[MOL] Posssible Cure for Germ-Cell Testicular Cancer [01453] Medicine On Line


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[MOL] Posssible Cure for Germ-Cell Testicular Cancer



Cure Possible for Most Patients with Germ-Cell Testicular Cancer

[Drug & Ther Perspect 13(10):4-7, 1999. 1999 Adis International Limited]

Introduction

Approximately 90% of patients with newly diagnosed germ-cell testicular cancer will be cured. Although delayed presentation correlates with more advanced stages of disease, treatment with cisplatin-containing regimens means that cure is now possible for some of these patients. However, patients with metastases or highly active disease have lower cure rates and more effective treatments are sought.

Radial inguinal orchiectomy is essential initial treatment for patients with suspected testicular cancer. However, subsequent treatment varies depending on disease stage (see Patient care guidelines), and to some extent patient and clinician preference.

Incidence Varies but Rare Overall

Testicular cancer is the most common solid malignancy in young men. Although the incidence of the disease has more than doubled in the last 30 years, testicular cancer is still rare, representing about 1% of all cancers in men.[2] The incidence varies according to:[3]

Men at high risk of testicular cancer are those with maldescended testis or with previous testicular cancer.[1,2]

Initial Presentation is Often Diffuse Swelling

Patients most frequently present with diffuse testicular pain, swelling and/or a feeling described as a lump or hardness associated with a heavy feeling in the lower abdomen or scrotum.[2]

Exclude Infection

As infectious epididymitis, orchitis or testicular torsion is more common than tumour, a course of antibacterials is usually given.[1,2] If testicular discomfort or enlargement persists for 2 to 3 weeks, testicular ultrasound examination should be performed. In patients with testicular carcinoma, one or more discrete intratesticular masses or diffuse abnormalities are usually seen on ultrasound.[1]

Almost All Tumours Originate from Germ Cells

Between 95 and 97% of all testicular cancers are germ-cell tumours.[1,2] This type of tumour is divided into seminoma and nonseminoma (47 and 37% of germ-cell tumours, respectively); the remainder of germ-cell tumours are mixed seminoma and nonseminoma. Treatment for mixed seminoma and nonseminoma tumours should be the same as for nonseminoma, as these latter tumours are the more clinically aggressive.[1]

The remaining 3 to 5% of testicular cancers are very rare (Leydig cell tumours, sertoli cell tumours, malignant lymphoma and sarcoma) and are not included in this article.[2]

About 90% of Patients Are Cured

Testicular cancer is one of the most curable malignancies with cure rates for most patients of between 85 and 92%.[2]

All patients with suspected testicular cancer should have a radial inguinal orchiectomy with ligation of the spermatic cord at the internal ring;[1] this procedure should confirm the diagnosis.

The disease should then be staged to predict prognosis and to define further treatment requirements.[2] Different staging classifications are widely used. The Royal Marsden Hospital Classification (see table 1) is based on radiological evaluation following orchiectomy without retro-peritoneal lymph-node dissection (RPLND). Other systems use pathological information gained from the RPLND.

Radiotherapy for Early Seminoma

Radiotherapy has traditionally been the treatment of choice for patients with stage I, IIA or IIB testicular cancer (see Patient care guidelines).[1,2] Following orchiectomy, patients receive radiation treatment to the retroperitoneal and ipsilateral pelvic lymph nodes. Survival rates are about 95 and 90% for patients with stage I and stage II disease, respectively.[4]

Although radiation therapy has few adverse effects, this type of treatment is associated with an increased incidence of peptic ulcers and late secondary malignancies.[2] In an attempt to reduce the risk of toxicity associated with treatment, the use of single agent (carboplatin) chemo-therapy is being investigated in Europe as an alternative to radiotherapy. This approach may also improve the patient's quality of life; however, relapse rates are unlikely to be lower.[2]

Surveillance an Option for Some

A surveillance policy is an option in patients with stage I disease (seminoma or nonseminoma) following orchiectomy.[1,2] Surveillance is an intensive follow-up schedule involving history, physical examination, blood tests and x-ray imaging, that requires a large amount of patient cooperation. About 20% of patients will relapse. Although surveillance is a standard treatment option for patients with nonseminoma, surveillance of patients with stage I seminoma is difficult. This is because of the long natural history of the disease (relapse can occur >5 years after presentation) and lack of markers for follow-up.[2,5] Therefore, in some countries such as the US, surveillance is not recommended for stage I seminoma and most patients are treated with radiotherapy.

RPLND More Common in the US

The other standard treatment of stage I nonseminomatous disease is RPLND. This treatment option is more frequently used in the US than in Europe (where patients usually undergo surveillance).[1,2] The major drawback to RPLND is that about 90% of patients will receive unnecessary anaesthesia and surgery. Other adverse effects of RPLND are loss of anterograde ejaculation and infertility. These occur in 90% of men undergoing traditional RPLND, but the incidence of these is much lower (about 10%) in men undergoing nerve-sparing RPLND.[6]

RPLND is also a treatment option for patients with stage II nonseminomatous tumour (see Patient care guidelines).

Chemotherapy for More Advanced Disease . . .

Cisplatin and etoposide (with or without bleomycin) is the current standard therapy for patients with testicular cancer requiring chemotherapy (i.e. patients with more advanced disease).[1]

Patients with stage II nonseminomatous cancer and those with more advanced disease but no nonpulmonary visceral metastases (good risk) are usually treated with 3 or 4 cycles of standard chemotherapy administered at 3-week intervals.[1] Cure rates may be as high as 90% in these good-risk patients.[1] However, this treatment is not as effective in poor-risk patients (those with nonpulmonary visceral metastases and high serum concentrations of tumour markers), with only 50 to 60% of these patients being cured. Thus, more effective treatment regimens are being investigated for these patients.

. . . And Relapse

Similar regimens are used in patients who relapse following other treatment interventions. Chemotherapy is effective in many of these patients.[1,2]

Chemotherapy Used as an Early Option?/ Although not currently recommended in the US, chemotherapy (2 cycles of a cisplatin-containing regimen) has been successfully used to treat patients with stage I nonseminomatous disease.[1]

Tumour Markers Useful for Follow-Up

Approximately 70 to 80% of germ-cell testicular tumours produce proteins that are relatively specific and measurable in serum (see table 2). Persistently elevated levels or reappearance of previously normalised values of alpha-fetoprotein and beta-human chorionic gonadotropin (HCG) following radical orchiectomy suggests continued production of the tumour markers by malignant cells.[2] Thus, serum tumour-marker measurement can be useful in the follow-up of treated testicular cancer and identifying relapse.[2]

Is residual Mass Malignant?

Following chemotherapy for metastatic nonseminomas, there may be residual masses in the lung, mediastinum or retroperitoneum. These masses may contain purely benign tissue (fibrosis or necrosis) or potentially malignant tissue (viable cancer cells or mature teratoma).[2]

It is important to decide whether the mass is benign or malignant and therefore whether resection is indicated. Resection of benign masses is of no therapeutic benefit, may adversely affect the patient and is costly, whereas resection of mature teratoma prevents regrowth of malignant cells. In addition, if cancer cells are present in the resected tissue, further chemotherapy is recommended.

Unfortunately, to date there are no easy noninvasive means of distinguishing between benign and malignant masses. Positron emission tomography scanning may be helpful, but the limited data currently available are contradictory.

How to Detect Disease Early

As with all cancers, it has been suggested that the earlier the detection of disease, the better the outcome. As a result, education and screening of the male population have been assessed.

Education Important . . .

Public education about the early signs and symptoms of testicular cancer may reduce the delay before presentation. Delay in presentation is often due to ignorance: patients may not know about testicular cancer or may think that the testicular mass has been caused by a small trauma.[2]

General practitioners should be educated on how to perform testicular examination correctly and to discriminate between abnormalities.[2] Clinicians should maintain a high degree of suspicion about the cause of swelling of the testis and should consider the possibility of malignancy. Patients with suspicious swelling of the testis unresponsive to antibacterials should be referred to a urologist for testicular ultrasound.

. . . But Screening Not Justified

Mortality rates are unlikely to decrease as a result of screening the male population because of the low incidence of the disease. Most of the examinations will be normal and nearly all abnormalities found will be nonmalignant.[2] Moreover, there does not appear to be a relationship between the stage of the disease, the value of serum tumour markers, the localisation of metastasis, and the size of the tumour; the cure rate for both limited and metastatic disease is high.

Testicular self-examination is of unproven benefit as this technique can result in identification of nonmalignant masses. Furthermore, there is no evidence that practising testicular self-examination results in the patient presenting any earlier.

References

  1. Bosl GJ, Motzer RJ. Testicular germ-cell cancer. New Engl J Med 1997 Jul 24; 337 (4): 242-53
  2. ten Bokkel Huinink D, Keizer HJ. Testicular cancer: screening, diagnostic and therapeutic considerations. Dis Manage Health Outcomes 1998 Aug; 4 (2): 57-72
  3. Einhorn LH, Richie JP, Schipley WU, et al, editors. 4th ed. Cancer of the testis. Philadelphia: Lippincott, 1993: 1126-51
  4. Devita VT, Hellman S, Rosenberg S, editors. Cancer: principles and practice of oncology. 5th ed. Philadelphia: JB Lippincott, 1997: 128: 2186-92
  5. Cullen M, James N. Adjuvant therapy for stage I testicular cancer. Tumour review. Cancer Treat Rev 1996; 22: 253-64
  6. Donohue JP, Thornhill JA, Foster RS, et al. Retroperitoneal lymphadenectomy for clinical stage A testis cancer (1965-1989): modifications of technique and impact on ejaculation. J Urol 1993; 149: 237-43