ESMO testicular cancer
What is the most common chromosomal abnormality in testicular GCTs?
12p isochromosome
When observing stage I seminoma pts, what is the relapse rate? Where do most relapses occur?
15% of pts will relapse 85% of relapses are in the P-A nodes
RT dose in stage I and IIA seminoma
20 - 25 Gy + 10 Gy boost to LAD
What RT dose can induce temporary azoospermia? Doses greater than what may cause permanent aspermia?
20- 50 cGy will cause temporary azoospermia. Doses > 50 cGy
What is the most common age group for GCC?
25- 40 yrs
How should pts with NSGCT and persistently positive tumor markers after orchiectomy be treated?
3 BEP/ 4 EP
Management of TIN in the contralateral testis
3% and 5% of testicular cancer patients have TIN in the contralateral testis with the highest risk (∼30%) in men with testicular atrophy (volume <12 ml) and age <40 years The majority of European Germ Cell Cancer Consensus group (EGCCCG) experts did not consider a routine biopsy of the contralateral testis as indicated [V, C] The condition may be managed by surveillance, irradiation with 20 Gy in 2 Gy fractions (with potential damage to the contralateral, non-affected testis by scattered radiation) or orchiectomy, depending on fertility issues.
In a pt with a prior Dx of testicular cancer, what is the cumulative incidence (at 25 yrs) of contralat testicular seminoma?
3.6%
What is the relapse rate in pts with stage I NSGCT after orchiectomy → RPLND?
5%- 10%, most commonly to the lungs.
5y OS of Poor risk metastatic Non seminoma
50%
Management of residual mass in retroperitoneum after BEP in Seminoma
50% will disappear during active surveillance PET/CT sensitive if mass > 3cm, negative tumor markers
5y OS of Intermediate risk metastatic Non seminoma
80-83%
5y OS of Good risk metastatic Non seminoma
92-94%
What is the chance of pelvic/ inguinal nodal involvement from testicular cancer?
< 3%
Which tumor markers are used for staging: before or after surgery?
After orchiectomy and before other treatment begins (surgery, radiation therapy, or chemotherapy), and not those obtained at the time of diagnosis.
Percentage of pure seminomas and non seminomas
Approximately 50% of the TGCTs are pure seminomas and 50% are non-seminomas. The vast majority of GCT arise in the testicles with ∼5% occurring outside of the gonads, i.e. extragonadal germ cell tumour (EGGCT) EGGCTs are usually found in the body's mid-line, e.g. retroperitoneum, mediastinum or cerebrum, sometimes posing diagnostic difficulties.
Following P-A relapse in pts observed following transinguinal orchiectomy for stage I seminoma, what are the appropriate Tx options?
BEP (Bleomycin, Etoposide, Cisplatin) (naive or treated previously with RT)
Management of a patient with pure seminoma stage IIA and ulcerative colitis
BEPx3
Treatment of a patient with stage I disease who fails to normalize tumor markers after surgery
BEPx3
Per NCCN 2010, which pts with NSGCTs should have a CT chest?
CT chest should be ordered in pt with a positive CT abdomen/ pelvis or abnl CXR
In BEP which is considered the most active drug
Cisplatin
What is the best established risk factor for testicular cancer?
Cryptorchidism increases the risk of testicular cancer by ~ 5 times
For pts treated with P-A RT following transinguinal orchiectomy for stage I seminoma, what is the relapse rate? Where do relapses occur?
For pts treated with P-A RT following transinguinal orchiectomy for stage I seminoma, relapse occurs in 0.5%- 5% of pts. Most relapses occur within 2 yrs. In-field relapses are extremely rare; most relapses are mediastinal, lung, left supraclavicular, or (if risk factors are present) inguinal.
Treatment of good risk and intermediate/poor risk
Good x 3BEP/4EP Intermediate/Poor x 4BEP/VIP
Follow up of patients treated with seminoma
H& P, LDH, AFP, and β-HCG q3- 4mos for yrs 1- 3, q6mos for yrs 4- 7, then annually. CT abdomen/ pelvis should be performed at every visit and CXR at every other visit.
Refractory disease in seminoma (PD after 2nd line or within a month of completing their initial chemotherapy)
High-dose chemotherapy (Cisplatin/Etoposide) with autologous stem cell rescue
When testosterone replacement should be offered
Hypogonadism is present in 11%-35% of TGCT survivors, depending on cut-off levels of testosterone used, age, cumulative cisplatin dose and follow-up duration. Therefore, determination of testosterone levels is recommended during follow-up, although it is not always clear when and at what testosterone level replacement should be offered
Stage I, II, III of testicular cancer
I Node negative II Node positive III Distant metastases
Define IIA, IIB, IIC of testicular cancer
IIA single or multiple lymph nodes, each < 2 cm in size IIB single or multiple lymph nodes, >2 cm but < 5 cm in size IIC lymph node, >5 cm in greatest dimension
Define stage II of testicular cancer
In order to be classified as stage II, metastases must be limited to the retroperitoneal lymph nodes and all the markers must be in the S0 to S1 or "good-risk" range inclusive of all of the following: -Lactic dehydrogenase (LDH) <1.5 of the upper limit of normal; -Alpha fetoprotein (AFP) <1000 ng/mL; and -Human chorionic gonadotropin (hCG) <5000 mIu/mL
Role of PET/CT in germ cell tumors
Limited utility in the initial staging of patients with GCTs because of the frequent occurrence of false-negative results. PET scanning is more commonly used for the evaluation of post-therapy residual masses than for initial diagnostic evaluation. (seminoma, residual mass > 3 cm, negative tumor markers)
BEP Vs EP
Nonsignificant difference in DFS and OS favoring BEP. Choice based on lung function
What is the classic presentation of testicular cancer?
Painless testicular mass
Lymphatic drainage of the testis
Para-aortic nodes
HD chemotherapy with stem cell rescue
Phase III trial, no difference in OS compared to standard chemotherapy
How should an NSGCT be definitively diagnosed?
Radical inguinal orchiectomy Do not Bx a testicular mass
What is the major toxicity associated with RPLND?
Retrograde ejaculation resulting in infertility;
Treatment of patients with brain metastases in Seminoma
Systemic chemotherapy is used initially (Cisplatin and etoposide penetrate the brain in the presence of metastases)
T3, T4 in testicular cancer
T3 Tumor invades the spermatic cord T4 Tumor invades the scrotum
What is the preferred primary surgical Tx for a unilat testicular tumor?
Transinguinal orchiectomy
What imaging modality is preferred for primary evaluation of a testicular mass?
USS (identifies lesions up to 1mm)
How does the presence of pure choriocarcinoma affect the prognosis?
Very high β-HCG and poor prognosis
Which histology of NSGCTs is most commonly associated with an elevated AFP?
Yolk sac tumors
Normalization of bHCG and AFP after succesful treatment
a 10-fold decrease or normalization of these levels should be evident after 2 weeks and/ or 25 to 30 days, respectively, of successful treatment.
When prophylactic orchiectomy is recommended
cryptorchidism presenting after puberty
What are the half-lives of β-HCG and AFP?
β-HCG is 24-36 hrs. The half-life for AFP is 5 days
How commonly is β-HCG elevated in testicular seminoma? What are unrelated etiologies for elevated β-HCG and AFP?
β-HCG is elevated in 15% of seminoma marijuana HCC, cirrhosis, hepatitis, and pregnancy can elevate AFP.
Management of residual mass in retroperitoneum after BEP in Non-seminoma
≥1 cm RPLND <1 cm in the long axial dimension, surveillance
Management of stage I Non-seminoma
● 75 % are cured with orchiectomy alone and do not require further treatment ● Treatment at the time of recurrence is almost always curative ● If high risk adjuvant treatment with 1-2 BEP/RPLND
Management of stage I Seminoma
● 85 % are cured with orchiectomy ● We recommend active surveillance rather than adjuvant therapy ● For patients who decline active surveillance, 1 single dose Carboplatin 7AUC or RT (20 Gy) The predictive value of 'risk factors', such as rete testis infiltration and tumour size ≥4 cm, is controversial, but these factors are sometimes used to apply one course of carboplatin (AUC 7) or radiotherapy (20 Gy/10 fractions to para-aortic target volume) as adjuvant treatment.
Why an accurate diagnosis of stage IIA is complicated? Is it the same with IIB, IIC?
● A significant number of men with normal size retroperitoneal nodes (clinical stage I) will have cancer discovered if RPLND is performed, and a significant number of men with mild adenopathy (stage IIA) will be found to have benign nodes (pathological stage I) if RPLND is performed ● Stage IIB/IIC diagnosis is straightforward
Define Good risk and intermediate risk Seminoma
● Any primary site ● Metastasis limited to lungs (good, if other then intermediate) ●Normal serum AFP, β-hCG <1000 IU/L
What imaging studies, labs, and evaluation should be ordered following transinguinal orchiectomy for seminoma?
● CXR ● CT abdomen/ pelvis, ● AFP, β-HCG, and LDH ● If the CT is positive, bone scan should be added. ● Consider sperm banking
Name 5 histologic types of NSGCTs.
● Embryonal cell carcinoma ● Choriocarcinoma ● Yolk sac tumor ● Teratoma ● Mixed
Following transinguinal orchiectomy, what is the optimal Tx for stage I seminoma, stage IIA- IIB seminoma, and stage IIC or greater seminoma?
● For patients who decline active surveillance, 1 single dose Carboplatin 7AUC or RT ● IIA (≤ 2 cm): RT ● IIB (> 2 and ≤ 5 cm) : 3 BEP/ 4 EP ● IIC (> 5 cm): 3 BEP/ 4 EP
Management of stage II Seminoma
● IIA (≤ 2 cm): RT ● IIB (> 2 and ≤ 5 cm) : 3 BEP/ 4 EP ● IIC (> 5 cm): 3 BEP/ 4 EP The treatment options consist of either cisplatin-based chemotherapy or radiotherapy to para-aortic and ipsilateral iliac lymph nodes with 30 Gy in 2 Gy fractions
Management of stage II Non-seminoma
● IIA RPLND 80-90% cure rate If tumor markers fail to normalise after surgery, x 3BEP rather RPLND ● IIB/ IIC x3BEP/ 4EP
High risk stage I Non-seminoma
● LVI ● Predominance of an embryonal carcinoma (EC) component in the primary tumor ● Pathologic tumor stage T3 or T4 If any present, recurrence is 40%
Name 5 risk factors for GCTs
● Prior personal Hx of GCT ● Positive family Hx ● Cryptorchidism ● Testicular dysgenesis ● Klinefelter syndrome
Men with seminoma who relapse after chemotherapy
● TIP (Paclitaxel 175, Ifosfamide 1500, Cisplatin 25) ● VeIP (Vinblastine 0,11, Ifosfamide 1200, Cisplatin 20) ● VIP (Etoposide 75, Ifosfamide 1200, Cisplatin 20) This regimen is only used for those rare patients whose initial chemotherapy did not include etoposide
Define Good risk, Intermediate risk and Poor risk Non Seminoma
● Testicular or retroperitoneal primary tumor ● Metastases limited to the lung ● AFP < 1000 IU/L, β-HCG < 5000 IU/L, LDH< 1,5 UNL Poor risk Mediastinal primary site with or without metastases ●Metastases to organs other than the lungs (eg, liver, bone, or brain metastases) ●Tumor markers: •Serum AFP >10,000 ng/mL and/or •β-hCG >50,000 international units/L and/or •LDH >10 times the upper limit of normal
