the pt. side and legs straight, with feet stabilized with a foam wedge underneath the knees. Position penis out of field Shielding Contra-lateral testis is shielded with a lead clamshell device. Mean dose values to the contralateral testicle. PA PA + IL iliac Without shield 1.86 cGy 3.89 cGy With shield 0.65 cGy 1.48 cGy

32. Stage I: Field margins Superior : T10–T11 interspace Inferior: L5–S1 interspace Lateral: transverse process For left testis: cover renal hilum Dose 20 Gy in 10# to para -aortic ± pelivic lymph node by ap -pa field Elective para-aortic field for stage I seminoma

33. Stage II Superior: T10 –T11 interspace Inferior: superior aspect of acetabulum Lateral: transverse process ( appx 9 cm wide in PA region) down to L5–S1 interspace then diagonally to the lateral edge of the acetabulum , then vertically downward to the median border of the obturator foramen For left testis: cover left renal hilum Paraaortic and ipsilateral inguinal field for stage II left testicular seminoms , with inclusion of the renal hilus .

34. Stage II a- 25Gy in 20 # by AP-PA Stage II b & IIc 25 Gy in 20 # 10 Gy in 5 #

35. Complications : Radiotherapy Acute nausea, vomiting, diarrhea Late small bowel obstruction, chronic diarrhea, peptic ulcer disease (<2% with <35 Gy ) Second cancers: 5–10% increased risk vs. general population after RT With testicular shielding, most patients will have oligospermia by 4 months that lasts ~1 year Infertility: 50% of patients have subfertile counts on presentation or after surgery. After RT, 30% able to have children

36. 50 cGy causes transient azospermia with recovery at 1 year, but only 50% of patients reach their baseline 80–100 cGy causes total azospermia with recovery 1–2 year later for some patients 200 cGy causes sterilization Testicular shield reduces testicle dose by 2–3x Kidneys: limit at least 70% <20 Gy

37. Chemotherapy Indications As an alternative to adjuvant RT for stages I–II seminoma Adjuvant therapy for stages II–IV seminoma Regimens Single-agent one cycle of carboplatin become an alternative for stage I seminoma Regimens including BEP x 3 cycles, EP x 4 cycles, PVB, and VIP for stages II–IV diseases

38. “I always had the size difference there, but I didn’t know…I would’ve still been waiting if it hadn’t started hurting, it just got so painful I couldn’t sit on my bike a n y mor e .” -Lance Armstrong