304 CHAPTER 6 Urological neoplasia

Testicular cancer: management of non-seminomatous germ cell tumors (NSGCT)

Following radical orchiectomy and formal staging, the patient may require a retroperitoneal lymph node dissection (RPLND). Joint management involves urology and medical oncology in most cases of NSCGT.

In the presence of elevated AFP, a seminoma would be managed as for teratoma. Combination chemotherapy, introduced in the 1980s, revolutionized the treatment of metastatic testicular teratoma, which was hitherto virtually untreatable.

The IGCCCG prognostic staging is often used in treatment planning at some centers. General treatment options following radical orchiectomy and staging for NSCGT are outlined here (see Table 6.18 for stage grouping).

Stage I

•Surveillance is appropriate for reliable patients with no risk factors. It has a 25–30% relapse rate.

•Requires close follow-up with imaging (CT, CXR), tumor markers, and physical examination

•RPLND: modified unilateral template/nerve-sparing. Up to 70–75% will be pathologically negative (pN0).

•RPLND offers cure in 95% with negative nodes and may cure lowvolume nodal disease. Only 5% will relapse.

•Chemotherapy with two cycles of bleomycin, etoposide, cisplatin (BEP) yields 95% survival.

Stage IIa/IIb

Controversy exists regarding the most effective treatment regimen. Options include RPNLD with modified bilateral template, RPNLD + adjuvant chemotherapy, or primary chemotherapy.

•RPNLD and no tumor found: observe

•RPNLD and positive nodes: two cycles of adjuvant chemotherapy

•RPNLD and high-volume disease or residual tumor left behind: three cycles adjuvant chemotherapy

Stage IIC or III

•Chemotherapy is the initial treatment, with either 3 or 4 cycles depending on risk. Complete responses are frequently observed.

•Partial responses with residual retroperitoneal masses undergo full bilateral RPNLD (nerve-sparing, if applicable). Follow-up is based on pathological findings:

•Residual masses: fibrosis in 40%, teratoma in 40%, and viable malignancy in 20%

•Malignancy present and post-resection tumor markers elevated or tumor left behind: use salvage chemotherapy

•Malignancy present and post-resection tumor markers normal and no tumor left behind: 2 cycles of chemotherapy can be given

•Teratoma/fibrosis only: observation only

TESTICULAR CANCER: NSGCT 305

Table 6.18 Simplified stage grouping for testis cancer, including S stage

Simplified stage groupings in testis cancer

ULN, upper limit of normal.

•With no response to primary chemotherapy, consider salvage chemotherapy (ifosfamide, vinblastine, cisplatin), or salvage bone marrow transplant.

Chemotherapy

Regardless of histology, patients with advanced germ cell tumors (cIIB– cIII) and those with elevated tumor markers following radical orchiectomy (cIS) are treated initially with platinum-based chemotherapy based on IGCCCG risk stratification.

Good risk

Use BEP regimen every 21 days x3 cycles

•Bleomycin 30 U IV weekly

•Etoposide 100 mg/m2 IV x 5 days

•Cisplatin 20 mg/m2 IV x5 days

Or EP regimen every 21 day x4 cycles

•Etoposide 100 mg/m2 IV x5 days

•Cisplatin 20 mg/m2 IV x5 days

306 CHAPTER 6 Urological neoplasia

Intermediateor high-risk disease

Use 4 cycles BEP every 21 days (as above), or the following given every 21 days x 4 cycles:

•Etoposide 75 mg/m2 IV x 5 days

•Ifosfamide 1.2 g/m2 IV x 5 days

•Cisplatin 20 mg/m2 IV x 5 days

Chemotherapy complications

•Bleomycin: pulmonary toxicity causing pulmonary fibrosis that can be life threatening

•Cisplatin: nephrotoxicity, ototoxicity, peripheral neuropathy

•Etoposide (VP16): hematological toxicity, alopecia, vascular toxicity, metabolic syndrome

•Ifosfamide: hemorrhagic cystitis (can be reduced by the use of MESNA)

•Secondary malignancy: leukemias, lymphomas, skin malignancies

•Infertility: 50% will have normal sperm counts 2 years after chemotherapy, 25% will remain azoospermic (many patients with testicular cancer will have abnormal semen parameters before radical orchiectomy)

Surveillance and follow-up after treatment

Surveillance for low-risk disease requires the following. Patients who undergo definitive therapy can have less aggressive follow-up the first 2 years, but follow-up is also to 10 years. The risk of relapse is highest in the first 2 years.

•Year 1: monthly clinic visit with serum markers and chest X-ray, abdominal CT months 3, 6, 9, and 12

•Year 2: bi-monthly clinic visit with serum markers and chest X-ray, abdominal CT month 24

•Years 3, 4, and 5: 3-monthly clinic visit with serum markers and chest X-ray

•Annual clinic visit with serum markers and chest X-ray thereafter to 10 years

RPLND

RPLND is the gold-standard staging investigation following radical orchiectomy. In the United States, it is the preferred approach for patients at high risk for retroperitoneal relapse (predominant embryonal carcinoma, lymphovascular invasion, or extension into the tunica or scrotum) if serum tumor markers have normalized. In the UK, RPLND is used only to remove or debulk residual mass post-chemotherapy.

Retroperitoneal lymphadenopathy is usually the first and only evidence of extragonadal metastasis of teratoma. For low-stage disease, a modified nerve-sparing template is used.

Open RPLND is the standard, with laparoscopic techniques applied at some centers. It is a technically challenging procedure that requires significant expertise.

TESTICULAR CANCER: NSGCT 307

Left-sided testicular tumor

The limits of dissection include the left common iliac artery medially and inferiorly up to the aortic bifurcation. Dissection continues along the aorta to the inferior mesenteric artery (IMA), and above the IMA, the dissection is carried out to the lateral edge of the inferior vena cava. The superior limit of the dissection is the renal vessels bilaterally. The ureter and gonadal vessels are the limit laterally.

The spermatic cord stump (marked by a nonabsorbable suture at the time of radical orchiectomy) is included in the specimen.

Right-sided testicular tumor

The limits of dissection include the right common iliac artery medially and inferiorly up to bifurcation of the aorta. Dissection continues along the aorta up to the IMA. Superior to the IMA, the dissection is carried out to the left ureter. Superior limit is the renal hilum bilaterally. On the right side, lateral limit is the ureter and the gonadal vessels.

The stump of the spermatic cord is included in the specimen.

Post-chemotherapy RPLND

Post-chemotherapy RPLND and resection of residual masses involves a complete bilateral resection including the supra hilar nodes. In the setting of post-chemotherapy RPLND, 40% will have teratoma, and 10–15% will have viable germ cell tumor.

RPLND complications

There is <1% mortality. Perioperative morbidity is 5–25% (atelectasis, ileus, lymphocele, pancreatitis, chylous ascites). Late bowel obstruction also occurs (1–2%). Ejaculatory dysfunction, when present, can be markedly decreased with nerve-sparing templates.