Testis cancer Flashcards
Nonguideline directed care of patients with testicular cancer is common, most frequently in the form om inappropriate imaging and overtreatment. What does it lead to?
Delayed definitive therapy
Unnecessary morbidity
Higher rates of relaps
How common is testicular cancer in western society?
3-10 cases per 100,000 males/year
Hur stor andel av urologisk cancer utgörs av testikelcancer?
5%
What is the most common type of testicular cancer and what are the two subgroups?
Germ cell tumours (90-95%)
Non-seminoma
Pure seminoma
Utredning för misstänkt testikeltumör?
Kliniskt examination -skrotum - palpabel resistens i buken -gynekomasti -palp supraklavikulärt Ultraljud Tumörmarkörer
What are the Serum Tumour markers (STMs) for testicular cancer?
AFP: produced by yolk sac cells
hCG expression of trophoblasts
LDH (lactate dehydrogenase)
When is hCG elevated with testicular cancer?
- all choriocarcinomas
- 50% embryonal carcinomas
What information can you gain from LDH (lactase dehydrogenase)-levels with testicular cancer?
- less specific
- proportional to tumour volume
- elevated in 80% of advanced testicular cancer
What is the proper course of action with life threatening disseminated testicular cancer?
Lifesaving chemotherapy with delayed orchiectomy after completion of induction chemotherapy
When should you perform and orchiectomy after diagnosing testicular cancer?
Preferably within 24-48 hours and no later than 10 days
When should you consider performing organ-sparing surgery with testicular cancer?
Synchronous bilateral testicular tumours
Metachronous contralateral tumours
A tumour in a solitary testis with normal pre-operative testosterone levels
What are the riskfactors for contralateral testicular tumours?
testicular volume <12 mL
a history of cryptorchidism or poor spermatogenesis
When is a contralateral biopsy not necessary (when performing surgery for testicular cancer)?
In patients older than 40 years without risk factors
What information do you need for a complete staging and grading of testicular cancer?
Histopathology
Postoperative tumour markers
CT
What are the histopathological criteria for testicular cancer?
- pT category
- histological type
- peri-tumoural venous and/or lymphatic invasion
- presence of GCNIS
Mention a few Non-seminomal cancers of the testicle:
Embryonal carcinoma Yolk sac tumour Trophoblastic tumours Teratoma, post-pubertal type Teratoma with somatic-type malignancies Mixed germ cell tumours
Mention two Benign tumours of the testicle:
Spermatocytic tumour
Teratoma, prepubertal type
Hur stor andel av testikelcancer utgörs av icke “Germ cell tumours”?
2-4% hos vuxna män
When should you perform a FDG PET CT with testicular cancer?
Only if you have a residual mass at least 6 week after chemotherapy when treating a seminoma
What are teh progsnostic risk factors for stage 1 testicular cancer?
(answer for both seminoma and non-seminoma)
Seminoma:
tumour size >4 cm
invasion of rete testis
Non-seminoma:
vascular invation in blood or lymphatic vessels
percentage of embryonal carcinoma >50%
proliferation rate >70%
What Germ Cell tumours doesn’t need any other therapy than orchiectomy?
Spermatocytic tumour
Prepubertal teratoma
What is the relapse risk with stage 1 seminoma?
15-20% in 5 years
How do you treat a relapse of testicular seminoma?
Chemotherapy
What is the overall cancer-specific survival rate of testicular seminomas?
97-100%
-even postponed therapy is efficient
What is the main drawback with surveillance instead of chemotherapy with testicular seminomas?
The need for more intesive follow-up
How should you treat stage 1 testicular seminoma?
Either:
Surveilance- at very low risk
-tumour size <4 cm without rete testis invasion
or
One-course carboplatin-based chemotherapy
How should you NOT treat stage one testicular seminoma?
Radiotherapy
Retroperitoneal lymph node dissection (RPLD)
Vad är uppföljningsprogrammet för stadium 1 testikel seminom?
DToch tumörmarkörer var 6:e månad i 2 år
DT och tumörmarkörer på slutet av år 3 och 5
When does a relaps in stadium 1 NSGCT (non seminoma germ cell tumour) most often occur?
80% in the first year
How often does stadium 1 NSGCT (non seminoma germ cell tumour) relapse?
30%
Where does stadium 1 NSGCT (non seminoma germ cell tumour) most often relapse?
60% in the retroperitoneum
How common is subclinical metastases in clinical stadium 1 NSGCT (non seminoma germ cell tumour)?
up to 30%
What is the result of surveillance vs Adjuvant chemotherapy in stadium 1 NSGCT (non seminoma germ cell tumour)?
Surveillance –> 30% recurrence/relapse
Adjuvant chemotherapy –> <2% recurrence/relapse
What is risk-adapted treatment in stadium 1 NSGCT (non seminoma germ cell tumours)?
Low risk (stage 1A- pT1, no vascular invasion) --> surveillance (if not willing one course of BEP)
High risk (stage 1B, pT2-4) –> one(two) courses of BEP
What does BEP stand for in the treatment for testicular cancer?
Cisplatin
Etoposide
Bleomycine
When should you perform a nerve-sparing retroperitoneal lymph node dissection on patients with stage 1 NSGC (non seminoma germ cell tumours)?
to highly selected aptients only:
those with contraindication to adjuvant chemotherapy and unwilling to accept surveillance
When should you perform a Brain scan (CT/MRI) on a patient with metastatic testicular cancer?
I case of symptoms
and patients with metastatic disease with multiple lung metastases
and/or high beta-hCG values.
Vilken utredning är obligat vid misstänkt metastaserad testikelcancer?
UL testiklar Tumörmarkörer DT-thorax+buk MRI kotpelare OM patienten har symptom DT-hjärna/MR OM patienten har symptom eller multipla lungmetastaser och/eller högt beta-hCG
Vad är skillnaden mellan stadium M1a och M1b vid metastaserad testikelcancer?
M1a: metastaser i regionala lymfkörtlar och/eller i lungorna
M1b: andra metastaser
Vad innebär stadium 1 testikelcancer?
Sjukdom begränsad till testikeln
Vad innebär stadium II testikelcancer?
Retroperitoneala lymfkörtelmetastaser
IIA <2 cm
IIB 2-5 cm eller fler än 5st
IIC >5 cm
Vad innebär stadium III testikelcancer?
IIIA lymfkörtelmetastaser som inte är regionala
IIIB lungmetastaser
IIIC metastaser till andra organ
Which patients with metastatic testicular cancer have a poor prognosis?
Not any patients with seminoma
Patients with non-seminoma and: mediastinal primary non-pulmoary visceral metastases AFP >10,000 ng/mL or hCG >50,000 IU/L (10,000 ng/mL9 or LD > 10 x ULN
What is the standard treatment for stage IIA/B seminoma
Radiotherapy
2:hands alternativ är BEPx3
What is the standard treatment for stage IIA/B NSGCT (non seminoma germ cell tumour)?
Chemotherapy
and RPLND of residual disease
What is the one exception to chemotherapy for stage IIA/B NSGCT (non seminoma germ cell tumour)?
Stage IIA NSGCT & pure teratoma without elevated markers
–> nerve sparing RPLND or surveillance
What is the cure rate of non-seminoma stage IIA testicular cancer?
98%
Which factors correlate with preserved fertility after chemotherapy for testicular cancer?
cisplatin-dose
FSH
age
What can you expect when it comes to fertility after chemotherapy for testicular cancer?
Most men with normal pre-treatment sperm analysis will return to normal by 3 years after chemo
When is the spermatogenesis at its lowest after chemotherapy for testicular cancer?
10-14 months after chemotherapy
How common it late realapse (>2 years) in
seminoma?
non-seminoma?
seminoma 1,4%
non-seminoma 3,2%
What are the differential diagnosises when a patient has a late relapse of testicular cancer?
Metastases from a new contralateral primary A new primary EGGCT Metastases from a new non - GCT primary Transformed teratoma Growing teratoma
How do you treat late relapse (>2 years) NSGCT?
Surgery
if incomplete result of surgery –>salvage chemotherapy
rapidly rising hCG –> induction salvage chemotherapy before surgery
How common is bilateral tumors at diagnosis?
1-2%
What is the predominate histology of testicular cancer?
Germ cell tumour (GCT)
Epidemiological risk factors for testicular cancer?
Testicular dysgenisis syndrome (cryptochidism, hypospadia, decreased spermatogenisis evidenced by sub or infertility)
Familial history of testicular tumours among first grade relatives
Presence of a contralateral tumour
What are the serum tumour markers for testicular cancer?
LDH lactate dehydrogenase
hCG human chorionic gonadotrophin
AFP alpha-fetoprotein
Gene that determines gonadal transition to a male
SRY
Under the influence of the SRY gene (sex-determining region of the Y chromosome), in the 7th to 8th week, cells in the genital ridge differentiate into seminiferous tubules containing spermatogonia and Sertoli cells. Without the SRY protein, ovarian follicles form.
The Sertoli cells begin to secrete Müllerian-inhibiting substance (MIS), acting locally and causing the Müllerian ducts to regress between 8-10 weeks, thus contributing to normal male phenotypic development.
Which cells produce testosterone?
Leydig cells
In the 9th-10th weeks, Leydig cells differentiate from genital ridge cells in response to SRY protein and are located between the seminiferous tubules. These cells begin to produce testosterone. There is a rise in both serum and testicular testosterone that peaks at 13 weeks before beginning to decline.
Between the 8th and 12th week, testosterone secretion stimulates the virilization of the wolffian ducts into the vas deferens, seminal vesicles, and ejaculatory ducts.
Table of timing of male gonadal development
Normal adult testis size and volume
On average, the normal adult testis measures 4-5cm long, 3cm wide, and 2.5cm deep with volume ranging 12-30ml.
Three types of histologic cells in testis
Seminiferous tubules, Sertoli cells, Leydig cells
Arterial blood supply to testis
Three:
1. Gonadal/Testicular
- Arises inferior to SMA, directly off of aorta
2. Cremasteric
- Arises from inferior epigastric artery
- Anastomoses with testicular artery within testis
3. Vasal
Left Testicle Lymphatic Drainage
The primary drainage pattern on the left is to the para-aortic and preaortic lymph nodes, followed by the interaortocaval nodes.
Right Testicle Lymphatic Drainage
On the right side, primary drainage is to the interaortocaval nodes, followed by the precaval and preaortic nodes.
It is more common for the lymphatic drainage of the right testis, and rare with left-sided tumors, to cross the midline and exhibit bilateral lymph node metastases
Drainage is right to left!
Layers of the scrotum and spermatic cord encountered during surgical exploration, progressing from superficial to deep
Skin, dartos, external spermatic fascia, cremasteric fascia, cremasteric muscle, internal spermatic fascia, tunica vaginalis (parietal then visceral), tunica albuginea
T staging of testicular tumors
N staging of testicular cancer
M staging of testicular cancer
Serum Tumor Marker Staging
Stage Grouping
Risk Classification for Sem and Non-Sem
Treatment options for stage IA and IB pure seminoma
(i) Surveillance (preferred)
(ii) Retroperitoneal Radiotherapy
(iii) Chemotherapy with carboplatin (1 or 2 cycles)
More than 80% of patients with stage I seminoma are cured with orchiectomy alone, therefore surveillance is the preferred approach, and the disease specific survival for stage I disease is 99% irrespective of the management strategy used.
AUA Guideline Algorithm for treatment of early testicular cancer
Surveillance for Stage IA and IB Seminoma
Risk factors for predicting relapse
In an analysis of over 600 patients, rete testis invasion and tumors ≥ 4 cm were identified as risk factors for predicting relapse.
For patients with 0, 1, or 2 of these risk factors the recurrence rates were 12%, 16%, and 32%, respectively.
NCCN recommends against a risk-adapted approach and supporting surveillance as the preferred strategy for all stage I patients.
Stage I Seminoma Surveillance NCCN and AUA
Types of testicular cancer
The vast majority are classified as germ cell tumors (95%), while the remaining are predominately sex cord/stromal tumors (mainly Leydig cell and Sertoli cell tumors). Germ cell tumors (GCT) are further designated as seminoma or non-seminoma germ cell tumors (NSGCT).
Risk factors for developing testicular cancer
Cryptorchidism, personal or family history, intra-tubular germ cell neoplasia (ITGCN).
It is felt that most GCTs arise from ITGCN and its presence is a major risk factor as 50% of men with ITGCN will develop a GCT within 5 years.
Histologic Subtypes of Testicular Cancer
Germ Cell Tumors:
- Seminoma
- Nonseminomatous Germ Cell Tumors: Embryonal, Choriocarcinoma, Teratoma, Yolk Sac (Endodermal Sinus Tumor)
Does Seminoma produce AFP? bHCG?
NO AFP
5% produce bHCG (because 5% contain syncytiotrophoblasts, which secrete bHCG)
Most common GCT in children/infants?
Yolk Sac (Endodermal Sinus Tumor)
Do Yolk Sac tumors produce AFP? bHCG?
Generally will produce AFP
NEVER bHCG
Classic pathologic finding of Yolk Sac Tumors?
Schiller-Duval bodies
Does choriocarcinoma produce AFP? bCHG?
NEVER AFP
Yes bHCG, usually high
Do pure teratomas produce AFP? bHCG?
Pure teratoma will produce neither, but pure teratoma is very rare in adults
What to do for evaluation of initial presentation of testicular mass?
Testicular US
- Homogeneous mass more likely to be seminoma
- Heterogeneous mass more likely to be NSGCT
No role for further imaging OF THE TESTIS at time of presentation
Microlithiasis: just recommend routine self-exam
Obtain tumor markers at time of diagnosis, prior to any intervention (AFP, LDH, bHCG)
AFP:
- Half life?
- Which testicular cancers produce?
- Why else elevated?
- What is a true elevation?
5-7 days
NOT PRODUCED by seminoma
Normal <10
Elevated in 50-80% of NSGCT
Embryonal carcinoma and yolk sac tumors produce AFP, seminoma and choriocarcinoma do not.
AFP may also be elevated in patients with liver disease, hepatocellular carcinoma, and stomach/pancreas/biliary duct/lung cancers.
Mildly elevated AFP may not represent germ cell tumor, thus the decision to treat a patient should not be made for an AFP level < 20.
bHCG:
- Half life?
- Which testicular cancers produce?
- Why else elevated?
- What is a true elevation?
Half life 24-36 hours
Elevated in 20-60% of NSGCT and 15% of seminomas
bHCG is elevated in embryonal carcinoma/choriocarcinoma/seminoma. Elevations may also be observed in liver, biliary, pancreas, stomach, lung, breast, kidney, and bladder cancers as well as secondary to marijuana use.
Significant hypogonadism may also cause low level elevation of HCG and these patients can be challenged with testosterone injections which normalize their HCG levels.
LDH:
- Half life?
- Which testicular cancers produce?
- Why else elevated?
- What is a true elevation?
Half life is 24 hours
Non-specific marker of GCT
Patients should not be treated due to elevated LDH alone
Role of miRNA in testicular cancer?
miR-371a-3p is the promising blood-based biomarker
Reliably detects all macroscopic GCT histologies, except for teratoma
miR-371a-3p holds promise in the following clinical scenarios:
1) patients with inconclusive testicular masses 2) surveillance after orchiectomy for early detection of relapse
3) response monitoring during chemotherapy 4) management of post-chemotherapy residual masses
5) surveillance after curative intent
short half-life of <24 hours
Staging: Tis
Germ Cell Neoplasia in Situ
Staging: T1
Confined to testis
NO LVI
Can be into epididymis
Can involve tunica albuginea but not vaginalis
Staging: T2
Testis with or without epididymal involvement
+LVI OR into tunica vaginalis
Staging: T3
Into spermatic cord
+/- LVI
Staging: T4
Into scrotum
+/- LVI
Staging: Clinical Nodes
N1
1-5 lymph nodes, all less than 2cm
Staging: Clinical Nodes
N2
> 5 LNs (less than 5 cm)
OR
LN 2-5 cm in size
Staging: Clinical Nodes
N3
LNs >5cm
Staging: M1a
Distant mets
- Nonregional LNs
OR
- Pulmonary nodules/mets
Staging: M1b
Distant mets OUTSIDE of nonregional LNs or lung
Staging: Serum Tumor Markers
S1
AFP - <1k
bHCG - <5k
LDH - <1.5x normal
Staging: Serum Tumor Markers
S2
AFP - 1k-10k
bHCG - 5k - 50k
LDH - 1.5 -10x normal
Staging: Serum Tumor Markers
S3
AFP - >10k
bHCG - >50k
LDH - >10x normal
Role of PET CT in testicular cancer
ONLY in seminoma to assess response to chemotherapy/determine if residual masses are active cancer
6-8 weeks after treatment
Risk factors for developing testis cancer including germ cell neoplasia in situ (GCNIS)?
history of UDT/cryptorchidism (4-6x, reduced by 2-3 x if orchidopexy prior to puberty)
family history
personal history of testis cancer
Risk of occult systemic disease for stage one testis cancer is lowest for :
pure seminoma vs. NSGCT
Pure seminomas are more sensitive to chemotherapy and radiation relative to NSGCT?
YES
The most undifferentiated type of NSGCT is?
embryonal carcinoma AND has totipotential capacity (differentiate into other NSGCT - yolk sac, choriocarcinoma, teratoma)
Why is presence of teratoma important for management?
Although histologically benign, may contain genetic anomalies found in malignant GCT → uncontrollable growth and invasion or transformation into somatic-type malignancies
universally resistant to chemo and radiation
ONLY curable by surgical resection
What are the testis cancer tumor markers and their associated histologies?
alpha fetoprotein (AFP) → yolk sac and embryonal (chorio and seminoma do NOT produce) → ½ life 5-7 days
human chorionic gonadotropin (hCG) → chorio and embryonal and syncytiotrophoblastic cells in seminoma → ½ life 24-36 h
lactate dehydrogenase (LDH) → nonspecific, best for estimating disease bulk
Staging for testis cancer is based on:
pathologic stage of tumor
post orchiectomy tumor markers
staging by PE and imaging
Testis TNM
Testis TNM stage:
Testis Risk Categories:
A solid mass on PE or imaging is:
GUIDELINE STATEMENT 1
malignant neoplasm until proven otherwise
When finding solid mass on PE or imaging, what is first step?
GUIDELINE STATEMENT 2
serum tumor. markers (AFP, hCG, and LDH) prior to any treatment
Prior to intervention for testicular mass, patients should be counseled:
GUIDELINE STATMENT 3
risk of hypogonadism and infertility
offered sperm banking (consider prior to orchiectomy if unclear status of contralateral or known subfertility)
What type of scrotal imaging should be used?
GUIDELINE STATEMENT 4
scrotal ultrasound with doppler (for unilateral or bilateral masses)
What workup is required for testicular microlithiasis?
GUIDELINE STATEMENT 5
testicular microlithiasis in absence of solid mass and risk factors doe snot confer and increased risk of malignant neoplasm and doesn’t require further evaluation
Patient with normal tumor markers (hCG and AFP) and indeterminate findings on PE or US, what is next step?
GUIDELINE STATEMENT 6
Repeat imaging 6-8 weeks
(< 2 cm 50-80% are not cancer → benign tumors, infarcts, Leydig cell nodules)
In initial workup of testicular lesion, any other imaging modalities besides US?
GUIDELINE STATEMENT 7
MRI should NOT be used in initial eval and dx of testicular lesion suspicious for neoplasm
Lesion determined by US and PE suspicious for malignancy, next steps after tumor markers?
GUIDELINE STATEMENT 8
with normal contralateral testis
inguinal orchiectomy (testis sparing not recommended, trans-scrotal discouraged)
GUIDELINE STATEMENT 9
testicular prosthesis should be discussed prior to orchiectomy
What is recommended when a patient underwent a scrotal orchiectomy and found to have a testis neoplasm?
GUIDELINE STATEMENT 10
increased risk of recurrence and may be considered for adjunctive tx (excision of scar or RT) for local control
Discuss role of testis sparing surgery, considerations, and surgical considerations?
GUDIELINE STATMENT 11A
tss through inguinal incision in pts wishing to preserve gonadal fx with masses < 2 cm and (1) equivocal US/PE and negative hCG and AFP (2) congenital, acquired or functionally solitary testis, or (3) b/l synchronous tumors
GUIDELINE STATMENT 11B
counseled regarding (1) high risk of local recurrence (2) need for monitoring with PE/US (3) role of adjuvant RT to testis to reduce local recurrence (4) impact of RT ons perm and testosterone (5) risk of testicular atrophy and need for tRT and/or subfertility/infertility
GUIDELINE STATMENT 11C
in addition to suspicious mass, multiple bx of ipsi testis normal parenchyma (GCNIS) should be obtained and evaluated by GU pathologist
In patients with hx of GCT or GCNIS the risk of second primary tumor in contralateral testis is:
GUIDELINE STATEMENT 12
Rare but significant increase risk
(2%overall, 70% metachronous, 30% synchronous)
In patient with GCNIS on testis biopsy or malignant neoplasm after TSS, what are recommendations and options:
GUIDELINE STATEMENT 13A
with GCNIS or s/p TSS → inform patients of r/b of surveillance, radiation, or orchiectomy
GUIDELINE STATEMENT 13B
recommend surveillance in pts who prioritize preservation of fertility and testicular androgen production
GUIDELINE STATEMENT 13C
recommend RT (18-20 Gy) or orchiectomy in patients who prioritize reduction of cancer risk taking into account the less risk of hypogonadism with RT
Discuss utility of serum tumor markers in treatment planning:
GUIDELINE STATEMENT 14
Nadir makers should be repeated at appropriate T ½ time interval after orchiectomy for staging and risk stratification
GUIDELINE STATEMENT 15
for pts with elevated AFP or hCG post orchiectomy, clinicians should monitor tumor markers to establish nadir levels before treatment only if nadir would influence treatment
In metastatic GCT (Stage IIC or III) planning for chemo what is the regimen based on?
GUIDELINE STATEMENT 16
IGCCCG risk stratification based on serum tumor markers (hCG, AFP, LDH) prior to chemo, staging imaging studies, and tumor histology from orchiectomy. Any post-pubertal male, should be treated as an adult
Describe Good Prognosis risk category for Seminoma and Non-Seminoma GCT:
Non-Seminoma
Testis/retroperitoneal primary, no non-pulmonary visceral mets, good markers
(AFP < 1000, hCG < 5000, LDH < 1.5 x norm)
56% of non-seminomas
5 yr PFS 89%
5 yr OS 92%
Seminoma
any primary site, no non-pulmonary visceral mets, normal AFP, any hCG, any LDH
90% seminomas
5 y PFS 82%
5 y OS 86%
Describe Intermediate Prognosis for Seminoma and Non-Seminoma GCT:
Non-Seminoma
testis/retroperitoneal primary, no non-pulmonary visceral mets, intermediate markers
(AFP > ,1000 < 10,000, hCG > 5,000 and < 50,000, and LDH > 1.5 x N and < 10 x N)
28% non-seminomas
5 y PFS 75%
5 yr OS 80%
Seminoma
any primary site, non-pulmonary visceral mets, normal AFP, any hCG, any LDH
10% seminomas
5 y PFS 67%
5 y OS 72%
Describe Poor Prognosis for Seminoma and Non-Seminoma GCT:
Non-Seminoma
mediastinal primary, non-pulmonary visceral mets, poor markers
(AFP > 10,000, hCG > 50,000, LDH >10 x N)
16% of non-seminomas
5 y PFS 41%
5 y Survival 48%
Seminoma
No patients classified as poor
Post orchiectomy elevated (AFP and hCG - 3 x normal), what should be done before treatments?
GUIDELINE STATEMENT 17
A rising trend should be confirmed before management decisions are made as false positive elevations may occur
Patients with newly diagnosed GCT, what imaging should be done?
GUIDELINE STATEMENT 18
CT scan A/P with IV contrast or MRI (if CT contra)
GUIDELINE STATEMENT 19A
Chest imaging
GUIDELINE STATMENT 19B
In setting rising of post-orchiectomy markers, mets on CT A/P, CXR or PE, A CHEST CT
GUIDELINE STATMENT 19C
Stage 1 seminoma, CXR (superior specificity) over Chest CT
GUIDELINE STATEMENT 19D
NSGCT Chest CT over CXR (especially if recommended adjuvant tx)
GUIDELINE STATEMENT 20
Newly dx GCT, do NOT obtain PET for staging
In newly dx GCT, how do you guide management decisions?
GUIDELINE STATEMENT 21
assign of TNM category
(image chest, A/P, post orchiectomy nadir AFP, hCG, and LDH)
GUIDELINE STATEMENT 22
Imaging w/in 4 weeks
Markers w/in 10days
Management decisions for newly dx GCT should be made with whom and based on which histology?
GUIDELINE STATEMENT 23
Multidisciplinary team (urology, med onc, rad onc, pathology, radiology)
GUIDELINE STATEMENT 24
Expert review of pathology in clinical scenarios where treatment decisions impacted
(review of expert alters subtype in 4-6%, 27% pathology reports revised)
In newly dx patients post orchiectomy with normal STM and equivocal findings on imaging for mets, how do you decide on tx?
GUIDELINE STATEMENT 25
Consider repeating imaging 6-8 weeks to clarify extent of dz before tx
Recommended tx for Seminoma GCT stage 1:
GUIDELINE STATEMENT 26
Surveillance after orchiectomy (<20% recurrence)
adjuvant RT and carboplatin-based chemo are less preferred (3-9% recurrence)
Recommended tx for pts w/Seminoma GCT and Stage IIa/b with LN < 3 cm? For IIB w/LN > 3 cm?
GUIDELINE STATEMENT 27
IIA/B LN < 3 cm: recommend RT(dog leg up to 30 Gy) or multi-agent cisplatin-based chemo (4 cycles EP or 3 cycles BEP) based on SDM
IIB LN >3 cm: chemotherapy recommended
Long term chemotherapy for GCT a/e:
cardiovascular, gastrointestinal, hematologic, infertility, secondary malignancy, neurologic, renal, pulmonary
Recommended tx for patients with NSGCT with elevated or rising post orchiectomy serum AFP and hCG:
GUIDELINE STATEMENT 28
risk appropriate multi-agent chemotherapy
Recommended treatment for Stage 1A NSGCT:
Reminder: IA pT1N0M0S0(beyond seminiferous tubules, still in testicle)
GUIDELINE STATEMENT 29
Surveillance preferred
RPLND or BEP x 1 (decline surveillance or non-compliance)
What are independent risk factors for relapse in NSGCT?
LVI and embryonal carcinoma
Recommended treatment for Stage 1B NSGCT:
Reminder IB: pT2-T4N0M0S0
GUIDELINE STATEMENT 30
surveillance, RPLND, or 1-2 BEP based on SDM
Patients with stage 1 NSGCT and any secondary somatic malignancy (teratoma with malignant transformation) in primary tumor, what is recommended tx:
GUIDELINE STATEMENT 31
RPLND
(teratoma has capacity to de-differentiate into somatic malignancy including sarcomas and carcinomas)
Patient with stage IIA NSGCT and S0, recommended tx:
Reminder IIA: any pTN1 (<5 nodes, < 2 cm) M0 S0 or S1 (in this question S0)
GUIDELINE STATEMENT 32
RPLND (benefit avoid chemo/remove teratoma) or chemotherapy
Patient with stage IIB NSGCT and S0, recommended tx:
Reminder: Stage IIB: Any pT, N2 (1 but <5 nodes with >2cm <5 cm, OR grown outside LN, OR > 5 nodes), M0S0 (this case) or S1
GUIDELINE STATEMENT 33
Risk-appropriate BEP vs. possible RPLND (select patients, S0)
Who should perform RPLND and how?
GUIDELINE STATMENT 34
referral to experience surgery at high volume center
GUIDELINE STATEMENT 35
experience and expertise with MIS can consider, acknowledge lack of long-term oncologic data
Describe an RPLND with curative intent:
GUIDELINE STATEMENT 36
*full b/l template with pts with suspicious LN on CT or intra-op or teratoma
*full b/l or modified template may be performed in clinically neg nodes
*right modified template may omit para-aortic LN below IMA (omission para-aortic LN above IMA controversial)
*left modified template may omit paracaval, precaval, and retrocaval LN (omission of interaortocaval LN controversial)
*nerve-sparing should be offered to preserve ejaculatory function
*nerve-sparing should NOT compromise quality of dissection
*complete retroaortic and/or retrocaval LND w/dissection and division of lumbar vessels should be performed within planned template
*ipsilateral gonadal vessels removed in ALL patients
*cephalad extent is crus of diaphragm to level of RA, caudad extent crossing of ureter over ipsilateral common iliac
After primary RPLND, what is recommended mgmt based on staging features:
GUIDELINE STATEMENT 37
Surveillance or chemo with stage II (not pure teratoma)
pN1 and/or pN1-3 pure teratoma → surveillance
pN2-3 → multi-agent chemotherapy (BEP)
What is surveillance protocol for Stage I seminoma:
GUIDELINE STATEMENT 38
H&P, cross-sectional imaging of abd +/- pelvis q 4-6 mo x 2 y, q6-12 mo yrs 3-5
routine chest and STM as indicated clinically
What is surveillance protocol for Stage I NSGCT:
GUIDELINE STATEMENT 39
After Orchiectomy: H&P and STM (AFP, hCG, +/- LDH) q2-3 mo x 1 year, q 2-4 mo in year 2, q 4-6 mo in year 3, q 6-12 mo years 4-5, >5 if indicated
GUIDELINE STATEMENT 40
CXR + CT A +/- P q 3-6 mo year 1 (start 3 mo), q 4-12 mo in year 2, once year 3-5
Men with higher risk of relapse should be imaged at shorter intervals (e.g. LVI)
Patients who relapse should be treated according to what? Stage 1 GCT on surveillance have what risk of relapse > 5 years?
GUIDELINE STATMENT 41
pts with relapse on surveillance should be fully restaged and treated based on new TMN-s status
GUIDELINE STATEMENT 42
Stage I GCT on surveillance < 1% late relapse after 5 y, annual serologic and radiographic assessment should be performed as indicated based on clinical concerns
How should survivors of GCT be monitored for hormonal status and long term sequelae of treatment?
GUIDELINE STATEMENT 43
monitor for s/s hypogonadism, if present serum AM testosterone and LH
GUIDELINE STATEMENT 44
survivors s/p chemo and/or RT → elevated risk CVD, establish PCP to manage modifiable risk factors (diet, exercise, smoking, lipids, BP, glucose)
GUIDELINE STATEMENT 45
survivors s/p chemo and/or RT → elevated risk secondary malignancy, establish PCP for checkups and cancer screening
What are important questions to ask a young man who presents with scrotal swelling?
urethral discharge/unprotected sex
dysuria/hematuria
back pain (myalgia)
hx of UDT
Shortness of breath
trauma
constitutional sxs (weight loss/night sweats)
headache
pain
What are important aspect of physical exam with suspected testicular mass?
lung exam
testis/spermatic cord
hydrocele
gynecomastia
inguinal exam
abdominal exam
what are all possible elements of post orchiectomy workup and why?
MRI brain if headache or neuro sxs
sperm banking if not done prior
repeat STM
CT A/P
CXR (ok if CT A/P normal and STM normal after orchiectomy) vs. CT (poor prognostic features or sob)
Bone scan: clinical features warrant ALP + scan (pain, fracture?)
what is the primary mechanism of spread of testicular tumors?
lymphatic
what is important testing to conduct prior to chemo, if lung mets or pulm sxs/hx?
PFTs
If abnormal avoid Bleomycin
What are short term and long term a/e of Bleomycin?
Pulmonary fibrosis
Raynaud’s
What are short term and long term a/e of Etoposide?
Myelosuppression
What are short term and long term a/e of Cisplatin?
Neurotoxicity
Nephrotoxicity
Ototoxicity
Describe risks and concerns for consent for post-chemo RPLND?
risks retrograde ejaculation, vascular injury, blood txfn, possible grafting of vessels, nephrectomy. chylous ascites, ileus, bowel/ureteral injury
*minimize perioperative FiO2 and fluid overload (Bleo)
Describe operative steps of RPLND?
- Transabdominal midline incision (xiphoid to below umbilicus)
- (can do robotic if can justify)
- Incise posterior peritoneum from ileocecal valve to ligament of Treitz
- Mobilize right colon, small bowel, and duodenum off RP to expose great vessels with clear exposure of renal veins; IMV can be divided to facilitate mobilization of left colon mesentery if necessary
- Split and roll technique with ligation/division of all lumbar vessels to allow complete mobilization of great vessels to facilitate a complete dissection; L3 most important for ejaculation (sympathetic chains just above common iliacs
- Complete resection of remainder of right spermatic cord
- Nerve sparing can be attempted if no compromised of oncologic principles/complete resection, but not required
Describe template for post chemo RPLND:
lateral → right and left ureter
Inferior → ureter crossing iliac
Superior → renal vessels (suprahilar not routinely required)
How do you diagnose chylous ascites?
CT A/P shows fluid ascites, air in small and large bowel
JP triglycerides elevated (like 1000)
What are the management steps for chylous ascites?
1st line: diuretic with fluid & salt restriction and low fat diet with medium chain fatty acid supplement
2nd line: if persistent for weeks, NPO/TPN
What do you do for 3 cm RP mass after RPLND for NSGCTin patient with known teratoma?
High dose chemo/BMT
VeIP (etoposide, ifosfamide, cisplatin, mesna)
TIP (paclitaxel, ifosfamide, cisplatin, mesna)
What is treatment for stage Ib (pT2N0M0S0) seminoma?
Surveilance, XRT or chemo - Carboplatin 1 (preferred) or 2 cycles
What are the side effects of carboplatin?
short term myelosuppression
long term secondary malignancy and heart disease
What are side effects of RT?
short term: nausea, emesis, diarrhea, leukopenia
long term: dyspepsia, PUD, oligospermia, secondary malignancy
Patient with recurrent seminoma s/p EP x 4, with residual RP mass (originally 6 cm now 4 cm). Next steps? If positive, next steps?
PET scan (CT PET)
> 6 weeks after completion chemo
Next steps:
RPLND vs. Surveillance (controversy, both acceptable per NCCN)
What are common presentations in testicular carcinoma?
- Painless testicular enlargement–most common
- Testicular mass–firm lump or nodule
- Testicular pain–heaviness, aching, acute pain~10%
- Gynecomastia–%5
- Abdominal mass or pain
- Respiratory problems
When performing orchiectomy for testicular mass, when would you recommend biopsy of contralateral side?
US abnormal
UDT or poor spermatogenesis
Marked atrophy (volume <12)
Half lives of STM?
BhCG 24-46 h (check 1 week)
AFP 5-7 days (check 4 weeks)
LDH 4 days
Treatment options for IB seminoma?
- Surveillance: best option with low risk (tumor size < 4 cm, no rete testis invasion, recurrence as low as 6%); need compliance, concern for radiation (CTs)
- EBRT: seminoma very radiosensitivity, long term radiation toxicity < 2% (cardiac disease doubled, risk secondary malignancy); para aortic field and ipsi nodes (“dog leg”) 20 Gy in 10 fx; relapse 1-3%
- Single dose carboplatin: noncompliant patients; equivalent relapse to RT, short term a/e thrombocytopenia and GI toxicity
Describe surveillance for IB seminoma post orchiectomy? After RT or chemo?
Orchiectomy:
HPI: 1 year: q3-6 mo, 2-3 year: q6-12 mo, 4-5 year: 1 x year
A/P CT: at 3, 6, 12 mo, 2-3 year q 6-12 mo, 4-5 year: q 12-24 mo
CXR: if clinically indicated, sxs consider CT
Chemo/RT
HPI: 1-2 year: q6-12 mo, 3-5 year 1 x year
A/P CT: 1-3 year: q1 x year, 4-5 year not indicated
CXR: if clinically indicated, sxs consider CT
Tx of IIA seminoma? And IIB?
IIA:
Traditional (preferred): EBRT to para-aortic and ipsi iliac PLN → 30 Gy
OR
Primary chemotherapy: EP x 4 or BEP x 3 for multiple positive LN
IIB:
Preferred: Primary chemotherapy: EP x 4 or BEP x 3
RT in non-bulky cases include para-aortic and ipsi iliac LN → 36 Gy
For stage IIC or III seminoma what determines tx?
Risk factors
Good risk: any primary site, no non-pulm visceral mets, normal AFP, any hCG or LDH
Intermediate risk: any primary site, non-pulmonary visceral mets, normal AFP, any hCG or LDH
Poor risk: no seminoma is poor risk
Treatment for good risk IIC or III seminoma? intermediate risk?
Good risk: Primary chemo EP x 4 or BEP x 3
Intermediate risk: BEP x 4 or VIP x 4 or clinical trial
How do you manage post-chemo residual mass for seminoma?
Likely fibrosis or necrosis
< 3 cm → surveillance
>3 cm → PET scan > 6 weeks after chemo, if + RPLND or chemo (conventional dose VeIP or TIP, or high dose chemo)
risk factors for testicular carcinoma?
gonadal dysgenesis
h/o prior testis tumor
CIS or intraepithelial germ cell neoplasia
UDT (intra-abd → seminoma, inguinal after pexy → NSGCT)
HIV
FHx
Infertility with Klinefelter’s
Hypospadias
Name primary GCT (relative frequency) and non-GCT?
Primary Germ Cell Tumors: seminoma (60%), embryonal carcinoma (20%), teratocarcinoma (15%), teratoma (5%), chorio (1%), yolk sac (<1%)
Non Germ Cell Tumors: only 10% malignant, orchiectomy and surveillance: Leydig cell tumor, Sertoli cell tumor
Describe path of testicular carcinoma spread?
Primarily via Lymphatics
RP node mets → cisterna chyli → thoracic duct → supra-diaphragmatic nodes → extra-nodal/distant mets
**exception is chorio or yolk sac which can demonstrate hematogenous spread
Describe nodal spread pattern for right testis tumor? left testis tumor?
Right: Interaortocaval → precaval → preaortic → right common iliac → right external iliac
Left: paraaortic → preaortic → left common iliac → interaortocaval → precaval → paracaval
*lymphatic spread goes from right to left in RP
What are treatment options for stage IB NSGCT?
- Surveillance (only pT2)
- Patient needs to be very compliant with rigorous surveillance
- >50% embryonal may increase risk of relapse and make surveillance inferior to tx
- LVI most important factor to predict occult mets
- SWENOTECA trial, all men stage I NSGCT no LVI underwent surveillance, BPE x 1, or BEP x 2, recurrence 12%, 1%, 0%
- Chemo
- 1 cycle BEP or 2 cycles (teratoma resistant, risk of infertility, secondary cancer, cardiac dz)
- NS-RPLND (appropriate for stage I and IIA
Risk of teratoma at RPLND? if in orchiectomy and if not?
In orchiectomy: 2-19%
Not in orchiectomy: 5-7%
What are the types of RPLND? Templates?
- Standard: includes full b/l dissection from above the RV to below aortic bifurcation, anejaculation approached 100% since sympathetic ganglia were sacrificed
- Superior: L adrenal, renal veins, below SMA
- Inferior: aortic bifurcation, IMA is sacrificed
- Medial: to contralateral ureter
- Lateral: renal hilum, ureter, iliac bifurcation
- Limited: area overlying aorta below IMA spared, most post-ganglionic sympathetics preserved, ejaculation 80-90% pts
- Superior: L adrenal, renal veins, below SMA
- Inferior: above IMA (IMA spared)
- Medial: lateral to aorta
- Lateral: renal hilum, ureter, iliac bifurcation
- NS-RPLND: preserves branches sympathetic chain over aorta, 100% ejaculation; not usually recommended for grossly pos nodes, usually performed in combo with limited dissection
What percentage of IB are upstaged to stage II on RPLND?
30%
If LN are grossly positive on RPNLD (stage IIB: >2 cm < 5 cm) what intraoperative template adjustment is made?
bilateral suprahilar dissections extending 4-6 cm above renal arteries to expose crura of diaphragm, IMV ligated, SMA identified and preserved, cisterna chyli is clipped
Superior: first hepatic vein (IVC)
Inferiorly: renal arteries
Laterally: medial aspect of adrenal glands
If nodes + near IMA → extend to lower aorta and contralateral common iliac (retrograde lymph spread)
If nodes + superior to IMA → lower aorta preserved
Potential complications of RPLND?
- IVC laceration: proximal and distal control, oversew with 4-0 Prolene, hold pressure, if cannot control, consult vascular
- IMA injury: ligate if necessary since collateral circulation (marginal artery of Drummond)
- IMA supplies distal half of transverse colon, descending colon, sigmoid, and rectum
- SMA supplies proximal half of transverse colon, ascending colon, and small bowel
- Cisterna Chyle laceration: located right of L1-L2, ligate if recognized intraop, unrecognized will result in chylous ascites
- Dx by paracentesis, NPO, TPN or low fat, high protein, medium chain triglycerides diet, possible somatostatin analogues
NSGCT stage IA, IB without risk factors, IIA, IIB treated with primary RPLND, what is tx for various nodal stages?
N0 → surveillance
N1 → surveillance (preferred) or chemotherapy (EP x 2)
N2 0→ chemotherapy (preferred - EP x 2) or surveillance
N3 → chemotherapy (BEP x 3 or EP x 4)
NSGCT IIA/IIB s/o RPLND, WITHOUT adjuvant chemo surveillance?
H&P and markers: 1 year: q2 mo, 2 year
NSGCT IIA/IIB s/o RPLND, WITH adjuvant chemo surveillance?
NSGCT Stage I s/p RPLND or chemo, surveillance?
NSGCT Stage 1 primary active surveillance w/o risk factors?
Risk factors: LVI, invasion of spermatic cord or scrotum, embryonal
NSGCT Stage 1 primary active surveillance w/ risk factors?
Risk factors: LVI, invasion of spermatic cord or scrotum, embryonal
NSGCT II/III after complete response to chemo +/- RPLND?
What can cause AFP elevation?
hepatoma, pancreas carcinoma, bronchogenic carcinoma
elevated in fetal yolk sac tumor, embryonal, teratocarcinoma
infants < 1 yo
Liver dysfunction (hepatitis, cirrhosis)
What can cause bhCG elevation?
chorio, seminoma, teratocarcinoma, embryonal
cross reacts with FSH, LH, TSH
marijuana users
What can cause LDH elevation?
seminoma and non-seminoma
Isoenzyme 1 is most useful
monitor treatment when AFP and bhCG normalized
useful for “bulky” seminoma
Stage IIC NSGCT, how do you determine the number of chemo cycles?
- Good risk: treat with EP x 4 or BEP x 3
AFP < 1,000, HCG < 5,000, LDH < 1.5 X N (S0 or S1)
- Intermediate risk: treat BEP x 4
AFP 1,000-10,000, HCG 5,000-50,000, LDH 1.5-10 x N (S2)
- High risk: treat BEP x 4 or VIP x 4
AFP > 10,000, HCG >50,000, LDH 10 x N (S3)
Mediastinal primary
Potential complications and treatment from RPLND?
- ARDS → bleomycin → increases w/ increased FIO2 and over-hydration
- Ventilate patients with RA and do not use FIO2 > 25-30%
- Use colloid to crystalloid ratio 2:1
- Prefer RBC over crystalloid
- Mass invades duodenum → perform duodenal resection
- IMA is encased in tumor → divide IMA as long as marginal artery intact
- Ureter is encased or invaded by tumor → nephroureterectomy
- Tumor invades aorta, IVC, lilac vessels → excise and replace affected vessels, perform vascular patch
- Psoas muscle involved by tumor → resect psoas fascia and affected muscle
- Tumor thrombus present in IVC below renal veins → ligate vena cava below renal veins, pts will develop temporary lower extremity edema
- Tumor invades the wall of IVC below the renal veins → legate the vena cava below renal veins, pts will develop temporary lower extremity edema
- Sigmoid mesentery is adherent to mass → resect the mesentery and mesenteric vessels, make sure the marginal artery and vein remain intact
What chemotherapy regimens are used in salvage setting for testicular cancer?
- VeIP (VP-16, Ifosfamide, Cisplatin) → mesna to protect bladder from Ifosfamide, 30% durable responses
- TIP (Paclitaxel, Ifosfamide, Cisplatin) → mesna to protect bladder from Ifosfamide, 25% durable responses
- Gemcitabine/Ifosfamide/Cisplatin → small study reporting 54% response rate
- High dose chemotherapy → with autologous peripheral blood derived stem cell support, unfavorable prognosis group (incomplete previous response, high markers, high volume, extratesticular primary, late relapse)
- 2 cycles of high dose Carboplatin plus Etoposide, w/ or w/o Cyclophosphamide (or Ifosfamide) → 20% durable responses
Follow up regimen after salvage chemotherapy for testicular cancer?
CXR and markers q3 mo x 2 years, then q6 mo x 3
CT A/P q 6 mo
How do you manage post chemotherapy residual mass for NSGCT? Seminoma?
NSGCT → residual mass should be excised as completely as possible if > 1 cm
Markers have to normalize before RPLND, if elevated → further chemotherapy
Seminoma → residual mass > 3 cm and normal markers → PET CT vs. surveillance → Indeterminate → repeat PET 6-8 weeks vs. bx → Positive → RPLND vs. bx
If there is mixed pathology seminoma and nonseminoma, how do you treat?
NSGCT recommendations
what are primary landing sites for left and right testicular tumors?
Left → para-aortic → preaortic
Right → interaortocaval → precaval → right iliac
describe the nerve sparing elements of RPLND? why important?
prevent anejaculation or other ejaculatory dysfunction
ID and preserve sympathetic trunks (L1-4) as they course posterior to the IVC on the right and anterior to aorta on the left, they coalesce just inferior to the IMA at inferior hypogastric plexus
What are treatment options for scrotal contamination in testis cancer?
- Stage 1 pure seminoma → extend RP radiation to include ipsi scrotum and inguinal nodes (risk of azoospermia)
- Stage 1 NSGCT → widely excise previous scar and spermatic cord at time of RPLND, or separate procedure if no RPLND, perform formal hemiscrotectomy in case of gross contamination but ill not eliminate risk of relapse
- Advanced dz → tx with full dose platinum chemo → examine inguinal nodes at f/up
**contamination increased recurrence but not OS
Which nodal status is chemo indicated for post RPLND Stage IA/B or IIA/B treated with primary RPLND? Which regimens?
Follow up post primary RPLND in need of adjuvant chemotherapy?
CXR and markers q3 mo x 2 years, the q 6 mo x 3 years
CT scan q 6 mo
Treatments for clinical stage IIA NSGCT with negative markers?
Primary NS-RPLND
OR
Primary chemotherapy EP x 4 or BEP x 3
Treatments for clinical stage IIB NSGCT with negative markers?
Treatments for clinical stage IIA NSGCT with persistent markers elevation?
Primary chemotherapy → BEP x 3, EP x 4
Treatments for clinical stage IIB NSGCT with positive markers?
Primary chemotherapy: BEP x 3, EP x 4
Primary chemotherapy for early clinical stages with persistent marker elevation:
What is growing teratoma syndrome?
RP masses that contain teratomas enlarge (sometimes quickly) in the face of normal STM. Usually benign, but warrant surgical excision, if left alone may spread and compromise vital organ function (bowel, ureters, vessels) by local invasion
Why can testis tumors cause gynecomastia?
NSGCT can produce elevated levels of estradiol
Leydig cell tumors promote peripheral conversion of testosterone to estrogen (but will not cause elevation in STM)
What if you remove a testicular tumor in a patient with clinical symptoms (e.g. gynecomastia), elevated STM, and a supraclavicular node, and the pathology shows scar and no active malignancy?
“burned” out testis tumor or extragonadal
Must perform excisional bx or FNA of supraclavicular node
Describe risk classification post-orchiectomy for NSGCT and seminoma
Post orchiectomy for NSGCT, with NED, with isolated bHCG elevation, what can be the cause?
Elevated LH
Single testicle → low testosterone → anterior pituitary increased LH which has cross reactivity with bhCG
Give testosterone injection and retest (if goes down, no further action)
