The Fellow on Call: The Heme/Onc Podcast

Episode 129: Testicular Cancer Series, Pt 3 – Disseminated and Relapsed/Refractory Disease
Release date: February 12, 2025
Hosts: Roanoke (A), Vivek (B), Dan (C)

Episode Overview

This episode continues the podcast’s deep dive into testicular cancer—focusing on disseminated (metastatic) and relapsed/refractory disease. The hosts highlight the rationale behind risk stratification, discuss historical and current frontline chemotherapy regimens, and review management strategies for relapse and salvage therapy, including the role of stem cell transplantation. The tone is conversational and collegial, with the hosts mixing core oncology concepts, landmark studies, and personal anecdotes to illuminate key decisions in testicular cancer care.

Key Discussion Points & Insights

1. Case Introduction and Risk Stratification (02:55 – 07:47)

Case summary: 28-year-old male with mixed non-seminomatous germ cell tumor (NSGCT), lung metastases, and rising post-orchiectomy tumor markers—intermediate risk disseminated disease.
Risk stratification:
- Determined by histology (seminoma vs. non-seminoma), location of metastases, and nadir post-orchiectomy tumor markers (AFP, beta-HCG, LDH).
- System developed by International Germ Cell Cancer Collaborative Group (IGCCCG) and published in JCO 1997, validated in 2021 with updated survival estimates.
- Memorable quote:
  “At a certain point, an acronym becomes less useful when you just keep adding letters and it was published in JCO in 1997.” – Dan (04:29)
Seminoma:
- Rare to have elevated tumor markers.
- Only “favorable” and “intermediate” risk stratifications; excellent prognosis overall.
- Extra-retroperitoneal/extra-pulmonary metastases = intermediate risk.
Non-seminoma:
- Uses specific cut-offs for tumor marker nadirs:
  - Intermediate: AFP >1,000, beta-HCG >5,000, LDH >1.5x ULN
  - Poor: AFP >10,000, beta-HCG >50,000, LDH >10x ULN
- Mnemonic: “1, 5, and 1.5” (06:23)

2. Modern First-line Regimens and Historical Context (07:47 – 15:50)

Standard regimen:
- BEP (Bleomycin, Etoposide, Cisplatin) x4 cycles for intermediate and poor-risk disease.
How BEP became standard:
- Historical PVB (Cisplatin, Vinblastine, Bleomycin) gave ~60% cure rates.
- Addition of Etoposide (from salvage setting success) led to BEP.
- Randomized trial in the 1980s: BEP = PVB in efficacy, but less myalgia/peripheral neuropathy.
- Quote:
  “So over the years, there were several prospective studies to optimize dosing... Let’s see if we can move [what works in salvage] up in sequence.” – Roanoke (09:12)
How BEP is given:
- Bleomycin weekly; Etoposide and Cisplatin days 1–5; repeat every 21 days (10:44)
VIP vs. BEP:
- VIP (Etoposide, Ifosfamide, Cisplatin) considered for primary mediastinal NSGCT due to higher ARDS risk with BEP post-resection (15% vs. 2.5%; 12:54).
- Otherwise, BEP remains preferred due to lower toxicity.
- Quote:
  “I will say, the VIP regimen we should not give to VIPs... It’s actually not that good in many cases.” – Vivek (11:25)

3. Treatment Duration and Choice for Favorable-Risk Disease (15:50 – 17:38)

De-escalation:
- BEP x3 cycles (9 weeks) = standard after 1989 RCT showed comparable efficacy to BEP x4 for favorable risk patients.
- EP (Etoposide/Cisplatin) x4 cycles is also reasonable, especially in patients with pulmonary contraindication to Bleomycin, based on indirect and retrospective data.
- Key point: There’s a lack of direct RCT comparison of BEP x3 vs. EP x4.
- Quote:
  “This led to a randomized study in favorable risk patients... It found no difference in outcomes between the two groups.” – Dan (16:23)

4. Management of Residual Masses (17:38 – 20:21)

Residual disease in seminoma:
- <3 cm: Observe with imaging; most necrotic.
- 3 cm: PET-CT; resect or biopsy if PET-avid.
- Quote:
  “Observation is very reasonable if tumors are less than 3 cm with serial imaging, as most are just tumor necrosis... For non-seminoma, however, requires resection for residual masses.” – Roanoke (18:56)
Residual disease in NSGCT:
- Must resect all residual masses after chemotherapy due to risk of teratoma (chemo-resistant).

5. Relapsed/Refractory Disease: Approach and Salvage Regimens (20:21 – 26:33)

Late, localized relapse (after two years):
- Surgery preferred.
Early or disseminated relapse (<2 years):
- Salvage chemotherapy is standard.
Salvage chemo options:
- TIP (Paclitaxel, Ifosfamide, Cisplatin) – ~60% durable CR in favorable population.
- VEIP (Vinblastine, Ifosfamide, Cisplatin) – ~25% durable CR; higher-risk population.
- Poor prognosis for relapsed primary mediastinal NSGCT.
- Quote:
  “The durable cure rate for relapsed primary mediastinal non-seminomatous germ cell tumors... was 0% in the relapse setting. So it really shows an area of unmet need.” – Vivek (21:41)

6. High-Dose Chemotherapy and Stem Cell Rescue (22:44 – 26:33)

Rationale:
- Testicular cancer is highly chemosensitive. If further chemo is needed, high doses (esp. of carboplatin) can be used, with stem cell rescue to recover marrow.
Two approaches:
- Indiana (Tandem autologous transplants): High-dose carboplatin + etoposide, two cycles with stem cell rescue; 63% CR in high-risk population.
- Memorial Sloan Kettering (Triplet transplant): One round of TAXOL/Ifosfamide, then three successive high-dose carboplatin + etoposide with rescue; ~50% CR.
- Quote:
  “So it’s a tandem autologous stem cell transplant, where they get two stem cell rescues. The durable CR rate was 63%... Primary mediastinal germ cell tumor patients could be cured.” – Vivek (24:41)
The TIGER trial:
- Ongoing international study directly comparing high-dose chemotherapy with transplantation to standard salvage regimens in second-line setting.
- Data anticipated soon; might redefine the salvage paradigm.

Notable Quotes & Moments

On risk stratification and management:
“Really, though, intermediate and poor risk are treated the same. So if you remember 1, 5, and 1.5... that’s really all you need to know if you were going to take a test on this and how to manage it.” – Dan (06:35)
On the progression of testicular cancer therapy:
“It’s pretty cool: something works well in the second line. Let’s see if we can move it up in sequence and see if we can improve outcomes.” – Roanoke (09:14)
On stem cell transplantation:
“This is the part where we talk about stem cell transplant, which seems absolutely ridiculous. And there were two groups that developed two different regimens for this... [explains two center approaches].” – Vivek (22:44)
On the lack of new breakthroughs:
“I feel like, based on our discussions today, it’s very evident that not a lot has changed in testicular cancer management in quite some time. So it’ll be, you know, almost 20 years since the last bits of data came out in this setting.” – Roanoke (27:01)
Memorable banter:
- The opening wine-tasting anecdote (01:00 – 02:13) brings levity before the deep dive.
- “I will say, the VIP regimen we should not give to VIPs. It’s actually not that good...” – Vivek (11:25)

Timestamps for Key Segments

[02:55] Case Summary: Intermediate risk metastatic NSGCT
[04:09] IGCCCG Risk Stratification overview
[07:47] Application to case; importance of tumor marker nadir and role of brain MRI
[08:46] Historical context: Emergence of BEP as standard chemotherapy
[12:54] When to use VIP over BEP (primary mediastinal NSGCT and reasons)
[15:50] Favorable risk: De-escalation to BEP x3 or EP x4 cycles
[17:38] Residual disease management: Seminoma vs. non-seminoma
[20:21] Approach to relapsed disease: Role of surgery and when to use salvage chemotherapy
[20:54] TIP and VEIP salvage regimens (durable CR rates, limitations)
[22:44] High-dose chemotherapy and stem cell transplant: Indiana and MSK approaches, upcoming TIGER trial

Summary Table: Management Overview

| Setting | First-line Regimen | Comments | |----------------------------------------|---------------------------------------|---------------------------------------------------------------------| | Favorable risk NSGCT | BEP x3 OR EP x4 | Both options reasonable; no direct RCT comparison. | | Intermediate/Poor risk NSGCT | BEP x4 | VIP x4 if primary mediastinal to reduce ARDS risk post-surgery. | | Residual mass post-chemotherapy | NSGCT: Resection mandatory | Seminoma: Observe or PET/resect for >3 cm masses. | | First relapse, late/localized (>2 yr) | Surgery | | | Early/disseminated relapse (<2 yr) | TIP or VEIP x4 | Limited prospective data, lower CR rates for mediastinal primaries. | | Further relapse/high-risk | High-dose chemo + autologous SCT | Indiana (tandem) or MSK (triplet); TIGER RCT comparing to salvage. |

Closing Thoughts

The episode provides a comprehensive, evidence-based approach to disseminated and relapsed/refractory testicular cancer—from frontline stratification and chemotherapy selection to salvage options and transplant. The hosts highlight the durability and limitations of current therapy, landmark studies guiding today's practice, and the high bar for cure even in advanced disease.

[26:33] Memorable summary:
“…This is an exquisitely chemosensitive disease. So if you can preserve some marrow in a freezer somewhere and then just give a myeloablative dose of chemotherapy, you have a good shot.” – Dan

[27:01] Forward-looking:
“Not a lot has changed in testicular cancer management in quite some time...so that'll be something to look forward to for sure.” – Roanoke

For in-depth visuals and referenced studies, see show notes linked in the episode.

The Fellow on Call: The Heme/Onc Podcast

Episode 129: Testicular Cancer Series, Pt 3 – Disseminated and Relapsed/Refractory Disease
Release date: February 12, 2025
Hosts: Roanoke (A), Vivek (B), Dan (C)

Episode Overview

Key Discussion Points & Insights

1. Case Introduction and Risk Stratification (02:55 – 07:47)

Case summary: 28-year-old male with mixed non-seminomatous germ cell tumor (NSGCT), lung metastases, and rising post-orchiectomy tumor markers—intermediate risk disseminated disease.
Risk stratification:
- Determined by histology (seminoma vs. non-seminoma), location of metastases, and nadir post-orchiectomy tumor markers (AFP, beta-HCG, LDH).
- System developed by International Germ Cell Cancer Collaborative Group (IGCCCG) and published in JCO 1997, validated in 2021 with updated survival estimates.
- Memorable quote:
  “At a certain point, an acronym becomes less useful when you just keep adding letters and it was published in JCO in 1997.” – Dan (04:29)
Seminoma:
- Rare to have elevated tumor markers.
- Only “favorable” and “intermediate” risk stratifications; excellent prognosis overall.
- Extra-retroperitoneal/extra-pulmonary metastases = intermediate risk.
Non-seminoma:
- Uses specific cut-offs for tumor marker nadirs:
  - Intermediate: AFP >1,000, beta-HCG >5,000, LDH >1.5x ULN
  - Poor: AFP >10,000, beta-HCG >50,000, LDH >10x ULN
- Mnemonic: “1, 5, and 1.5” (06:23)

2. Modern First-line Regimens and Historical Context (07:47 – 15:50)

Standard regimen:
- BEP (Bleomycin, Etoposide, Cisplatin) x4 cycles for intermediate and poor-risk disease.
How BEP became standard:
- Historical PVB (Cisplatin, Vinblastine, Bleomycin) gave ~60% cure rates.
- Addition of Etoposide (from salvage setting success) led to BEP.
- Randomized trial in the 1980s: BEP = PVB in efficacy, but less myalgia/peripheral neuropathy.
- Quote:
  “So over the years, there were several prospective studies to optimize dosing... Let’s see if we can move [what works in salvage] up in sequence.” – Roanoke (09:12)
How BEP is given:
- Bleomycin weekly; Etoposide and Cisplatin days 1–5; repeat every 21 days (10:44)
VIP vs. BEP:
- VIP (Etoposide, Ifosfamide, Cisplatin) considered for primary mediastinal NSGCT due to higher ARDS risk with BEP post-resection (15% vs. 2.5%; 12:54).
- Otherwise, BEP remains preferred due to lower toxicity.
- Quote:
  “I will say, the VIP regimen we should not give to VIPs... It’s actually not that good in many cases.” – Vivek (11:25)

3. Treatment Duration and Choice for Favorable-Risk Disease (15:50 – 17:38)

De-escalation:
- BEP x3 cycles (9 weeks) = standard after 1989 RCT showed comparable efficacy to BEP x4 for favorable risk patients.
- EP (Etoposide/Cisplatin) x4 cycles is also reasonable, especially in patients with pulmonary contraindication to Bleomycin, based on indirect and retrospective data.
- Key point: There’s a lack of direct RCT comparison of BEP x3 vs. EP x4.
- Quote:
  “This led to a randomized study in favorable risk patients... It found no difference in outcomes between the two groups.” – Dan (16:23)

4. Management of Residual Masses (17:38 – 20:21)

Residual disease in seminoma:
- <3 cm: Observe with imaging; most necrotic.
- 3 cm: PET-CT; resect or biopsy if PET-avid.
- Quote:
  “Observation is very reasonable if tumors are less than 3 cm with serial imaging, as most are just tumor necrosis... For non-seminoma, however, requires resection for residual masses.” – Roanoke (18:56)
Residual disease in NSGCT:
- Must resect all residual masses after chemotherapy due to risk of teratoma (chemo-resistant).

5. Relapsed/Refractory Disease: Approach and Salvage Regimens (20:21 – 26:33)

Late, localized relapse (after two years):
- Surgery preferred.
Early or disseminated relapse (<2 years):
- Salvage chemotherapy is standard.
Salvage chemo options:
- TIP (Paclitaxel, Ifosfamide, Cisplatin) – ~60% durable CR in favorable population.
- VEIP (Vinblastine, Ifosfamide, Cisplatin) – ~25% durable CR; higher-risk population.
- Poor prognosis for relapsed primary mediastinal NSGCT.
- Quote:
  “The durable cure rate for relapsed primary mediastinal non-seminomatous germ cell tumors... was 0% in the relapse setting. So it really shows an area of unmet need.” – Vivek (21:41)

6. High-Dose Chemotherapy and Stem Cell Rescue (22:44 – 26:33)

Rationale:
- Testicular cancer is highly chemosensitive. If further chemo is needed, high doses (esp. of carboplatin) can be used, with stem cell rescue to recover marrow.
Two approaches:
- Indiana (Tandem autologous transplants): High-dose carboplatin + etoposide, two cycles with stem cell rescue; 63% CR in high-risk population.
- Memorial Sloan Kettering (Triplet transplant): One round of TAXOL/Ifosfamide, then three successive high-dose carboplatin + etoposide with rescue; ~50% CR.
- Quote:
  “So it’s a tandem autologous stem cell transplant, where they get two stem cell rescues. The durable CR rate was 63%... Primary mediastinal germ cell tumor patients could be cured.” – Vivek (24:41)
The TIGER trial:
- Ongoing international study directly comparing high-dose chemotherapy with transplantation to standard salvage regimens in second-line setting.
- Data anticipated soon; might redefine the salvage paradigm.

Notable Quotes & Moments

On risk stratification and management:
“Really, though, intermediate and poor risk are treated the same. So if you remember 1, 5, and 1.5... that’s really all you need to know if you were going to take a test on this and how to manage it.” – Dan (06:35)
On the progression of testicular cancer therapy:
“It’s pretty cool: something works well in the second line. Let’s see if we can move it up in sequence and see if we can improve outcomes.” – Roanoke (09:14)
On stem cell transplantation:
“This is the part where we talk about stem cell transplant, which seems absolutely ridiculous. And there were two groups that developed two different regimens for this... [explains two center approaches].” – Vivek (22:44)
On the lack of new breakthroughs:
“I feel like, based on our discussions today, it’s very evident that not a lot has changed in testicular cancer management in quite some time. So it’ll be, you know, almost 20 years since the last bits of data came out in this setting.” – Roanoke (27:01)
Memorable banter:
- The opening wine-tasting anecdote (01:00 – 02:13) brings levity before the deep dive.
- “I will say, the VIP regimen we should not give to VIPs. It’s actually not that good...” – Vivek (11:25)

Timestamps for Key Segments

[02:55] Case Summary: Intermediate risk metastatic NSGCT
[04:09] IGCCCG Risk Stratification overview
[07:47] Application to case; importance of tumor marker nadir and role of brain MRI
[08:46] Historical context: Emergence of BEP as standard chemotherapy
[12:54] When to use VIP over BEP (primary mediastinal NSGCT and reasons)
[15:50] Favorable risk: De-escalation to BEP x3 or EP x4 cycles
[17:38] Residual disease management: Seminoma vs. non-seminoma
[20:21] Approach to relapsed disease: Role of surgery and when to use salvage chemotherapy
[20:54] TIP and VEIP salvage regimens (durable CR rates, limitations)
[22:44] High-dose chemotherapy and stem cell transplant: Indiana and MSK approaches, upcoming TIGER trial

Summary Table: Management Overview

Closing Thoughts

[27:01] Forward-looking:
“Not a lot has changed in testicular cancer management in quite some time...so that'll be something to look forward to for sure.” – Roanoke

For in-depth visuals and referenced studies, see show notes linked in the episode.

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Episode 129: Testicular Cancer Series, Pt 3 - Disseminated and relapsed/refractory disease

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Summary

The Fellow on Call: The Heme/Onc Podcast

Episode Overview

Key Discussion Points & Insights

1. Case Introduction and Risk Stratification (02:55 – 07:47)

2. Modern First-line Regimens and Historical Context (07:47 – 15:50)

3. Treatment Duration and Choice for Favorable-Risk Disease (15:50 – 17:38)

4. Management of Residual Masses (17:38 – 20:21)

5. Relapsed/Refractory Disease: Approach and Salvage Regimens (20:21 – 26:33)

6. High-Dose Chemotherapy and Stem Cell Rescue (22:44 – 26:33)

Notable Quotes & Moments

Timestamps for Key Segments

Summary Table: Management Overview

Closing Thoughts

Summary

The Fellow on Call: The Heme/Onc Podcast

Episode Overview

Key Discussion Points & Insights

1. Case Introduction and Risk Stratification (02:55 – 07:47)

2. Modern First-line Regimens and Historical Context (07:47 – 15:50)

3. Treatment Duration and Choice for Favorable-Risk Disease (15:50 – 17:38)

4. Management of Residual Masses (17:38 – 20:21)

5. Relapsed/Refractory Disease: Approach and Salvage Regimens (20:21 – 26:33)

6. High-Dose Chemotherapy and Stem Cell Rescue (22:44 – 26:33)

Notable Quotes & Moments

Timestamps for Key Segments

Summary Table: Management Overview

Closing Thoughts