Treatment/Prognosis

Question 1

Following transinguinal orchiectomy, what is the optimal Tx for stage I seminoma, stages IIA–IIB seminoma, and stage IIC or greater seminoma?

Answer 1

1. Stage I seminoma → surveillance is preferred (Can consider adj RT or single-agent carboplatinum.)
2. Stages IIA–IIB → adj RT preferred. (Can consider multiagent chemo)
3. Stage IIC or greater → multiagent chemo

Question 2

For pts undergoing surveillance for stage I seminoma, what are the 15-yr relapse, DSS and OS rates?

Answer 2

For pts undergoing surveillance for stage I seminoma, the 15-yr relapse rate was 18.9% (96% before yr 5). 15-yr DSS and OS rates were 99.3% and 91.6%. (Mortensen et al., Eur Urol 2014)

Question 3

For pts undergoing surveillance for stage I seminoma, where do most relapses occur?

Answer 3

85% of relapses are in the infradiaphragmatic P-A nodes. Observation should therefore include regular CT assessment of the abdomen and pelvis.

Question 4

What pathologic factors are associated with increased risk of relapse following transinguinal orchiectomy for stage I seminoma?

Answer 4

Pathologic factors associated with risk of relapse following transinguinal orchiectomy include:

tumor size >4 cm
LVSI
β-HCG >200 IU/L
Rete testis invasion
(Warde P et al., JCO 2002; Mortensen et al., Eur Urol 2014; Kollmannsberger et al., JCO 2015)

Question 5

Following P-A relapse in pts observed following transinguinal orchiectomy for stage I seminoma, what are the appropriate Tx options?

Answer 5

Following P-A relapse in pts observed following transinguinal orchiectomy for stage I seminoma, retroperitoneal RT (for nodes <5 cm) or multiagent chemo are reasonable Tx options.

Question 6

For pts treated with P-A RT following transinguinal orchiectomy for stage I seminoma, what is the relapse rate? Where do relapses occur?

Answer 6

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 SCV, or (if risk factors are present) inguinal. Surveillance should include regular CXR.

Question 7

What data support the option of adj chemo for stage I seminoma following transinguinal orchiectomy?

Answer 7

MRC-UK TE19 randomized 1,447 stage I seminoma pts to adj RT (2 Gy/fx to 20 or 30 Gy) vs. 1 cycle of carboplatin. Carboplatin demonstrated noninf 5-yr RFS (94.7% for carboplatin vs. 96% for RT). (Oliver R et al., Lancet 2005, JCO 2011)

Question 8

In a stage I seminoma pt, what factors would favor active Tx over surveillance?

Answer 8

In a stage I seminoma pt, concern over pt adherence with f/u may favor active Tx.

Question 9

Why is P-A RT not part of the definitive management of pts with stage IIC seminoma?

Answer 9

P-A RT is not part of the definitive management of pts with stage IIC seminoma d/t high rates of distant failure (mediastinal, lung, SCV, or bone). Thus, chemo is needed. In 1 series, 5-yr RFS among stage IIC pts treated with orchiectomy and RT alone was only 44%. (Chung PW et al., Eur Urol 2004)

Question 10

What is the appropriate Tx for pts with stages I–IIB seminoma following relapse after adj P-A RT?

Answer 10

Pts with stages I–IIB seminoma who relapse following adj P-A RT should be treated with salvage chemo.

Question 11

How should seminoma pts with stage IIC or greater be treated?

Answer 11

4 cycles of cisplatin/etoposide (+/- bleomycin) are appropriate for seminoma pts with stage IIC or greater.

Question 12

What is the appropriate RT field for stage I seminoma pts?

Answer 12

Stage I seminoma pts (if receiving adj RT) should have the P-A nodes treated. MRC-UK TE 10 randomized 478 pts to P-A RT +/– pelvic RT and found equivalent 3-yr RFS (96%) (Fossa SD et al., JCO 1999). 4 pelvic failures occurred in the P-A group (vs. none in the P-A + pelvic group).

Question 13

For adj stage I seminoma, what are the borders for a P-A field and LN regions are being targeted?

Answer 13

1. Borders for a P-A field (for adj stage I seminoma):
   Superior: T10–11 has been the historical standard, however, cranial reduction to T11–12 reduces kidney, stomach, and small bowel dose without compromise in RFS. (Bruns F et al., Acta Oncol 2005)

Inferior: L4–L5

Lateral: 2 cm on vertebral bodies. If left-sided primary, give 1-cm border on left renal hilum and sacroiliac joint. CT-based planning using vascular and nodal anatomy may help avoid marginal misses. (Martin JM et al., Radiother Oncol 2005)

2. LNs within P-A field (for adj stage I seminoma):
   Right sided: at least the paracaval, precaval, and interaortocaval regions

Left sided: at least the lat-aortic and preaortic regions

Question 14

What is the appropriate field for a stages IIA–IIB seminoma pt and what LN regions are being targeted?

Answer 14

Modified dog-leg radiotherapy (excluding inguinal LN regions) would be appropriate d/t similar DFS and lower acute grade 3 toxicities compared to standard dog-leg field radiotherapy (NCCN guidelines, Classen et al., JCO 2003)
Superior: T11–12

Inferior: top of acetabulum (note: in pts with prior pelvic or scrotal Sg, place inf border at the top of the ipsi obturator foramen to cover ipsi inguinal nodes)

Ipsilateral: defined by a line from tip of the transverse process of the 5th lumbar vertebra to the superolat border of the ipsi acetabulum

Contralateral: inclusion of transverse process in P-A area down to L5–S1, then diagonally in parallel with ipsi border

2. LNs within modified dog-leg fields: paracaval, precaval, interaortocaval, lat-aortic, preaortic, ipsi common iliac, external iliac and proximal internal iliac regions

Question 15

What is a reasonable dose and fractionation schedule for stage I seminoma?

Answer 15

For stage I seminoma, common Rx doses include:

Stage IA. 25 Gy in 1.25 Gy/fx

Stage IB. 25.5 Gy in 1.5 Gy/fx

Stage IC. 20 Gy in 2 Gy/fx

The MRC-UK TE 18 trial compared 2 Gy/fx to 20 Gy vs. 30 Gy and found equivalent relapse rates at 5 yrs. (Jones WG et al., JCO 2005)

Question 16

What is a reasonable dose and fractionation schedule for stages IIA–IIB seminoma?

Answer 16

For stage IIA–IIB seminoma, the “dogleg” or modified dog-leg field may be treated with a similar dose–fractionation as stage I. Gross LAD may be boosted with an additional 5–10 Gy in 2 Gy/fx (∼30 Gy for IIA, ∼35 Gy for IIB).

Question 17

What pathologic subtype of seminoma can be treated with orchiectomy alone?

Answer 17

Spermatocytic seminoma can be treated with orchiectomy alone. This tumor is seen in older pts and, while the precursor cell is unknown, is probably not a true seminoma.

Question 18

What RT dose can induce temporary azoospermia? Doses greater than what may cause permanent aspermia?

Answer 18

RT doses as low as 0.2–0.5 Gy will cause temporary azoospermia. Doses >0.5 Gy can cause extended or permanent aspermia.

Question 19

What should be done to reduce the testicular RT dose during Tx for testicular seminoma?

Answer 19

During RT for testicular seminoma, a clamshell should be used to reduce the dose to the contralat testis.