Radiation Oncology/Penis
Appearance
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Epidemiology
[edit | edit source]- US - 1500 cases annually, <2% of GU cancers
- Incidence is dramatically higher in the developing world
- US - 0.2 / 100,000
- Bombay - 1.8 / 100,000 (10-fold increase)
- Sao Paolo - 28 / 100,000 (another 15-fold increase)
- Uganda - most common male malignancy
- Risk factors
- Phimosis - narrowed opening of the prepuce resulting in non-retractile foreskin. Odds ratio 10
- Smegma
- Circumcision - in Uganda, circumcised tribes 0.5 vs. uncircumcised tribes 2.9 / 100,000
- HPV - primarily 16, prevalence 30-70%
- Age - meadian age at diagnosis in US is 60
- Tobacco
- Premalignant lesions
HPV16
- Amsterdam; 2007 PMID 17925550 -- "Human papillomavirus-16 is the predominant type etiologically involved in penile squamous cell carcinoma." (Heideman DA, J Clin Oncol. 2007 Oct 10;25(29):4550-6.)
- Molecular and serologic analysis of HPV on 83 penile SCC vs. age-matched controls
- Outcome: HPV DNA in 55% samples - HPV16 75%. HPV18 and HPV6 seropositivity associated, but not by molecular findings
- Conclusion: HPV16 is the main HPV type associated with penile SCC
Histology
[edit | edit source]- Squamous cell (95%)
- Papillary
- Basaloid
- Warty
- Sarcomatoid
- Verrucous (up to 25%)
- Melanoma
- Lymphoma
- Basal cell
- Urethral
Grading
[edit | edit source]Differentiation grading systems for SCC
- Broder's grading system
- I - well differentiated with keratinization, prominent intercellular bridges, and keratin pearls
- II to III - greater nuclear atypia, increased mitotic activity, and decreased keratin pearls
- IV - deeply invasive, marked nuclear pleomorphism, nuclear mitoses, necrosis, lymphatic and perineural invasion, and no keratin pearls
- Maiche’s system score
- currently seems to be the most suitable staging system [1]
Staging
[edit | edit source]AJCC Current Staging
[edit | edit source]AJCC 7th Edition (2009)
Primary Tumor:
- Tis - carcinoma in situ
- Ta - non-invasive verrucous carcinoma
- T1
- T1a - invades subepithelial connective tissue without lymphovascular invasion and is not poorly differentiated (i.e. tumor is grade 1-2 of 4)
- T1b - invades subepithelial connective tissue with lymphovascular invasion or is poorly differentiated (i.e. tumor is grade 3-4 of 4)
- T2 - invades corpus spongiosum or cavernosum
- T3 - invades urethra
- T4 - invades other adjuacent structures (including prostate)
Regional Lymph Nodes: include superficial and deep inguinal, internal and external iliac, pelvic lymph nodes
- Clinical assessment (based on palpation or imaging):
- cN0 - none
- cN1 - palpable mobile unilateral inguinal LN
- cN2 - palpable mobile multiple or bilateral inguinal LN
- cN3 - fixed inguinal nodal mass or pelvic lymphadenopathy
- Regional Lymph Nodes (pathologic assessment):
- pN0 - none
- pN1 - metastasis in single inguinal LN
- pN2 - multiple or bilateral inguinal lymph nodes
- pN3 - extranodal extension or pelvic lymph node involvement
Distant Metastases:
- M0 - no
- M1 - yes
Stage Grouping:
- 0 - Tis or Ta
- I - T1a N0
- II - T1b-T3 N0
- IIIA - T1-3 N1
- IIIB - T1-3 N2
- IV - T4, N3, M1
Changes from 6th Edition:
- T1 subdivided into T1a and T1b based on LVI and grade
- Prostate invasion moved from T3 to T4. T3 limited to urethral invasion
- Added new schemes for clinical vs pathologic lymph node assessment
- T1b (new subdivision) becomes Stage II and T1a remains Stage I
- Any LN+ is now at least Stage III. Divided into IIIA and IIIB.
Older staging systems
[edit | edit source]AJCC 6th Edition (2002)
Primary Tumor:
- Tis - carcinoma in situ
- Ta - non-invasive verrucous carcinoma
- T1 - invades subepithelial connective tissue
- T2 - invades corpus spongiosum or cavernosum
- T3 - invades urethra or prostate
- T4 - invades other adjuacent structures
Regional Lymph Nodes:
- N0 - none
- N1 - single superficial inguinal lymph node
- N2 - multiple or bilateral superficial inguinal lymph nodes
- N3 - deep inguinal or pelvic lymph nodes (unilateral or bilateral)
Distant Metastases:
- M0 - no
- M1 - yes
Stage Grouping:
- I - T1 N0
- II - T1 N1, T2 N0-1
- III - T1-2 N2, T3 N0-2
- IV - T4, N3, M1
Other staging systems
[edit | edit source]Jackson's Staging
- Stage I (A) - tumor is confined to glans, prepuce or both
- Stage II (B) - tumor extends onto shaft of penis; no nodal or distant metastases
- Stage III (C) - tumor has inguinal nodal metastases that are operable
- Stage IV (D) - tumor involves adjacent structures and is associated with inoperable inguinal metastasis or distant metastasis
Spread
[edit | edit source]Lymph Nodes
- Drainage to superficial inguinal -> deep inguinal -> external iliac
- At presentation
- 50% clinically enlarged
- 50% disease
- 50% reactive - so should treat first with a course of ABX
- 50% clinically negative
- 20% occult disease
- Decision on who should undergo inguinal dissection one of the hardest in penile CA management. Sentinel LN reasonable option
- 50% clinically enlarged
- Highly correlates with T-stage and grade (PMID 11342906)
- T1 11%, T2 63%, T3 63%
- G1 15%, G2 67%, G3 75%
Risk Group | Stage & Grade | LN (+) |
---|---|---|
Low | T1 G1 | 0% |
Intermediate | T1 G2-3, T2 G1 | 33% |
High | T2 G2-3, T3 G1-3 | 83% |
- LN+ correlates with 5-year survival:
- N0 - 80-90%
- N1 - 70%
- N2-3 inguinal - 35%
- N3 pelvic - 20%
- Overall N+ 40-50%
Mets
- <10% M+ at presentation
Sentinel Lymph Node
[edit | edit source]- Netherlands Cancer Institute; 2009 PMID 19414668 -- "Two-center evaluation of dynamic sentinel node biopsy for squamous cell carcinoma of the penis." (Leijte JA, J Clin Oncol. 2009 Jul 10;27(20):3325-9. Epub 2009 May 4.)
- Prospective. 323 patients (from 611 cN0 patients).
- Outcome: Technical success rate 97%. LN+ in 24%. Inguinal recurrences (false-negative SLNB) 7%
- Toxicity: 5% (mostly seroma/lymphocele and infections)
- Conclusion: SLNB suitable procedure to stage clinically N0 penile cancer
Treatment Guidelines
[edit | edit source]- NCI Guidelines are driven by TNM staging
Stage | TNM | Recommendation |
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Stage 0 |
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Stage 1 |
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Stage 2 |
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Stage 3 |
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Stage 4 |
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- European Association of Urologists guidelines are driven by TNM and by lesion grade
Group | Stage | Recommendation |
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Low Risk |
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All Others |
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Surgery vs. RT
[edit | edit source]- Lausanne, 2006 (Switzerland) PMID 16949770 -- "Treatment of penile carcinoma: To cut or not to cut?" (Ozsahin M, Int J Radiat Oncol Biol Phys. 2006 Nov 1;66(3):674-9.)
- Retrospective. 60 patients, 5 surgery, 22 surgery + adjuvant RT, 29 primary RT. Mean F/U 62 months
- 5-year OS: surgery 53% vs. RT 56% (NS). RT failures underwent surgical salvage
- Local failure: Median time to LR failure 14 months; Surgery (+/- RT) 13% vs. RT 56% (SS)
- Patients treated with RT: penis preservation 52%. 5-year probability of intact penis 43%
- Conclusion: Surgery better LR rate, RT better penile preservation, OS same
Brachytherapy
[edit | edit source]- Princess Margaret, 2005 (Canada) 1989-2003 PMID 15890588 -- "Penile brachytherapy: results for 49 patients." (Crook JM, Int J Radiat Oncol Biol Phys. 2005 Jun 1;62(2):460-7.)
- Retrospective. 49 patients. T1 51%, T2 33%. G1 31%, G2 45%. RT treated 23 with PDR BT, 22 Iridium BT, 4 seeds BT to 60 Gy. Medium F/U 2.7 years
- 5-year OS: 78%, CSS 90%
- Local failure: 15%, all salvaged by surgery. Regional failure 20%. Distant failure 10%
- 5-year penile preservation: 86%
- Side effects: soft tissue necrosis 16%, urethral stenosis 12%