Case Report
The Role of Salvage Hemiscrotectomy in Testicular Cancer After Scrotal Contamination: A Case Report and Literature Review Reshma Khetpal,1 Matthew D. Katz,2 Michelle Cox,3 Konstantinos Arnaoutakis1 Clinical Practice Points A 51-year-old man had radical inguinal orchiectomy
Alpha fetoprotein levels normalized after left hemi-
associated with spontaneous tumor rupture for a suspected testicular cancer with normal serum alpha fetoprotein (AFP) levels. He was found to have stage IIB seminoma and then presented with increasing AFP levels after orchiectomy while receiving platinum based chemotherapy.
scrotectomy and proximal spermatic cord stump repeat resection. The patient remained disease-free after 1 year of follow-up. This case addresses the concept of appropriate salvage therapy after scrotal contamination.
Clinical Genitourinary Cancer, Vol. 12, No. 3, e103-5 ª 2014 Published by Elsevier Inc. Keywords: Adjuvant chemotherapy, Blood-testis barrier, Germ cell testicular cancer, Radical inguinal orchiectomy, Scrotal violation, Tumor spillage
Introduction Ninety-five percent of testicular cancers are germ cell tumors with a 5-year survival rate of nearly 95%. Sophisticated surgical techniques, use of tumor markers to guide treatment options, and platinum-based chemotherapy have led to these significantly improved outcomes. Radical inguinal orchiectomy is recommended for suspected testicular cancers to establish the histologic diagnosis in addition to providing definitive treatment. However, tumor spillage at the time of radical orchiectomy (spontaneous vs. iatrogenic) or scrotal violation in the form of transcrotal incision or biopsy can lead to suboptimal local tumor control resulting possibly in higher rates of recurrence, local and distant. In such cases, optimal strategy for salvage therapy is not well defined because of lack of prospective randomized data. Here, in addition to literature review, we report the case of a 51-year-old man who presented with an increasing alpha fetoprotein (AFP) level after radical inguinal orchiectomy despite treatment with the appropriate 1
Department Department 3 Department University of 2
of Hematology Oncology of Urology of Pathology Arkansas for Medical Sciences, Little Rock, AR
Submitted: Oct 21, 2013; Revised: Nov 30, 2013; Accepted: Dec 23, 2013; Epub: Dec 27, 2013 Address for correspondence: Reshma Khetpal, MD, UAMS, 2512 Riverfront Dr, Condo 3, Little Rock, AR 72202 E-mail contact: [email protected]
1558-7673/$ - see frontmatter ª 2014 Published by Elsevier Inc. http://dx.doi.org/10.1016/j.clgc.2013.12.004
chemotherapy regimen, who was salvaged successfully with hemiscrotectomy and proximal spermatic cord repeated resection.
Case Presentation A 51-year-old African American man presented with left testicular swelling. He had a computed tomography (CT) scan of the abdomen and pelvis, which showed the left testicular mass and enlarged left periaortic lymph nodes (Fig. 1). The largest was 4.1 cm in diameter. He had a chest x-ray which was normal. Lactate dehydrogenase (LDH) was elevated at 323 IU/L (normal range, 100-248 IU/L). Beta human chorionic gonadotrophin (hCG) was 5.4 mIU/mL (normal range, 0.0-9.9 mIU/mL). AFP was 8.7 ng/mL (normal range, 0.0-9.0 ng/mL). He also had a testicular ultrasound which showed marked enlargement and heterogeneity of the left testicle with microlithiasis. The right testicle was normal. The patient then underwent a left radical orchiectomy. Pathology revealed a 4.6-cm pure seminoma with hemorrhage and necrosis. The tumor extended into the spermatic cord and was present at the spermatic cord margin. There was rupture of the tunica albuginea in an area involved with seminoma and an adherent tumor was present on the inked capsular surface of the testicle. Angiolymphatic invasion was present. There was also peritesticular tissue excised on the left side which was involved with seminoma. The patient’s findings correlated with a pT3 local stage and a clinical stage of IIB. Three weeks after surgery his beta hCG was 12.6 mIU/mL, AFP 6.4 ng/mL, and LDH was 148 IU/L. A repeat surgery was not
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Salvage Hemiscrotectomy After Scrotal Contamination Figure 1 Computed Tomography Scan of the Abdomen With Enlarged Left Periaortic Lymph Nodes Before Orchiectomy
Figure 3 Microscopic Examination of the Hemiscrotectomy Specimen Showed Residual Necrotic Tumor, but no Viable Neoplasm was Present. The Necrotic Tumor Appears as Brightly Eosinophilic Sheets of “Ghost” Tumor Cells With Faint Outlines of the Individual Neoplastic Cells Visible. The Necrotic Tumor Retained Positive Staining for CD117 and Placental Alkaline Phosphatase Immunohistochemical Stains
recommended at this time. Three cycles of BEP (bleomycin, etoposide, cisplatin) chemotherapy every 3 weeks was recommended. We proceeded with BEP: bleomycin 30 U on day (d)2, d9, and d16, etoposide 100 mg/m2 on d1 to 5, and cisplatin 20 mg/m2 on d1 to 5 for every cycle. After completion of the first cycle, his AFP started increasing and continued to increase to 149.8 ng/mL after the completion of 3 cycles of chemotherapy. His beta hCG and LDH were within the normal range. His CT scan of chest/ abdomen/pelvis was essentially normal (Fig. 2). Positron emission tomography/CT and brain magnetic resonance imaging scans were
also essentially normal. He underwent left groin exploration with left hemiscrotectomy. Final pathology showed necrotic seminoma present with no viable tumor cells identified and a negative proximal margin (Fig. 3). His AFP was 9.4 ng/mL and 6.9 ng/mL after 1 month and 3 months after the hemiscrotectomy, respectively. He was lost to follow-up at that point for a year. After re-establishing care, he was asymptomatic and his tumor markers were normal on subsequent yearly follow-up visits.
Discussion Figure 2 Computed Tomography Scan of the Abdomen With no Significantly Enlarged Lymph Nodes After Chemotherapy
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Radical inguinal orchiectomy has been recommended as standard of care in the initial management of testicular cancer for nearly 100 years.1 To prevent tumor spillage, exploration is through an inguinal incision which makes en bloc removal of the spermatic cord with a testis enclosed within the intact tunics, technically feasible after early ligation of the spermatic cord.2 Scrotal violation can occur as a consequence of any scrotal or inguinal intervention that leads to tumor spillage which then can result in local seeding, and potentially harbors the route of lymphatic drainage.3 Some of the surgical procedures that could lead to scrotal violation include transcrotal biopsy and transcrotal orchiectomy. In the era of radical inguinal orchiectomy, scrotal violation is still common and in one study the incidence rate was 17% (n ¼ 13).3 Scrotal contamination can occur secondary to scrotal violation leading to tumor spillage resulting from rupture of tumor during its delivery through a suboptimal incision or from spontaneous tumor rupture and spillage as evident in our case. Scrotal contamination and tumor spillage might result in higher rates of local recurrence, an observation based on the historical study conducted in 1925 which reported a local recurrence rate of 24% in patients with testicular cancer after transcrotal orchiectomy.4 A retrospective metaanalysis revealed statistically significant differences in the local
Reshma Khetpal et al recurrence rate among the scrotal violation and inguinal group studies, although no statistical differences in distant recurrence or survival rates in all groups was found.5 However, another report indicates possibly also an increased risk of distant disease.3 Besides guiding treatment strategies, serum AFP and beta hCG are the most sensitive and specific markers for initial diagnosis, staging, predicting recurrence, and prognosis of testicular germ cell tumors.6 Nearly 85% of patients with disseminated testicular germ cell tumors will have increased hCG and/or AFP levels.6 AFP is not secreted by seminoma, so serum elevation of AFP denotes the presence of nonseminomatous elements even if histology is positive for pure seminoma, similar to the patient in our case report. Laboratory error, hepatocellular cancer, and cirrhosis should be considered in differential diagnosis because a false increase level of AFP is very rare.6 Different local treatment options for scrotal violation have been proposed like inguinal node dissection, pelvic lymphadenectomy, scrotal irradiation, and hemiscrotectomy.7-9 These procedures could be potentially disfiguring and disturbing for the patient and have an associated morbidity. Authors from one retrospective study concluded that adjuvant hemiscrotectomy alone does not completely eliminate the risk of local recurrences and it is argued that it might be unnecessary if chemotherapy is given. A critical aspect of local recurrence appears to be the presence of the residual tumor in the scrotectomy specimen.2 In our case study, chemotherapy, which was indicated for his stage of disease, was given to the patient but it appeared to be inadequate to provide the local control presumptively due to the bloodetestis barrier.10 There is a possibility that certain organ sites such as the hemiscrotum and the cord remnant are less sensitive to systemic therapy. These are the sites that should also be considered as sites of relapse in cases of increasing levels of tumor markers with a negative radiographic work-up, especially when other sanctuary sites such as the brain or the contralateral testis are excluded as sites of relapse. Our patients’ serum AFP started increasing during chemotherapy with no radiographic evidence of recurrence, thereby warranting a salvage local therapy in the form of hemiscrotectomy leading to normalization of his serum AFP level with no evidence of disease after 1 year of follow-up. Before the hemiscrotectomy, a discussion among the medical team regarding further second line chemotherapy and the decision was made to treat possible distant resistant disease. However, it was believed that local control was more important because of unique features of his disease (positive margins and tumor spillage).
Based on our literature review, the role of hemiscrotectomy alone is debatable because hemiscrotectomy does not eliminate the risk of relapse. In addition, chemotherapy alone after scrotal contamination decreases the risk of recurrence substantially and the patient might not need hemiscrotectomy. However, these conclusions are based on retrospective studies, which always includes some inherent bias.2,5 Contrary to these observations, our patient needed chemotherapy followed by salvage hemiscrotectomy to render him disease-free. We did not expose him to more salvage chemotherapy considering the toxicities with systemic therapy in addition to resistance due to possible bloodetestis barrier and instead adopted a local approach.
Conclusion Local treatment in cases of gross tumor spillage, especially when positive margins are present, is probably necessary and chemotherapy alone is not a sufficient treatment. Because there are no randomized prospective trials conducted for patients with scrotal contamination and such prospective studies are obviously unlikely to be undertaken, a patient-directed approach is the most prudent strategy.
Disclosure The authors have stated that they have no conflicts of interest.
References 1. Kober GM. Sarcoma of the testicle, conclusions based upon 114 cases. Am J Med 1899; 117:149-65. 2. Leibovitch I, Baniel J, Foster RS, et al. The clinical implications of procedural deviations during orchiectomy for nonseminomatous testis cancer. J Urol 1995; 154:935-9. 3. Aki FT, Bilen CY, Tekin MI, Ozen H. Is scrotal violation per se a risk factor for local relapse and metastases in stage I nonseminomatous testicular cancer? Urology 2000; 56:459-62. 4. Dean AL Jr. The treatment of teratoid tumors of the testes with radium and the x-ray. J Urol 1925; 13:149-65. 5. Capelouto CC, Clark PE, Ransil BJ, Loughlin KR. A review of scrotal violation in testicular cancer: is adjuvant local therapy necessary? J Urol 1995; 153: 981-5. 6. Nichols CR, Timmerman R, Foster RS, et al. Neoplasms of the testis. In: Bast RC Jr, Kufe DW, Pollock RE, et al, eds. Holland-Frei Cancer Medicine, 5th edition. Hamilton, ON: BC Decker; 2000; 1596-621. 7. Markland C, Kedia K, Fraley EE. Inadequate orchiectomy in patients with testicular tumors. JAMA 1984; 224:1025-6. 8. Zagars GK, Babaian RJ. Stage I testicular seminoma: rationale for postorchiectomy radiation therapy. Int J Radiat Oncol Biol Phys 1987; 13:155-62. 9. Boileau MA, Steers WD. Testis tumor: the clinical significance of the tumorcontaminated scrotum. J Urol 1984; 132:51-4. 10. Dave DS, Leppert JT, Rajfer J. Is the testis a chemo-privileged site? Is there a blood-testis barrier? Rev Urol 2007; 9:28-32.
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The Role of Salvage Hemiscrotectomy in Testicular Cancer After Scrotal Contamination: A Case Report and Literature Review Reshma Khetpal,1 Matthew D. Katz,2 Michelle Cox,3 Konstantinos Arnaoutakis1 Clinical Practice Points A 51-year-old man had radical inguinal orchiectomy
Alpha fetoprotein levels normalized after left hemi-
associated with spontaneous tumor rupture for a suspected testicular cancer with normal serum alpha fetoprotein (AFP) levels. He was found to have stage IIB seminoma and then presented with increasing AFP levels after orchiectomy while receiving platinum based chemotherapy.
scrotectomy and proximal spermatic cord stump repeat resection. The patient remained disease-free after 1 year of follow-up. This case addresses the concept of appropriate salvage therapy after scrotal contamination.
Clinical Genitourinary Cancer, Vol. 12, No. 3, e103-5 ª 2014 Published by Elsevier Inc. Keywords: Adjuvant chemotherapy, Blood-testis barrier, Germ cell testicular cancer, Radical inguinal orchiectomy, Scrotal violation, Tumor spillage
Introduction Ninety-five percent of testicular cancers are germ cell tumors with a 5-year survival rate of nearly 95%. Sophisticated surgical techniques, use of tumor markers to guide treatment options, and platinum-based chemotherapy have led to these significantly improved outcomes. Radical inguinal orchiectomy is recommended for suspected testicular cancers to establish the histologic diagnosis in addition to providing definitive treatment. However, tumor spillage at the time of radical orchiectomy (spontaneous vs. iatrogenic) or scrotal violation in the form of transcrotal incision or biopsy can lead to suboptimal local tumor control resulting possibly in higher rates of recurrence, local and distant. In such cases, optimal strategy for salvage therapy is not well defined because of lack of prospective randomized data. Here, in addition to literature review, we report the case of a 51-year-old man who presented with an increasing alpha fetoprotein (AFP) level after radical inguinal orchiectomy despite treatment with the appropriate 1
Department Department 3 Department University of 2
of Hematology Oncology of Urology of Pathology Arkansas for Medical Sciences, Little Rock, AR
Submitted: Oct 21, 2013; Revised: Nov 30, 2013; Accepted: Dec 23, 2013; Epub: Dec 27, 2013 Address for correspondence: Reshma Khetpal, MD, UAMS, 2512 Riverfront Dr, Condo 3, Little Rock, AR 72202 E-mail contact: [email protected]
1558-7673/$ - see frontmatter ª 2014 Published by Elsevier Inc. http://dx.doi.org/10.1016/j.clgc.2013.12.004
chemotherapy regimen, who was salvaged successfully with hemiscrotectomy and proximal spermatic cord repeated resection.
Case Presentation A 51-year-old African American man presented with left testicular swelling. He had a computed tomography (CT) scan of the abdomen and pelvis, which showed the left testicular mass and enlarged left periaortic lymph nodes (Fig. 1). The largest was 4.1 cm in diameter. He had a chest x-ray which was normal. Lactate dehydrogenase (LDH) was elevated at 323 IU/L (normal range, 100-248 IU/L). Beta human chorionic gonadotrophin (hCG) was 5.4 mIU/mL (normal range, 0.0-9.9 mIU/mL). AFP was 8.7 ng/mL (normal range, 0.0-9.0 ng/mL). He also had a testicular ultrasound which showed marked enlargement and heterogeneity of the left testicle with microlithiasis. The right testicle was normal. The patient then underwent a left radical orchiectomy. Pathology revealed a 4.6-cm pure seminoma with hemorrhage and necrosis. The tumor extended into the spermatic cord and was present at the spermatic cord margin. There was rupture of the tunica albuginea in an area involved with seminoma and an adherent tumor was present on the inked capsular surface of the testicle. Angiolymphatic invasion was present. There was also peritesticular tissue excised on the left side which was involved with seminoma. The patient’s findings correlated with a pT3 local stage and a clinical stage of IIB. Three weeks after surgery his beta hCG was 12.6 mIU/mL, AFP 6.4 ng/mL, and LDH was 148 IU/L. A repeat surgery was not
Clinical Genitourinary Cancer June 2014
- e103
Salvage Hemiscrotectomy After Scrotal Contamination Figure 1 Computed Tomography Scan of the Abdomen With Enlarged Left Periaortic Lymph Nodes Before Orchiectomy
Figure 3 Microscopic Examination of the Hemiscrotectomy Specimen Showed Residual Necrotic Tumor, but no Viable Neoplasm was Present. The Necrotic Tumor Appears as Brightly Eosinophilic Sheets of “Ghost” Tumor Cells With Faint Outlines of the Individual Neoplastic Cells Visible. The Necrotic Tumor Retained Positive Staining for CD117 and Placental Alkaline Phosphatase Immunohistochemical Stains
recommended at this time. Three cycles of BEP (bleomycin, etoposide, cisplatin) chemotherapy every 3 weeks was recommended. We proceeded with BEP: bleomycin 30 U on day (d)2, d9, and d16, etoposide 100 mg/m2 on d1 to 5, and cisplatin 20 mg/m2 on d1 to 5 for every cycle. After completion of the first cycle, his AFP started increasing and continued to increase to 149.8 ng/mL after the completion of 3 cycles of chemotherapy. His beta hCG and LDH were within the normal range. His CT scan of chest/ abdomen/pelvis was essentially normal (Fig. 2). Positron emission tomography/CT and brain magnetic resonance imaging scans were
also essentially normal. He underwent left groin exploration with left hemiscrotectomy. Final pathology showed necrotic seminoma present with no viable tumor cells identified and a negative proximal margin (Fig. 3). His AFP was 9.4 ng/mL and 6.9 ng/mL after 1 month and 3 months after the hemiscrotectomy, respectively. He was lost to follow-up at that point for a year. After re-establishing care, he was asymptomatic and his tumor markers were normal on subsequent yearly follow-up visits.
Discussion Figure 2 Computed Tomography Scan of the Abdomen With no Significantly Enlarged Lymph Nodes After Chemotherapy
e104
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Clinical Genitourinary Cancer June 2014
Radical inguinal orchiectomy has been recommended as standard of care in the initial management of testicular cancer for nearly 100 years.1 To prevent tumor spillage, exploration is through an inguinal incision which makes en bloc removal of the spermatic cord with a testis enclosed within the intact tunics, technically feasible after early ligation of the spermatic cord.2 Scrotal violation can occur as a consequence of any scrotal or inguinal intervention that leads to tumor spillage which then can result in local seeding, and potentially harbors the route of lymphatic drainage.3 Some of the surgical procedures that could lead to scrotal violation include transcrotal biopsy and transcrotal orchiectomy. In the era of radical inguinal orchiectomy, scrotal violation is still common and in one study the incidence rate was 17% (n ¼ 13).3 Scrotal contamination can occur secondary to scrotal violation leading to tumor spillage resulting from rupture of tumor during its delivery through a suboptimal incision or from spontaneous tumor rupture and spillage as evident in our case. Scrotal contamination and tumor spillage might result in higher rates of local recurrence, an observation based on the historical study conducted in 1925 which reported a local recurrence rate of 24% in patients with testicular cancer after transcrotal orchiectomy.4 A retrospective metaanalysis revealed statistically significant differences in the local
Reshma Khetpal et al recurrence rate among the scrotal violation and inguinal group studies, although no statistical differences in distant recurrence or survival rates in all groups was found.5 However, another report indicates possibly also an increased risk of distant disease.3 Besides guiding treatment strategies, serum AFP and beta hCG are the most sensitive and specific markers for initial diagnosis, staging, predicting recurrence, and prognosis of testicular germ cell tumors.6 Nearly 85% of patients with disseminated testicular germ cell tumors will have increased hCG and/or AFP levels.6 AFP is not secreted by seminoma, so serum elevation of AFP denotes the presence of nonseminomatous elements even if histology is positive for pure seminoma, similar to the patient in our case report. Laboratory error, hepatocellular cancer, and cirrhosis should be considered in differential diagnosis because a false increase level of AFP is very rare.6 Different local treatment options for scrotal violation have been proposed like inguinal node dissection, pelvic lymphadenectomy, scrotal irradiation, and hemiscrotectomy.7-9 These procedures could be potentially disfiguring and disturbing for the patient and have an associated morbidity. Authors from one retrospective study concluded that adjuvant hemiscrotectomy alone does not completely eliminate the risk of local recurrences and it is argued that it might be unnecessary if chemotherapy is given. A critical aspect of local recurrence appears to be the presence of the residual tumor in the scrotectomy specimen.2 In our case study, chemotherapy, which was indicated for his stage of disease, was given to the patient but it appeared to be inadequate to provide the local control presumptively due to the bloodetestis barrier.10 There is a possibility that certain organ sites such as the hemiscrotum and the cord remnant are less sensitive to systemic therapy. These are the sites that should also be considered as sites of relapse in cases of increasing levels of tumor markers with a negative radiographic work-up, especially when other sanctuary sites such as the brain or the contralateral testis are excluded as sites of relapse. Our patients’ serum AFP started increasing during chemotherapy with no radiographic evidence of recurrence, thereby warranting a salvage local therapy in the form of hemiscrotectomy leading to normalization of his serum AFP level with no evidence of disease after 1 year of follow-up. Before the hemiscrotectomy, a discussion among the medical team regarding further second line chemotherapy and the decision was made to treat possible distant resistant disease. However, it was believed that local control was more important because of unique features of his disease (positive margins and tumor spillage).
Based on our literature review, the role of hemiscrotectomy alone is debatable because hemiscrotectomy does not eliminate the risk of relapse. In addition, chemotherapy alone after scrotal contamination decreases the risk of recurrence substantially and the patient might not need hemiscrotectomy. However, these conclusions are based on retrospective studies, which always includes some inherent bias.2,5 Contrary to these observations, our patient needed chemotherapy followed by salvage hemiscrotectomy to render him disease-free. We did not expose him to more salvage chemotherapy considering the toxicities with systemic therapy in addition to resistance due to possible bloodetestis barrier and instead adopted a local approach.
Conclusion Local treatment in cases of gross tumor spillage, especially when positive margins are present, is probably necessary and chemotherapy alone is not a sufficient treatment. Because there are no randomized prospective trials conducted for patients with scrotal contamination and such prospective studies are obviously unlikely to be undertaken, a patient-directed approach is the most prudent strategy.
Disclosure The authors have stated that they have no conflicts of interest.
References 1. Kober GM. Sarcoma of the testicle, conclusions based upon 114 cases. Am J Med 1899; 117:149-65. 2. Leibovitch I, Baniel J, Foster RS, et al. The clinical implications of procedural deviations during orchiectomy for nonseminomatous testis cancer. J Urol 1995; 154:935-9. 3. Aki FT, Bilen CY, Tekin MI, Ozen H. Is scrotal violation per se a risk factor for local relapse and metastases in stage I nonseminomatous testicular cancer? Urology 2000; 56:459-62. 4. Dean AL Jr. The treatment of teratoid tumors of the testes with radium and the x-ray. J Urol 1925; 13:149-65. 5. Capelouto CC, Clark PE, Ransil BJ, Loughlin KR. A review of scrotal violation in testicular cancer: is adjuvant local therapy necessary? J Urol 1995; 153: 981-5. 6. Nichols CR, Timmerman R, Foster RS, et al. Neoplasms of the testis. In: Bast RC Jr, Kufe DW, Pollock RE, et al, eds. Holland-Frei Cancer Medicine, 5th edition. Hamilton, ON: BC Decker; 2000; 1596-621. 7. Markland C, Kedia K, Fraley EE. Inadequate orchiectomy in patients with testicular tumors. JAMA 1984; 224:1025-6. 8. Zagars GK, Babaian RJ. Stage I testicular seminoma: rationale for postorchiectomy radiation therapy. Int J Radiat Oncol Biol Phys 1987; 13:155-62. 9. Boileau MA, Steers WD. Testis tumor: the clinical significance of the tumorcontaminated scrotum. J Urol 1984; 132:51-4. 10. Dave DS, Leppert JT, Rajfer J. Is the testis a chemo-privileged site? Is there a blood-testis barrier? Rev Urol 2007; 9:28-32.
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