Oncology-Testicle 2

Front 1

What should the treatment be for clinical stage II NSGCT?

Back 1

The decision to treat patients with clinical stage II NSGCT initially with either RPLND or cisplatin-based chemotherapy depends primarily on (1) extent of disease, (2) serum tumor marker status, and (3) presence or absence of tumor-related back pain.

Patients best suited for RPLND are those with clinical stage IIA and some IIB tumors with ipsilateral disease restricted to the primary landing zone and normal serum tumor markers ( Bosl and Motzer, 1997 ; Bosl et al, 2005 ). The presence of suprahilar, retrocrural, pelvic, or inguinal lymphadenopathy, contralateral or multifocal disease, or back pain implies either unresectable disease or metastases beyond the locoregional lymph nodes, and these patients should receive initial cisplatin-based chemotherapy ( Bosl et al, 2005 ).

Patients with clinical IIA or IIB tumors and elevated serum levels of tumor markers should be considered for primary cisplatin-based chemotherapy, because this usually reflects systemic disease.

Front 2

In patients treated with RPLND that were N1 disease, who would then need to go on to adjuvant chemotherapy versus simple surveillance?

Back 2

After RPLND, a meticulous pathologic assessment of the retroperitoneal lymph nodes is essential to assess prognosis and direct further therapy ( Motzer and Bosl, 1993 ). With the exception of the Testicular Cancer Intergroup Study, most investigators have reported that the risk of relapse is related to the size and/or number of involved lymph nodes ( Motzer and Bosl, 1993 ; Sheinfeld et al, 1994) . Careful observation is preferred in compliant patients with fully resected low-volume (pN1) disease, that is, fewer than five positive nodes and all nodes less than 2 cm with no evidence of extranodal extension, because these patients have a low risk of relapse ( Pizzocaro et al, 1985 ; Richie et al, 1991 ; Rabbani et al, 2001). Three cycles of cisplatin, etoposide, and bleomycin (PEB) or four cycles of etoposide and cisplatin (EP) will be necessary in the event of relapse.

Front 3

For patients that undergo RPLND who should be considered for adjuvant chemotherapy afterwards?

Back 3

Conversely, patients with high-volume nodal disease have a relapse rate of 50% to 90% ( Fraley et al, 1985 ; Williams et al, 1987 ; Donohue et al, 1995 ); therefore, patients with at least 6 positive nodes, any node greater than 2 cm, or any extranodal extension should be considered for two cycles of adjuvant cisplatin-based chemotherapy.

Front 4

Who would be a candidate for the shortened two cycles of cisplatin based chemotherapy?

Back 4

It is important to note that only patients who are completely resected and are clinically free of disease after RPLND are candidates for two cycles of cisplatin-based chemotherapy to prevent relapse. The management of patients with incompletely resected adenopathy or with any clinical evidence of disease (elevated β-hCG and/or AFP, lung nodule, retrocrural adenopathy) is the same as that for patients with systemic metastasis: three or four cycles of cisplatin-based chemotherapy.

Front 5

What is fertility like in men with low stage germ cell tumors after orchiectomy and on surveillance? what about after RPLND?

Back 5

Up to 60% of patients diagnosed with testicular cancer have subnormal pretreatment semen analysis ( Nijman et al, 1988 ). When compared with healthy controls or males with lymphoma, testicular cancer patients were found to have lower total sperm counts and higher serum follicle-stimulating hormone (FSH) levels. Similar findings have also been reported in patients with carcinoma in situ ( Petersen et al, 1999 ). These abnormal parameters before treatment suggest a primary germ cell defect in testicular cancer patients. After orchiectomy, improvement in sperm parameters is seen, implying a reversible defect in fertility that may be due to circulating β-hCG or psychological stress. Despite this high incidence of oligospermia at the time of diagnosis, 65% of men are able to impregnate their partner after orchiectomy while on surveillance ( Herr et al, 1998 ).

Antegrade ejaculation can be preserved in 95% to 98% of clinical stage I patients undergoing nerve-sparing RPLND. Paternity rates as high as 76% have been reported after RPLND for stage I disease ( Foster et al, 1994 ). In this sub-fertile population, primary nerve-sparing RPLND does not significantly affect fertility.

Front 6

Why are we so frightened by Bleomycin in the peri-operative setting? What should these patients get pre-op and how should they be managed post-op?

Back 6

A restrictive pulmonary fibrosis due to alveolar edema and increased collagen deposition after bleomycin treatment can occur ( Hay et al, 1991 ). This pulmonary fibrosis is believed to increase susceptibility to alveolar edema when patients are exposed to high levels of inspired oxygen concentration and fluid overload ( Goldiner et al, 1978 ; Zwikler et al, 1994 ). Donat and Levy (1998) reviewed perioperative pulmonary complications of 77 patients treated with RPLND after bleomycin chemotherapy and found a 57% rate of pulmonary complications. Preoperative symptoms, pulmonary function testing, and history of acute bleomycin were not predictive of postoperative pulmonary complications. The strongest risk factors for postoperative complications were overall fluid requirements and blood transfusions ( Donat and Levy, 1998 ). Meticulous management of intravenous fluid in the perioperative period is imperative in patients treated with bleomycin-containing chemotherapy regimens.

Front 7

For patients that have normal serum tumor markers after primary chemotherapy what are indications for RPLND in a post-chemotherapy setting?

Back 7

*Whereas most clinicians agree that surgical exploration is indicated for patients with normal tumor markers and residual radiographic abnormalities, at the present time there are no standard guidelines for observation rather than adjunctive surgery ( Bajorin et al, 1992 ; Sheinfeld et al, 1997 ). Reported variables for patients in whom surgery can be safely omitted include residual masses less than 1.5 cm ( Stomper et al, 1985 ; Carter et al, 1987 ), “normal” post-chemotherapy CT and absence of teratomatous elements in the primary tumor ( Gelderman et al, 1988 ) and more than 90% volume reduction of the pre-chemotherapy mass, a residual mass less than 1.5 cm, and no teratoma in the primary tumor.

Front 8

What are 5 basic cell types of germ cell tumors, their typical age of diagnosis, & incidence rates of pure forms?

Back 8

1.) Seminoma: Age: Classic 35-39yo (10 to 60yo range); Spermatocytic >50yo; Incidence: 30-60%

2.) Embryonal: Age: 25-35yo; Incidence: 3-4% (though present in 40% NSGCT’s)

3.)Yolk sac: Age: infancy or childhood (unless found in mixed tumors); Incidence: <1%

5.)Teratoma Age: 20-30yo; Incidence 5-10%

6.)Choriocarcinoma Age: 20-30yo Incidence 1%

Front 9

What are the 3 subtypes of pure seminomas, and the % for which these are found among seminomas?

Back 9

Classic/Typical - 82-85%

Anaplastic - 5-10% (higher rate of bHCG production, increased local and metastatic invasion) Orch plus radiation gives stage for stage equivalent results to typical seminoma.

Spermatocytic - 2-12% (NO association w/ cryptorchidism, half occur in men over 50, never metastasizes…inguinal orch is enough)

Front 10

What % of Classic Seminomas produce bHCG? What is this related to?

Back 10

Syncytiotrophoblastic elements occur in 10-15% of pts, which corresponds to the frequency of bHCG production

Front 11

What 2 cell types must be found in a pt diagnosed with choriocarcinoma?

Back 11

Syncytiotrophoblasts

Cytotrophoblasts

Front 12

What is the most common testis tumor in children and infants? What biochemical marker is associated with this tumor?

Back 12

Yolk sac tumor (Yolk sac has EMBRYOID BODIES resembling 1-2 week old embryos)

Alpha-fetoprotein

Front 13

What percentage of GCT’s have more than one histological type? What is the most common mixture of subtypes?

Back 13

60% of all GCT’s are mixed

Embryonal, yolk sac, teratoma, syncytiotrophoblasts

Front 14

Among men, what is the risk of having CIS? In men who have had testicular cancer what is the risk of developing a GCT or having CIS in the contralateral testicle?

Back 14

General population risk is 0.8%
Risk in men who have had testicular cancer is 5.2%

Both of these are equal to the risk of testis cancer in the given situation

Front 15

There is a group of men who are high risk for developing CIS. What risk factors do these men have?

Back 15

History of Testicular Ca (5-6%)

Extragonadal germ cell tumors

EGCT (40%)

Cryptorchidism (3%)

Contralateral testis with unilateral testis CA (5-6%)

Atrophic contralateral testis with unilateral testis CA (30%)

Somatosexual ambiguity (25-100%)

Infertility (0.4-1.1%)

Front 16

What does Campbells recommend in regards to biopsy of men with GCT to look for contralateral CIS?

Back 16

Don’t biopsy due to the protracted course of CIS, the side effects of therapy (radiation, chemo, orchiectomy), and because the 2nd primary of GCT responds well to treatment. Recommend close observation of high risk men.

Front 17

What is the lifetime probability of a man developing Testicular Cancer? If a 29 year old man is diagnosed with a solid tumor, what is the most likely type of cancer? What about a 35 year old man?

Back 17

1/500 or 0.2%

Nix: most common solid tumor of men age 20-34 is testicular cancer

Pearson: not testicular cancer, this is 2nd most likely cancer in men age 35-40 years in the US.

Front 18

What % of testicular cancers are bilateral?

Back 18

-2.8% (Most common if bilateral is seminoma)

Front 19

What is cryptorchidism? What is the relative risk of testicular cancer in pts with a h/o cryptorchidism? In a pt with a h/o unilateral cryptorchidism, what is the probability of developing testicular cancer in the contralateral testicle? Does early orchiopexy prevent a cryptorchid testicle from undergoing tumorogenesis? If not, then why do we do it?

Back 19

Testicular maldescent

RR: 3-14x normal expected incidence

Malig contra testicle: 5-10%

No, orchiopexy does not prevent carcinoenesis

Orchiopexy allows for clinical surveillance of the previously impalpable gonad.

Front 20

Describe the lymphatic drainage of the right and left testicle respectively. In which direction can cross over drainage occur?

Back 20

Right: To the interaortocaval region at level of 2nd vertebral body. There is cross-over from right to left (rare in N1 disease/more common in N2)

Left: To the para-aortic region in the compartment bounded by the left ureter, the left renal vein, the aorta and the origin of the IMA

From right to left

Front 21

What tumor type does not abide by the normal lymphatic spread of testicular cancer, and how does it spread?

Back 21

Pure choriocarcinoma spreads through vascular invasion as well

Front 22

What anatomic structure plays an important role in causing the typical pattern of dissemination usually seen in metastatic testicular cancer.

Back 22

Tunica albuginea, which is a natural barrier to expansile local growth

Front 23

Why might we find inguinal node metastasis in a patient with testicular cancer?

Back 23

Scrotal involvement of the primary tumor (T4)

Prior inguinal or scrotal surgery

Retrograde lymphatic spread secondary to massive RP

Front 24

What is the usual presentation of testicular cancer? What percentage of pts present with symptoms of metastasis, and what are some? What’s included in the differential for testicular mass? What is the imaging modality of choice in evaluating any scrotal mass?

Back 24

Testicular nodule or painless swelling of one nut. Classically, a lump/swelling/hardness of the testis

10% and can include neck mass, cough/dyspnea (pulmonary mets), GI disturbances (retroduodenal mets), lumbar back pain (bulky retroperitoneal dz involving psoas), bone pain, CNS or PNS disturbances (cerebral, spinal, or nerve root involvement), or LE swelling (iliac or caval compression or thrombosis). Gynecomastia is seen in ~5% of ptnts and is a systemic endocrine manifestation.

Torsion, epididymitis, orchitis, hydrocele, hernia, hematoma, spermatocele, sphyilitic gumma.

Scrotal U/S, look for hypoechoic areas within the tunica albuginea

Front 25

What three factors are considered in the clinical staging of testicular cancer?

Back 25

Pathologic evaluation of the primary tumor (tumor type, extent of local invasion)

Evaluation of metastatic disease based on imaging studies (Chest Xray and CT abd/pelvis)

Tumor markers

Front 26

What is the ½ life of AFP? Where in humans is this normally produced? Which tumors produce AFP? Which don’t?

Back 26

5-7days

fetal yolk sac, liver, GI tract

Produce AFP: Pure embryonal, teratocarcinoma, yolk sac, mixed

Don’t produce AFP: Pure seminoma, Pure choriocarcinoma

Front 27

What is the 1/2 life of HCG? What tumors produce HCG?

Back 27

24-36hrs

Produce HCG
Choriocarcimoma: 100%
Embryonal : 40-60%
Seminoma: 5-10% (syncytiotrophoblasts)—usually relatively low elevation of bHCG (<500ng/ml)

Front 28

What % of patients with NSGCT have elevated AFP? HCG? Either AFP or HCG?

Back 28

AFP: 50-70%

HCG: 40-60%

AFP and/or HCG: 90%

Front 29

What is LDH most useful as a marker of with regards to testicular cancer?

Back 29

Burden or extent of disease (tumor “bulk”)

Front 30

Is normalization of tumor markers after treatment indicative of absence of residual disease?

Back 30

No. Normalization of marker levels can’t be equated to the absence of residual disease. Between 10-20% of patients treated with combined chemo for bulky mets and then undergoing RPLND were found to have viable tumor despite normal preop tumor marker levels.

Front 31

What are causes of false positive elevations in tumor markers (non testicular cancer elevations)?

Back 31

AFP: liver damage from drugs (anesthetics, chemo, antiepileptics), viral hepatitis, EtOH

HCG: Hypogonadism, Smoking the Reefer

Front 32

What % of seminomas are clinically confined to the testis? What % of NSGCT present with mets on diagnosis?

Back 32

65-85% of seminomas are clinically confined to the testis

60-70% of NSGCT present with mets on diagnosis

Front 33

What is the treatment of choice for low stage seminoma (Stage I, ie T1-3, N0 M0 S0)?

Back 33

Radical inguinal orchiectomy then radiation (low dose and usually 25Gy to paraaortic nodes only): Survival for Stage I seminoma with this is >95%

Front 34

What patients with low stage seminoma can be considered for surveillance? Why even consider surveillance? What is the relapse rate for surveillance with low stage seminoma?

Back 34

Surveillance patients: Compliant, tumor<6cm, absence of vascular invasion, normal bHCG

Can consider surveillance for stage 1, due to reported long-term side effects of radiation (Infertility, GI, second malignanciesàthese are low though).

17% relapse at a median of 15 months if radiation isn’t given, though overall survival is comparable @ ~98%.

Front 35

What is the treatment of choice following orchiectomy of Stage IIa and IIb (N+ but less then 5 cm in volume ie N1-2) seminoma, and what is the 5-year survival in patients treated this way? What about for Stage IIc ( > 5 cm of nodal involvement ie N3) or Stage III (M+ dz) seminoma? What % of these ptnts achieve complete response and remain disease free up to 4yrs later?

Back 35

Post-orchiectomy retroperitoneal radiation; 5-year survival is 80% (72-90% range)

Cisplatin-based chemo; 90% remain disease free up to 4 yrs later

Front 36

What are the 3 treatment options for low-stage NSGCT (Stage I and IIa)? What is the survival for these tumors overall?

Back 36

Surgery: RPLND

Surveillance

Chemo: 2 cycles of BEP

Survival is 96-98%

Front 37

What are the main advantages of RPLND compared to the other treatment options for low-stage NSGCT? What are some postoperative complications associated with RPLND?

Back 37

Diagnosis: clinical understaging occurs 20-25% of the time by nonsurgical means. RPLND is the only modality that can accurately delineate pathologic stage I from pathologic stage II disease. Also, complete eradication of N1-N2 tumors is possible in the majority of cases.

Ileus, lymphocele, pancreatitis, ejaculatory dysfunction.

Front 38

Give an appropriate surveillance schedule for Stage 1 NSGCT. What else must be considered before putting a patient on surveillance?

Back 38

PE, CXR, Tumor markers monthly for 1st year, every 2 months for the 2nd year and every 3 to 6 months afterward;

CT should be done every 2-3 months for the 1st 2 years and at least every 6 months thereafter

Follow pt for minimum of 5 to 10 years after ochiectomy

Patient reliability and compliance must be considered

Front 39

What are the main risk factors for relapse?

Back 39

Significant percentage of embryonal tumor

Local extent of disease (T2 or greater)

Vascular or lymphatic invasion (most important)

Front 40

What with the treatment of choice for bulky stage II NSGCT?

Back 40

RPLND +/- adjuvant chemo or close surveillance

Front 41

What modality is the treatment of choice for Stage IIc and Stage III NSGCT treated? How are these patient further subdivided? What are the goals of treatment for each of these groups?

Back 41

Primary Chemo after radical orchiectomy

Patients are divided into low-risk and high-risk groups based on the chance of recurrence

Low risk: maintain high cure rates while minimizing toxicity (3 cycles BEP)

High risk: improve proportion of patients achieving complete response while maintaining tolerable treatment side effects. (4 cycles BEP)

Front 42

What NSGCT subtype is resistant to chemo? What % of men with Stage 1 NSGCT treated with chemo will have this subtype found in the RP years after treatment? Are all teratomas malignant?

Back 42

Teratoma

9-19% (argument for RPLND)

No. Teratomas are only malignant after puberty

Front 43

What is the most concerning bleomycin related toxicity and how can intra and post operative management affect this?

Back 43

Pulmonary fibrosis (one study showed this in 8 of 93 pts)

Minimize this risk by
Reduce FiO2 post op (less than 0.25)
Restrict free H20 intra-op and immediately post op

Front 44

hat is the most common sex cord mesenchymal tumor? What pathological crystal is associated with these? Are these benign or malignant?

Back 44

Interstitial cell tumor (Leydig cell tumor)à 1-3% of testicular tumors

Reinke’s crystal

10% malignant, rest benign, up to one-fourth occur in prepubertal kids and present w/ precocious puberty. No association w/ cryptochidism

Most show increased testosterone production or at least some endocrinologic imbalance

In most adults…symptoms are feminization and decreased libido

After orch..RPLND is recommended if tumor shows signs of malignancy, which is rare (most benign)

Front 45

What is gonadoblastoma associated with?

Back 45

Gonadal dysgenesis

Must have 3 elements: Sertoli cells, Interstitial cells, germ cells

Have characteristic Call-Exner bodies

Vast majority of pts are phenotypic females

Front 46

What nerve must be located and avoided during a radical orchiectomy?

Back 46

Ilioinguinal

Front 47

Why secure the cord vessels with a permanent ligature such as silk?

Back 47

To identify the stump in event of RPLND

Front 48

What differences in management should be made in the event of scrotal violation?

Back 48

If low stage seminomaàextend the radiation portals to include the ipsilateral groin and scrotum

If low stage NSGCT, widely excise the scrotal scar and spermatic cord remnant at the time of RPLND. Not good candidates for surveillance

Patients treated with full dose platinum based chemo should have the cord stump removed at the time of RPLND. However given the relative absence of local relapse after systemic treatment, extensive groin dissection or hemiscrotectomy isn’t needed

Front 49

What if the patient gets chemo prior to orch?

Back 49

25% will still have viable cancer in the testis and 30% will have teratomas

Front 50

What lymph nodes are associated with Right sided testicular drainage? Left sided?

Back 50

Right: InteraortocavalàPrecaval + Paracaval

Left: Para-aortic and preaorticàinteraortocaval

Front 51

T/F: A guy with negative CT’s but persistently elevated markers after radical orchiectomy for NSGCT should have an RPLND since tumor is likely in his nodes but the nodes aren’t enlarged.

Back 51

False: He should undergo chemo since systemic disease is likely present

Front 52

What patients with Stage II disease should have chemo rather than RPLND?

Back 52

The presence of suprahilar, retrocrural, pelvic or inguinal lymphadenopathy

Contralateral or multifocal disease

Back pain

Front 53

Which patients with Stage II disease after RPLND should be considered for 2 cycles of cisplatin based chemo?

Back 53

Patients with high volume nodal disease relapse 50-90% of the time

Patients with 6 or more positive nodes, any node larger than 2cm or any extranodal extension

Incomplete resectionà3-4 cycles of cisplatin

Front 54

If pt has post-chemo mass and you perform excision, should you stop there?

Back 54

No. Do bilateral RPLND

Front 55

Why is the management of post-chemo residual mass from seminoma, although controversial, approached differently than NSGCT?

Back 55

Rare to have teratoma in this setting compared to NSGCT
Technically often more difficult due to desmoplastic reaction from chemo with obliteration of tissue planes

Front 56

What percentage of testicular tumors arise from a cryptorchid testicle?

Back 56

*10% of testicular tumors are from crytorchid testicles.

*If you have a patient with a testicular tumor you roll the DICE to see if they had an undescended testicle.