The Fellow on Call: The Heme/Onc Podcast

Episode 128: Testicular Cancer Series, Pt 2 – Stage 1 and 2
Date: January 29, 2025
Hosts: Ronak (A), Vivek (B), Dan (C)

Brief Overview

This episode continues the series on testicular cancer, focusing on the management of Stage 1 and 2 disease. The hosts break down the evidence, treatment options, and shared decision-making strategies for both seminoma and non-seminomatous germ cell tumors (NSGCTs). With an emphasis on high cure rates and minimizing overtreatment, the hosts review key studies, practical guidelines, and evolving management paradigms vital for board exams and clinical care.

Key Discussion Points & Insights

1. Testicular Cancer: A Success Story

• Testicular cancer, particularly in early stages, has cure rates nearing 100%.

  “Testicular cancer management really is one of the success stories of oncology.” – Ronak [02:10]

2. Case Introduction: Stage 1 Seminoma ([03:01])

• 28-year-old with a classic presentation: scrotal mass, negative tumor markers, pure seminoma, no lymphovascular invasion, negative post-orchiectomy imaging.
• Staging Basics:
  • Stage 1: Localized to testis
  • Stage 2: Retroperitoneal nodes involved
  • Stage 3: Distant nodes or metastasis

Management Options:

• Active Surveillance: Preferred to minimize toxicity; involves frequent monitoring.
• Adjuvant Carboplatin (AUC 7, 1–2 cycles)
• Radiation: 20 Gy in 10 fractions to retroperitoneal nodes

Evidence:

• Surveillance Data:
  • 19% relapse rate at 15 years (Danish Registry)
  • 75% of relapses within 2 years; nearly 100% overall survival
  • Reference: European Urology, 2016 ([04:12])
• Non-Inferiority Trial (EORTC JCO 2011):
  • Carboplatin vs. radiation: 5% vs. 4% relapse rates at 5 years
  • Minimal absolute reduction in contralateral recurrence risk (from 0.01%) ([04:56])
• Risk Factors for Relapse:
  • Tumor size, rete testis invasion — but evidence is insufficient to guide risk-adapted therapy ([06:15])

“In general, we recommend active surveillance as standard of care to prevent long term toxicity from either chemotherapy or radiation.” – Dan [06:43]

3. Stage 1 Non-Seminomatous Germ Cell Tumor (NSGCT) ([08:32])

• Critical: Ensure tumor markers normalize post-orchiectomy. If not, repeat imaging and consider as disseminated disease.
• Management Options:
  • Active Surveillance
  • BEP Chemotherapy (1 cycle)
  • Retroperitoneal Lymph Node Dissection (RPLND)

Key Data:

• 30% relapse rate on surveillance; 10-year disease-specific survival 96% (Danish Registry, 15-year median follow-up)
• Treatment Efficacy:
  • BEP x1 vs. RPLND: 99% vs. 92% recurrence-free survival at 2 years (German trial, JCO 2008)
  • No overall survival difference
  • Toxicity risks: BEP (bleomycin pulmonary toxicity, neuropathy), RPLND (ejaculatory dysfunction ~10%)

Clinical Nuance:

• Risk factors (embryonal predominance, LVI) not strong enough to change management plan.
• Surveillance preferred for reliably compliant patients, as ~75% avoid further therapy ([10:50])

“Doing active surveillance sometimes scares people because we’re doing nothing, but in reality, we are doing something.” – Ronak [13:33]

4. Stage 2 Disease: Seminoma vs. Non-Seminoma ([14:01])

Stage 2 Seminoma:

• Node Size Guides Therapy:

  • <2 cm: Radiation or chemotherapy (either is reasonable)
  • ≥2 cm: Chemotherapy required (BEP x3 or EP x4)

• Radiation Dose:

  • 30 Gy total over several weeks

• Chemotherapy Regimen:

  • BEP = Bleomycin, Etoposide, Cisplatin
  • EP = Etoposide, Cisplatin (avoids bleomycin)

• Cisplatin is standard (better than carboplatin per JCO 1993)

• Relapse Data:

  • <2 cm nodes: No difference between chemo and radiation
  • ≥2 cm: 5% relapse with chemo vs. 12% with radiation (Annals of Oncology 2015)
  • Secondary malignancy: 4% radiation, 2% chemotherapy

Emerging Evidence:

• SEMS trial (JCO 2023): Single-arm phase II studied RPLND in selected seminoma stage 2 (1–3 cm nodes)
  • Recurrence rate 22%, all salvaged with chemo ([16:30])

Stage 2 NSGCT:

• Key: Radiation not effective

• Node involvement and size determine if RPLND or chemotherapy

  • ≥2 cm node, or >5 nodes: BEP x3 or EP x4
  • <2 cm and ≤5 nodes: RPLND preferred, chemotherapy is an option
  • Pathologic staging after RPLND guides adjuvant therapy ([18:45])

• Historical Studies:

  • RPLND was standard until adjuvant chemo (cisplatin, vinblastine, etoposide) allowed selective salvage at relapse (reducing overtreatment)
  • NCCN: Adjuvant chemo for pathologic nodes >2 cm or >5 nodes (EP x2 cycles), though active surveillance is emerging as viable

“Radiation is never really an option. In non seminoma, the cutoff of 2 cm for stage 2 still applies.” – Dan [18:51]

5. Recent Data & Shifting Paradigms ([22:04])

• University of Indiana Prospective Data (JCO 2022):
  • 97 stage 2 NSGCT patients post-RPLND
  • No difference in relapse-free survival with/without adjuvant chemo for N1/N2
  • 5-year relapse-free survival ~85% for N2 disease
  • Suggests surveillance may be preferable over routine adjuvant chemo (EP x2)

“Hey, maybe we should reconsider that. But the NCCN guidelines do say that chemotherapy with EP times two cycles is a preferred management option.” – Vivek [23:28]

6. Resection of Residual Tumors (NSGCT only) ([24:16])

• Any residual mass after chemotherapy must be surgically resected due to risk of teratoma (chemo- and radio-resistant)

Notable Quotes & Memorable Moments

• Host Ronak's resilience:

  “I've done this podcast now with a bleeding hand, with COVID twice, and I'm sure some other injury along the way. But now I can say that my speech may also be impaired because of some dental work.” – Ronak [01:15]

• Classic Oncologist Humor:

  “Dan is not allowed to record any podcast when he's on vacation… that was ridiculous.” – Vivek [01:44]
  “I'm just honored that you've spent the time here with us and not taken this opportunity to get a face tattoo while your face is still numb.” – Dan [01:53]

• Guiding Principle:

  “The name of the game in a lot of cases because of those high cure rates is trying to spare people the effects of therapy.” – Dan [25:34]

• Wise Reminder:

  “Platinum agents do increase the risk of cardiovascular toxicity. Etoposide. These are not easy treatments. And so we should really think about whether our patient needs these treatments or if we're just over treating them.” – Vivek [26:12]

Timestamps for Important Segments

• [03:01] – Case presentation: Stage 1 seminoma
• [04:12] – Surveillance and long-term outcomes for Stage 1 seminoma
• [07:52] – Options & evidence for Stage 1 NSGCT
• [14:01] – Transition to Stage 2 disease: Principles and practical differences
• [16:30] – New study: SEMS trial on RPLND in early metastatic seminoma
• [18:45] – Stage 2 NSGCT treatment pathways and historical perspective
• [22:04] – University of Indiana data: Surveillance vs. adjuvant chemo for N2 disease
• [24:16] – Resection of residual disease in NSGCT after chemotherapy
• [25:28] – Final thoughts, summarizing principle of minimizing therapy toxicity

Key Takeaways

• Active surveillance is preferred for most stage 1 testicular cancers (seminoma or NSGCT), provided reliable follow-up is possible.
• Both radiation and chemotherapy are highly effective for stage 1 seminoma, but given toxicities/long-term risks, overtreatment should be avoided.
• For stage 2, node size and tumor type drive management: Seminoma (radiation/chemo for <2 cm, chemo for ≥2 cm), NSGCT (RPLND for small/few nodes, chemo otherwise).
• Recent data support expanding surveillance, even in patients with higher-volume nodal disease, challenging older standards of reflexive adjuvant therapy.
• All residual masses after treatment for NSGCT must be surgically addressed due to the possibility of teratoma or residual viable cancer.

For Clinical Practice & Exams

• Always assess tumor markers post-orchiectomy and ensure normalization before final staging and management.
• Know cutoff points for lymph node size and number for deciding between active surveillance, RPLND, chemo, and radiation.
• Be familiar with major studies and trial results referenced in the guidelines.
• Prioritize sparing young patients from unnecessary toxicities whenever possible.

[Skip to 04:12 for algorithms on active surveillance and relapse rates.
Jump to 14:01 for a deep-dive on Stage 2 decision-making and treatment rationales.
Check show notes for referenced studies and flowcharts.]