Testis cancer

What are 3 advantages to doing RPLND?

1) Accurate pathological staging 2) Low morbidity 3) Minimal risk of relapse due to chemoresistant GCT

What are treatment options for Stage IIA NSGCT? (HINT: 2 options, 1 is recommended)

1) Chemotherapy: - recommended (especially with S1!) - 4 X EP or 3 X BEP 2) RPLND: - only if S0 - adjuvant therapy is dictated by nodal staging - for pN1 and especially pN2, can give 2 X EP or 2 X BEP - for pN3 disease, do 3 X BEP or 4 X EP

What are the treatment options for Stage IIB NSGCT?

1) Chemotherapy: - strongly recommended, especially with S1 - 4 X EP or 3 X BEP - do subsequent RPLND if unchanged mass on repeat imaging 2) RPLND: - only if S0 - adjuvant therapy is dictated by nodal staging - for pN1 and especially pN2, can give 2 X EP or 2 X BEP - for pN3 disease, do 3 X BEP or 4 X EP

List 4 potential complications for post chemo RPLND. What is the overall complication rate for RPLND? What about post-chemo RPLND?

1) Chylous ascities (3%) 2) Renovascular injury (3%) 3) SBO (3%) 4) Pulmonary compromise (especially with prior bleomycin exposure) Complication rate: a) RPLND: 8% b) RPLND post chemo: 18% Complication rate higher due to desmoplastic reaction around tumor as well as tumor size.

List 5 risk factors for testicular cancer.

1) Crytpo-orchidism: RR is 4-6 (reduces to RR 2-3 with pre-pubertal orchidopexy) 2) Intra-tubular germ cell neoplasia (ITGCN): 50% of men with this develop testis cancer in 5 years 3) Family history

What is the difference between early or late relapse when talking about recurrence following first line chemo for NSGCT?

1) Early relapse: recurrence before 2 years from completing initial treatment 2) Late relapse: recurrence after 2 years from completing initial treatment

What are 2 predictors for occult (silent) metastasis following orchiectomy for Stage 1 NSGCT?

1) LVI 2) Embryonal predominance (>40%) This is found in about 30% of men with Stage 1 NSGCT (occult mets in these men can be up to 80%). Men with none of these factors still have an occult mets rate of 15%. Important to note that despite these increased rates of relapse, treatment at time of recurrence for Stage 1 NSGCT is almost always curative!

What are 3 toxicities of RT for testicular cancer?

1) Leukopenia (5-15%) 2) Oligospermia (8%) 3) GI complications (5%)

For stage I seminoma, what are 2 risk factors that are predictors of relapse?

1) Rete testis invasion 2) Tumors >4cm

What are the 2 sub-categories within germ cell tumors?

1) Seminomas (more common) 2) Non-seminomas

What 3 elements go into CLINICAL staging of testicular cancer?

1) Staging imaging 2) Tumor pathology 3) Post orchiectomy serum tumor markers

What are treatment options are offered for Stage I NSGCT (3 options)?

1) Surveillance 2) RPLND 3) Cisplatin-based chemotherapy

What are treatment options are offered for Stage IA and IB pure seminoma? (3 options).

1) Surveillance 2) Radiotherapy 3) Chemotherapy (1 or 2 cycles with carboplatin)

What are 2 commonly used second line/salvage chemo regimens?

1) TIP: - paclitaxel - ifosfamide - cisplatin 2) VeIP: - vinblastine - ifosfamide - cisplatin Patients responding to salvage chemo need to have salvage surgery as well.

List 3 side effects of carboplatin (short-term).

1) Thrombocytopenia/myelosuppresion (12%) 2) GI complications (8%) 3) Nephrotoxicity

What percentage of men present with metastatic disease from testicular cancer on first presentation?

10-30%

What is the overall recurrence rate for Stage I seminoma managed with surveillance?

13%. Of these, 92% occurred in the first 3 years. Almost all of these recurrences were IGCCCG GOOD risk.

With post-chemo RPLND for NSGCT, what should be done if pathology shows viable tumor along with teratoma and fibrosis?

2 cycles of conventional chemo If incomplete response, then do second line (salvage) chemo, followed by RPLND. No role for PET (viable NSGCT are not FDG-PET avid).

How many cycles of BEP are recommended by NCCN for Stage 1 NSGCT? What's the relapse rate?

2 cycles. Relapse rate with 2 cycles is <5%. Recurrences were all IGCCCG good risk and 100% cancer specific survival.

What percentage of non-retroperitoneal masses in metastatic NSGCT post-chemo will be viable tumor?

20% (will be either viable tumor or teratoma)

What is the overall risk of relapse with surveillance for Stage 1 NSGCT?

26% (12% with none of the risk factors)

How many Stage 1 NSGCT patients undergoing RPLND are upstaged to Stage II?

30%

What percentage of overall men with Stage 1 NSGCT will harbor micrometastatic disease?

30%

What percentage of patients are clinically understaged even after CT?

30% (harbor occult mets without CT detection)

What is the rate of discordance in pathology between primary NSGCT retroperitoneal mass and non-retroperitoneal spread post-chemotherapy?

30-45%

What is the treatment for Stage IIC NSGCT?

4 X EP or 3 X BEP

For advanced seminoma, what percentage of patients will have a mass post-chemo? How much of this mass is viable tumor?

60-80% 10% is viable tumor, most is desmoplastic reaction (fibrosis). Larger masses (>3cm) however correspond to higher viable tumor percentages.

What percentage of patients with Stage I seminoma are cured by orchiectomy alone? How about the disease specific survival?

80% are cured with orchiectomy alone Disease specific survivial = 99% irrespective of treatment modality

What percentage of Stage I NSGCT are cured with radical orchiectomy alone?

70%

What percentage of patients does radiotherapy prevent relapse in for stage I seminoma?

96%

What are the 3 chemotherapy agents used for patients wanting to have chemotherapy for treatment of Stage 1 NSGCT?

BEP 1) Bleomycin 2) Etoposide 3) Cisplatin

How do you generally manage advanced stage (Stage III) testicular cancer?

Dictated by risk stratification, but mainstay is chemotherapy.

What areas are radiation administered to for Stage I seminoma?

Dog leg: bilat para-aortic nodes and ipsilateral pelvic nodes PA strip: just para-aortic nodes (NCCN recommends this for stage IA and IB seminoma)

What is the template used for RT for treating Stage IIA or IIB pure seminoma?

Dog-leg (targeting the ipsilateral iliac nodes)

In select cases of IIB pure seminoma, chemotherapy can be an option (ex: nodes >3cm). What is the recommended chemo and regimen? (HINT: 2 options)

EP X 4 or BEP X 3

What is the treatment for IIC pure seminoma?

EP X 4 or BEP X 3

When do the vast majority of relapses occur for Stage 1 NSGCT?

First 2 years.

What is the treatment algorithm for Stage III pure seminoma based on risk?

GOOD risk: EP X 4 or BEP X 3 INTERMEDIATE risk: BEP X 4 **no such thing as POOR risk seminoma

What is the treatment algorithm for Stage III NSGCT based on risk?

GOOD risk: EP X 4 or BEP X 3 INTERMEDIATE risk: BEP X 4 POOR risk: BEP X 4 or VIP X 4 (etoposide/vinblastine, ifosfamide, cisplatin) or Clinical trials

What is the main type of testicular cancer?

Germ cell tumors = MAIN type Others: - stromal tumors - lymphoma

What is the recommended treatment algorithm for post-chemo masses in pure seminoma?

If residual mass is <3cm and markers negative --> SURVEILLANCE If residual mass is >3cm with normal markers --> PET (6 weeks post chemo) If PET is positive --> RPLND

What are criteria for good and intermediate prognosis for testicular GCT risk classification?

International GC Cancer Collaborative Group (IGCCCG)

How common are late relapses of NSGCT? Where are the recurrences and what should be done?

Late relapse rate: 3% Mainly occur in RP. These patients need RPLND as they are usually chemoresistant.

What is Stage III testicular cancer basically?

M1a/b AND/OR >/=S2

What is Stage II testicular cancer basically?

N1-3 and S0-1

How many doses of carboplatin should be given for stage I seminoma?

NCCN recommends either 1 or 2. Relapse rates are slightly lower with 2 doses of carboplatin (3% versus 4%).

For advanced NSGCT, what should be done post-chemo if there is any residual masses with negative markers? How much of this mass is viable tumor?

Need to be resected (RPLND). Usually 10-20% is viable tumor. 50% is fibrosis, the other 40% is teratoma.

If RPLND is negative for LN involvement, is the risk of distant disease 0?

No, 10% of patients will still relapse at a different site.

Does lymphatic spread always happen superiorly in testicular cancer?

No. Once it spreads to primary landing sites (interaortocaval and para-aortic), it can continue to spread superiorly into the cysterna chyli, thoracic ducts, and supraclavicular nodes OR can spread inferiorly to common and external iliac nodes.

What is the utility of LDH as a marker for testis cancer?

Non-specific marker for GCT. Measures disease burden, may help prognosticate.

When is radiotherapy administered to the inguinal scar or ipsilateral scrotal contents?

Only if scrotal violation occurred during the orchiectomy.

What is the prognosis with brain metastases for testicular cancer?

Poor. Usually need primary chemo and RT.

What is the mainstay of treatment of Stage IIA and IIB pure seminoma? What are the cumulative doses for each?

Radiotherapy. IIA: 30Gy IIB: 36Gy Overall survival is close to 100%

Due to renovascular injury and tumor size, nephrectomy might be necessary during post-chemo RPLND. What is the rate of nephrectomy, and what is the single strongest predictor of needing nephrectomy?

Rate of needing Nx: 15% Strongest predictor: RP mass >10cm

The TE18 (EORTC 30942) trial compared standard RT for Stage I seminoma between 2 different doses: 30Gy in 15Fr versus 20Gy in 10Fr. What did it show?

Relapse free rates were HIGHER in the 20Gy and 10Fr group (97% versus 95%). Raises the concern of secondary malignancy from RT.

The TE10 (Testicular Tumor Working group) compared PA strip versus dog-leg for RT template. What did the study show?

Relapse rate was the same (4%), but PA-strip had significantly less side effects.

What is the one major morbidity of RPLND? What 2 measures are done to minimize this morbidity?

Retrograde ejaculation. Modified templates and nerve sparing techniques help minimize this risk.

What is the initial site of mets for testicular cancer?

Retroperitoneum (70-80% of the time)

Which sided testicular cancer has more contralateral nodal involvement?

Right testis, as lymphatic drainage (and therefore nodal spread) occurs right to left.

What is the most common presentation (in terms of pathology) for testicular cancer?

Seminomas, localized. Represents about 50% of all cases of testis cancer.

For early relapse in NSGCT, what is the treatment? The exception is when tumor markers are decreasing and RP masses are growing. What is this called, and what do these patient need.

Second line/salvage chemo Exception: called Growing Teratoma syndrome. These patients need RPLND with resection of non-RP sites.

What is the radiation dosing and schedule given for Stage I seminoma?

Seminoma is very radiosensitive, so low dose good enough. 20 Gy given in 10 fractions. Use a scrotal shield!

EORTC 30982 randomized men with Stage I seminoma to either adjuvant chemo (1 dose carboplatin) or adjuvant RT. What did it show for relapse free rates?

Similar relapse free rates between 1x carboplatin and RT (95% versus 96%).

Even though cisplatin based chemo has been standard for most testicular cancer, what's the idea behind carboplatin for Stage I seminoma?

Single agent carboplatin achieves similar cures while reducing chemo toxicity.

With post-chemo RPLND for NSGCT, what should be done if pathology shows teratoma and fibrosis?

Surveillance! No additional treatment.

What structure can get injured during RPLND that can cause retrograde ejaculation?

Sympathetic trunks. They are postganglionic fibers that run paravertebral and bilaterally. Posterior to vena cava, anterior to aorta, and coalesce at inferior hypogastric plexus (caudal to IMA).

What is the most common type of cancer to affect 20-40 year old men?

Testicular cancer.

What are the S staging for testicular cancer?

These are levels taken post orchiectomy, usually after 4-6 weeks.

What is the half life of each tumor marker for testicular cancer: a) AFP b) B-HCG c) LDH

a) 5-7 days b) 1-2 days c) 1 day

What are the first nodes that testicular cancer goes to from: a) right testicle b) left testicle

a) Interaortocaval (at L2) b) Para-aortic nodes (bordered by renal vein superiorly, origin of IMA inferiorly, aorta medially, ureter laterally)

What does the modified template for RPLND generally entail for: a) right sided spread b) left sided spread

a) Nodes removed from: - right ureter - paracaval - interaortocaval - pre- and para-aortic above IMA b) Nodes removed from: - para-aortic medial to left ureter - interaortocaval - pre-aortic above IMA

What are sub-divisions under the following types of germ cell testicular cancer: a) seminoma (2) b) non-seminoma germ cell tumors (NSGCT) (5)

a) SEMINOMA: - classic seminoma - spermatocytic seminoma b) NSGCT: - embryonal - yolk sac - choriocarcinoma - teratoma - mixed GCT 50% of all testis cancer is seminoma, the other 50% are all the other types of NSGCT

Which tumors generally produce: a) AFP only (1) b) B-HCG only (2) c) Both (1)

a) Yolk sac b) Seminoma, choriocarcinoma c) Embryonal

What is the drainage pathway for the: a) right testicle b) left testicle

a) infrarenal inter-aortocaval nodes, paracaval and para-aortic nodes b) para-aortic nodes, inter-aortocaval nodes

What is the TNM staging of testicular cancer?

pT0: no tumor pTis: intratubular germ cell neoplasia pT1: limited to testis/epididymis without LVI (may invade tunica albuginea) pT2: tumor limited to testis/epididymis with LVI OR tumor invades tunica vaginalis pT3: invades spermatic cord +/- LVI pT4: invades scrotum +/- LVI Clinical regional nodal staging: Nx: cannot be assessed N0: no regional node mets N1: Mets in 1 or more nodes <2cm N2: 1 or more nodes 2-5cm N3: 1 or more nodes >5cm PIC: Pathological regional lymph nodes and Distant Mets